Elderly men over 65 years of age with late-onset hypogonadism benefit as much from testosterone treatment as do younger men.

PubMed

Saad, Farid; Yassin, Aksam; Haider, Ahmad; Doros, Gheorghe; Gooren, Louis

2015-04-01

To investigate the potential benefits of testosterone administration to elderly men (>65 years) with late-onset hypogonadism (LOH) in comparison with younger men and to assess the safety of testosterone administration to elderly men. A total of 561 hypogonadal men from two registry studies were divided into age groups of ≤65 years (group Y, n=450; range, 32-65 years) and >65 years (group O, n=111; range, 66-84 years). Following an initial 6-week interval, all men were treated with 3-month injections of parenteral testosterone undecanoate for up to 6 years. Over the 6 years, there was a progressive decrease of body weight and waist circumference. Beneficial effects on lipids and other metabolic factors and on psychological and sexual functioning progressed over the first 24 to 42 months and were sustained. Rather than a deterioration, there was an improvement of urinary parameters. Prostate volume and prostate-specific antigen increased moderately. Hematocrit levels increased but remained within safe margins. The benefits of restoring serum testosterone in men with LOH were not significantly different between men older than 65 years of age and younger men. There were no indications that side effects were more severe in elderly men. The effects on prostate and urinary function and hematocrit were within safe margins. Age itself need not be a contraindication to testosterone treatment of elderly men with LOH.

Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, Imran; Engström, Annette; Vahter, Marie

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), inmore » 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.« less

Can treatment of nocturia increase testosterone level in men with late onset hypogonadism?

PubMed

Kim, Jong Wook; Chae, Ji Yun; Kim, Jin Wook; Yoon, Cheol Yong; Oh, Mi Mi; Park, Hong Seok; Kim, Je Jong; Moon, Du Geon

2014-04-01

To assess the effect of desmopressin on serum testosterone level in men with nocturia and late onset hypogonadism. We prospectively enrolled men with nocturia and symptoms of late onset hypogonadism. Desmopressin (0.1 mg) was administered once daily to patients for 12 weeks, and we then compared serum testosterone levels, electrolytes, frequency volume chart indices, and changes in the International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Aging Male's Symptom scales before and after treatment. Patients with a history of cardiovascular disease or hyponatremia, those using hypnotics, and those who had primary hypogonadism or hypogonadotrophic hypogonadism were excluded from the study. Sixty-two men (mean age, 68.4 years) completed pre- and post-treatment questionnaires and underwent laboratory testing. At the end of the study, the testosterone levels in men with low testosterone levels (<3.5 ng/mL) increased after the 12-week desmopressin treatment (2.85 ± 0.58 to 3.97 ± 1.44 ng/mL; P = .001). Mean scores had decreased from 17.7 to 13.9 (IPSS), 3.8 to 3.2 (IPSS-Quality of Life), and 33.7 to 31.1 (Aging Male's Symptom). On the frequency volume chart, nocturnal urine volume, nocturnal polyuria index, actual number of nocturia events, nocturia index, and nocturnal bladder capacity index were significantly decreased. Desmopressin improved nocturia and other urinary symptoms. Moreover, serum testosterone levels increased significantly in men with low testosterone levels after 12-week desmopressin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Hormone levels of world class cyclists during the Tour of Spain stage race

PubMed Central

Lucia, A; Diaz, B; Hoyos, J; Fernandez, C; Villa, G; Bandres, F; Chicharro, J

2001-01-01

Objectives—To evaluate the hormonal response to strenuous endurance exercise performed by elite athletes. Methods—Nine professional cyclists (mean (SD) age 28 (1) years; mean (SD) VO2MAX 75.3 (2.3) ml/kg/min) who participated in a three week tour race (Vuelta a España 1999) were selected as subjects. Morning urinary levels of 6-sulphatoxymelatonin (aMT6s) and morning serum levels of testosterone, follicle stimulating (FSH), luteinising hormone (LH), and cortisol were measured in each subject at t0 (before the competition), t1 (end of first week), t2 (end of second week), and t3 (end of third week). Urine samples of aMT6s were also evaluated in the evening at t0, t1, t2, and t3. Results—Mean urinary aMT6s levels had increased significantly (p<0.01) during the day after each stage (1091 (33) v 683 (68) ng/ml at t1; 955 (19) v 473 (53) ng/ml at t2; 647 (61) v 337 (47) ng/ml at t3). Both morning and evening aMT6s levels decreased significantly during the study. A similar pattern was observed for morning serum levels of cortisol and testosterone. Conclusions—The results suggest that the basal activity of the pineal gland, adrenal glands, and testis may be decreased after consecutive days of intense, long term exercise. Key Words: melatonin; gonadotrophins; testosterone; cortisol; endurance exercise PMID:11726480

Use of selenium-silymarin mix reduces lower urinary tract symptoms and prostate specific antigen in men.

PubMed

Vostalova, Jitka; Vidlar, Ales; Ulrichova, Jitka; Vrbkova, Jana; Simanek, Vilim; Student, Vladimir

2013-12-15

The aim of this double-blind, placebo controlled clinical trial was to assess the effects of a combination of selenium and silymarin in men with lower urinary tract symptoms, benign prostatic hyperplasia and a prostate specific antigen (PSA) ≤2.5ng/ml. The volunteers were randomized to two groups: the first one (n=26) received 240μg selenium (in the form of yeast l-selenomethionine) plus 570mg silymarin daily for 6 months and the second (n=29) received placebo. Outcome measures were changes in the International Prostate Symptom Score (IPSS), bladder volume (V), urinary flow rate, ultrasound estimated postvoid residual urine volume (RV), serum PSA, testosterone and selenium levels, safety clinical biochemistry, hematology and oxidative stress parameters at baseline and on day 180. The results showed statistically significant differences (p<0.05) between treatment and control groups for the following parameters: IPSS score, urodynamic parameters: maximal rate of urine flow (Qmax), average flow (Qave), V and RV, total PSA value and serum selenium levels. There was a significant reduction in PSA in the selenium-silymarin group but no effect on blood testosterone level. Overall the treatment was well-tolerated with no adverse effects. Copyright © 2013 Elsevier GmbH. All rights reserved.

Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats

PubMed Central

YANG, BI-CHENG; JIN, LI-LI; YANG, YI-FANG; LI, KUN; PENG, DAN-MING

2014-01-01

Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO2 fluid extract (SFE-CO2) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO2 extract may be a useful agent in BPH treatment. PMID:24944593

Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats.

PubMed

Yang, Bi-Cheng; Jin, Li-Li; Yang, Yi-Fang; Li, Kun; Peng, Dan-Ming

2014-07-01

Benign prostatic hyperplasia (BPH) can lead to lower urinary tract symptoms. Rape pollen is an apicultural product that is composed of nutritionally valuable and biologically active substances. The aim of the present study was to investigate the protective effect of rape pollen supercritical CO 2 fluid extract (SFE-CO 2 ) in BPH development using a testosterone-induced BPH rat model. BPH was induced in the experimental groups by daily subcutaneous injections of testosterone for a period of 30 days. Rape pollen SFE-CO 2 was administered daily by oral gavage concurrently with the testosterone injections. Animals were sacrificed at the scheduled termination and the prostates were weighed and subjected to histopathological examination. Testosterone, dihydrotestosterone (DHT), 5α-reductase and cyclooxygenase-2 (COX-2) levels were also measured. BPH-induced animals exhibited an increase in prostate weight with increased testosterone, DHT, 5α-reductase and COX-2 expression levels. However, rape pollen SFE-CO 2 treatment resulted in significant reductions in the prostate index and testosterone, DHT, 5α-reductase and COX-2 levels compared with those in BPH-induced animals. Histopathological examination also demonstrated that rape pollen SFE-CO 2 treatment suppressed testosterone-induced BPH. These observations indicate that rape pollen SFE-CO 2 inhibits the development of BPH in rats and these effects are closely associated with reductions in DHT, 5α-reductase and COX-2 levels. Therefore, the results of the present study clearly indicate that rape pollen SFE-CO 2 extract may be a useful agent in BPH treatment.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

PubMed

Debruyne, Frans M J; Behre, Hermann M; Roehrborn, Claus G; Maggi, Mario; Wu, Frederick C W; Schröder, Fritz H; Jones, Thomas Hugh; Porst, Hartmut; Hackett, Geoffrey; Wheaton, Olivia A; Martin-Morales, Antonio; Meuleman, Eric; Cunningham, Glenn R; Divan, Hozefa A; Rosen, Raymond C

2017-02-01

To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. Results support prostate safety of TRT in newly diagnosed men with HG. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Testosterone-secreting adrenal adenoma in a peripubertal girl

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.

1987-11-13

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started fourmore » months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.« less

Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

PubMed Central

Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron

2016-01-01

In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581

Serum Testosterone Concentrations and Urinary Bisphenol A, Benzophenone-3, Triclosan, and Paraben Levels in Male and Female Children and Adolescents: NHANES 2011–2012

PubMed Central

Scinicariello, Franco; Buser, Melanie C.

2016-01-01

Background: Exposure to environmental phenols (e.g., bisphenol A, benzophenone-3, and triclosan) and parabens is widespread in the population. Many of these chemicals have been shown to have anti-androgenic effects both in vitro and in vivo. Objective: We examined the association of bisphenol A (BPA), benzophenone-3 (BP-3), triclosan (TCS), and parabens with serum total testosterone (TT) levels in child and adolescent participants (ages 6–19 years) in the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Methods: We performed multivariable linear regression to estimate associations between natural log–transformed serum TT and quartiles of urinary BPA, BP-3, TCS, and parabens in male and female children (ages 6–11 years) and adolescents (ages 12–19 years). Results: BP-3 and BPA were associated with significantly lower TT in male adolescents, and BPA was associated with significantly higher TT in female adolescents. TT was not consistently associated with TCS or total parabens in children or adolescents of either sex. Conclusions: To our knowledge, this is the first study to report an association of both BP-3 and BPA with serum TT in adolescents. Associations between BPA and TT differed according to sex in adolescents, with inverse associations in boys and positive associations in girls. BP-3 was associated with significantly lower TT in adolescent boys only. However, because of the limitations inherent to the cross-sectional study design, further studies are needed to confirm and elucidate on our findings. Citation: Scinicariello F, Buser MC. 2016. Serum testosterone concentrations and urinary bisphenol A, benzophenone-3, triclosan, and paraben levels in male and female children and adolescents: NHANES 2011–2012. Environ Health Perspect 124:1898–1904; http://dx.doi.org/10.1289/EHP150 PMID:27383665

Hyperandrogenism in adolescent girls: relationship with the somatotrophic axis.

PubMed

Hernandez, María Isabel; López, Patricia; Gaete, Ximena; Villarroel, Claudio; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Cassorla, Fernando

2017-05-01

During puberty there is a physiologic increase in adrenal and ovarian androgens. It has been suggested that the somatotrophic axis may be related to the development of hyperandrogenism and anovulation in non-obese adult women with polycystic ovarian syndrome (PCOS). The objective of the study was to investigate whether ovarian androgen secretion in young postmenarchal girls is related to the function of their somatotropic axis. This was a cross-sectional study of adolescent girls. We studied non-obese adolescent girls with hyperandrogenism (HA; n = 21) matched with control girls (C; n = 25) for chronological age, age at menarche and body mass index. We obtained a fasting blood sample for measurement of serum glucose, insulin, 17-hydroxyprogesterone (17OH-Prog), dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, sex hormone-binding globulin (SHBG), total testosterone, IGF-I, IGF-II, IGFBP-1, IGFBP-3, ghrelin, leptin, AMH (antiMüllerian hormone), luteinizing hormone (LH) and follicle stimulating hormone (FSH) during the follicular phase of the menstrual period. We performed an oral glucose tolerance test to determine blood glucose, insulin and ghrelin levels and urine samples to measure urinary GH (growth hormone) levels. As expected, the hyperandrogenic girls had significantly higher Ferriman scores, basal total testosterone, free androgen index (FAI), androstenedione, AMH, and basal LH levels compared with the girls in controls. Serum IGF-I, IGF-II, IGFBP-3 and urinary GH did not differ between HA and C. There was a correlation between urinary GH and FAI in all girls (r 0.29, p < 0.05). In addition, in HA girls FAI correlated with insulin, homeostasis model assessment (HOMA) and ghrelin. We observed a correlation between urinary GH and FAI in the hyperandrogenic and control girls, suggesting that the function of the somatotrophic axis may influence the secretion of androgens in adolescent girls.

Long-term effects of treatment on endocrine function in children with brain tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duffner, P.K.; Cohen, M.E.; Anderson, S.W.

1983-11-01

Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion ofmore » cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.« less

Elevated phthalates' exposure in children with constitutional delay of growth and puberty.

PubMed

Xie, Changming; Zhao, Yan; Gao, Lianlian; Chen, Jiao; Cai, Depei; Zhang, Yunhui

2015-05-15

Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay. Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = -45.7, p = 0.017; MEP: β = -31.6, p = 0.022; total phthalates: β = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower urinary tract symptoms.

PubMed

Vidlar, Ales; Vostalova, Jitka; Ulrichova, Jitka; Student, Vladimir; Stejskal, David; Reichenbach, Richard; Vrbkova, Jana; Ruzicka, Filip; Simanek, Vilim

2010-10-01

Lower urinary tract symptoms (LUTS) are a common condition in older men. The objective of the present study was to evaluate the efficacy and tolerability of cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and clinically confirmed chronic non-bacterial prostatitis. Forty-two participants received either 1500 mg of the dried powdered cranberries per d for 6 months (cranberry group; n 21) or no cranberry treatment (control group; n 21). Physical examination, International Prostate Symptom Score, quality of life (QoL), five-item version of the International Index of Erectile Function (IIEF-5), basic clinical chemistry parameters, haematology, Se, testosterone, PSA (free and total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine volume at baseline, and at 3 and 6 months, and urine ex vivo anti-adherence activity were determined in all subjects. In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score, QoL, urination parameters including voiding parameters (rate of urine flow, average flow, total volume and post-void residual urine volume), and lower total PSA level on day 180 of the study. There was no influence on blood testosterone or serum CRP levels. There was no statistically significant improvement in the control group. The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level.

Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms

PubMed Central

Li, Jing; Tian, Yanxin; Guo, Shimeng; Gu, Haifeng; Yuan, Qianting; Xie, Xin

2018-01-01

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies. PMID:29351556

Associations between male testosterone and immune function in a pathogenically stressed forager-horticultural population

PubMed Central

Trumble, Benjamin C; Blackwell, Aaron D; Stieglitz, Jonathan; Thompson, Melissa Emery; Suarez, Ivan Maldonado; Kaplan, Hillard; Gurven, Michael

2016-01-01

Objectives Despite well-known fitness advantages to males who produce and maintain high endogenous testosterone levels, such phenotypes may be costly if testosterone-mediated investment in reproductive effort trade-off against investment in somatic maintenance. Previous studies of androgen-mediated trade-offs in human immune function find mixed results, in part because most studies either focus on a few indicators of immunity, are confounded by phenotypic correlation, or are observational. Here the association between male endogenous testosterone and 13 circulating cytokines are examined before and after ex vivo antigen stimulation with phytohaemagglutinin (PHA) and lipopolysaccharides (LPS) in a high pathogen population of Bolivian forager-horticulturalists. Materials and Methods A Milliplex 13-plex cytokine panel measured cytokine concentration in whole blood samples from 109 Tsimane men aged 40–89 (median=50 years) before and after antigen stimulation with PHA and LPS. Urinary testosterone was measured via enzyme immunoassay; demographic and anthropometric data were collected as part of the Tsimane Health and Life History Project. Results Higher endogenous testosterone was associated with down-regulated responses in all cytokines after PHA stimulation (but significantly in only 2/13 cytokines), controlling for age and body mass index. In contrast, testosterone was not significantly associated with down-regulation of cytokines after LPS stimulation. MANOVAs indicate that men with higher testosterone showed reduced cytokine responses to PHA compared to LPS (p=0.0098). Discussion Endogenous testosterone appears to be immunomodulatory rather than immunosuppressive. Potentially costlier forms of immune activation like those induced by PHA (largely T-cell biased immune activation) are down-regulated in men with higher testosterone, but testosterone has less impact on potentially less costly immune activation following LPS stimulation (largely B-cell mediated immunity). PMID:27465811

Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline.

PubMed

Bhasin, Shalender; Cunningham, Glenn R; Hayes, Frances J; Matsumoto, Alvin M; Snyder, Peter J; Swerdloff, Ronald S; Montori, Victor M

2006-06-01

The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men. The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer. The Task Force received no corporate funding or remuneration. The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group. Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications. The drafts prepared by the panelists with the help of a professional writer were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Committee, and Council. The version approved by the Council was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and in some patients by measurement of free or bioavailable testosterone level, using accurate assays. We recommend testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 3 ng/ml without further urological evaluation, erythrocytosis (hematocrit > 50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) greater than 19, or class III or IV heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.

Impact of a folic acid-enriched diet on urinary tract function in mice treated with testosterone and estradiol

PubMed Central

Keil, Kimberly P.; Abler, Lisa L.; Altmann, Helene M.; Wang, Zunyi; Wang, Peiqing; Ricke, William A.; Bjorling, Dale E.

2015-01-01

Aging men are susceptible to developing lower urinary tract symptoms, but the underlying etiology is unknown and the influence of dietary and environmental factors on them is unclear. We tested whether a folic acid-enriched diet changed urinary tract physiology and biology in control male mice and male mice with urinary dysfunction induced by exogenous testosterone and estradiol (T+E2), which mimics changing hormone levels in aging humans. T+E2 treatment increased mouse urine output, time between voiding events, and bladder capacity and compliance. Consumption of a folic acid-enriched diet moderated these changes without decreasing prostate wet weight or threshold voiding pressure. One potential mechanism for these changes involves water balance. T+E2 treatment increases plasma concentrations of anti-diuretic hormone, which is offset at least in part by a folic acid-enriched diet. Another potential mechanism involves neural control of micturition. The folic acid-enriched diet, fed to T+E2-treated mice, increased voiding frequency in response to intravesicular capsaicin infusion and increased mRNA abundance of the capsaicin-sensitive cation channel transient receptor potential vanilloid subfamily member 1 (Trpv1) in L6 and S1 dorsal root ganglia (DRG) neurons. T+E2 treatment and a folic acid-enriched diet also modified DNA methylation, which is capable of altering gene expression. We found the enriched diet increased global DNA methylation in dorsal and ventral prostate and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or reverse T+E2-mediated alteration in urinary function in part by normalizing water balance and enhancing or preserving afferent neuronal function. PMID:25855514

A neuroendocrine predisposition for homosexuality in men.

PubMed

Dörner, G; Rohde, W; Stahl, F; Krell, L; Masius, W G

1975-01-01

In male rats, androgen deficiency during a critical hypothalamic organizational period was shown to give rise to a predominantly female-differentiated brain, homosexual behavior, and demonstration of a positive estrogen feedback effect. A positive estrogen feedback effect was also induced in intact homosexual men in contrast to intact heterosexual and bisexual men. Thus in 21 homosexual men an intravenous injection of 20 mg Presomen (Premarin) produced a significant decrease of serum LH levels followed by an increase above initial LH values. In 20 heterosexual and in five bisexual men, by contrast, intravenous estrogen administration, while producing a significant decrease of the serum LH level, was not followed by an increase above the initial LH values. Using a radioimmunoassay, plasma testosterone levels and 24-hr urinary excretions of unconjugated testosterone of adult homosexual men were found to be in the normal range as observed in heterosexual men. This finding suggests that homosexual men possess a predominantly female-differentiated brain which may be activated to homosexual behavior by normal or approximately normal androgen levels in adulthood.

Exposure to organophosphate pesticides and male hormone profile in floriculturist of the state of Morelos, Mexico.

PubMed

Blanco-Muñoz, Julia; Morales, Magally Mayanin; Lacasaña, Marina; Aguilar-Garduño, Clemente; Bassol, Susana; Cebrián, Mariano E

2010-07-01

Studies on experimental animals have found that organophosphate (OP) pesticides may act as endocrine disruptors; however, their effects on the human hormonal profile have not yet been adequately characterized. We evaluate the association between exposure to OP pesticides, measured through dialkyl phosphate (DAP) metabolites urinary levels, and the male hormone profile. A cross-sectional study was performed in 104 floriculturists of Morelos, Mexico. A structured questionnaire was applied to get information on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, and work history. DAP metabolites [dimethylphosphate (DMP), dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate] were determined using gas-liquid chromatography. Serum levels of FSH, LH, prolactin, testosterone, inhibin B and estradiol were determined using enzyme-linked immunosorbent assay. Multiple linear regression was used to study the association between DAP metabolite levels and male hormonal profile. Data were adjusted by p,p'-dichlorodiphenyldichloroethene serum levels and other potential confounders. There was a negative association between inhibin B and urinary levels of DMP, DEP, DETP and total DAP metabolites. DEP levels were negatively associated with serum FSH concentrations, but marginally and positively associated with those of testosterone. DETP was marginally associated with lower LH serum levels. There were no other significant associations among OP metabolites and serum hormone levels. Inhibin B and FSH vary according to levels of DAP metabolites in men occupationally exposed to OP pesticides. These results suggest that OP pesticides could act as endocrine disruptors in humans; however, most hormonal values fell within the wide normal range and associations were small. There is, therefore, a need for further investigation to elucidate their biological and clinical relevance.

Stable isotope ratio profiling of testosterone preparations.

PubMed

Cawley, Adam; Collins, Michael; Kazlauskas, Rymantas; Handelsman, David J; Heywood, Robert; Longworth, Mitchell; Arenas-Queralt, Andrea

2010-01-01

Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) is the preferred method of confirming the administration of exogenous testosterone by athletes. This relies on synthetic testosterone preparations being depleted in (13) C compared to natural testosterone. There is concern, however, about the existence of synthetic testosterone products that are unexpectedly (13) C-enriched and which may allow athletes to circumvent the current GC-C-IRMS test. Further to the reported studies of legitimate pharmaceutical-grade testosterone products, a detailed analysis of seized materials from border-level seizures was required to obtain intelligence concerning trends in 'black market' testosterone manufacture and distribution. The sample set collected for this study between 2006 and 2009 inclusive provided a δ(13) C range (n = 266) of -22.9‰ to -32.6‰ with mean and median values of -28.4‰ and -28.6‰, respectively. Within this distribution there were 24 samples (9%) confirmed to have δ(13) C values in the range reported for endogenous urinary steroid metabolites (≥ -25.8‰). The benefit of δ(13) C profiling for testosterone preparations was demonstrated by the ability to identify specific seized products that can be target tested for future intelligence purposes. In addition, the potential of stable hydrogen isotope ratio ((2) H/(1) H; δ(2) H) discrimination to complement δ(13) C analysis was investigated. Methodologies for the determination of δ(2) H values by gas chromatography-thermal conversion-isotope ratio mass spectrometry (GC-TC-IRMS) were developed to provide a δ(2) H range (n = 173) of -177‰ to -268‰ with mean and median values of -231‰ and -234‰, respectively. Copyright © 2010 John Wiley & Sons, Ltd.

Normal Pubertal Development in Daughters of Women With PCOS: A Controlled Study.

PubMed

Legro, Richard S; Kunselman, Allen R; Stetter, Christy M; Gnatuk, Carol L; Estes, Stephanie J; Brindle, Eleanor; Vesper, Hubert W; Botelho, Julianne C; Lee, Peter A; Dodson, William C

2017-01-01

Daughters of women with polycystic ovary syndrome (PCOS) are thought to be at increased risk for developing stigmata of the syndrome, but the ontogeny during puberty is uncertain. We phenotyped daughters (n = 76) of mothers with PCOS and daughters (n = 80) from control mothers for reproductive and metabolic parameters characteristic of PCOS. We performed a matched case/control study at Penn State Hershey Medical Center that included non-Hispanic, white girls 4 to 17 years old. We obtained birth history, biometric, ovarian ultrasounds, whole-body dual-energy X-ray absorptiometry scan for body composition, 2-hour glucose challenged salivary insulin levels, and two timed urinary collections (12 hours overnight and 3 hours in the morning) for gonadotropins and sex steroids. We measured integrated urinary levels of adrenal (dehydroepiandrosterone sulfate) and ovarian [testosterone (TT)] steroids. Other endpoints included integrated salivary insulin levels and urinary luteinizing hormone levels. There were no differences in detection rates or mean levels for gonadotropins and sex steroids in timed urinary collections between PCOS daughters and control daughters, nor were there differences in integrated salivary insulin levels. Results showed that 69% of Tanner 4/5 PCOS daughters vs 31% of control daughters had hirsutism defined as a Ferriman-Gallwey score >8 (P = 0.04). There were no differences in body composition as determined by dual-energy X-ray absorptiometry between groups in the three major body contents (i.e., bone, lean body mass, and fat) or in ovarian volume between groups. Matched for pubertal stage, PCOS daughters have similar levels of urinary androgens and gonadotropins as well as glucose-challenged salivary insulin levels. Copyright © 2017 by the Endocrine Society

Puberty, ovarian cycle, pregnancy, and postpartum ovulation in captive Sichuan golden monkeys (Rhinopithecus roxellana) based on changes in urinary and fecal gonadal steroid metabolites.

PubMed

Muren; Kusuda, Satoshi; Doi, Osamu; Naito, Hitomi; Hashikawa, Hisashi

2017-01-01

The purpose of this study was to evaluate the reproductive status and clarify the reproductive physiology of captive Sichuan golden monkeys. The concentrations of urinary estradiol-3-glucuronide (E 2 G) and pregnanediol-glucuronide (PdG) or fecal estradiol-17β (E 2 ) and PdG in two females, and fecal testosterone concentrations in a male, were measured continuously using enzyme immunoassays. On the basis of these hormone profiles, the follicular phase, luteal phase, and ovarian cycle were calculated to be 14.7 ± 4.8, 10.4 ± 2.8, and 25.1 ± 3.3 days, respectively. The first ovulation (puberty) in a female monkey was observed at 5.1 years old, and the first pregnancy was diagnosed at 6.4 years old. For the first 2 months of pregnancy (204 days), fecal E 2 and PdG maintained constant high values and then increased until parturition. These profiles were similar to urinary E 2 G and PdG changes. During the last trimester of a twin pregnancy, fecal PdG was up to approximately three times higher compared with a single pregnancy. Therefore, fecal PdG levels in late pregnancy may be effective for the detection of a twin pregnancy. The first postpartum ovulation occurred 66 (fetal death and artificial rearing), 143 (fetal death), and 189 (natural suckling) days after parturition. The anovulation period of the natural suckling case was longer than the others. Conception and postpartum ovulation were detected between September and January. Fecal testosterone levels of the male were correlated with the fecal E 2 level of the nonpregnancy period in exhibited together female. Our results reported that urinary (E 2 G and PdG) and fecal (E 2 and PdG) hormone measurement is effective for monitoring the reproductive status, thereby expanding knowledge of the reproductive endocrinology of this endangered species. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens.

PubMed

Anderson, R A; Wallace, A M; Kicman, A T; Wu, F C

1997-08-01

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.

Hormonal disturbances in visceral leishmaniasis (kala-azar).

PubMed

Verde, Frederico Araujo Lima; Verde, Francisco Agenor Araujo Lima; Neto, Augusto Saboia; Almeida, Paulo César; Verde, Emir Mendonça Lima

2011-05-01

This study presents a cross-sectional analysis of the hormonal alterations of patients with visceral leishmaniasis. The diagnosis was established by the bone marrow aspiration and polymerase chain reaction test. Primary adrenal insufficiency was observed in 45.8% of patients; low aldosterone/renin plasma ratio in 69.4%; low daily urinary aldosterone excretion in 61.1%; and low transtubular potassium gradient in 68.0%. All patients had normal plasma antidiuretic hormone (ADH) concentrations, hyponatremia, and high urinary osmolality. Plasma parathyroid hormone was low in 63%; hypomagnesemia was present in 46.4%, and increased Mg(++)(EF) in 100%. Primary thyroid insufficiency was observed in 24.6%, and secondary thyroid insufficiency in 14.1%. Normal follicle-stimulating hormone plasma levels were present in 81.4%; high luteinizing hormone and low testosterone plasma levels in 58.2% of men. There are evidences of hypothalamus-pituitary-adrenal axis abnormalities, inappropriate aldosterone and ADH secretions, and presence of hypoparathyroidism, magnesium depletion, thyroid and testicular insufficiencies.

Male hypogonadism.

PubMed

Basaria, Shehzad

2014-04-05

Male hypogonadism is a clinical syndrome that results from failure to produce physiological concentrations of testosterone, normal amounts of sperm, or both. Hypogonadism may arise from testicular disease (primary hypogonadism) or dysfunction of the hypothalamic-pituitary unit (secondary hypogonadism). Clinical presentations vary dependent on the time of onset of androgen deficiency, whether the defect is in testosterone production or spermatogenesis, associated genetic factors, or history of androgen therapy. The clinical diagnosis of hypogonadism is made on the basis of signs and symptoms consistent with androgen deficiency and low morning testosterone concentrations in serum on multiple occasions. Several testosterone-replacement therapies are approved for treatment and should be selected according to the patient's preference, cost, availability, and formulation-specific properties. Contraindications to testosterone-replacement therapy include prostate and breast cancers, uncontrolled congestive heart failure, severe lower-urinary-tract symptoms, and erythrocytosis. Treatment should be monitored for benefits and adverse effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Urinary testosterone levels of wild male bonobos (Pan paniscus) in the Lomako Forest, Democratic Republic of Congo.

PubMed

Marshall, Andrew J; Hohmann, Gottfried

2005-01-01

We collected urine samples from seven male bonobos (Pan paniscus) in the Eyengo community, Lomako Forest, Democratic Republic of Congo, and assayed them for testosterone (T). T levels averaged 525 pmol/mg Cr in adult males, and 309 pmol/mg Cr in subadult males. We collected hormonal and behavioral data during a period of relative social instability following the recent arrival of two immigrant males. In concordance with predictions derived from the challenge hypothesis [Wingfield et al., American Naturalist 136:829-846, 1990], which relates T to levels of reproductive aggression, the alpha male had the highest circulating levels of T. When we removed the two recent immigrant males from the analysis, there was a significant positive correlation between T levels and dominance rank for the long-term resident males (n=5, P=0.001, r2=0.98). These are the first data on T levels in wild bonobos, and the results suggest that further study of the relationship between T levels and social context in this species could inform current models relating hormones and aggression in wild apes. (c) 2005 Wiley-Liss, Inc.

Red wine and component flavonoids inhibit UGT2B17 in vitro

PubMed Central

2012-01-01

Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analyzed using HPLC; and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8%, the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HPLC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 μM despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolizing enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the health implications. PMID:22958586

Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor.

PubMed

Clark, Richard V; Hermann, David J; Cunningham, Glenn R; Wilson, Timothy H; Morrill, Betsy B; Hobbs, Stuart

2004-05-01

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.

Steroid profiles of professional soccer players: an international comparative study.

PubMed

Strahm, E; Sottas, P-E; Schweizer, C; Saugy, M; Dvorak, J; Saudan, C

2009-12-01

Urinary steroid profiling is used in doping controls to detect testosterone abuse. A testosterone over epitestosterone (T/E) ratio exceeding 4.0 is considered as suspicious of testosterone administration, irrespectively of individual heterogeneous factors such as the athlete's ethnicity. A deletion polymorphism in the UGT2B17 gene was demonstrated to account for a significant part of the interindividual variability in the T/E between Caucasians and Asians. Here, the variability of urinary steroid profiles was examined in a widely heterogeneous cohort of professional soccer players. The steroid profile of 57 Africans, 32 Asians, 50 Caucasians and 32 Hispanics was determined by gas chromatography-mass spectrometry. Significant differences have been observed between all ethnic groups. After estimation of the prevalence of the UGT2B17 deletion/deletion genotype (African: 22%; Asian: 81%; Caucasian: 10%; Hispanic: 7%), ethnic-specific thresholds were developed for a specificity of 99% for the T/E (African: 5.6; Asian: 3.8; Caucasian: 5.7; Hispanic: 5.8). Finally, another polymorphism could be hypothesised in Asians based on specific concentration ratio of 5alpha-/5beta-androstane-3alpha,17beta-diol in urine. These results demonstrate that a unique and non-specific threshold to evidence testosterone misuse is not fit for purpose. An athlete's endocrinological passport consisting of a longitudinal follow-up together with the ethnicity and/or the genotype would strongly enhance the detection of testosterone abuse. Finally, additional genotyping studies should be undertaken to determine whether the remaining unexplained disparities have an environmental or a genetic origin.

Simultaneous Detection of Androgen and Estrogen Abuse in Breeding Animals by Gas Chromatography-Mass Spectrometry/Combustion/Isotope Ratio Mass Spectrometry (GC-MS/C/IRMS) Evaluated against Alternative Methods.

PubMed

Janssens, Geert; Mangelinckx, Sven; Courtheyn, Dirk; De Kimpe, Norbert; Matthijs, Bert; Le Bizec, Bruno

2015-09-02

The administration of synthetic homologues of naturally occurring steroids can be demonstrated by measuring (13)C/(12)C isotopic ratios of their urinary metabolites. Gas chromatography-mass spectrometry/combustion/isotope ratio mass spectrometry (GC-MS/C/IRMS) was used in this study to appraise in a global approach isotopic deviations of two 17β-testosterone metabolites (17α-testosterone and etiocholanolone) and one 17β-estradiol metabolite (17α-estradiol) together with those of 5-androstene-3β,17α-diol as endogenous reference compound (ERC). Intermediate precisions of 0.35‰, 1.05‰, 0.35‰, and 0.21‰, respectively, were observed (n = 8). To assess the performance of the analytical method, a bull and a heifer were treated with 17β-testosterone propionate and 17β-estradiol-3-benzoate. The sensitivity of the method permitted the demonstration of 17β-estradiol treatment up to 24 days. For 17β-testosterone treatment, the detection windows were 3 days and 24 days for the bull and the heifer, respectively. The capability of GC-MS/C/IRMS to demonstrate natural steroid abuse for urinary steroids was eventually compared to those of mass spectrometry (LC-MS/MS) when measuring intact steroid esters in blood and hair.

The histological and histometrical effects of Urtica dioica extract on rat's prostate hyperplasia.

PubMed

Moradi, Hamid Reza; Erfani Majd, Naeem; Esmaeilzadeh, Saleh; Fatemi Tabatabaei, Sayed Reza

2015-01-01

Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg(-1) testosterone subcutaneously, G3 received 50 mg kg(-1) nettle root extract orally, G4 received 50 mg kg(-1) nettle root extract orally and 10 mg kg(-1) testosterone, G5 received 10 mg kg(-1) almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly.

Urinary testosterone-metabolite levels and dominance rank in male and female bonobos (Pan paniscus).

PubMed

Sannen, Adinda; Van Elsacker, Linda; Heistermann, Michael; Eens, Marcel

2004-04-01

The correlation between testosterone (T) and dominance rank may vary among species, and is expected to become stronger as the importance of aggressive competition for rank increases. However, it may also vary among social situations within a species, showing a stronger correlation during socially unstable periods. Knowledge on this topic in great apes, especially in females, is scant. This study presents the first data on the relationship between T and dominance rank in both sexes of the bonobo ( Pan paniscus). For each period (four socially unstable and two stable ones), linear rank orders were determined and subsequently correlated with the accompanying mean urinary T-metabolite concentrations (measured as immunoreactive 5alpha-androstan-17alpha-ol-3-one). No correlation between these two variables was found for either sex among individuals during socially unstable or stable periods. Also, within an individual over the six periods, no relationship of T with rank could be demonstrated. These results suggest that either the outcomes of aggressions have no influence on T levels, or such clear outcomes appear insufficiently frequent to affect T levels over longer periods. Even during the unstable periods, the rate of aggressions was not higher than during stable periods, suggesting that frequencies of aggression have little effect on rank. Further analyses indeed demonstrated no correlation between frequencies of overall aggressions or any type of aggressive behavior separately, or rank. Perhaps factors other than the frequency of displayed aggressions alone have a marked influence on a bonobo's rank, for example, coalition partners. Overall, in bonobos, T apparently does not form a physiological reflection of social status.

Detection of Synthetic Testosterone Use by Novel Comprehensive Two-Dimensional Gas Chromatography Combustion Isotope Ratio Mass Spectrometry (GC×GCC-IRMS)

PubMed Central

Tobias, Herbert J.; Zhang, Ying; Auchus, Richard J.; Brenna, J. Thomas

2011-01-01

We report the first demonstration of Comprehensive Two-dimensional Gas Chromatography Combustion Isotope Ratio Mass Spectrometry (GC×GCC-IRMS) for the analysis of urinary steroids to detect illicit synthetic testosterone use, of interest in sport doping. GC coupled to IRMS (GCC-IRMS) is currently used to measure the carbon isotope ratios (CIR, δ13C) of urinary steroids in anti-doping efforts; however, extensive cleanup of urine extracts is required prior to analysis to enable baseline separation of target steroids. With its greater separation capabilities, GC×GC has the potential to reduce sample preparation requirements and enable CIR analysis of minimally processed urine extracts. Challenges addressed include on-line reactors with minimized dimensions to retain narrow peaks shapes, baseline separation of peaks in some cases, and reconstruction of isotopic information from sliced steroid chromatographic peaks. Difficulties remaining include long-term robustness of on-line reactors and urine matrix effects that preclude baseline separation and isotopic analysis of low concentration and trace components. In this work, steroids were extracted, acetylated, and analyzed using a refined, home-built GC×GCC-IRMS system. 11-hydroxy-androsterone (11OHA) and 11-ketoetiocolanolone (11KE) were chosen as endogenous reference compounds (ERC) because of their satisfactory signal intensity, and their CIR was compared to target compounds (TC) androsterone (A) and etiocholanolone (E). Separately, a GC×GC-qMS system was used to measure testosterone (T)/EpiT concentration ratios. Urinary extracts of urine pooled from professional athletes, and urine from one individual that received testosterone gel (T-gel) and one individual that received testosterone injections (T-shot) were analyzed. The average precisions of δ13C and Δδ13C measurements were SD(δ13C) approximately ± 1‰ (n=11). The T-shot sample resulted in a positive for T use with a T/EpiT ratio of > 9 and CIR measurements of Δδ13C > 5‰, both fulfilling World Anti-Doping Agency criteria. These data show for the first time that synthetic steroid use is detectable by GC×GCC-IRMS without need for extensive urine cleanup. PMID:21846122

Characterization of urinary metabolites of testosterone, methyltestosterone, mibolerone and boldebone in greyhound dogs.

PubMed

Williams, T M; Kind, A J; Hyde, W G; Hill, D W

2000-06-01

Androgenic steroids are used in female greyhound dogs to prevent the onset of estrus; moreover, these steroids also have potent anabolic activity. As anabolic steroids increase muscle mass and aggression in animals, the excessive use of these agents in racing greyhounds gives an unfair performance advantage to treated dogs. The biotransformation of most anabolic steroids has not been determined in greyhound dogs. The objective of the present study was to identify the urinary metabolites of testosterone, methyltestosterone, mibolerone, and boldenone in greyhound dogs. These steroids were administered orally (1 mg/kg) to either male or female greyhound dogs and urine samples were collected pre-administration and at 2, 4, 8, 12, 24, 72, and 96 h post-administration. Urine extracts were analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) to identify major metabolites and to determine their urinary excretion profiles. Major urinary metabolites, primarily glucuronide, conjugated and free, were detected for the selected steroids. Sulfate conjugation did not appear to be a major pathway for steroid metabolism and excretion in the greyhound dog. Phase I biotransformation was also evaluated using greyhound dog liver microsomes from untreated dogs. The identification of several in vivo steroid metabolites generated in this study will be useful in detecting these steroids in urine samples submitted for drug screening.

Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus.

PubMed

Nagai, T; Mimura, N; Tomizawa, T; Monden, T; Mori, M

1998-12-01

A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia.

Dose-dependent testosterone sensitivity of the steroidal passport and GC-C-IRMS analysis in relation to the UGT2B17 deletion polymorphism.

PubMed

Strahm, Emmanuel; Mullen, Jenny E; Gårevik, Nina; Ericsson, Magnus; Schulze, Jenny J; Rane, Anders; Ekström, Lena

2015-01-01

The newly implemented Steroid Module of the Athlete Biological Passport has improved doping tests for steroids. A biomarker included in this passport is the urinary testosterone glucuronide to epitestosterone glucuronide (T/E) ratio, a ratio greatly affected by a deletion polymorphism in UGT2B17. Suspect urine doping tests are further analyzed with gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) to determine the origin of the androgen. In this study, we investigated the sensitivity of the steroidal module and the IRMS analysis, in subjects administered with three doses of testosterone enanthate (500, 250, and 125 mg), in relation to the UGT2B17 polymorphism. All subjects carrying the UGT2B17 enzyme reached the traditionally used threshold, a T/E ratio of 4, after all three administered doses, whereas none of the subjects devoid of this enzyme reached a T/E of 4. On the other hand, using the athlete biological passport and IRMS analysis, all three doses could be detected to a high degree of sensitivity. The concentrations of all steroids included in the steroidal module were dose dependently increased, except for epitestosterone which decreased independent of dose. The decrease in epitestosterone was significantly associated with circulatory levels of testosterone post dose (rs =0.60 and p=0.007). In conclusion, these results demonstrate that administration of a single dose of 125-500 mg testosterone enanthate could be detected using the athlete biological passport, together with IRMS. Since IRMS is sensitive to testosterone doping independent of UGT2B17 genotype, also very small changes in the steroidal passport should be investigated with IRMS. Copyright © 2015 John Wiley & Sons, Ltd.

Discordant genotyping results using DNA isolated from anti-doping control urine samples.

PubMed

Choong, Eva; Schulze, Jenny J; Ericsson, Magnus; Rane, Anders; Ekström, Lena

2017-07-01

The UGT2B17 gene deletion polymorphism is known to correlate to urinary concentration of testosterone-glucuronide and hence this genotype exerts a large impact on the testosterone/epitestosterone (T/E) ratio, a biomarker for testosterone doping. The objective of this study was to assess if DNA isolated from athletes' urine samples (n = 713) obtained in routine doping controls could be targeted for genotyping analysis for future integration in the athlete's passport. A control population (n = 21) including both urine and blood DNA was used for genotyping concordance test. Another aim was to study a large group (n = 596) of authentic elite athletes in respect of urinary steroid profile in relation to genetic variation. First we found that the genotype results when using urine-derived DNA did not correlate sufficiently with the genotype obtained from whole blood DNA. Secondly we found males with one or two UGT2B17 alleles had higher T/E (mean 1.63 ± 0.93) than females (mean 1.28 ± 1.08), p˂0.001. Unexpectedly, we found that several male del/del athletes in power sports had a T/E ˃1. If men in power sport exert a different urinary steroid profile needs to be further investigated. The other polymorphisms investigated in the CYP17A1, UGT2B7 and UGT2B15 genes did not show any associations with testosterone and epitestosterone concentrations. Our results show that genotyping using urine samples according to our method is not useful in an anti-doping setting. Instead, it is of importance for the anti-doping test programs to include baseline values in the ABP to minimize any putative impact of genotype. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The histological and histometrical effects of Urtica dioica extract on rat’s prostate hyperplasia

PubMed Central

Moradi, Hamid Reza; Erfani Majd, Naeem; Esmaeilzadeh, Saleh; Fatemi Tabatabaei, Sayed Reza

2015-01-01

Benign prostatic hyperplasia (BPH) is a common disease in human that gradual overgrowth of the prostate gland leads to impinge on the urethra with impairment in urinary function. Numerous plants improve uncontrolled growth of the prostate gland and improve urinary tract symptoms associated with BPH. In this study, 25 healthy adult male Wistar rats were divided randomly in five groups: G1 (Control group) received ordinary feed without any treatment, G2 received 10 mg kg-1 testosterone subcutaneously, G3 received 50 mg kg-1 nettle root extract orally, G4 received 50 mg kg-1 nettle root extract orally and 10 mg kg-1 testosterone, G5 received 10 mg kg-1 almond oil (Almond oil was used as testosterone solvent) subcutaneously. After six weeks, volume and weight of each lobe were measured and samples were taken. The 5 to 6 µm thickness sections were made using paraffin embedding method and stained by hematoxylin and eosin and periodic acid-Schiff. The results showed that prostate volume and ratio of prostate to body weight were increased significantly in the testosterone. Histological and histometrical results showed that dorsal and lateral type 1 and 2 lobes were not changed significantly but the ventral and anterior lobes have changed significantly. Over all, the nettle root could prevent from some of prostatic hyperplasia effects, so that percentage of folded alveoli in ventral lobe reduced insignificantly. PMID:25992248

Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men With Late-Onset Hypogonadism.

PubMed

Permpongkosol, Sompol; Khupulsup, Kalayanee; Leelaphiwat, Supatra; Pavavattananusorn, Sarawan; Thongpradit, Supranee; Petchthong, Thanom

2016-08-01

The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. The main outcome measure was dynamic parameter changes during testosterone supplementation. TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Bisphenol A and reproductive hormones and cortisol in peripubertal boys: The INMA-Granada cohort.

PubMed

Mustieles, Vicente; Ocón-Hernandez, Olga; Mínguez-Alarcón, Lidia; Dávila-Arias, Cristina; Pérez-Lobato, Rocío; Calvente, Irene; Arrebola, Juan P; Vela-Soria, Fernando; Rubio, Soledad; Hauser, Russ; Olea, Nicolás; Fernández, Mariana F

2018-03-15

Bisphenol A (BPA) is a well-known endocrine disrupting compound. Although several studies have investigated the effect of BPA exposure and reproductive hormones in humans, results have been inconsistent. To explore the cross-sectional relationship between bisphenol A (BPA) exposure and reproductive hormones/cortisol among peripubertal boys. Urinary BPA and serum hormones were assessed in 172 boys belonging to the INMA "Environment and Childhood" Granada birth cohort in their follow-up at 9-11years of age. BPA concentrations were quantified by liquid chromatography-mass spectrometry, and levels of serum total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol were measured by electrochemiluminescence immunoassay. After adjustment for confounders, linear regression models showed that each natural-log unit increase in urinary BPA concentrations was associated with a 19% increase in geometric mean (GM) serum TT levels, and a 16% decrease in GM serum cortisol levels. When urinary BPA concentrations were categorized in tertiles, boys in the 3rd tertile showed 49% higher TT levels and 23% lower cortisol concentrations compared to boys in the 1st tertile. Additionally, urinary BPA concentrations were also significantly associated with higher TT:LH and TT:cortisol ratios, but not with serum LH or FSH levels. Our results suggest the possible endocrine disrupting potential of BPA during this important period of development. Although action at the testis or pituitary cannot be ruled out, our findings are compatible with a possible involvement of BPA at the adrenal gland, resulting in a differential production of androgens/cortisol. However, given the cross-sectional design of our study, the heterogeneous results reported in the literature, and the scant experimental research on BPA effects at the adrenal gland, the present findings should be interpreted with caution. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of testosterone administration based on the carbon isotope ratio profiling of endogenous steroids: international reference populations of professional soccer players.

PubMed

Strahm, E; Emery, C; Saugy, M; Dvorak, J; Saudan, C

2009-12-01

The determination of the carbon isotope ratio in androgen metabolites has been previously shown to be a reliable, direct method to detect testosterone misuse in the context of antidoping testing. Here, the variability in the 13C/12C ratios in urinary steroids in a widely heterogeneous cohort of professional soccer players residing in different countries (Argentina, Italy, Japan, South Africa, Switzerland and Uganda) is examined. Carbon isotope ratios of selected androgens in urine specimens were determined using gas chromatography/combustion/isotope ratio mass spectrometry (GC-C-IRMS). Urinary steroids in Italian and Swiss populations were found to be enriched in 13C relative to other groups, reflecting higher consumption of C3 plants in these two countries. Importantly, detection criteria based on the difference in the carbon isotope ratio of androsterone and pregnanediol for each population were found to be well below the established threshold value for positive cases. The results obtained with the tested diet groups highlight the importance of adapting the criteria if one wishes to increase the sensitivity of exogenous testosterone detection. In addition, confirmatory tests might be rendered more efficient by combining isotope ratio mass spectrometry with refined interpretation criteria for positivity and subject-based profiling of steroids.

Hormonal Perturbations in Occupationally Exposed Nickel Workers

PubMed Central

Beshir, Safia; Ibrahim, Khadiga Salah; Shaheen, Weam; Shahy, Eman M.

2016-01-01

BACKGROUND: Nickel exposure is recognized as an endocrine disruptor because of its adverse effects on reproduction. AIM: This study was designed to investigate the possible testiculo-hormonal perturbations on workers occupationally exposed to nickel and to assess its effects on human male sexual function. METHODS: Cross-sectional comparative study, comprising 105 electroplating male non-smoker, non-alcoholic workers exposed to soluble nickel and 60 controls was done. Serum luteinizing hormone, follicle stimulating hormone, testosterone levels and urinary nickel concentrations were determined for the studied groups. RESULTS: Serum luteinizing hormone, follicle stimulating hormone, urinary nickel and the simultaneous incidence of more than one sexual disorder were significantly higher in the exposed workers compared to controls. The occurrence of various types of sexual disorders (decreased libido, impotence and premature ejaculation) in the exposed workers was 9.5, 5.1 and 4.4 folds respectively than the controls. CONCLUSIONS: Exposure to nickel produces possible testiculo-hormonal perturbations in those exposed workers. PMID:27335607

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. III. Higher 5 alpha-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone.

PubMed

Anderson, R A; Wallace, A M; Wu, F C

1996-03-01

The administration of exogenous testosterone (T) to eugonadal men causes suppression of gonadotropin secretion and thus of spermatogenesis. This is currently being investigated as a possible method of hormonal male contraceptive, but complete suppression of spermatogenesis to azoospermia is induced in only 50-70% of Caucasian men; the remainder maintain a low rate of spermatogenesis. The basis for this polymorphism in response is unclear. The enzyme 5 alpha-reductase (5 alpha R) converts T to dihydrotestosterone (DHT) and is important in determining the magnitude of the androgen stimulus in some tissues. We investigated whether the maintenance of spermatogenesis in men remaining oligozoospermic while receiving suppressive doses of T is associated with evidence of increased 5 alpha R activity. Thirty-three normal men were given 200 mg T enanthate (TE), im, weekly in a clinical trial of hormonal male contraception. The MCR of T (MCRT) and the conversion ratio of T to DHT (CRT-DHT) were measured by infusion of [3H]T, plasma levels of DHT and androstanediol glucuronide (AdiolG) were measured by RIA, and 24-h urinary steroid metabolites were measured by capillary column gas chromatography. Sperm density decreased in all men; 18 achieved azoospermia by 20 weeks of treatment, and the remainder had a mean sperm density of 2.0 +/- 0.8 x 10(5)/mL at that time. This treatment caused increases in plasma T levels and MCRT, but with no differences between azoospermic and oligozoospermic responders. There were no differences in CRT-DHT plasma DHT, or AdiolG before treatment, but after 16 weeks, CRT-DHT had increased in the oligozoospermic responders, but not in the azoospermic responders. TE treatment increased plasma DHT and AdiolG levels in both groups, but the increases in both 5 alpha R metabolites were significantly greater in the oligozoospermic responders. Urinary excretion of etiocholanolone and androsterone was increased after 16 weeks of TE treatment, but did not differ between the two groups, andetiocholanolone/androsterone ratios did not differ greatly from unity. There was no change in urinary excretion of tetrahydrocortisol, allo-tetrahydrocortisol, or cortisone after 16 weeks of TE treatment in either group. These results suggest that after TE administration there is a selective increase in 5 alpha R activity in those men who remain oligozoospermic, but not in those becoming azoospermic. This difference in the androgenic milieu may underlie the incomplete suppression in the oligozoospermic responders, in whom a low rate of spermatogenesis is maintained despite the apparent absence of gonadotropins.

The problem of anti-doping control of luteinizing hormone in boxing.

PubMed

Llouquet, Jean Louis; Crepin, Nathalie; Lasne, Françoise

2013-04-01

Luteinizing hormone (LH) is physiologically produced by the anterior pituitary gland. Male athletes may use pharmaceutical LH for doping since it increases the production of testosterone by testes. This hormone is thus on the World Anti-Doping Agency (WADA) list of substances prohibited for males. Anti-doping laboratories perform the assay of this hormone in urine and report abnormally elevated results. We observed a highly significant prevalence of abnormal results in samples taken after a boxing match. Comparison of the descriptive statistics for 426 LH values observed in boxing and other sports showed significant differences. An experimental study comparing urinary LH levels in 17 boxers before and after a match demonstrated a clear increase after the match. The same observation was made for urinary follicle stimulating hormone (FSH) in all of the eight boxers tested for this other pituitary gonadotropin. These observations have consequences for anti-doping controls, as the reference range for urinary LH levels must take into account the specificities of boxers. They also suggest consequences for the health of boxers. Although to our knowledge such observations have never been described, other pituitary disorders have been reported. Our results deserve further investigation from a medical point of view. Copyright © 2013 John Wiley & Sons, Ltd.

The Presence Of Strange Males' Odor Induces Behavioral Responses And Elevated Levels Of Low Molecular Weight Proteins Excreted In The Urine Of Mature Water Vole Males (Arvicola amphibius L).

PubMed

Nazarova, Galina G; Proskurniak, Lyudmila P; Yuzhik, Ekaterina I

2016-03-01

We hypothesized that low molecular weight urinary proteins play a role in male-male chemical communication in the water vole, Arvicola ampibius L. We studied the effect of placing soiled litter from strange males into the cage of another sexually mature male on the intensity of its digging and scattering, urination on the litter, and alteration in the levels of low molecular weight proteins (15-25 kDa) excreted in the urine before and after 4 days of exposure as determined by chip electrophoresis. The intensity of digging and scattering was positively correlated with levels of testosterone in serum of males exposed to strange male odors (r = 0.56; P < 0.01), as well as with the concentration of low molecular weight proteins in the donor's urine (r = 0.52, P < 0.05). At the end of the experiment, the level of low molecular weight protein in excreted urine was elevated in the males exposed to the strange male's litter. These results highlight the importance of quantitative inter-individual variation of low molecular weight urinary proteins in the modulation of the physiology and behavior of conspecifics.

Long-duration space flight and bed rest effects on testosterone and other steroids.

PubMed

Smith, Scott M; Heer, Martina; Wang, Zuwei; Huntoon, Carolyn L; Zwart, Sara R

2012-01-01

Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P < 0.01) on landing day after these flights and after short-duration space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. There was no evidence for decrements in testosterone during long-duration space flight or bed rest.

Testosterone and the Prostate.

PubMed

Tan, Ronny B W; Silberstein, Jonathan L; Hellstrom, Wayne J G

2014-10-01

Late-onset hypogonadism, lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), and prostate cancer commonly coexist in the aging male. Due to a better understanding of the physiology and impact of testosterone on benign and malignant diseases of the prostate, the view toward testosterone replacement therapy (TRT) in these individuals has changed dramatically over time. This communication evaluates the effects of testosterone on benign prostatic growth and prostate cancer and reviews the evidence for TRT for men with BPE and prostate cancer. A literature review was performed with regards to TRT in men with prostate cancer as well as the effect of testosterone on the growth of benign prostate tissue and prostate cancer carcinogenesis. To evaluate the evidence for an effect of testosterone on the growth of benign prostate tissue and the development of prostate cancer and TRT in men with prostate cancer. TRT does not exacerbate LUTS. Current evidence is lacking but suggests that TRT may not increase the risk of subsequent diagnosis of prostate cancer, and is unlikely to impact recurrence or progression for men with treated prostate cancer, but longer follow-up is needed. There is no evidence to suggest that TRT is contraindicated in men with BPE or effectively treated prostate cancer. Tan RBW, Silberstein JL, and Hellstrom WJG. Testosterone and the prostate. Sex Med Rev 2014;2:112-120. Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

PubMed Central

Soljancic, Andrea; Ruiz, Arnaldo Lopez; Chandrashekar, Kiran; Maranon, Rodrigo; Liu, Ruisheng; Juncos, Luis A.

2013-01-01

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol. PMID:23552495

[Effect of transderrmal testosterone on the quality of life of men with androgen deficiency and chronic prostatitis in routine clinical practice].

PubMed

Vinarov, A Z; Rozhivanov, R V

2018-03-01

To evaluate the effect of Androgel on the quality of life of patients with androgen deficiency (hypogonadism) and chronic prostatitis in everyday practice. This open multicenter observational non-interventional study comprised 401 men with testosterone deficiency and chronic prostatitis who were treated with topical applications of 1% testosterone gel of (Androgel) at a dose of 50 or 100 mg in routine clinical practice for three months. The primary endpoint was the health related quality of life. Also, the patients filled out AMS, I-PSS, NIH-CPSI questionnaires to assess the quality of life related to chronic prostatitis, lower urinary tract symptoms, and aging. Secondary endpoints included changes in the overall score of the International Index of Erectile Function (IIEF-5), changes in body weight and waist circumference, the reasons for treatment discontinuation and any adverse events that occurred during treatment. Mean total testosterone levels at baseline and three months were 9.5 (95% CI 9.2-9.7) nmol/L and 16.5 (95% CI 16.1-16.9) nmol/l (p<0.001), respectively. There were statistically significant (p<0.001) differences in scores on all questionnaires. Mean scores at baseline and at three months for AMS, IIEF-5, I-PSS, NIH-CPSI questionnaires were 44.6 (95% CI 43.2-45.9) and 25.8 (95% CI 24.8-26.7); 12.7 (95% CI 12.2-13.2) and 19.3 (95% CI, 18.8-19.8); 14.5 (95% CI 13.7-15.3) and 5.6 (95% CI 5.2-6.1); 27.8 (95% CI 26,5-29.1) and 10.0 (95% CI 9.1-10.9), respectively. There were positive changes in body weight and waist circumference: at baseline and three months these parameters were 95 (95% CI 93.6-96.3) and 91.4 (95% CI 90.1-92.7) kg and 102.9 (95% CI 101.8-104.1) and 98.3 (95% CI 97.3-99.3) cm, respectively. No clinically significant adverse events were observed during follow-up. Transdermal therapy with 1% testosterone gel (Androgel) is highly effective and safe in the management of androgen deficiency (hypogonadism). Its use in patients with chronic prostatitis and hypogonadism results in an improvement in low urinary tract symptoms, symptoms of chronic prostatitis, alleviates pelvic pain and thus leads to significant improvements in the quality of life.

Effect of Pulsed Electromagnetic Field Therapy on Prostate Volume and Vascularity in the Treatment of Benign Prostatic Hyperplasia: A Pilot Study in a Canine Model

PubMed Central

Leoci, Raffaella; Aiudi, Giulio; Silvestre, Fabio; Lissner, Elaine; Lacalandra, Giovanni Michele

2014-01-01

BACKGROUND Benign prostatic hyperplasia (BPH) is a result of urogenital aging. Recent studies suggest that an age-related impairment of the blood supply to the lower urinary tract plays a role in the development of BPH and thus may be a contributing factor in the pathogenesis of BPH. The canine prostate is a model for understanding abnormal growth of the human prostate gland. We studied the efficacy of pulsed electromagnetic field therapy (PEMF) in dogs to modify prostate blood flow and evaluated its effect on BPH. METHODS PEMF (5 min, twice a day for 3 weeks) was performed on 20 dogs affected by BPH. Prostatic volume, Doppler assessment by ultrasonography, libido, semen quality, testosterone levels, and seminal plasma volume, composition and pH were evaluated before and after treatment. RESULTS The 3 weeks of PEMF produced a significant reduction in prostatic volume (average 57%) without any interference with semen quality, testosterone levels or libido. Doppler parameters showed a reduction of peripheral resistances and a progressive reduction throughout the trial of the systolic peak velocity, end-diastolic velocity, mean velocity, mean, and peak gradient of the blood flow in the dorsal branch of the prostatic artery. The pulsatility index and the resistance index did not vary significantly over time. CONCLUSIONS The efficacy of PEMF on BPH in dogs, with no side effects, suggests the suitability of this treatment in humans and supports the hypothesis that impairment of blood supply to the lower urinary tract may be a causative factor in the development of BPH. Prostate 74:1132–1141, 2014. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:24913937

Effect of Urinary Bisphenol A on Androgenic Hormones and Insulin Resistance in Preadolescent Girls: A Pilot Study from the Ewha Birth & Growth Cohort

PubMed Central

Lee, Hye Ah; Kim, Young Ju; Lee, Hwayoung; Gwak, Hye Sun; Park, Eun Ae; Cho, Su Jin; Kim, Hae Soon; Ha, Eun Hee; Park, Hyesook

2013-01-01

To assess the effect of urinary bisphenol A (BPA) on repeated measurements of androgenic hormones and metabolic indices, we used multivariate analysis of variance (MANOVA) adjusted for potential confounders at baseline. During July to August 2011, 80 preadolescent girls enrolled in the Ewha Birth & Growth Cohort study participated in a follow-up study and then forty-eight of them (60.0%) came back one year later. Baseline levels of estradiol and androstenedione were higher in the BPA group than in the non-BPA group. One year later, girls in the high BPA exposure group showed higher levels of androstenedione, testosterone, estradiol, and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index, than those in the other groups (p < 0.05). In MANOVA, estradiol and androstenedione showed significant differences among groups, while dehydroepiandrosterone, insulin, and HOMA-IR showed marginally significant differences. Exposure to BPA may affect endocrine metabolism in preadolescents. However, further investigation is required to elucidate the mechanisms linking BPA with regulation of androgenic hormones. PMID:24189184

Detection of testosterone administration based on the carbon isotope ratio profiling of endogenous steroids: international reference populations of professional soccer players

PubMed Central

Strahm, E; Emery, C; Saugy, M; Dvorak, J; Saudan, C

2009-01-01

Background and objectives: The determination of the carbon isotope ratio in androgen metabolites has been previously shown to be a reliable, direct method to detect testosterone misuse in the context of antidoping testing. Here, the variability in the 13C/12C ratios in urinary steroids in a widely heterogeneous cohort of professional soccer players residing in different countries (Argentina, Italy, Japan, South Africa, Switzerland and Uganda) is examined. Methods: Carbon isotope ratios of selected androgens in urine specimens were determined using gas chromatography/combustion/isotope ratio mass spectrometry (GC-C-IRMS). Results: Urinary steroids in Italian and Swiss populations were found to be enriched in 13C relative to other groups, reflecting higher consumption of C3 plants in these two countries. Importantly, detection criteria based on the difference in the carbon isotope ratio of androsterone and pregnanediol for each population were found to be well below the established threshold value for positive cases. Conclusions: The results obtained with the tested diet groups highlight the importance of adapting the criteria if one wishes to increase the sensitivity of exogenous testosterone detection. In addition, confirmatory tests might be rendered more efficient by combining isotope ratio mass spectrometry with refined interpretation criteria for positivity and subject-based profiling of steroids. PMID:19549614

Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

PubMed Central

Chen, Chee Keong; Mohamad, Wan Mohd Zahiruddin Wan; Ooi, Foong Kiew; Ismail, Shaiful Bahari; Abdullah, Mohamad Rusli; George, Annie

2014-01-01

Background: Eurycoma longifolia Jack (ElJ) has been shown to elevate serum testosterone and increased muscle strength in humans. This study investigated the effects of Physta® a standardized water extract of ElJ (400 mg/day for 6 weeks) on testosterone: epitestosterone (T:E) ratio, liver and renal functions in male recreational athletes. Methods: A total of 13 healthy male recreational athletes were recruited in this double blind, placebo-controlled, cross-over study. The participants were required to consume either 400 mg of ElJ or placebo daily for 6 weeks in the first supplementation regimen. Following a 3 week wash-out period, the participants were requested to consume the other supplement for another 6 weeks. Mid-stream urine samples and blood samples were collected prior to and after 6 weeks of supplementation with either ElJ or placebo. The urine samples were subsequently analyzed for T:E ratio while the blood samples were analyzed for liver and renal functions. Results: T:E ratio was not significantly different following 6 weeks supplementation of either ElJ or placebo compared with their respective baseline values. Similarly, there were no significant changes in both the liver and renal functions tests following the supplementation of ElJ. Conclusions: Supplementation of ElJ i.e. Physta® at a dosage of 400 mg/day for 6 weeks did not affect the urinary T:E ratio and hence will not breach any doping policies of the International Olympic Committee for administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions. PMID:25013692

Plasma testosterone levels in Alzheimer and Parkinson diseases.

PubMed

Okun, M S; DeLong, M R; Hanfelt, J; Gearing, M; Levey, A

2004-02-10

Testosterone deficiency, a treatable condition commonly seen in aging men, has been linked to Parkinson disease (PD) and Alzheimer disease (AD). In normal subjects, low testosterone levels are associated with cognitive and neuropsychiatric symptoms, yet the relationship between testosterone levels and cognitive function in PD and AD remains unclear. To examine the relationship of testosterone levels to age and cognitive function in PD and AD. Plasma testosterone levels were determined in men enrolled in a clinical registry of subjects with PD and AD, and neuropsychological testing was performed on subjects who consented. Testosterone levels in men with PD were compared with those in men with AD. In both groups, the relationship between testosterone levels and neuropsychological test scores was analyzed, adjusting for age and education. Linear regression analysis revealed that testosterone levels decreased with age in male PD patients (p < 0.03) and male AD patients (p < 0.07). The rate of decline was similar for the two groups. In PD patients, lower testosterone levels were associated with poorer performance on Trails B Seconds (p < 0.02). There is a similar age-related decline in plasma testosterone levels in men with either PD or AD. Previously described associations between low testosterone levels and frontal lobe dysfunction in normal aged men, together with these results, suggest that the hormonal deficiency may act as a "second hit" to impair cognitive function in neurodegenerative disease.

Long-Duration Space Flight and Bed Rest Effects on Testosterone and Other Steroids

PubMed Central

Heer, Martina; Wang, Zuwei; Huntoon, Carolyn L.; Zwart, Sara R.

2012-01-01

Context: Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. Objective: The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. Design: Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. Setting: Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. Participants: All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. Main Outcome Measures: Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. Results: Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P < 0.01) on landing day after these flights and after short-duration space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. Conclusions: There was no evidence for decrements in testosterone during long-duration space flight or bed rest. PMID:22049169

Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

PubMed

Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

2014-07-01

Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. © 2014 by the Society for the Study of Reproduction, Inc.

Gestational Exposure to Elevated Testosterone Levels Induces Hypertension via Heightened Vascular Angiotensin II Type 1 Receptor Signaling in Rats1

PubMed Central

Chinnathambi, Vijayakumar; More, Amar S.; Hankins, Gary D.; Yallampalli, Chandra; Sathishkumar, Kunju

2014-01-01

ABSTRACT Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. PMID:24855104

Testosterone-Fatty Acid esterification: a unique target for the endocrine toxicity of tributyltin to gastropods.

PubMed

Leblanc, Gerald A; Gooding, Meredith P; Sternberg, Robin M

2005-01-01

Over the past thirty years, a global occurrence of sexual aberration has occurred whereby females among populations of prosobranch snails exhibit male sex characteristics. This condition, called imposex, has been causally associated with exposure to the biocide tributyltin. Tributyltin-exposed, imposex snails typically have elevated levels of testosterone which have led to the postulate that this endocrine dysfunction is responsible for imposex. This overview describes recent evidence that supports this postulate. Gastropods maintain circulating testosterone levels and administration of testosterone to females or castrates stimulates male sex differentiation in several snail species. Studies in the mud snail (Ilyanassa obsoleta) have shown that gastropods utilize a unique strategy for regulating free testosterone levels. Excess testosterone is converted to fatty acid esters by the action of a testosterone-inducible, high capacity/low affinity enzyme, acyl-CoA:testosterone acyl transferase, and stored within the organisms. Free testosterone levels are regulated during the reproductive cycle apparently due to changes in esterification/desterification suggesting that testosterone functions in the reproductive cycle of the organisms. Testosterone esterification provides a unique target in the testosterone regulatory machinery of snails that is altered by tributyltin. Indeed, imposex and free testosterone levels were elevated in field collected snails containing high tin levels, while testosterone-fatty acid ester pools were reduced in these organisms. These observations indicate that tributyltin elevates free testosterone by reducing the retention of testosterone as fatty acid-esters. This endocrine effect of tributyltin may be responsible for imposex.

The contribution of hepatic inactivation of testosterone to the lowering of serum testosterone levels by ketoconazole.

PubMed

Wilson, V S; LeBlanc, G A

2000-03-01

Hepatic biotransformation processes can be modulated by chemical exposure and these alterations can impact the biotransformation of endogenous substrates. Furthermore, chemically mediated alterations in the biotransformation of endogenous steroid hormones have been implicated as a mechanism by which steroid hormone homeostasis can be disrupted. The fungicide ketoconazole has been shown to lower serum testosterone levels and alter both gonadal synthesis and hepatic inactivation of testosterone. The present study examined whether the effects of ketoconazole on the hepatic biotransformation of testosterone contribute to its lowering of serum testosterone levels. Results also were used to validate further the use of the androgen-regulated hepatic testosterone 6alpha/15alpha-hydroxylase ratio as an indicator of androgen status. Male CD-1 mice were fed from 0 to 160 mg/kg ketoconazole in honey. Four h after the initial treatment, serum testosterone levels, gonadal testosterone secretion, and hepatic testosterone hydroxylase activity decreased, and the hepatic testosterone 6alpha/15alpha-hydroxylase ratio increased in a dose-dependent manner. Immunoblot analysis indicated that the transient decline in hepatic biotransformation was not due to reduced P450 protein levels. Rather, hepatic testosterone biotransformation activities were found to be differentially susceptible to direct inhibition by ketoconazole. Differential inhibition was also responsible for the increase seen in the 6alpha/15alpha-hydroxylase ratio. The changes in serum testosterone levels could be explained by decreased gonadal synthesis of testosterone and were not impacted by decreased hepatic biotransformation of testosterone. These results demonstrate that changes in the hepatic hydroxylation of testosterone by ketoconazole, and perhaps other chemicals, have little or no influence serum testosterone levels.

Reduction in 24-hour plasma testosterone levels in subjects who showered 15 or 30 minutes after application of testosterone gel.

PubMed

de Ronde, Willem; Vogel, Syarda; Bui, Hong N; Heijboer, Annemieke C

2011-03-01

To investigate whether showering, to prevent the involuntary transfer of testosterone to others through skin contact, either 15 or 30 minutes after application of testosterone gel would significantly affect plasma testosterone levels. Prospective 3-way crossover trial. University hospital in the Netherlands. Ten agonadal female-to-male transsexuals who had sex-reassignment surgery at least 3 months earlier. Subjects were randomized to one of three application regimens for testosterone gel 50 mg/day, each lasting 7 days: testosterone application after showering (standard regimen), shower was taken 30 minutes after testosterone application, or shower was taken 15 minutes after testosterone application. Subjects then crossed over to each of the other two application regimens for a total of 21 days of study participation. On day 7 of each application regimen, mean plasma testosterone levels were determined before testosterone application and at 1, 4, 7, and 10 hours after application. With the standard regimen, mean plasma testosterone levels at all time points after application were in the normal range: mean ± SD average concentration 994 ± 1026 ng/dl. When a shower was taken 30 or 15 minutes after application, plasma testosterone levels at 1, 4, 7, and 10 hours were significantly lower: mean ± SD average concentration 401 ± 231 ng/dl for 30 minutes after application (p<0.01) and 320 ± 248 ng/dl for 15 minutes after application (p<0.01). Showering within 30 minutes after application of testosterone gel 50 mg/day reduces absorption of testosterone and results in unacceptably low plasma testosterone levels in most users. Therefore, this strategy cannot be recommended to prevent involuntary transfer of testosterone.

The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women.

PubMed

Sinha-Hikim, I; Arver, S; Beall, G; Shen, R; Guerrero, M; Sattler, F; Shikuma, C; Nelson, J C; Landgren, B M; Mazer, N A; Bhasin, S

1998-04-01

Measurements of total and free testosterone levels in women have lacked precision and accuracy because of limited assay sensitivity. The paucity of normative data on total and free testosterone levels in healthy women has confounded interpretation of androgen levels in women with human immunodeficiency virus (HIV) infection and other disease states. Therefore, the objectives of this study were to develop sensitive assays for the measurement of the low total and free testosterone levels in women to define the range for these hormones during the normal menstrual cycle and assess the total and free testosterone levels in HIV-infected women. By using a larger volume of serum, increasing the incubation time, and reducing the antibody concentration, the sensitivity of the total testosterone assay was increased to 0.008 nmol/L, and that of the free testosterone assay was increased to 2 pmol/L. The mean percent free testosterone was 1.0 +/- 0.1% of the total testosterone. Serum total and free testosterone levels in the follicular and luteal phases were not significantly different, but both demonstrated a modest preovulatory increase, 3 days before the LH peak. Serum total [0.50 +/- 0.32 (14.60 +/- 9.22) vs. 1.2 +/- 0.7 nmol/L (34.3 +/- 21.0 ng/dL); P < 0.0001] and free testosterone levels (5.56 +/- 2.70 (1.58 +/- 0.80) vs. 12.8 +/- 5.5 pmol/L (3.4 +/- 1.7 pg/mL); P < 0.0001) were significantly lower in HIV-infected women (n = 37) than in healthy women (n = 34). Serum total and free testosterone levels were also significantly lower in HIV-infected women who were menstruating normally. There were no significant differences in serum total and free testosterone levels between those who had lost weight and those who had not. Testosterone levels correlated inversely with plasma HIV ribonucleic acid copy number. Serum FSH, but not LH, levels were significantly higher in HIV-infected women than in controls. Using assays with sufficient sensitivity, we defined the range for total and free testosterone levels during the normal menstrual cycle. Serum total and free testosterone levels are lower in HIV-infected women and correlate inversely with plasma HIV ribonucleic acid levels. The hypothesis that androgen deficiency contributes to wasting in HIV-infected women remains to be tested.

"Low Testosterone Levels in Body Fluids Are Associated With Chronic Periodontitis".

PubMed

Kellesarian, Sergio Varela; Malmstrom, Hans; Abduljabbar, Tariq; Vohra, Fahim; Kellesarian, Tammy Varela; Javed, Fawad; Romanos, Georgios E

2017-03-01

There is a debate over the association between low testosterone levels in body fluids and the occurrence of chronic periodontitis (CP). The aim of the present systematic review was to assess whether low testosterone levels in body fluids reflect CP. In order to identify studies relevant to the focus question: "Is there a relationship between low testosterone levels in body fluids and CP?" an electronic search without time or language restrictions was conducted up to June 2016 in indexed databases using different keywords: periodontitis, chronic periodontitis, periodontal diseases, testosterone, and gonadal steroid hormones. A total of eight studies were included in the present systematic review. The number of study participants ranged from 24 to 1,838 male individuals with ages ranging from 15 to 95 years. Seven studies measured testosterone levels in serum, two studies in saliva, and one study in gingiva. Four studies reported a negative association between serum testosterone levels and CP. Two studies reported a positive association between decreased testosterone levels in serum and CP. Increased levels of salivary testosterone among patients with CP were reported in one study; whereas one study reported no significant difference in the concentration of salivary testosterone between patients with and without CP. One study identified significant increase in the metabolism of testosterone in the gingiva of patients with CP. Within the limits of the evidence available, the relationship between low testosterone levels and CP remains debatable and further longitudinal studies and control trials are needed.

“Low Testosterone Levels in Body Fluids Are Associated With Chronic Periodontitis”

PubMed Central

Kellesarian, Sergio Varela; Malmstrom, Hans; Abduljabbar, Tariq; Vohra, Fahim; Kellesarian, Tammy Varela; Javed, Fawad; Romanos, Georgios E.

2016-01-01

There is a debate over the association between low testosterone levels in body fluids and the occurrence of chronic periodontitis (CP). The aim of the present systematic review was to assess whether low testosterone levels in body fluids reflect CP. In order to identify studies relevant to the focus question: “Is there a relationship between low testosterone levels in body fluids and CP?” an electronic search without time or language restrictions was conducted up to June 2016 in indexed databases using different keywords: periodontitis, chronic periodontitis, periodontal diseases, testosterone, and gonadal steroid hormones. A total of eight studies were included in the present systematic review. The number of study participants ranged from 24 to 1,838 male individuals with ages ranging from 15 to 95 years. Seven studies measured testosterone levels in serum, two studies in saliva, and one study in gingiva. Four studies reported a negative association between serum testosterone levels and CP. Two studies reported a positive association between decreased testosterone levels in serum and CP. Increased levels of salivary testosterone among patients with CP were reported in one study; whereas one study reported no significant difference in the concentration of salivary testosterone between patients with and without CP. One study identified significant increase in the metabolism of testosterone in the gingiva of patients with CP. Within the limits of the evidence available, the relationship between low testosterone levels and CP remains debatable and further longitudinal studies and control trials are needed. PMID:27645514

Urinary concentrations of benzophenone-type ultra violet light filters and reproductive parameters in young men.

PubMed

Adoamnei, Evdochia; Mendiola, Jaime; Moñino-García, Miriam; Vela-Soria, Fernando; Iribarne-Durán, Luz M; Fernández, Mariana F; Olea, Nicolás; Jørgensen, Niels; Swan, Shanna H; Torres-Cantero, Alberto M

2018-04-01

Benzophenone (BP)-type ultraviolet (UV) light filters are chemicals frequently added to personal care products, insect repellents, sunscreens, and beverage and food packaging to diminish the harmful effects of UV sunlight on human skin or foodstuffs. BP-type UV filters have shown negative effects on male reproduction function in in vitro and animal models, but human epidemiologic studies are limited. The goal of this study was to examine associations between urinary concentrations of BP-type UV filters and semen quality and reproductive hormone levels. This is a cross-sectional study with 215 young university students (18-23 years old) recruited between 2010 and 2011 in Southern Spain (Murcia Region). All men provided a urine, blood and semen sample on a single day. Urinary concentrations of 2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2'-dihydroxy-4-methoxybenzophenone (BP-8) and 4-hydroxybenzophenone (4OH-BP) were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, sperm counts, motility and morphology. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), inhibin B and estradiol (E2). Associations between urinary concentrations of BP-type UV filters and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders. Ninety-seven percent of the men had detectable urinary concentrations of at least one of the five BP-type UV filters quantified. After adjustment for important covariates (body mass index, smoking status and time of blood sample collection), there was a significant positive association between urinary BP-1 and BP-3 concentrations and serum FSH levels (β = 0.08, 95%CI: 0.009; 0.15 and β = 0.04, 95%CI: 0.0002; 0.08, respectively). Urinary BP-1 concentration was also significantly positively associated with T/E2 (β = 0.04, 95%CI: 0.002; 0.07) and negatively with inhibin b/FSH (β = -0.11, 95%CI: -0.21; -0.006) ratio. No significant associations were found between other urinary BP-type UV filters and other reproductive hormone levels or between any semen parameters and any of the urinary BP-type UV filters quantified. Our results suggest that, in young men, urinary BP-type UV filters may be associated with a modest alteration of some reproductive hormones, but the effects we report on reproductive function are likely to be small, and of unclear clinical significance. Further research is needed to replicate these findings in other male populations. Copyright © 2018 Elsevier GmbH. All rights reserved.

Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men.

PubMed

Leder, Benjamin Z; Finkelstein, Joel S

2005-12-01

Both estrogens and androgens play important roles in skeletal development and maintenance in men. The relative importance of estrogens and androgens in male bone metabolism, however, remains undefined. Anastrozole is an oral aromatase inhibitor that decreases estrogen production and increases androgen production in men. Currently, anastrozole is being investigated as a potential agent for the treatment of hypogonadism in aging men. Because anastrozole lowers estrogen levels and raises androgen levels, its effect on bone metabolism is difficult to predict. To assess the effects of anastrozole on bone turnover, we randomized 37 elderly (ages 62-74) mildly hypogonadal men (serum testosterone <350 ng/dl) to receive either anastrozole 1 mg daily (n=12), anastrozole 1 mg twice weekly (n=11), or daily placebo (n=14) for 12 weeks. Serum gonadal steroid levels, serum and urine biochemical markers of bone turnover, serum osteoprotegerin, and total body bone mineral density were measured at baseline and week 12. Mean serum levels of total and bioavailable testosterone increased substantially in both treated groups. Specifically, mean +/- SD bioavailable testosterone levels increased from 99+/-31 ng/dl to 207+/-65 ng/dl in the group receiving 1 mg of anastrozole daily and from 115+/-37 ng/dl to 178+/-55 ng/dl in the subjects receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both groups). Serum estradiol levels decreased modestly in both treated groups (from 26+/-8 pg/ml to 17+/-6 pg/ml in the daily treatment group and from 27+/-8 pg/ml to 17+/-5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both groups). Despite these hormonal changes, no increases in biochemical markers of bone resorption were observed. Specifically, mean serum N-telopeptide and urinary deoxypyridinoline concentrations remained stable in both treated groups over the 12-week treatment period. Similarly, serum biochemical markers of bone formation (osteocalcin and amino-terminal propeptide of type 1 collagen), serum osteoprotegerin, and total body bone mineral density did not change. These data demonstrate that although short-term administration of anastrozole decreases serum estradiol levels in elderly men with mild hypogonadism, this intervention does not adversely affect bone metabolism over a 12-week period. This lack of an effect may be due to the concomitant increase in testosterone production, the relative modest effect on estradiol production, or a combination of both factors. These results suggest that anastrozole therapy is unlikely to have an adverse effect on bone metabolism when taken over extended periods and may prove to be a valuable method of normalizing testosterone production in older men.

Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer.

PubMed

Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick; Maisonobe, Pascal; de la Taille, Alexandre

2014-10-01

To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics. The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3 change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse events and changes in laboratory parameters. The intent-to-treat population comprised 322 patients; 39 (12.1%) had non-assessable PCA3 scores at baseline, and 109/322 (33.9%), 215/313 (68.7%) and 232/298 (77.9%) had non-assessable PCA3 scores at 1, 3 and 6 months, respectively. Baseline Gleason score was the only variable associated with non-assessability of PCA3 score at 6 months (P = 0.017) - the hazard of having a non-assessable PCA3 score at 6 months was 1.824-fold higher (95% confidence interval 1.186-2.805) in patients with a Gleason score ≥8 vs those with a Gleason score ≤6. The median PCA3 scores at baseline were significantly higher in patients aged ≥65 years vs those aged <65 years and in patients with a serum PSA level <100 ng/mL vs those with serum PSA level of >200 ng/mL. The median PCA3 score was significantly lower in patients with metastasis than in patients with no metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels decreased from 45.5 ng/mL at baseline to 1.2 ng/mL after 6 months, and as expected, >90% of patients achieved castrate levels of testosterone (<50 ng/dL) at 1, 3, and 6 months during triptorelin treatment. The safety profile reported from this study is consistent with the known safety profile of triptorelin. These data from the Triptocare study suggest that urinary PCA3 or TMPRSS2-ERG score are not reliable markers of cancer stage in advanced prostate cancer. Urinary PCA3 and TMPRSS2-ERG scores do not appear to be useful in assessing response to ADT in advanced prostate cancer, with most patients having non-assessable scores after 6 months of treatment. © 2013 The Authors. BJU International © 2013 BJU International.

Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide-phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate pathway.

PubMed

Higashi, Yukihito

2017-06-01

It is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy. Both lower urinary tract symptoms/benign prostatic hypertrophy and vascular dysfunction have cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes mellitus, aging, obesity and smoking. Inactivation of the phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate-nitric oxide pathway causes lower urinary tract symptoms/benign prostatic hypertrophy through an enhancement of sympathetic nervous activity, endothelial dysfunction, increase in Rho-associated kinase activity and vasoconstriction, and decrease in blood flow of pelvic viscera. Both endogenous nitric oxide and exogenous nitric oxide act as vasodilators on vascular smooth muscle cells through an increase in the content of cyclic guanosine 3',5'-monophosphate, which is inactivated by phosphodiesterase type 5. In a clinical setting, phosphodiesterase type 5 inhibitors are widely used in patients with lower urinary tract symptoms/benign prostatic hypertrophy. Phosphodiesterase type 5 inhibitors might have beneficial effects on vascular function through not only inhibition of cyclic guanosine 3',5'-monophosphate degradation, but also increases in testosterone levels and nitric oxide bioavailability, increase in the number and improvement of the function of endothelial progenitor cells, and decrease in insulin resistance. In the present review, the relationships between lower urinary tract symptoms/benign prostatic hypertrophy, the phosphodiesterase type 5-nitric oxide-cyclic guanosine 3',5'-monophosphate pathway, vascular function and cardiovascular outcomes are examined. © 2017 The Japanese Urological Association.

Association of testosterone levels and heroin usage characteristics in male heroin users.

PubMed

Wang, Zhuo; Zhou, Xiao-Bo; Yang, Xiao-Rong; Song, Hui; Cao, Bing-Rong; Yin, Fei; Kang, Lin; An, Zhen-Mei; Li, Jing

2017-05-01

Previous studies have shown that heroin abuse can alter the gonadal functions. Few studies examined the association between testosterone levels and heroin use in the existing literature. We aimed to determine the association between gonadal hormones and heroin usage characteristics over 12 weeks of abstinence in heroin users. We collected data on patient demographics and heroin use patterns for 65 men aged 18 to 45 and for 29 age-matched healthy controls. Serum levels of total testosterone, estradiol, and prolactin were assessed at 5 time points. Testosterone levels gradually increased and prolactin levels decreased in heroin users in this study. In heroin users, a significant positive correlation was observed between the way of using drug and the testosterone levels, the way of using drug and the estradiol levels, between the duration of heroin dependence and the testosterone levels, between the duration of heroin dependence and the estradiol levels on D0, and between relapse time and testosterone levels on D84. Our data reveal testosterone might promote injection drug use and repeated relapse in male heroin users.

Prenatal Testosterone Exposure Decreases Aldosterone Production but Maintains Normal Plasma Volume and Increases Blood Pressure in Adult Female Rats.

PubMed

More, Amar S; Mishra, Jay S; Hankins, Gary D; Kumar, Sathish

2016-08-01

Plasma testosterone levels are elevated in pregnant women with preeclampsia and polycystic ovaries; their offspring are at increased risk for hypertension during adult life. We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na(+) and K(+) levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg(8)-vasopressin. The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. Accordingly, plasma aldosterone levels were lower in testosterone females. Plasma volume and serum and urine Na(+) and K(+) levels were not significantly different between control and testosterone females; however, prenatal testosterone exposure significantly increased plasma vasopressin and angiotensin II levels and arterial pressure in adult females. In testosterone females, mesenteric artery contractile responses to angiotensin II were significantly greater, while contractile responses to vasopressin were unaffected. Angiotensin II type-1 receptor expression was increased, while angiotensin II type-2 receptor was decreased in testosterone arteries. These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. Elevated angiotensin II and vasopressin levels along with enhanced vascular responsiveness to angiotensin II may serve as an underlying mechanism to maintain plasma volume and Na(+) and K(+) levels and mediate hypertension in adult testosterone females. © 2016 by the Society for the Study of Reproduction, Inc.

Association between Serum Testosterone and PSA Levels in Middle-Aged Healthy Men from the General Population.

PubMed

Elzanaty, Saad; Rezanezhad, Babak; Dohle, Gert

2017-04-01

The aim of the present study was to evaluate the association between serum testosterone and PSA levels in middle-aged healthy men from the general population. Based on 119 healthy men from the general population, total testosterone and PSA levels were measured. Demographic data regarding BMI, waist-to-hip ratio, smoking, and alcohol consumption were also collected. Men were classified into two groups according to testosterone levels; hypogonadal (testosterone ≤ 12 nmol/l), and eugonadal (testosterone > 12 nmol/l). The mean age of the subjects was 55 years (range 46-60 years). No significant correlation between serum testosterone and PSA levels was found (p = 0.60). PSA levels were similar when compared between hypogonadal and eugonadal men (1.4 µg/l vs. 1.4 µg/l, p = 0.90). When using a multivariate analysis model adjusted for the age of the subjects, BMI, waist-to-hip ratio, smoking, and alcohol consumption, a positive significant association between testosterone and PSA levels was found (β = 0.03, 95 % CI = 0.003-0.062, p = 0.03). Only after adjusted multivariate analysis, our results indicated that testosterone was associated with PSA levels in middle-aged healthy men.

Sex differences in the analgesic effects of ICI 182,780 and Flutamide on ureteral calculosis in rats.

PubMed

Affaitati, Giannapia; Ceccarelli, Ilaria; Fiorenzani, Paolo; Rossi, Cosmo; Pace, Maria Caterina; Passavanti, Maria Beatrice; Aurilio, Caterina; Sorda, Giuseppina; Danielli, Barbara; Giamberardino, Maria Adele; Aloisi, Anna Maria

2011-01-01

To better define the involvement of gonadal hormones in the sex differences observed in experimental visceral pain, we administered antagonists of estrogen receptors (ICI 182,780 [ICI]) or androgen receptors (Flutamide [FLU]) to adult male and female rats suffering from artificial ureteral calculosis. Subjects were divided into groups and treated with one of the substances (ICI, FLU) or sweet almond oil (OIL, vehicle) for 5 days, starting 2 days before surgery. On day 3, animals underwent surgery, with half receiving an artificial calculosis (Stone) and half only a sham procedure. The animals' behavior (number and duration of ureteral crises) and blood hormone levels (estradiol and testosterone) were determined in all groups. In OIL-treated rats the number and duration of crises were higher in females than in males. The administration of ICI or FLU resulted in hormonal effects in males and behavioral effects in females. In males ICI treatment increased estradiol plasma levels and FLU increased testosterone plasma levels; in females ICI and FLU treatments both decreased the number and duration of the ureteral crises. These results, confirming previous findings of higher sensitivity of females than males to urinary tract pain, showed the modulatory effects of estrogen and androgen antagonists on the behavioral responses induced by pain but only in females. Copyright © 2010 Elsevier Inc. All rights reserved.

Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

PubMed Central

Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

2014-01-01

Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. PMID:24765590

CSF and plasma testosterone in attempted suicide.

PubMed

Stefansson, Jon; Chatzittofis, Andreas; Nordström, Peter; Arver, Stefan; Åsberg, Marie; Jokinen, Jussi

2016-12-01

Very few studies have assessed testosterone levels in the cerebrospinal fluid in suicide attempters. Aggressiveness and impulsivity are common behavioural traits in suicide attempters. Dual-hormone serotonergic theory on human impulsive aggression implies high testosterone/cortisol ratio acting on the amygdala and low serotonin in the prefrontal cortex. Our aim was to examine the CSF and plasma testosterone levels in suicide attempters and in healthy volunteers. We also assessed the relationship between the testosterone/cortisol ratio, aggressiveness and impulsivity in suicide attempters. 28 medication-free suicide attempters and 19 healthy volunteers participated in the study. CSF and plasma testosterone sulfate and cortisol levels were assessed with specific radio-immunoassays. The Karolinska Scales of Personality was used to assess impulsivity and aggressiveness. All patients were followed up for cause of death. The mean follow-up period was 21 years. Male suicide attempters had higher CSF and plasma testosterone levels than age- matched male healthy volunteers. There were no significant differences in CSF testosterone levels in female suicide attempters and healthy female volunteers. Testosterone levels did not differ significantly in suicide victims compared to survivors. In male suicide attempters, the CSF testosterone/cortisol ratio showed a significant positive correlation with both impulsivity and aggressiveness. Higher CSF testosterone levels may be associated with attempted suicide in young men through association with both aggressiveness and impulsivity, a key endophenotype in young male suicide attempters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low- and high-testosterone individuals exhibit decreased aversion to economic risk.

PubMed

Stanton, Steven J; Mullette-Gillman, O'Dhaniel A; McLaurin, R Edward; Kuhn, Cynthia M; LaBar, Kevin S; Platt, Michael L; Huettel, Scott A

2011-04-01

Testosterone is positively associated with risk-taking behavior in social domains (e.g., crime, physical aggression). However, the scant research linking testosterone to economic risk preferences presents inconsistent findings. We examined the relationship between endogenous testosterone and individuals' economic preferences (i.e., risk preference, ambiguity preference, and loss aversion) in a large sample (N = 298) of men and women. We found that endogenous testosterone levels have a significant U-shaped association with individuals' risk and ambiguity preferences, but not loss aversion. Specifically, individuals with low or high levels of testosterone (more than 1.5 SD from the mean for their gender) were risk and ambiguity neutral, whereas individuals with intermediate levels of testosterone were risk and ambiguity averse. This relationship was highly similar in men and women. In contrast to received wisdom regarding testosterone and risk, the present data provide the first robust evidence for a nonlinear association between economic preferences and levels of endogenous testosterone.

Urine stability and steroid profile: towards a screening index of urine sample degradation for anti-doping purpose.

PubMed

Mazzarino, Monica; Abate, Maria Gabriella; Alocci, Roberto; Rossi, Francesca; Stinchelli, Raffaella; Molaioni, Francesco; de la Torre, Xavier; Botrè, Francesco

2011-01-10

The presence of microorganisms in urine samples, under favourable conditions of storage and transportation, may alter the concentration of steroid hormones, thus altering the correct evaluation of the urinary steroid profile in doping control analysis. According to the rules of the World Anti-Doping Agency (WADA technical document TD2004 EAAS), a testosterone deconjugation higher than 5% and the presence of 5α-androstane-3,17-dione and 5β-androstane-3,17-dione in the deconjugated fraction, are reliable indicators of urine degradation. The determination of these markers would require an additional quantitative analysis since the steroids screening analysis, in anti-doping laboratories, is performed in the total (free+conjugated) fraction. The aim of this work is therefore to establish reliable threshold values for some representative compounds (namely 5α-androstane-3,17-dione and 5β-androstane-3,17-dione) in the total fraction in order to predict directly at the screening stage the potential microbial degradation of the urine samples. Preliminary evidence on the most suitable degradation indexes has been obtained by measuring the urinary concentration of testosterone, epitestosterone, 5α-androstane-3,17-dione and 5β-androstane-3,17-dione by gas chromatography-mass spectrometric every day for 15 days in the deconjugated, glucuronide and total fraction of 10 pools of urines from 60 healthy subjects, stored under different pH and temperature conditions, and isolating the samples with one or more markers of degradation according to the WADA technical document TD2004EAAS. The threshold values for 5α-androstane-3,17-dione and 5β-androstane-3,17-dione were therefore obtained correlating the testosterone deconjugation rate with the urinary concentrations of 5α-androstane-3,17-dione and 5β-androstane-3,17-dione in the total fraction. The threshold values suggested as indexes of urine degradation in the total fraction were: 10 ng mL(-1) for 5α-androstane-3,17-dione and 20 ng mL(-1) for 5β-androstane-3,17-dione. The validity of this approach was confirmed by the analysis of routine samples for more than five months (i.e. on a total of more than 4000 urine samples): samples with a concentration of total 5α-androstane-3,17-dione and 5β-androstane-3,17-dione higher than the threshold values showed a percentage of free testosterone higher than 5 of its total amount; whereas free testosterone in a percentage higher than 5 of its total amount was not detected in urines with a concentration of total 5α-androstane-3,17-dione and 5β-androstane-3,17-dione lower than the threshold values. Copyright © 2010 Elsevier B.V. All rights reserved.

Testosterone urinary excretion rate increases during hypergravity in male monkeys

NASA Technical Reports Server (NTRS)

Strollo, F.; Barger, L.; Fuller, C.

2000-01-01

Real and simulated microgravity impairs T secretion both in animals and in the human. To verify whether hypergravity might enhance T secretion as a consequence of an opposite mechanical effect, 6 male monkeys were centrifuged at 2 G for 3 weeks after a 1 G stabilization period lasting 3 weeks and then taken back to 1 G for 1 week and urine were collected daily for T excretion measurement. Significantly higher level were observed during the initial 2 G phase as compared to pre- and post centrifugation periods and the trend was the same during the remaining 2 G period. This may reflect changes in testicular perfusion rather than endocrine adaptation per se.

Association of testosterone and BDNF serum levels with craving during alcohol withdrawal.

PubMed

Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Gröschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas

2016-08-01

Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-related testosterone decline in a Brazilian cohort of healthy military men.

PubMed

Nardozza Júnior, Archimedes; Szelbracikowski, Sergio dos Santos; Nardi, Aguinaldo Cesar; Almeida, Jose Carlos de

2011-01-01

Androgen decline in the aging man has become a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be accompanied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil. To determine the pattern of blood testosterone concentrations decline with age in a cohort of Brazilian healthy military men. We retrospectively reviewed data on serum testosterone measurements of healthy individuals that had undergone a routine check-up at the Military Biology Institute. Blood samples were obtained early in the morning, and total testosterone concentration was determined using a commercial chemoluminescent immunoassay. Mean values were analyzed in five age groups: ≤ 40, 41 to 50, 51 to 60, 61 to 70, and > 70 years. Mean total testosterone levels. 1,623 subjects were included in the analysis; mean age was 57 years (24 to 87), and mean testosterone level was 575.5 ng/dL (25.0 to 1308.0 ng/dL). The evaluation of age-related changes in total testosterone levels revealed a progressive reduction in serum levels of this hormone with increasing age. Testosterone levels below 300 ng/dL were reported in 321 participants, a prevalence of nearly 20% in the study population. In agreement with other findings, a reduction of total testosterone levels with age was reported for healthy Brazilian men.

Moderating effects of salivary testosterone levels on associations between job demand and psychological stress response in Japanese medical workers

PubMed Central

HIROKAWA, Kumi; MIWA, Machiko; TANIGUCHI, Toshiyo; TSUCHIYA, Masao; KAWAKAMI, Norito

2015-01-01

Levels of job stress have been shown to be inversely associated with testosterone levels, but some inconsistent results have been documented. We investigated the moderating effects of testosterone levels on associations between job stress-factors and psychological stress responses in Japanese medical workers. The participants were 63 medical staff (20 males and 43 women; mean age: 30.6 years; SD=7.3) in Okayama, Japan. Their job-stress levels and psychological stress responses were evaluated using self-administered questionnaires, and their salivary testosterone collected. Multiple regression analyses showed that job demand was positively associated with stress responses in men and women. An interaction between testosterone and support from colleagues had a significant effect on depression and anxiety for women. In women with lower testosterone levels, a reducing effect of support from colleagues on depression and anxiety was intensified. In women with higher testosterone levels, depression and anxiety levels were identical regardless of support from colleagues. Testosterone may function as a moderator between perceived work environment and psychological stress responses for female medical workers. PMID:26632120

A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain.

PubMed

Heany, Sarah J; van Honk, Jack; Stein, Dan J; Brooks, Samantha J

2016-02-01

Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.

The Association between Nonylphenols and Sexual Hormones Levels among Pregnant Women: A Cohort Study in Taiwan

PubMed Central

Chang, Chia-Huang; Tsai, Ming-Song; Lin, Ching-Ling; Hou, Jia-Woei; Wang, Tzu-Hao; Tsai, Yen-An; Liao, Kai-Wei; Mao, I-Fang; Chen, Mei-Lien

2014-01-01

Background Nonylphenol (NP) has been proven as an endocrine disrupter and had the ability to interfere with the endocrine system. Though the health effects of NP on pregnant women and their fetuses are sustained, these negative associations related to the mechanisms of regulation for estrogen during pregnancy need to be further clarified. The objective of this study is to explore the association between maternal NP and hormonal levels, such as estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and progesterone. Methods A pregnant women cohort was established in North Taiwan between March and December 2010. Maternal urine and blood samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. A mixed-effects model using a generalised estimating equation (GEE) was applied to assess the associations between maternal NP concentration and plasma hormones throughout the three trimesters. Results In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27, 4.21, and 4.10 µg/g cre. in the first, second, and third trimesters respectively. A natural log-transformation of urinary NP concentrations were significantly associated with LH in the GEE model (β = −0.23 mIU/ml, p<0.01). Conclusion This perspective cohort study demonstrates that negative association occurs between maternal NP exposure and plasma LH levels. The estrogen-mimic effect of NP might influence the negative feedback on LH during pregnancy. PMID:25148048

Daily Bisphenol A Excretion and Associations with Sex Hormone Concentrations: Results from the InCHIANTI Adult Population Study

PubMed Central

Galloway, Tamara; Cipelli, Riccardo; Guralnik, Jack; Ferrucci, Luigi; Bandinelli, Stefania; Corsi, Anna Maria; Money, Cathryn; McCormack, Paul; Melzer, David

2010-01-01

Background Bisphenol A (BPA) is a high production volume chemical widely used in packaging for food and beverages. Numerous studies have demonstrated that BPA can alter endocrine function in animals, yet human studies remain limited. Objective We estimated daily excretion of BPA among adults and examined hypothesized associations with serum estrogen and testosterone concentrations. Methods We conducted cross-sectional analyses using data from the InCHIANTI Study, a prospective population-based study of Italian adults. Our study included 715 adults between 20 and 74 years old. BPA concentrations were measured by liquid chromatography–mass spectrometry in 24-hr urine samples. The main outcome measures were serum concentrations of total testosterone and 17β-estradiol. Results Geometric mean urinary BPA concentration was 3.59 ng/mL [95% confidence interval (CI), 3.42–3.77 ng/mL], and mean excretion was 5.63 μg/day (5th population percentile, 2.1 μg/day; 95th percentile, 16.4 μg/day). We found higher excretion rates among men, younger respondents, and those with increasing waist circumference (p = 0.013) and weight (p = 0.003). Higher daily BPA excretion was associated with higher total testosterone concentrations in men, in models adjusted for age and study site (p = 0.044), and in models additionally adjusted for smoking, measures of obesity, and urinary creatinine concentrations (β = 0.046; 95% CI, 0.015–0.076; p = 0.004). We found no associations with the other serum measures. We also found no associations with the primary outcomes among women, but we did find an association between BPA and SHBG concentrations in the 60 premenopausal women. Conclusion Higher BPA exposure may be associated with endocrine changes in men. The mechanisms involved in the observed cross-sectional association with total testosterone concentrations need to be clarified. PMID:20797929

Physiological levels of testosterone kill salmonid leukocytes in vitro

USGS Publications Warehouse

Slater, C.H.; Schreck, C.B.

1997-01-01

Adult spring chinook salmon (Oncorhynchus tshawytscha) elaborate high plasma concentrations of testosterone during sexual maturation, and these levels of testosterone have been shown to reduce the salmonid immune response in vitro. Our search for the mechanism of testosterone's immunosuppressive action has led to the characterization of an androgen receptor in salmonid leukocytes. In the present study we examined the specific effects that testosterone had on salmonid leukocytes. Direct counts of viable leukocytes after incubation with and without physiological levels of testosterone demonstrate a significant loss of leukocytes in cultures exposed to testosterone. At least 5 days of contact with testosterone was required to produce significant immunosuppression and addition of a 'conditioned media' (supernatant from proliferating lymphocytes not exposed to testosterone) did not reverse the immunosuppressive effects of testosterone. These data lead us to conclude that testosterone may exert its immunosuppressive effects by direct action on salmonid leukocytes, through the androgen receptor described, and that this action leads to the death of a significant number of these leukocytes.

Testosterone levels in suicide attempters with bipolar disorder

PubMed Central

Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.

2013-01-01

Objective The best known neurobehavioral effects of testosterone are on sexual function and aggression. However, testosterone and other androgens may be involved in the pathophysiology of mood disorders and suicidal behavior. This is the first study to examine whether there is a relation between testosterone levels and clinical parameters in bipolar suicide attempters. Methods Patients with a DSM-IV diagnosis of a bipolar disorder (16 males and 51 females), in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters, including lifetime suicidal behavior, were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Results The number of major depressive episodes, the maximum lethality of suicide attempts, and the testosterone levels were higher in men compared to women. Current suicidal ideation scores were higher in women compared to men. Controlling for sex, we found that testosterone levels positively correlated with the number of manic episodes and the number of suicide attempts. Conclusion Our findings are consistent with previous observations of the association between testosterone levels and parameters of mood and behavior. This study suggests that testosterone levels may be related to the course of bipolar disorder and suicidal behavior. Further studies of the role of testosterone in the neurobiology of mood disorders and suicidal behavior are merited. PMID:22858352

A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

PubMed

Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

2016-02-01

In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The "trouble" with salivary testosterone.

PubMed

Granger, Douglas A; Shirtcliff, Elizabeth A; Booth, Alan; Kivlighan, Katie T; Schwartz, Eve B

2004-11-01

In a series of studies, we identify several specific issues that can limit the value of integrating salivary testosterone in biosocial research. Salivary testosterone measurements can be substantially influenced during the process of sample collection, are susceptible to interference effects caused by the leakage of blood (plasma) into saliva, and are sensitive to storage conditions when samples have been archived. There are gender differences in salivary testosterone levels and variance, the serum-saliva association, the relationship of salivary testosterone to age and pubertal development, and the stability of individual differences in salivary testosterone levels over time. The findings have important implications at several levels of analysis for research that aims to test biosocial models of testosterone--behavior relationships. Recommendations are provided to steer investigators around these "troubles" with salivary testosterone.

Quantitative measurement of salivary testosterone in Korean adults by stable isotope-dilution liquid chromatographyelectrospray-tandem mass spectrometry.

PubMed

Lee, Sanghoo; Kwon, Soonho; Shin, Hye-Jin; Park, Jimyeong; Lim, Hwan-Sub; Lee, Kyoung-Ryul; Kim, Young-Jin

2010-11-01

Salivary testosterone levels in Korean adults were quantitatively measured for the first time by liquid chromatography-electrospray-tandem mass spectrometry (LC ESI MS/MS). Salivary testosterone was separated on a multiple reaction monitoring (MRM) chromatogram within 7 min. The LC ESI MS/MS assay was validated over the linearity range of 0.01-2.00 ng/ml (r=0.99987) using testosterone-d(3) as an internal standard. The lower limit of quantification (LOQ) was 0.01 ng/ml. The intra- and inter-assay precisions were 1.54% to 4.09% and 0.96% to 4.29%, respectively. The mean recovery was 93.32% (range 88.43-98.05%). The validated assay was then applied to measure the salivary testosterone levels of Korean adults. In men, the salivary testosterone level collected between 9:00-11:00 am was approximately 2.8 times higher than that in women (P < 0.0001). Salivary testosterone levels in both sexes negatively correlated with age. The present assay would also be useful in measuring salivary testosterone levels in clinical laboratories.

The biocide tributyltin reduces the accumulation of testosterone as fatty acid esters in the mud snail (Ilyanassa obsoleta).

PubMed Central

Gooding, Meredith P; Wilson, Vickie S; Folmar, Leroy C; Marcovich, Dragoslav T; LeBlanc, Gerald A

2003-01-01

Imposex, the development of male sex characteristics by female gonochoristic snails, has been documented globally and is causally associated with exposure to the ubiquitous environmental contaminant tributyltin (TBT). Elevated testosterone levels in snails also are associated with TBT, and direct exposure to testosterone has been shown to cause imposex. We discovered previously that the mud snail (Ilyanassa obsoleta)biotransforms and retains excess testosterone primarily as fatty acid esters. The purpose of this study was to determine whether TBT interferes with the esterification of testosterone, resulting in the elevated free (unesterified) testosterone levels associated with imposex. Exposure of snails to environmentally relevant concentrations of TBT (> or = 1.0 ng/L as tin) significantly increased the incidence of imposex. Total (free + esterified) testosterone levels in snails were not altered by TBT; however, free testosterone levels increased with increasing exposure concentration of TBT. TBT-exposed snails were given [14C

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients.

PubMed

Rovira-Llopis, Susana; Bañuls, Celia; de Marañon, Aranzazu M; Diaz-Morales, Noelia; Jover, Ana; Garzon, Sandra; Rocha, Milagros; Victor, Victor M; Hernandez-Mijares, Antonio

2017-07-01

Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesion molecules and leukocyte-endothelium cell interactions were evaluated. Testosterone levels were lower in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFα, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabetic patients, while rolling velocity was reduced. Testosterone levels correlated negatively with glucose, HOMA-IR, HbA1c, triglycerides, nonHDL-c, ApoB, hs-CRP and AIP, and positively with HDL-c and ApoA1. The multivariable regression model showed that HDL-c, HOMA-IR and age were independently associated with testosterone. Furthermore, testosterone levels correlated positively with membrane potential and rolling velocity and negatively with ROS production, VCAM-1, rolling flux and adhesion. Our data highlight that low testosterone levels in diabetic men are related to impaired metabolic profile and mitochondrial function and enhanced inflammation and leukocyte-endothelium cell interaction, which leaves said patients at risk of cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

"Nice guys finish last": influence of mate choice on reproductive success in Long-Evans rats.

PubMed

Winland, C; Bolton, J L; Ford, B; Jampana, S; Tinker, J; Frohardt, R J; Guarraci, F A; Zewail-Foote, M

2012-02-01

The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long-Evans rats. Mating behavior was observed in sexually naïve, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (>50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as "attractive" or "non-attractive" by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, "attractive" males sired significantly FEWER pups than "non-attractive" males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive advantage. Copyright © 2011 Elsevier Inc. All rights reserved.

The Effect of Testosterone Topical Solution in Hypogonadal Men With Suboptimal Response to a Topical Testosterone Gel.

PubMed

Burns, Patrick R; Kim, Edward D; Ruff, Dustin D; Seftel, Allen D

2018-05-01

This study evaluated the effect of axillary administration of a 2% testosterone solution (Axiron ® ) in hypogonadal (HGN) men who had had a suboptimal response to treatment with a commercially available topical testosterone gel. HGN men averaging 57 years old, with a mean body mass index of 31.9 kg/m 2 and median baseline testosterone level (T-level) of 185.2 ng/dL, who had failed to reach normal T-levels with a topical testosterone gel (Androgel 1.62%, Androgel, Testim, or Fortesta) were treated with a 2% testosterone solution until T-levels reached a normal range (from ≥300 to ≤1,050 ng/dL) or for up to 9 weeks. Outcomes included the cumulative percentage of men with a serum T-level in the normal range during treatment with Axiron and improvement in symptoms of low energy level and low sexual drive. During the study, 95% of HGN men (72/78) attained a T-level in the normal range. The median T-level at endpoint was 495.7 ng/dL, a threefold increase over baseline, p < .001, 70% achieving normal T-levels within the first 2 weeks of treatment. In a post hoc analysis, all subjects with baseline body mass indexes >35 kg/m 2 ( n = 19) achieved T-levels in the normal range. Prior to treatment, over 61% of subjects (48/78) reported impairment in either energy level or sexual drive. After treatment (or testosterone normalization), energy level improved in 75% of subjects and sexual drive improved in 70%. Topical 2% testosterone solution is a safe and effective treatment for HGN men who have had a suboptimal response to previous treatment with topical testosterone gels.

Oxidative stress, testosterone, and cognition among Caucasian and Mexican-American men with and without Alzheimer's disease.

PubMed

Cunningham, Rebecca L; Singh, Meharvan; O'Bryant, Sid E; Hall, James R; Barber, Robert C

2014-01-01

The use of testosterone among aging men has been increasing, but results from studies addressing the effectiveness of testosterone replacement therapy have been equivocal. Given our prior pre-clinical studies that reported a major influence of oxidative stress on testosterone's neuroprotective effects, we investigated whether the negative effects of testosterone on brain function were predicted by oxidative load. In order to test our hypothesis, we determined whether circulating total testosterone and luteinizing hormone correlated with cognition in a subset of the Texas Alzheimer's Research & Care Consortium (TARCC) cohort, consisting of Caucasian (n = 116) and Mexican-American (n = 117) men. We also assessed whether oxidative stress (as indexed by homocysteine levels) modified this relationship between sex hormones and cognition, and whether the levels of two antioxidants, superoxide dismutase-1 and glutathione S-transferase (GST), varied as a function of circulating testosterone. In a low oxidative stress environment, testosterone was positively associated with the level of the antioxidant, GST, while no deleterious effects on cognitive function were noted. In contrast, under conditions of high oxidative stress (homocysteine levels >12 μmol/L), testosterone and luteinizing hormone were associated with cognitive impairment, but only among Caucasians. The ethnic difference was attributed to significantly higher GST levels among Mexican-Americans. While testosterone may be beneficial under conditions of low oxidative stress, testosterone appears to have negative consequences under conditions of elevated oxidative stress, but only in Caucasians. Mexican-Americans, however, were protected from any deleterious effects of testosterone, potentially due to higher levels of endogenous antioxidant defenses such as GST.

Testosterone and Aggression.

ERIC Educational Resources Information Center

Archer, John

1994-01-01

Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodentia: Muridae).

PubMed

Luis, Juana; Ramírez, Lorena; Carmona, Agustín; Ortiz, Guadalupe; Delgado, Jesús; Cárdenas, René

2009-01-01

Paternal behavior and testosterone plasma levels in the Volcano Mouse Neotomodon alstoni (Rodentia: Muridae). Although initially it was thought that testosterone inhibited the display of paternal behavior in males of rodents, it has been shown that in some species high testosterone levels are needed for exhibition of paternal care. In captivity, males of Volcano Mouse (Neotomodon alstoni) provide pups the same care provided by the mother, with the exception of suckling. Here we measured plasmatic testosterone concentrations 10 days after mating, five and 20 days postpartum, and 10 days after males were isolated from their families in order to determine possible changes in this hormone, associated to the presence and age of pups. Males of Volcano Mouse exhibited paternal behavior when their testosterone levels were relatively high. Although levels of this hormone did not change with the presence or pups age, males that invested more time in huddling showed higher testosterone levels. It is possible that in the Volcano Mouse testosterone modulates paternal behavior indirectly, as in the California mouse.

Relationships between testosterone levels and cognition in patients with Alzheimer disease and nondemented elderly men.

PubMed

Seidl, Jennifer N Travis; Massman, Paul J

2015-03-01

Previous research suggests that low levels of testosterone may be associated with the development of Alzheimer disease (AD), as well as poorer performance on certain neuropsychological tests and increased risk of depression. This study utilized data from 61 nondemented older men and 68 men with probable AD. Testosterone levels did not differ between the groups. Regression analyses in men with AD revealed that testosterone levels did not significantly predict performance on neuropsychological tests or a measure of depression. Among controls, testosterone levels predicted estimated premorbid verbal IQ and performance on a verbal fluency test. Findings suggest that testosterone is not associated with most neuropsychological test performances in patients with AD. © The Author(s) 2014.

Salivary testosterone levels in men at a U.S. sex club.

PubMed

Escasa, Michelle J; Casey, Jacqueline F; Gray, Peter B

2011-10-01

Vertebrate males commonly experience elevations in testosterone levels in response to sexual stimuli, such as presentation of a novel mating partner. Some previous human studies have shown that watching erotic movies increases testosterone levels in males although studies measuring testosterone changes during actual sexual intercourse or masturbation have yielded mixed results. Small sample sizes, "unnatural" lab-based settings, and invasive techniques may help account for mixed human findings. Here, we investigated salivary testosterone levels in men watching (n = 26) versus participating (n = 18) in sexual activity at a large U.S. sex club. The present study entailed minimally invasive sample collection (measuring testosterone in saliva), a naturalistic setting, and a larger number of subjects than previous work to test three hypotheses related to men's testosterone responses to sexual stimuli. Subjects averaged 40 years of age and participated between 11:00 pm and 2:10 am. Consistent with expectations, results revealed that testosterone levels increased 36% among men during a visit to the sex club, with the magnitude of testosterone change significantly greater among participants (72%) compared with observers (11%). Contrary to expectation, men's testosterone changes were unrelated to their age. These findings were generally consistent with vertebrate studies indicating elevated male testosterone in response to sexual stimuli, but also point out the importance of study context since participation in sexual behavior had a stronger effect on testosterone increases in this study but unlike some previous human lab-based studies.

TESTOSTERONE LEVELS ACHIEVED BY MEDICALLY TREATED TRANSGENDER WOMEN IN A UNITED STATES ENDOCRINOLOGY CLINIC COHORT.

PubMed

Liang, Jennifer J; Jolly, Divya; Chan, Kelly J; Safer, Joshua D

2018-02-01

Most transgender women depend on medical treatment alone to lower testosterone levels in order to align physical appearance with gender identity. The medical regimen in the United States typically includes spironolactone and estrogens. The purpose of this cross-sectional study was to assess the testosterone suppression achieved among transgender women treated with spironolactone and estrogens. Testosterone and estradiol levels were extracted from the electronic medical records of 98 anonymized transgender women treated with oral spironolactone and oral estrogen therapy at the Endocrinology Clinic at Boston Medical Center. Patients starting therapy required about 9 months to reach a steady-state testosterone, with significant heterogeneity of levels achieved among patients. Patients with normal body mass index (BMI) had higher testosterone levels, whereas patients with obese BMI had lower testosterone levels throughout treatment. Stratification of patients by age or spironolactone dosage revealed no significant difference in testosterone levels achieved. At steady state, patients in the highest suppressing quartile were able to achieve testosterone levels of 27 ng/dL, with a standard deviation of 21 ng/dL. Measured serum estradiol levels did not change over time and did not correlate with dosage of estradiol administered. Among a cohort of transgender women treated with spironolactone and estrogen, the highest suppressing quartile could reliably achieve testosterone levels in the female range at virtually all times. The second highest suppressing quartile could not achieve female levels but remained below the male range virtually all of the time. One quartile was unable to achieve any significant suppression. BMC = Boston Medical Center BMI = body mass index CPY = cyproterone acetate LC-MS/MS = liquid chromatography-tandem mass spectrometry Q = quartile.

Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population.

PubMed

Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

2015-01-01

High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits.

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

PubMed

Wang, C; Eyre, D R; Clark, R; Kleinberg, D; Newman, C; Iranmanesh, A; Veldhuis, J; Dudley, R E; Berman, N; Davidson, T; Barstow, T J; Sinow, R; Alexander, G; Swerdloff, R S

1996-10-01

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

The testosterone conundrum: The putative relationship between testosterone levels and prostate cancer.

PubMed

Loughlin, Kevin R

2016-11-01

The controversy surrounding the relationship between testosterone and prostate cancer has existed for decades. The literature surrounding this topic is confusing and at times contradictory. There is no level-one quality evidence that confirms or refutes the relationship between either high or low serum testosterone levels and the subsequent development of prostate cancer. This commentary aims to review the issues involved and to provide an interpretation as to the causes of the confusion and to provide a framework for ongoing discussion and investigation. A Medline and PubMed search was conducted using search terms: testosterone levels and prostate cancer to identify pertinent literature. There is no consistent evidence that a single testosterone level is predictive of prostate cancer risk. The development of prostate cancer is a complex biologic process potentially involving genetics,dietary, life style and hormonal factors. Serum testosterone levels do not accurately reflect the internal prostatic milieu. Finally, if testosterone levels are to be considered in the etiology of prostate cancer they should be measured and interpreted on a chronic basis with multiple measurements over a period of years. Copyright © 2016 Elsevier Inc. All rights reserved.

No evidence for the immunocompetence handicap hypothesis in male humans.

PubMed

Nowak, Judyta; Pawłowski, Bogusław; Borkowska, Barbara; Augustyniak, Daria; Drulis-Kawa, Zuzanna

2018-05-09

The observations that testosterone might be immunosuppressive, form the basis for the immunocompetence handicap hypothesis (ICHH). According to ICHH only high-quality individuals can maintain high levels of testosterone and afford the physiological cost of hormone-derived immunosuppression. The animal and human studies that attempted to support the ICHH by precisely defined impairment of immunity associated with high testosterone levels are inconclusive. Furthermore, human studies have used only selected immune functions and varying testosterone fractions. This is the first study examining the relationship between multiple innate and adaptive immunity and serum levels of free testosterone, total testosterone, DHT and DHEA in ninety-seven healthy men. Free testosterone and marginally DHT levels were positively correlated with the strength of the influenza post-vaccination response. Total testosterone and DHEA showed no immunomodulatory properties. Our findings did not support ICHH assumptions about immunosuppressive function of androgens. In the affluent society studied here, men with higher levels of free testosterone could afford to invest more in adaptive immunity. Since the hormone-immune relationship is complex and may depend on multiple factors, including access to food resources, androgens should be treated as immunomodulators rather than implicit immunosuppressants.

Lack of evidence for meteorological effects on infradian dynamics of testosterone

NASA Astrophysics Data System (ADS)

Celec, Peter; Smreková, Lucia; Ostatníková, Daniela; Čabajová, Zlata; Hodosy, Július; Kúdela, Matúš

2009-09-01

Climatic factors are known to influence the endocrine system. Previous studies have shown that circannual seasonal variations of testosterone might be partly explained by changes in air temperature. Whether infradian variations are affected by meteorological factors is unknown. To analyze possible effects of meteorological parameters on infradian variations of salivary testosterone levels in both sexes, daily salivary testosterone levels were measured during 1 month in 14 men and 17 women. A correlation analysis between hormonal levels and selected meteorological parameters was performed. The results indicate that high testosterone levels are loosely associated with cold, sunny and dry weather in both sexes. However, only the correlations between testosterone and air temperature (men) and actual cloudiness (women) were statistically significant ( p < 0,05). Although some correlations reached the level of statistical significance, the effects of selected meteorological parameters on salivary testosterone levels remain unclear. Further longer-term studies concentrating on air temperature, cloudiness and average relative humidity in relation to the sex hormone axis are needed.

Effects of Transdermal Testosterone on Natriuretic Peptide Levels in Women: A Randomized Placebo-Controlled Pilot Study

PubMed Central

Lin, Eleanor; McCabe, Elizabeth; Newton-Cheh, Christopher; Bloch, Kenneth; Buys, Emmanuel; Wang, Thomas; Miller, Karen K.

2011-01-01

Objective To investigate whether testosterone administration alters natriuretic peptide levels in women. Design Three-month, double-blind, randomized, placebo-controlled study. Setting Clinical research center. Patients 51 women with hypoandrogenemia due to hypopituitarism. Intervention Transdermal testosterone (300 mcg daily) or placebo patch. Main Outcome Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Results NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months (p = 0.009). The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model of assessment-insulin resistance (p = 0.008). Change in NT-proBNP over three months was inversely associated with change in free testosterone levels (ρ = −0.41, p = 0.01). Conclusions Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system. Clinical Trials Registration Number NCT00027430 PMID:22137497

Intra-sexual competition alters the relationship between testosterone and ornament expression in a wild territorial bird.

PubMed

Martínez-Padilla, J; Pérez-Rodríguez, L; Mougeot, F; Ludwig, S; Redpath, S M

2014-05-01

In a reliable signalling system, individual quality is expected to mediate the costs associated with ornamental displays, with relatively lower costs being paid by individuals of higher quality. These relative costs should depend not only on individual quality, but also on levels of intra-sexual competition. We explored the current and delayed effects that testosterone implants have on bird ornamentation in populations with contrasted population densities, as a proxy for intra-sexual competition. In a replicated experiment, we manipulated testosterone in 196 yearling male red grouse Lagopus lagopus scoticus in autumn in populations of high and low levels of intra-sexual competition. Males were assigned to one of three exogenous testosterone (T) treatments: empty implants (T0), small T implants (T1) or larger T implants (T2). We monitored subsequent changes in testosterone levels, ornament size and carotenoid-based colouration, carotenoid levels and body condition from autumn to spring. Testosterone implants increased testosterone levels, comb redness and comb size, and decreased body condition but these effects depended on levels of intra-sexual competition. Specifically, T2-implanted birds increased testosterone levels and comb size more, and reduced body condition more, in populations where intra-sexual competition was low. In the following spring, testosterone levels of T2-treated birds kept increasing in populations where intra-sexual competition was high but not in populations where intra-sexual competition was low. Our results highlight that levels of intra-sexual competition alter the relationship between testosterone levels and ornament expression, influencing their condition-dependence; they also indicate that the outcome of standard hormone manipulation conducted in free-living animals vary depending on the population context. Copyright © 2014 Elsevier Inc. All rights reserved.

Patterns of testosterone in three Nearctic-Neotropical migratory songbirds during spring passage.

PubMed

Covino, Kristen M; Morris, Sara R; Moore, Frank R

2015-12-01

Preparation for breeding may overlap extensively with vernal migration in long-distance migratory songbirds. Testosterone plays a central role in mediating this transition into breeding condition by facilitating changes to physiology and behavior. While changes in testosterone levels are well studied in captive migrants, these changes are less well known in free-living birds. We examined testosterone levels in free-living Nearctic-Neotropical migrants of three species during their vernal migration. Testosterone levels increased during the migratory period in males of all three species but significantly so in only two. Testosterone levels in females remained the same throughout their migration. Our results support the extensive overlap between vernal migration and breeding preparation in male songbirds. The pattern of testosterone changes during vernal migration is far from clear in females. Copyright © 2015 Elsevier Inc. All rights reserved.

Di-Isobutyl Phthalate (DIBP) Hazard Identification [Abstract ...

EPA Pesticide Factsheets

The hazard potential for DIBP is being evaluated as part of EPA’s Integrated Risk Information System (IRIS) Toxicological Review. DIBP is a plasticizer that confers flexibility and durability in industrial and consumer products. A literature search identified a relatively small epidemiology and animal toxicology database for DIBP. The epidemiological database includes studies that assessed the relationship between urinary concentrations of the DIBP metabolite mono-isobutyl phthalate (MIBP)and developmental, neurodevelopmental, immunological or breast cancer outcomes. There is limited support for associations between MIBP and inflammatory biomarker levels and decreased masculine play behavior. The animal toxicological database includes studies that assessed “phthalate syndrome” male reproductive developmental endpoints after in utero DIBP exposure. Data from the largest developmental study, Saillenfait et al. (2008), shows changes in anogenital distance, male reproductive organ weights, and litter incidence of phthalate syndrome endpoints in the lower dose range after early gestational exposure. Other studies observed increased fetal mortality, male postnatal and adult growth decrements, decreased fetal testicular testosterone and changes in expression of genes in androgen production pathways. The developmental reproductive effects observed in animal studies are consistent with the reduced testicular testosterone mode of action that is well-characterize

Steroid 5 alpha-reductase deficiency in a 65-year-old male pseudohermaphrodite: the natural history, ultrastructure of the testes, and evidence for inherited enzyme heterogeneity.

PubMed

Imperato-McGinley, J; Peterson, R E; Leshin, M; Griffin, J E; Cooper, G; Draghi, S; Berenyi, M; Wilson, J D

1980-01-01

We report a 65-yr-old male pseudohermaphrodite with steroid 5 alpha-reductase deficiency in whom there was no medical intervention before, during, or after puberty, enabling us to observe the natural history of this condition. The affected subject has an android build, with more facial and body hair than in previously described affected adults. Although the subject was raised as a girl, a male gender identity evolved with the events of puberty, but social factors have delayed the complete expression of a male gender role. Plasma levels of dihydrotestosterone and the in vivo conversion of radiolabeled testosterone to dihydrotestosterone were decreased. There was an elevated urinary etiocholanolone to androsterone ratio, typical of the syndrome. Characterization of 5 alpha-reductase enzyme activity in cultured genital skin fibroblasts demonstrated a pattern of enzyme activity distinctly different from three previously described families with this condition. There was decreased enzyme affinity for testosterone and NADPH. Also, the stability of the enzyme to elevated temperature was not protected by NADPH, resulting in rapid disappearance of enzyme activity after inhibition of protein synthesis with cycloheximide. Electron microscopic evaluation of the testes was carried out.

Finasteride therapy does not alter bone turnover in men with benign prostatic hyperplasia--a Clinical Research Center study.

PubMed

Tollin, S R; Rosen, H N; Zurowski, K; Saltzman, B; Zeind, A J; Berg, S; Greenspan, S L

1996-03-01

Benign prostatic hyperplasia is often treated with finasteride, which inhibits the conversion of testosterone to dihydrotestosterone (DHT). Aside from the prostate, other androgen-dependent tissues seem to be unaffected by selective DHT deficiency, but the effect on bone density in humans has not yet been defined. To study this question, we compared indices of bone turnover and bone mineral density in 35 men treated with finasteride with controls. Bone resorption was assessed by measuring urinary excretion of N-telopeptide cross-links of type I collagen and hydroxyproline, and bone formation was assessed by measuring serum osteoncalcin and bone-specific alkaline phosphatase. Bone density of the spine and hip were assessed by dual energy x-ray absorptiometry. We found that finasteride-treated patients had mean DHT levels 81% lower than controls (P < 0.0001). There were no significant differences between the two groups in any of the markers of bone turnover or measures of bone density. These results suggest that testosterone can maintain bone density in men even in the absence of DHT. Although long term studies are needed, our results suggest that men who take finasteride are not at increased risk for bone loss.

Serum Testosterone Levels in Prostate Cancer Patients Undergoing Luteinizing Hormone-Releasing Hormone Agonist Therapy.

PubMed

Morote, Juan; Comas, Inma; Planas, Jacques; Maldonado, Xavier; Celma, Ana; Placer, José; Ferrer, Roser; Carles, Joan; Regis, Lucas

2018-04-01

Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation therapy (ADT) and to diagnose castration resistance in patients with prostate cancer (PCa). Currently, the accepted castrate level of serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass spectrometry (LC MSMS) is the appropriate method to measure testosterone, especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are used in clinical laboratories, despite their lack of accuracy and reproducibility, because they are automatable, fast, sensitive, and inexpensive. We compared serum testosterone levels measured using LC MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing hormone (LHRH) agonist therapy. The median serum testosterone level was 14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6 ng/dL) with CLIA (P < .001). The serum testosterone levels, measured using LC MSMS, were < 20 ng/dL in 83 patients (65.9%), 20 to 50 ng/dL in 40 (31.7%), and > 50 ng/dL in 3 patients (2.4%). These ranges were found in 34 (27%), 72 (57.1%), and 20 (15.9%) patients when testosterone was measured using CLIA (P < .001). The castrate level of serum testosterone using LC MSMS and CLIA was 39.8 ng/dL (95% confidence interval [CI], 37.1-43.4 ng/dL) and 66.5 ng/dL (95% CI, 62.3-71.2 ng/dL), respectively. We found that CLIA overestimated the testosterone levels in PCa patients undergoing LHRH agonist therapy. Thus, the castration level was incorrectly considered inadequate with CLIA in almost 15% of patients. The true castration level of serum testosterone using an appropriate method is < 50 ng/dL. Copyright © 2017 Elsevier Inc. All rights reserved.

Growing Up Or Growing Old? Cellular Aging Linked With Testosterone Reactivity To Stress In Youth

PubMed Central

Drury, Stacy S.; Shirtcliff, Elizabeth A.; Shachet, Andrew; Phan, Jenny; Mabile, Emily; Brett, Zoë H.; Wren, Michael; Esteves, Kyle; Theall, Katherine P.

2014-01-01

Background Given the established relation between testosterone and aging in older adults, we tested whether buccal telomere length (TL), an established cellular biomarker of aging, was associated with testosterone levels in youth. Methods Children, mean age 10.2 years, were recruited from the greater New Orleans area and salivary testosterone was measured during both an acute stressor and diurnally. Buccal TL was measured using monochrome multiplex quantitative real-time PCR (MMQ-PCR). Testosterone and telomere length data was available on 77 individuals. The association between buccal TL and testosterone was tested using multivariate Generalized Estimating Equations (GEE) to account for clustering of children within families. Results Greater peak testosterone levels (β=-0.87, p < 0.01) and slower recovery (β=-0.56, p < 0.01) and reactivity (β = -1.22, p < 0.01) following a social stressor were significantly associated with shorter buccal TL after controlling for parental age at conception, child age, sex, sociodemographic factors and puberty. No association was initially present between diurnal measurements of testosterone or morning basal testosterone levels and buccal TL. Sex significantly moderated the relation between testosterone reactivity and buccal TL. Conclusions The association between testosterone and buccal TL supports gonadal maturation as a developmentally sensitive biomarker of aging within youth. As stress levels of testosterone were significantly associated with buccal TL, these findings are consistent with the growing literature linking stress exposure and accelerated maturation. The lack of association of diurnal testosterone or morning basal levels with buccal TL bolsters the notion of a shared stress-related maturational mechanism between cellular stress and the hypothalamic pituitary gonadal (HPG) axis. These data provide novel evidence supporting the interaction of aging, physiologic stress and cellular processes as an underlying mechanism linking negative health outcomes and early life stress. PMID:25010187

Effect of testosterone supplementation on sexual functioning in aging men: a 6-month randomized controlled trial.

PubMed

Emmelot-Vonk, M H; Verhaar, H J J; Nakhai-Pour, H R; Grobbee, D E; van der Schouw, Y T

2009-01-01

Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function. We have conducted a double-blind, randomized, placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level <13.7 nmol l(-1). Participants were randomly assigned to receive oral testosterone undecanoate or a placebo for 6 months. A total of 207 men completed the study. After treatment, there were no differences in scores on sexual function between the groups. Subanalysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies, desire of sexual contact and frequency of sexual contact, supplementation of testosterone did not result in improvement on any of these items in this group. In conclusion, the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function.

Patterns of testosterone prescription overuse.

PubMed

Jasuja, Guneet K; Bhasin, Shalender; Rose, Adam J

2017-06-01

There has been an increase in the prescribing of testosterone therapy in the past decade. There is concern that at least part of this increase is driven by advertising rather than sound medical practice. The purpose of this review is to summarize the recent trends in testosterone prescribing, and to examine whether testosterone is being appropriately prescribed as per guidelines. Both global and U.S. data reflect an overall increase in the use of testosterone in the last decade, although there are early signs of a decline in testosterone sales since 2014. This increased prescribing has been accompanied with an overall increase in testing for testosterone levels, prescription of testosterone without the appropriate diagnostic evaluation recommended by clinical practice guidelines, and apparent use of this therapy for unproven medical conditions. Research to date suggests that there is room to improve our prescribing of testosterone. Greater understanding of the potential provider-level and system-level factors that contribute to the current prescribing practices may help accomplish such improvement.

Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer.

PubMed

Scherr, Douglas; Pitts, W Reid; Vaughn, E Darracott

2002-02-01

It is well described in the urological literature that androgen deprivation can result in accelerated bone breakdown and osteoporosis. Therefore, we evaluate the degree of bone breakdown in patients on conventional androgen deprivation with those on diethylstilbesterol alone or in conjunction with luteinizing hormone releasing hormone agonists or orchiectomy. During an 18-month period a total of 54 patients with clinically localized prostate cancer and 24 with benign prostatic hyperplasia were evaluated. All patients with prostate cancer were either treated with external beam radiotherapy without androgen deprivation or were started on androgen deprivation therapy. All patients were prospectively followed and evaluated for serum testosterone and estradiol along with urinary collagen type I cross-linked N-telopeptides. Three separate morning urine samples on 3 separate months were collected on each patient and analyzed for N-telopeptides. To correct for different levels of renal function, all N-telopeptides were measured as a ratio of urinary N-telopeptides/urine creatinine. All patients with any bone or skeletal abnormalities were excluded from study as were those with osseous metastatic disease. There was a statistically significant (p < 0.05) higher level of urinary N-telopeptides/creatinine in patients on androgen deprivation therapy who were not treated with diethylstilbesterol. The estrogenic effect of diethylstilbesterol protects one from bone resorption. Patients on diethylstilbesterol did not have any higher levels of bone breakdown than patients with benign prostatic hyperplasia or those who never received any androgen deprivation. Rapid bone turnover and resorption can be prevented with 1 mg. diethylstilbesterol alone or in conjunction with other modes of androgen deprivation. Therefore, diethylstilbesterol should be considered as monotherpy in men who require long-term antiandrogen therapy.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

Prenatal and pubertal testosterone affect brain lateralization.

PubMed

Beking, T; Geuze, R H; van Faassen, M; Kema, I P; Kreukels, B P C; Groothuis, T G G

2018-02-01

After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in puberty. We performed a longitudinal study, investigating the relationship between prenatal testosterone concentrations in amniotic fluid, pubertal testosterone concentrations in saliva, and brain lateralization (measured with functional Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric Faces and Word Generation tasks. Thirty boys and 30 girls participated in this study at the age of 15 years. For boys, we found a significant interaction effect between prenatal and pubertal testosterone on lateralization of Mental Rotation and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal testosterone was positively related to the strength of lateralization in the right hemisphere, while in the boys with high prenatal testosterone levels, pubertal testosterone was negatively related to the strength of lateralization. For Word Generation, pubertal testosterone was negatively related to the strength of lateralization in the left hemisphere in boys. For girls, we did not find any significant effects, possibly because their pubertal testosterone levels were in many cases below quantification limit. To conclude, prenatal and pubertal testosterone affect lateralization in a task-specific way. Our findings cannot be explained by simple models of prenatal testosterone affecting brain lateralization in a similar way for all tasks. We discuss alternative models involving age dependent effects of testosterone, with a role for androgen receptor distribution and efficiency. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Environmentally relevant concentrations of nitrate increase plasma testosterone concentrations in female American alligators (Alligator mississippiensis).

PubMed

Hamlin, Heather J; Edwards, Thea M; McCoy, Jessica; Cruze, Lori; Guillette, Louis J

2016-11-01

Anthropogenic nitrogen is a ubiquitous environmental contaminant that is contributing to the degradation of freshwater, estuarine, and coastal ecosystems worldwide. The effects of environmental nitrate, a principal form of nitrogen, on the health of aquatic life is of increasing concern. We exposed female American alligators to three concentrations of nitrate (0.7, 10 and 100mg/L NO 3 -N) for a duration of five weeks and five months from hatch. We assessed growth, plasma sex steroid and thyroid hormone concentrations, and transcription levels of key genes involved in steroidogenesis (StAR, 3β-HSD, and P450 scc ) and hepatic clearance (Cyp1a, Cyp3a). Exposure to 100mg/L NO 3 -N for both five weeks and five months resulted in significantly increased plasma testosterone (T) concentrations compared with alligators in the reference treatment. No differences in 17β-estradiol, progesterone, or thyroid hormones were observed, nor were there differences in alligator weight or the mRNA abundance of steroidogenic or hepatic genes. Plasma and urinary nitrate concentrations increased with increasing nitrate treatment levels, although relative plasma concentrations of nitrate were significantly lower in five month, versus five week old animals, possibly due to improved kidney function in older animals. These results indicate that environmentally relevant concentrations of nitrate can increase circulating concentrations of T in young female alligators. Copyright © 2016 Elsevier Inc. All rights reserved.

Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results.

PubMed

Wenisch, Judith M; Mayr, Florian B; Spiel, Alexander O; Radicioni, Milko; Jilma, Bernd; Jilma-Stohlawetz, Petra

2014-03-01

Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

Interactive effects of testosterone and cortisol on hippocampal volume and episodic memory in middle-aged men.

PubMed

Panizzon, Matthew S; Hauger, Richard L; Xian, Hong; Jacobson, Kristen; Lyons, Michael J; Franz, Carol E; Kremen, William S

2018-05-01

Animal and human research suggests that testosterone is associated with hippocampal structure and function. Studies examining the association between testosterone and either hippocampal structure or hippocampal-mediated cognitive processes have overwhelmingly focused on the effects of testosterone alone, without considering the interaction of other neuroendocrine factors. The aim of the present study was to examine the interactive effects of testosterone and cortisol in relation to hippocampal volume and episodic memory in a sample of late-middle aged men from the Vietnam Era Twin Study of Aging. The average age of participants was 56.3 years (range 51-60). Salivary hormone samples were collected at multiple time-points on two non-consecutive at-home days, and an in-lab assessment. Area under the curve with respect to ground measures for cortisol and testosterone were utilized. Significant testosterone-by-cortisol interactions were observed for hippocampal volume, and episodic memory. When cortisol levels were elevated (1 SD above the mean), testosterone levels were positively associated with hippocampal volume and memory performance. However, when cortisol levels were low (1 SD below the mean), testosterone levels were inversely related to hippocampal volume and memory performance. These findings suggest that in context of high cortisol levels, testosterone may be neuroprotective. In contrast, low testosterone may also be neuroprotective in the context of low cortisol levels. To our knowledge this is the first demonstration of such an interaction in a structural brain measure and an associated cognitive ability. These results argue in favor of broadening neuroendocrine research to consider the simultaneous and interactive effects of multiple hormones on brain structure and function. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dominance, Politics, and Physiology: Voters' Testosterone Changes on the Night of the 2008 United States Presidential Election

PubMed Central

Stanton, Steven J.; Beehner, Jacinta C.; Saini, Ekjyot K.; Kuhn, Cynthia M.; LaBar, Kevin S.

2009-01-01

Background Political elections are dominance competitions. When men win a dominance competition, their testosterone levels rise or remain stable to resist a circadian decline; and when they lose, their testosterone levels fall. However, it is unknown whether this pattern of testosterone change extends beyond interpersonal competitions to the vicarious experience of winning or losing in the context of political elections. Women's testosterone responses to dominance competition outcomes are understudied, and to date, a clear pattern of testosterone changes in response to winning and losing dominance competitions has not emerged. Methodology/Principal Findings The present study investigated voters' testosterone responses to the outcome of the 2008 United States Presidential election. 183 participants provided multiple saliva samples before and after the winner was announced on Election Night. The results show that male Barack Obama voters (winners) had stable post-outcome testosterone levels, whereas testosterone levels dropped in male John McCain and Robert Barr voters (losers). There were no significant effects in female voters. Conclusions/Significance The findings indicate that male voters exhibit biological responses to the realignment of a country's dominance hierarchy as if they participated in an interpersonal dominance contest. PMID:19844583

Testosterone levels and cognition in elderly men: a review.

PubMed

Holland, J; Bandelow, S; Hogervorst, E

2011-08-01

Average testosterone levels and many cognitive functions show a decline with age. There is evidence to suggest that this association is not just age related. Results from cell culture and animal studies provide convincing evidence that testosterone could have protective effects on brain function. Alzheimer's disease (AD) is characterised by brain pathology affecting cognitive function and AD prevalence increases with age. Testosterone levels are lower in AD cases compared to controls, and some studies have suggested that low free testosterone (FT) may precede AD onset. Men with AD may show accelerated endocrinological ageing, characterised by an earlier lowering of thyroid stimulating hormone, an earlier increase in sex hormone binding globulin (SHBG), a subsequent earlier decrease in FT and an earlier increase in gonadotropin levels in response to this. Positive associations have been found between testosterone levels and global cognition, memory, executive functions and spatial performance in observational studies. However, non-significant associations were also reported. It may be that an optimal level of testosterone exists at which some cognitive functions are improved. This may be modified with an older age, with a shifting of the optimal testosterone curve to maintain cognition to the left and a lower optimal level thus needed to be beneficial for the brain. Genetic factors, such as APOE and CAG polymorphisms may further interact with testosterone levels in their effects on cognition. The roles of SHBG, gonadotropins, thyroid hormones and estrogens in maintaining cognitive function and preventing dementia in men are also not completely understood and should be investigated further. Hypogonadal men do not seem to benefit from testosterone supplementation but small scale, short term intervention studies in eugonadal men with and without cognitive impairments have shown promising results. Larger randomised, controlled trials are needed to further investigate testosterone treatment in protecting against cognitive decline and/or dementia. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

ESTROGEN LEVELS DO NOT RISE WITH TESTOSTERONE TREATMENT FOR TRANSGENDER MEN.

PubMed

Chan, Kelly J; Jolly, Divya; Liang, Jennifer J; Weinand, Jamie D; Safer, Joshua D

2018-04-01

Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any. Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up. With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up. These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men. Abbreviation: BMI = body mass index.

Yolk testosterone reduces oxidative damages during postnatal development

PubMed Central

Noguera, José Carlos; Alonso-Alvarez, Carlos; Kim, Sin-Yeon; Morales, Judith; Velando, Alberto

2011-01-01

Conditions experienced during early life can influence the development of an organism and several physiological traits, even in adulthood. An important factor is the level of oxidative stress experienced during early life. In birds, extra-genomic egg substances, such as the testosterone hormone, may exert a widespread influence over the offspring phenotype. Interestingly, testosterone can also upregulate the bioavailability of certain antioxidants but simultaneously increases the susceptibility to oxidative stress in adulthood. However, little is known about the effects of maternally derived yolk testosterone on oxidative stress in developing birds. Here, we investigated the role of yolk testosterone on oxidative stress of yellow-legged gull chicks during their early development by experimentally increasing yolk testosterone levels. Levels of antioxidants, reactive oxygen species and lipid oxidative damage were determined in plasma during nestlings' growth. Our results revealed that, contrary to control chicks, birds hatched from testosterone-treated eggs did not show an increase in the levels of oxidative damage during postnatal development. Moreover, the same birds showed a transient increase in plasma antioxidant levels. Our results suggest that yolk testosterone may shape the oxidative stress-resistance phenotype of the chicks during early development owing to an increase in antioxidant defences and repair processes. PMID:20659922

Testosterone and the metabolic syndrome.

PubMed

Muraleedharan, Vakkat; Jones, T Hugh

2010-10-01

Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia and sexual dysfunction along with improved quality of Life. However, there are no Long-term interventional studies to assess the effect of testosterone replacement on mortality in men with Low testosterone Levels. This article reviews the observational and interventional clinical data in relation to testosterone and metabolic syndrome.

Gender differences in serum testosterone and cortisol in patients with major depressive disorder compared with controls.

PubMed

Matsuzaka, Hisashi; Maeshima, Hitoshi; Kida, Sayaka; Kurita, Hirofumi; Shimano, Takahisa; Nakano, Yoshiyuki; Baba, Hajime; Suzuki, Toshihito; Arai, Heii

2013-01-01

Testosterone may have a role distinct from cortisol in the pathophysiology of depression. The hypothalamus-pituitary-adrenal (HPA) axis affects the functions of sex steroid hormones through interaction with corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH). The objective of this study was to investigate differences in serum levels of testosterone and cortisol in male and female patients with major depressive disorder (MDD). Participants included 87 inpatients with MDD at Juntendo University Koshigaya Hospital. Serum levels of testosterone and cortisol were assessed at admission. Matched controls included 128 healthy individuals. Data from MDD patients and controls were compared separately for men and women. Correlations between serum hormone levels and scores on the Hamilton Rating Scale for Depression (HAM-D) of patients were assessed by sex. Effects of various factors on testosterone and cortisol were analyzed using multiple regression analysis. In male patients with MDD, a significant negative correlation was seen between testosterone levels and the "retardation" score of HAM-D. However, serum testosterone levels were not significantly different in either male or female MDD patients compared with controls. Serum testosterone was negatively associated with the number of depressive episodes in male patients with MDD. Serum cortisol levels in female patients were significantly increased compared with female controls with no significant correlations between cortisol levels and HAM-D scores. The negative correlation between the sub-score of the HAM-D and testosterone may be associated with the biological pathophysiology of male depression. Findings of serum cortisol levels in women may suggest distinct characteristics of these hormones in men and women with MDD.

Plasma Testosterone Levels Increase with Expression of Male Ornaments During Mating, but not Incubation, in Japanese Barn Swallows.

PubMed

Hasegawa, Masaru; Arai, Emi; Sato, Megumi; Sakai, Hidetsugu

2017-08-01

Recent experimental studies involving the manipulation of sexual traits have demonstrated that sexual trait expression feeds back to testosterone levels, perhaps via social interactions, reinforcing the linkage between sexual trait expression and testosterone levels during the mating period. However, information on this reinforcement under the natural variation of sexual traits remains limited. Using Japanese barn swallows, Hirundo rustica gutturalis, in which extra-pair paternity is quite rare (< 3%), we studied the relationship between plasma testosterone level and a male sexual trait, throat patch size, during the mating and incubation periods. Given the importance of social interaction, we predicted that this relationship should be intense during the mating period, but not the incubation period, due to reduced social interaction during the latter. We found low plasma testosterone levels during the incubation period compared with those in the mating period, and plasma testosterone levels were significantly positively related to throat patch area during the mating period, but not the incubation period. Similar relationships were found in another sexual trait, the size of white tail spots. During the incubation period, body condition, instead of male sexual trait expression, was negatively related to plasma testosterone level, indicating that an intrinsic link, rather than reinforcement, is important during this period. These relationships are consistent with the hypothesis that social interaction reinforces the relationship between sexual traits and plasma testosterone levels. The current study provides evidence for a highly variable relationship between testosterone and ornamentation across breeding periods in the natural variation of sexual traits.

Different effects of acute and chronic immobilization stress on plasma testosterone levels in male Syrian hamsters.

PubMed

Tsuchiya, T; Horii, I

1995-01-01

Time-course variations in plasma testosterone levels after various periods of immobilization stress (10 min, 30 min, 2 h, 6 h) were examined in male Syrian hamsters. The immobilization stress consisted of placing the animals in a prone position and wrapping them with flexible steel wire gauze. This was done at room temperature. Testosterone levels were determined in blood samples taken after the hamsters were decapitated. Chronic (2 h, 6 h) immobilization stress produced a drastic and enduring fall in plasma testosterone levels. Reduction of plasma testosterone following the 6-h immobilization stress was observed even 18 h after the stress had been relieved. However, acute (10 min, 30 min) immobilization stress did not influence plasma testosterone. These findings indicated that the effect of immobilization stress on plasma testosterone in hamsters was not biphasic, which it is in rats. Further, these results suggest that immobilization stress in hamsters would be a valuable technique with which to investigate the effects of physiological ranges of testosterone on physiological and psychological functions.

Salivary testosterone: associations with depression, anxiety disorders, and antidepressant use in a large cohort study.

PubMed

Giltay, Erik J; Enter, Dorien; Zitman, Frans G; Penninx, Brenda W J H; van Pelt, Johannes; Spinhoven, Phillip; Roelofs, Karin

2012-03-01

Low circulating levels of testosterone have been associated with major depression, but there is more limited evidence for differences in patients with anxiety disorders. The use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants is associated with sexual side effects, warranting testing for interactions with testosterone. Data are from 722 male and 1380 female participants of The Netherlands Study of Depression and Anxiety (NESDA), who were recruited from the community, general practice care, and specialized mental health care. Depressive and anxiety diagnoses were assessed using the DSM-IV Composite International Diagnostic Interview. To smooth the episodic secretion, the four morning saliva samples per participant and the two evening samples were pooled before testosterone analysis. Morning median testosterone levels were 25.2 pg/ml in men and 16.2 pg/ml in women, with lower evening levels of 18.2 and 14.1 pg/ml, respectively. Significant determinants of testosterone levels were sex, age, time of the day, use of contraceptives, and smoking status. Female patients with a current (1-month) depressive disorder (effect size 0.29; P=0.002), generalized anxiety disorder (0.25; P=0.01), social phobia (0.30; P<0.001), and agoraphobia without panic disorder (0.30; P=0.02) had lower salivary testosterone levels than female controls. Higher testosterone levels were found in male and female participants using SSRIs than in non-users (effect size 0.26; P<0.001). Salivary testosterone levels are lower in female patients with a depressive disorder, generalized anxiety disorder, social phobia, and agoraphobia as compared to female controls. SSRIs may increase salivary testosterone in men and women. Copyright © 2011 Elsevier Inc. All rights reserved.

Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?

PubMed

Nahata, Leena; Yu, Richard N; Bhasin, Shalender; Cohen, Laurie E

2015-05-01

Male hypogonadism is a common disorder that is associated with low bone density, poor muscle mass, anemia, and sexual dysfunction. The Endocrine Society recently published a Clinical Practice Guideline for testosterone therapy in androgen-deficient men. Because treatment is frequently initiated in adolescence, the goal of this quality improvement initiative was to assess whether pediatric endocrinologists at a large tertiary care center follow these guidelines and to identify opportunities for improvement. We performed a retrospective chart review at Boston Children's Hospital. Inclusion criteria were as follows: current age ≥16 years, diagnosis of hypogonadism, and testosterone replacement therapy. Data were collected about current age, age at treatment initiation, diagnoses, pre- and on-treatment testosterone levels, route of testosterone administration and dose, bone density, hematocrit levels, and adherence with therapy. Fifty-nine patients were included. Fourteen (24%) were prescribed lower testosterone doses than those recommended in the Clinical Practice Guideline. Seven (12%) had no pre-treatment testosterone levels, and 10 (17%) had no on-treatment levels. In 49 patients with on-treatment testosterone levels, 36 had at least one value that was lower than the adult reference range. Ten (28%) of the 36 men with low testosterone levels had no dose adjustments. Thirty-seven (63%) of the 59 patients had no dual-energy X-ray absorptiometry scans, and 18 (31%) did not have hematocrit levels. Pediatric endocrinologists in this review did not consistently follow the Clinical Practice Guideline for testosterone therapy in hypogonadal adult males. Strategies that improve adherence to guidelines could help maximize the benefits of therapy and minimize treatment-associated risks.

Gender differences in financial risk aversion and career choices are affected by testosterone.

PubMed

Sapienza, Paola; Zingales, Luigi; Maestripieri, Dario

2009-09-08

Women are generally more risk averse than men. We investigated whether between- and within-gender variation in financial risk aversion was accounted for by variation in salivary concentrations of testosterone and in markers of prenatal testosterone exposure in a sample of >500 MBA students. Higher levels of circulating testosterone were associated with lower risk aversion among women, but not among men. At comparably low concentrations of salivary testosterone, however, the gender difference in risk aversion disappeared, suggesting that testosterone has nonlinear effects on risk aversion regardless of gender. A similar relationship between risk aversion and testosterone was also found using markers of prenatal testosterone exposure. Finally, both testosterone levels and risk aversion predicted career choices after graduation: Individuals high in testosterone and low in risk aversion were more likely to choose risky careers in finance. These results suggest that testosterone has both organizational and activational effects on risk-sensitive financial decisions and long-term career choices.

Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy.

PubMed

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-08-15

This article, Part 1 of the Endocrine Society of Australia's position statement on male hypogonadism, focuses on assessment of male hypogonadism, including the indications for testosterone therapy. (Part 2 will deal with treatment and therapeutic considerations.) Key points and recommendations are:Pathological hypogonadism arises due to diseases of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes (hypergonadotropic hypogonadism). It is a clinical diagnosis with a pathological basis, confirmed by hormone assays.Hormonal assessment is based on measurement of circulating testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Measurement of sex hormone-binding globulin levels can be informative, but use of calculated free testosterone is not recommended for clinical decision making.Testosterone replacement therapy is warranted in men with pathological hypogonadism, regardless of age.Currently, there are limited data from high-quality randomised controlled trials with clinically meaningful outcomes to justify testosterone treatment in older men, usually with chronic disease, who have low circulating testosterone levels but without hypothalamic, pituitary or testicular disease.Obesity, metabolic syndrome and type 2 diabetes are associated with lowering of circulating testosterone level, but without elevation of LH and FSH levels. Whether these are non-specific consequences of non-reproductive disorders or a correctable deficiency state is unknown, but clear evidence for efficacy and safety of testosterone therapy in this setting is lacking.Glucocorticoid and opioid use is associated with possibly reversible reductions in circulating testosterone level, without elevation of LH and FSH levels. Where continuation of glucocorticoid or opioid therapy is necessary, review by an endocrinologist may be warranted.Changes in management as result of the position statement: Men with pathological hypogonadism should be identified and considered for testosterone therapy, while further research is needed to clarify whether there is a role for testosterone in these other settings.

Cardiovascular issues in hypogonadism and testosterone therapy.

PubMed

Shabsigh, Ridwan; Katz, Mark; Yan, Grace; Makhsida, Nawras

2005-12-26

A systematic literature search was conducted to investigate the cardiovascular issues related to hypogonadism and testosterone therapy. Vascular cells contain sex steroid hormone receptors. Testosterone can exert effects on the vascular wall, either by itself or through aromatization as estrogen. Hypogonadism is associated with central obesity; insulin resistance; low levels of high-density lipoprotein (HDL); high cholesterol levels; and high levels of low-density lipoprotein (LDL), triglycerides, fibrinogen, and plasminogen activator-1. Some observational studies show a correlation between low testosterone and cardiovascular disease (CVD), and others show no correlation. Interventional studies do not reveal a direct long-term relation between testosterone therapy and CVD. Short-term data suggest cardiovascular benefits of testosterone. Testosterone therapy has beneficial and deleterious effects on cardiovascular risk factors. It improves insulin sensitivity, central obesity, and lowers total cholesterol and LDL. In some studies, testosterone therapy has an HDL-lowering effect, and in other studies this effect is insignificant. This should not be assumed to be atherogenic because it might be related to reverse cholesterol transport and effects on the HDL(3) subfraction. The cardiovascular effects of testosterone therapy may be neutral to beneficial. There is no contraindication for testosterone therapy in men with CVD and diagnosed hypogonadism with or without erectile dysfunction. Caution should be exercised regarding occasional increases in hematocrit levels, especially in patients with congestive heart failure. Conversely, evidence does not support testosterone therapy in aging men for the purpose of cardiovascular benefit, despite claims to this effect. Further research on the cardiovascular benefits and risks of testosterone is strongly recommended.

Testosterone

MedlinePlus

Serum testosterone ... In males, the testicles produce most of the testosterone in the body. Levels are most often checked to evaluate signs of abnormal testosterone such as: Early or late puberty (in boys) ...

Association of Testosterone Levels With Anemia in Older Men

PubMed Central

Roy, Cindy N.; Snyder, Peter J.; Stephens-Shields, Alisa J.; Artz, Andrew S.; Bhasin, Shalender; Cohen, Harvey J.; Farrar, John T.; Gill, Thomas M.; Zeldow, Bret; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Lewis, Cora E.; Matsumoto, Alvin M.; Molitch, Mark E.; Pahor, Marco; Swerdloff, Ronald S.; Cifelli, Denise; Hou, Xiaoling; Resnick, Susan M.; Walston, Jeremy D.; Anton, Stephen; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Schrier, Stanley L.; Ellenberg, Susan S.

2017-01-01

Importance In one-third of older men with anemia, no recognized cause can be found. Objective To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. Design, Setting, and Participants A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin Š12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. Interventions Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. Main Outcomes and Measures The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. Results The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. Conclusions and Relevance Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels. PMID:28241237

Modification Effects of Changes in Job Demands on Associations Between Changes in Testosterone Levels and Andropause Symptoms: 2-Year Follow-up Study in Male Middle-Aged Japanese Workers.

PubMed

Hirokawa, Kumi; Taniguchi, Toshiyo; Fujii, Yasuhito; Takaki, Jiro; Tsutsumi, Akizumi

2016-08-01

The purpose of this longitudinal study was to ascertain if changes in job demands modify associations between changes in testosterone levels and andropause symptoms in male Japanese workers. A baseline survey including job demands and the Aging Males' Symptoms scale, lifestyle factors, and blood levels of testosterone was conducted in 2007. Among 192 men (mean age ± SD 52.2 ± 7.6 years) who completed all relevant questionnaires and provided blood at baseline, 104 men (50.9 ± 7.2 years) were followed up in 2009. Changes of variables in 2 years were calculated (data of follow-up minus those of baseline). Testosterone levels were increased significantly, whereas job demands and somatic symptoms were reduced significantly, at follow-up. Changes in testosterone levels were negatively associated with changes in total andropause symptoms, psychological symptoms, and sexual symptoms (standardized β = -0.27, -0.24, and, -0.29, p < 0.05, respectively), after adjustment for confounders. Changes in job demands were positively associated with changes in somatic symptoms (standardized β = 0.21, p < 0.05). Significant interactions of changes in testosterone levels and job demands were noted for changes in psychological symptoms (standardized β = 0.26, p < 0.05). For men with a 1-SD reduction in job demands, negative associations between changes in testosterone levels and psychological symptoms were intensified, but not for men with a 1-SD increase in job demands. Andropause symptoms may be affected by changes in testosterone levels and job demands. Change in job demands may modify associations between changes in testosterone levels and andropause symptoms.

Association of testosterone levels and future suicide attempts in females with bipolar disorder

PubMed Central

Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.

2015-01-01

Background Considerable evidence suggests that testosterone may play a role in the pathophysiology of mood disorders in females. This is the first prospective study to examine whether blood testosterone levels predict suicide attempts in females with bipolar disorder. Methods Females with a DSM-IV diagnosis of a bipolar disorder in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Patients were followed up prospectively for up to 2.5 years. Results At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period. Limitations A limitation of the study is that the sample size is modest. Another limitation is that we did not have a bipolar nonattempter or healthy volunteer control group for comparison. Conclusion Testosterone levels may predict suicidal behavior in women with bipolar disorder. PMID:25012416

Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development.

PubMed

Amory, J K; Anawalt, B D; Bremner, W J; Matsumoto, A M

2001-01-01

Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences in serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins explain why some men fail to completely suppress their sperm counts to zero with weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain persistent spermatogenesis in some men treated with androgen-based contraceptive regimens.

Developmental changes in serum androgen levels of Eastern Screech-Owls (Megascops asio)

USGS Publications Warehouse

Kozlowski, Corinne P.; Hahn, D. Caldwell

2010-01-01

We studied androgen production during development in nestling Eastern Screech-Owls (Megascops asio) and hypothesized that gender and hatch order might influence serum levels of testosterone and androstenedione. Testosterone levels were highest immediately after hatching and declined significantly in the 4 weeks leading to fledging. The average level of testosterone for 1-7 day-old owls was 3.99 - 0.68 ng/ml. At 22-28 days of age, the average testosterone level for nestling owls was 0.83 - 0.18 ng/ml. Testosterone levels did not differ between males or females. The average testosterone level for male nestlings was 2.23 - 0.29 ng/ml and 2.39 - 0.56 ng/ml for female nestlings. The average level of androstenedione for nestling owls was 1.92 - 0.11 ng/ml and levels remained constant throughout development. Levels were significantly higher in males than females. The average androstenedione level was 1.77 - 0.16 ng/ml for male nestlings and 1.05 - 0.24 ng/ml for female nestlings. Hatching order did not affect levels of either androgen. Our results provide a foundation for future studies of androgen production by nestling owls.

Female pseudohermaphroditism with multiple caudal anomalies: Absence of Y-specific DNA sequences as pathogenetic factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seaver, L.H.; Grimes, J.; Erickson, R.P.

1994-05-15

46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosome (46,XX); one had a 46,XX,del(10)(q25.3{yields}qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Ymore » chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY (Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone. 32 refs., 1 fig., 2 tabs.« less

Testosterone and the metabolic syndrome

PubMed Central

Muraleedharan, Vakkat; Jones, T. Hugh

2010-01-01

Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia and sexual dysfunction along with improved quality of Life. However, there are no Long-term interventional studies to assess the effect of testosterone replacement on mortality in men with Low testosterone Levels. This article reviews the observational and interventional clinical data in relation to testosterone and metabolic syndrome. PMID:23148165

Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis.

PubMed

Cobo, Gabriela; Gallar, Paloma; Di Gioia, Cristina; García Lacalle, Concepción; Camacho, Rosa; Rodriguez, Isabel; Ortega, Olimpia; Mon, Carmen; Vigil, Ana; Lindholm, Bengt; Carrero, Juan Jesús

Testosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA). Single-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. Mean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome.

PubMed

Recabarren, Monica; Carrasco, Albert; Sandoval, Daniel; Diaz, Felipe; Sir-Petermann, Teresa; Recabarren, Sergio E

2017-09-07

The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

Hair and Salivary Testosterone, Hair Cortisol, and Externalizing Behaviors in Adolescents.

PubMed

Grotzinger, Andrew D; Mann, Frank D; Patterson, Megan W; Tackett, Jennifer L; Tucker-Drob, Elliot M; Harden, K Paige

2018-05-01

Although testosterone is associated with aggression in the popular imagination, previous research on the links between testosterone and human aggression has been inconsistent. This inconsistency might be because testosterone's effects on aggression depend on other moderators. In a large adolescent sample ( N = 984, of whom 460 provided hair samples), we examined associations between aggression and salivary testosterone, hair testosterone, and hair cortisol. Callous-unemotional traits, parental monitoring, and peer environment were examined as potential moderators of hormone-behavior associations. Salivary testosterone was not associated with aggression. Hair testosterone significantly predicted increased aggression, particularly at low levels of hair cortisol (i.e., Testosterone × Cortisol interaction). This study is the first to examine the relationship between hair hormones and externalizing behaviors and adds to the growing literature that indicates that androgenic effects on human behavior are contingent on aspects of the broader endocrine environment-in particular, levels of cortisol.

Circulating testosterone and feather-gene expression of receptors and metabolic enzymes in relation to melanin-based colouration in the barn owl.

PubMed

Béziers, Paul; Ducrest, Anne-Lyse; Simon, Céline; Roulin, Alexandre

2017-09-01

Knowledge of how and why secondary sexual characters are associated with sex hormones is important to understand their signalling function. Such a link can occur if i) testosterone participates in the elaboration of sex-traits, ii) the display of an ornament triggers behavioural response in conspecifics that induce a rise in testosterone, or iii) genes implicated in the elaboration of a sex-trait pleiotropically regulate testosterone physiology. To evaluate the origin of the co-variation between melanism and testosterone, we measured this hormone and the expression of enzymes involved in its metabolism in feathers of barn owl (Tyto alba) nestlings at the time of melanogenesis and in adults outside the period of melanogenesis. Male nestlings displaying smaller black feather spots had higher levels of circulating testosterone, potentially suggesting that testosterone could block the production of eumelanin pigments, or that genes involved in the production of small spots pleiotropically regulate testosterone production. In contrast, the enzyme 5α-reductase, that metabolizes testosterone to DHT, was more expressed in feathers of reddish-brown than light-reddish nestlings. This is consistent with the hypothesis that testosterone might be involved in the expression of reddish-brown pheomelanic pigments. In breeding adults, male barn owls displaying smaller black spots had higher levels of circulating testosterone, whereas in females the opposite result was detected during the rearing period, but not during incubation. The observed sex- and age-specific co-variations between black spottiness and testosterone in nestling and adult barn owls may not result from testosterone-dependent melanogenesis, but from melanogenic genes pleiotropically regulating testosterone, or from colour-specific life history strategies that influence testosterone levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Endogenous testosterone levels are associated with neural activity in men with schizophrenia during facial emotion processing.

PubMed

Ji, Ellen; Weickert, Cynthia Shannon; Lenroot, Rhoshel; Catts, Stanley V; Vercammen, Ans; White, Christopher; Gur, Raquel E; Weickert, Thomas W

2015-06-01

Growing evidence suggests that testosterone may play a role in the pathophysiology of schizophrenia given that testosterone has been linked to cognition and negative symptoms in schizophrenia. Here, we determine the extent to which serum testosterone levels are related to neural activity in affective processing circuitry in men with schizophrenia. Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as 32 healthy controls and 26 people with schizophrenia performed a facial emotion identification task. Whole brain analyses were performed to determine regions of differential activity between groups during processing of angry versus non-threatening faces. A follow-up ROI analysis using a regression model in a subset of 16 healthy men and 16 men with schizophrenia was used to determine the extent to which serum testosterone levels were related to neural activity. Healthy controls displayed significantly greater activation than people with schizophrenia in the left inferior frontal gyrus (IFG). There was no significant difference in circulating testosterone levels between healthy men and men with schizophrenia. Regression analyses between activation in the IFG and circulating testosterone levels revealed a significant positive correlation in men with schizophrenia (r=.63, p=.01) and no significant relationship in healthy men. This study provides the first evidence that circulating serum testosterone levels are related to IFG activation during emotion face processing in men with schizophrenia but not in healthy men, which suggests that testosterone levels modulate neural processes relevant to facial emotion processing that may interfere with social functioning in men with schizophrenia. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

The effect of testosterone on cardiometabolic risk factors in atorvastatin-treated men with late-onset hypogonadism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Okopień, Bogusław

2016-02-01

By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20-40mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100mg weekly, n=16) and not treated with this hormone (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy. Compared with the control age-, weight, and lipid-matched statin-naïve subjects with LOH (n=12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naïve patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity. Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

First case report of testosterone assay-interference in a female taking maca (Lepidium meyenii).

PubMed

Srikugan, L; Sankaralingam, A; McGowan, B

2011-03-25

A young female with prolonged intermenstrual bleeding was found to have raised total plasma testosterone of 25.8 nmol/l (NR<2.9 nmol/l) using the Roche Elecsys Testosterone I immunoassay without clinical features of virulisation. Few months ago investigations for lethargy and low libido had shown normal total testosterone of 0.8 nmol/l. Further history revealed that she was using maca extract to improve her lethargy and low libido. Maca is traditionally used for its aphrodisiac and fertility-enhancing properties. Maca use has not been shown to affect serum testosterone in mice and human studies. Immunoassay interference with maca was suspected. Testosterone immunoassays use monoclonal antibodies specifically directed against testosterone. They are prone to interference from androgenic compounds. Reanalysis of the original serum sample using Elecsys Testosterone II assay, a higher affinity assay, revealed a total testosterone level of 2.9 nmol/l. It is important to exclude assay interference when testosterone level is greater than 5 nmol/l without supportive clinical signs.

First case report of testosterone assay-interference in a female taking maca (Lepidium meyenii)

PubMed Central

Srikugan, L; Sankaralingam, A; McGowan, B

2011-01-01

A young female with prolonged intermenstrual bleeding was found to have raised total plasma testosterone of 25.8 nmol/l (NR<2.9 nmol/l) using the Roche Elecsys Testosterone I immunoassay without clinical features of virulisation. Few months ago investigations for lethargy and low libido had shown normal total testosterone of 0.8 nmol/l. Further history revealed that she was using maca extract to improve her lethargy and low libido. Maca is traditionally used for its aphrodisiac and fertility-enhancing properties. Maca use has not been shown to affect serum testosterone in mice and human studies. Immunoassay interference with maca was suspected. Testosterone immunoassays use monoclonal antibodies specifically directed against testosterone. They are prone to interference from androgenic compounds. Reanalysis of the original serum sample using Elecsys Testosterone II assay, a higher affinity assay, revealed a total testosterone level of 2.9 nmol/l. It is important to exclude assay interference when testosterone level is greater than 5 nmol/l without supportive clinical signs. PMID:22700073

Testosterone and Proactive-Reactive Aggression in Youth: the Moderating Role of Harsh Discipline.

PubMed

Chen, Frances R; Raine, Adrian; Granger, Douglas A

2018-01-20

This study tests a biosocial model of the link between testosterone and proactive-reactive aggression in youth at varying levels of harsh discipline. Given that proactive aggression is used to gain power and status and the importance of social learning in its formation, we hypothesized that testosterone would be associated with proactive aggression at higher levels of harsh discipline, and that this relationship would be more pronounced in boys than girls. Participants (n = 445; 50% male; M age = 11.92 years; 80% African-American) and their caregivers completed questionnaires including demographics, conflict tactics, and proactive-reactive aggression. Youth also provided a saliva sample for testosterone. Analyses revealed an interaction between testosterone and harsh discipline on proactive aggression in both boys and girls, and an interaction between testosterone and harsh discipline on reactive aggression in boys only. For those experiencing high levels of harsh discipline, testosterone was positively associated with proactive aggression, with the magnitude of the association increasing as harsh discipline increased. For below average levels of harsh discipline, there were protective effects of high testosterone for boy's reactive aggression and for girl's proactive aggression. The findings support basic tenets of the biosocial model which suggest that links between testosterone and aggressive behavior are dependent on contextual forces, highlighting the complex relationship between hormones, social context, and aggression. Novel findings include protective effects of high testosterone for those exposed to low levels of harsh discipline. Findings are discussed in light of the context-contingency effect and also within the differential susceptibility framework.

Reduction of calprotectin and phosphate during testosterone therapy in aging men: a randomized controlled trial.

PubMed

Pedersen, L; Christensen, L L; Pedersen, S M; Andersen, M

2017-05-01

To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 (FGF23), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. Randomized, double-blinded, placebo-controlled study. Odense Androgen Study-the effect of Testim and training in hypogonadal men. Men aged 60-78 years old with a low normal concentration of free of bioavailable testosterone <7.3 nmol/L and waist circumference >94 cm recruited from 2008 to 2009 (N = 48) by advertisement. Participants were randomized to receive 5-10 g gel/50-100 mg testosterone (Testim ® , Ipsen, France) or 5-10 g gel/placebo. The plasma levels of calprotectin and phosphate were significantly reduced in the group receiving testosterone therapy (gel) compared to the placebo group (p < 0.05). Testosterone treatment did not have any significant effect on plasma levels of FGF23 or soluble Klotho. The reduction in phosphate levels was inversely associated with bioavailable testosterone. Compared to the placebo group, 6 months of testosterone therapy (gel) reduced calprotectin and phosphate levels suggesting decreased inflammation and decreased cardiovascular risk.

Women's Preference for Attractive Makeup Tracks Changes in Their Salivary Testosterone.

PubMed

Fisher, Claire I; Hahn, Amanda C; DeBruine, Lisa M; Jones, Benedict C

2015-12-01

Previous research suggests that women's motivation to appear attractive is increased around the time of ovulation. However, the specific hormonal correlates of within-woman changes in motivation to appear attractive have not been investigated. To address this issue, we used a longitudinal design and a data-driven visual preference task. We found that women's preference for attractive makeup increases when their salivary testosterone levels are high. The relationship between testosterone level and preference for attractive makeup was independent of estradiol level, progesterone level, and estradiol-to-progesterone ratio. These results suggest that testosterone may contribute to changes in women's motivation to wear attractive makeup and, potentially, their motivation to appear attractive in general. Our results are also consistent with recent models of the role of testosterone in social behavior, according to which testosterone increases the probability of behaviors that could function to support the acquisition of mates and competition for resources. © The Author(s) 2015.

Hormonal Treatment of Transgender Women with Oral Estradiol.

PubMed

Leinung, Matthew C; Feustel, Paul J; Joseph, Jalaja

2018-01-01

Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

Relations between Prenatal Testosterone Levels and Cognitive Abilities at 4 Years.

ERIC Educational Resources Information Center

Finegan, Jo-Anne K.; And Others

1992-01-01

Compared children's cognitive abilities at four years and their prenatal amniotic fluid testosterone levels. For girls, prenatal testosterone levels were related in a curvilinear manner to language comprehension and classification abilities, and inversely related to counting and knowledge of number facts. For boys, no relationships were found. (BC)

Influence of Altered Mass Loading on Testosterone Levels and Testicular Mass

NASA Technical Reports Server (NTRS)

Wang, Tommy J.; Ortiz, R. M.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Effects of altered load on testosterone levels and testicular mass in mammals are not well defined. Two separate studies (loading;centrifuged; +2G(sub z) and unloading;hindlimb suspension;HLS) were conducted to provide a better understanding of the effects of mass loading on testosterone levels and testicular mass. Daily urine samples were collected, and testicular mass measured at the end of the study. +2G(sub z): Sprague-Dawley rats (230-250 g) were centrifuged for 12 days at +2G(sub z): 8 centrifuged (EC) and 8 off centrifuge controls (OCC). EC had lower body mass, however relative testicular mass was greater. EC exhibited an increase in excreted testosterone levels between days 2 (T2) and 6 (T6), and returned to baseline at T9. HLS: To assess the effects of unloading Sprague-Dawley rats (125-150 g) were studied for 12 days: 10 suspended (Exp) and 10 ambulatory (Ctl). Exp had lower body mass during the study, with reduced absolute and relative testicular mass. Exp demonstrated lower excreted testosterone levels from T5-T12. Conclusions: Loading appears to stimulate anabolism, as opposed to unloading, as indicated by greater relative testicular mass and excreted testosterone levels. Reported changes in muscle mass during loading and unloading coincide with similar changes in excreted testosterone levels.

Effect of sexual excitation on testosterone and nitric oxide levels of water buffalo bulls (Bubalus bubalis) with different categories of sexual behavior and their correlation with each other.

PubMed

Swelum, Ayman Abdel-Aziz; Saadeldin, Islam M; Zaher, Hany A; Alsharifi, Sawsan A M; Alowaimer, Abdullah N

2017-06-01

We studied the effect of sexual excitation on serum testosterone and nitric oxide (NO) levels in water buffalo bulls with different categories of sexual behavior and their correlation with each other. Buffalo bulls were classified according to their sexual behavior (including reaction time, sexual aggressiveness and mating ability): acceptable (good to excellent) (n=5), fair (n=5), and unacceptable (poor) (n=5) sexual behavior. Blood samples were collected from all animals immediately before and after sexual teasing and/or mounting to estimate the testosterone and NO levels using a commercial radioimmunoassay kit and Griess reaction test, respectively. Comparisons among groups were evaluated using a mixed-design analysis of variance. Pearson's correlation coefficients were calculated to determine the relationship between testosterone and NO levels before and after sexual excitation besides sexual behavior. The level of testosterone before sexual excitation was higher (p≤0.05) in bulls with acceptable and fair sexual behavior than in bulls with unacceptable sexual behavior (0.86±0.01, 0.69±0.02, and 0.29±0.02ng/mL, respectively). The level of NO was higher (p≤0.05) in bulls with acceptable and fair sexual behavior than in bulls with unacceptable sexual behavior (8.00±0.03, 7.66±0.19, and 6.29±0.33μM, respectively). Sexual excitation significantly (p<0.05) increase testosterone and NO levels in bulls with acceptable (1.45±0.01ng/mL and 19.04±0.32μM, respectively) or fair (0.92±0.02ng/mL and 14.95±0.34μM, respectively) sexual behavior, but not in bulls with unacceptable sexual behavior. The unacceptable sexual behavior bulls had significantly lower testosterone and NO levels than the other bulls. There was a strong correlation and association between serum testosterone and NO levels besides sexual behavior of buffalo bulls. In conclusion, the alteration in the testosterone and NO levels after sexual excitation depends on the sexual behavior category of buffalo-bull. Testosterone and NO can be used to create a sexual behavior score. The testosterone and NO levels of can be predicted via evaluation of sexual behavior of buffalo bull. Copyright © 2017 Elsevier B.V. All rights reserved.

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.

Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined formore » each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.« less

The effect of hypogonadism and testosterone-enhancing therapy on alkaline phosphatase and bone mineral density.

PubMed

Dabaja, Ali A; Bryson, Campbell F; Schlegel, Peter N; Paduch, Darius A

2015-03-01

To evaluate the relationship of testosterone-enhancing therapy on alkaline phosphatase (AP) in relation to bone mineral density (BMD) in hypogonadal men. Retrospective review of 140 men with testosterone levels of <350 ng/dL undergoing testosterone-enhancing therapy and followed for 2 years. Follicle-stimulating hormone, luteinising hormone, free testosterone, total testosterone, sex hormone binding globulin, calcium, AP, vitamin D, parathyroid hormone, and dual-energy X-ray absorptiometry (DEXA) scans were analysed. A subgroup of 36 men with one DEXA scan before and one DEXA 2 years after initiating treatment was performed. Analysis of the relationship between testosterone and AP at initiation of therapy using stiff linear splines suggested that bone turnover occurs at total testosterone levels of <250 ng/dL. In men with testosterone levels of <250 ng/dL, there was a negative correlation between testosterone and AP (R(2) = -0.347, P < 0.001), and no correlation when testosterone levels were between 250 and 350 ng/dL. In the subgroup analysis, the mean (sd) testosterone level was 264 (103) ng/dL initially and 701 (245), 539 (292), and 338 (189) ng/dL at 6, 12, and 24 months, respectively. AP decreased from a mean (sd) of 87 (38) U/L to 57 (12) U/L (P = 0.015), 60 (17) U/L (P < 0.001), and 55 (10) U/L (P = 0.03) at 6, 12, and 24 months, respectively. The BMD increased by a mean (sd) of 20 (39)% (P = 0.003) on DEXA. In hypogonadal men, the decrease in AP is associated with an increase in BMD on DEXA testing. This result suggests the use of AP as a marker of response to therapy. © 2014 The Authors. BJU International © 2014 BJU International.

The effects of chronic testosterone administration on body weight, food intake, and adipose tissue are changed by estrogen treatment in female rats.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Yanagihara, Rie; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Mayila, Yiliyasi; Kuwahara, Akira; Irahara, Minoru

2017-07-01

In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats. In addition, chronic testosterone administration increased hypothalamic CYP19a1 mRNA levels in OVX rats, whereas it did not alter CYP19a1 mRNA levels in OVX with estradiol-administered rats, indicating that conversion of testosterone to estrogens in the hypothalamus may be activated in testosterone-administered OVX rats. Furthermore, chronic testosterone administration decreased hypothalamic TNF-α mRNA levels in OVX rats, whereas it increased hypothalamic IL-1β mRNA levels in OVX with estradiol-administered rats. On the other hand, IL-1β and TNF-α mRNA levels in visceral and subcutaneous WAT and liver were not changed by chronic testosterone administration in both groups. These data indicate that the effects of chronic testosterone administration on BW, FI, WAT weight, and adipocyte size were changed by estradiol treatment in female rats. Testosterone has facilitative effects on BW gain, FI, and adiposity under the estradiol-supplemented condition, whereas it has inhibitory effects in the non-supplemented condition. Differences in the responses of hypothalamic factors, such as aromatase and inflammatory cytokines, to testosterone might underlie these opposite effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of centrifugation stress on pituitary-gonadal function in male rats

NASA Technical Reports Server (NTRS)

Gray, G. D.; Smith, E. R.; Damassa, D. A.; Davidson, J. M.

1980-01-01

The effects of centrifugation for various lengths of time on circulating levels of luteinizing hormone (LH) and testosterone in male rats were investigated. In a chronic 52-day experiment, centrifugation at 4.1 G significantly reduced LH and testosterone levels for the entire period. Centrifugation at 2.3 G had less effect inasmuch as LH levels were not significantly decreased and testosterone levels were significantly reduced only during the first few days of centrifugation. In more acute experiments, centrifugation at 4.1 G for 4 h resulted in reduced testosterone levels, whereas centrifugation for 15 min did not significantly alter the hormone levels. These results indicate that centrifugation can decrease circulating LH and testosterone levels if the gravitational force is of sufficient magnitude and is maintained for a period of hours. Chronic centrifugation may also inhibit the acute excitatory response of LH to handling and ether stress.

The androgen-deficient aging male: current treatment options.

PubMed

Tenover, J Lisa

2003-01-01

All delivery forms of testosterone should be equally efficacious in treating the androgen-deficient aging male if adequate serum testosterone levels are obtained. The testosterone preparations available in North America include the oral undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal transdermal patch, and the transdermal gels. Selection of a specific testosterone preparation for replacement therapy depends on many factors, including the magnitude and pattern of serum testosterone levels produced, side effects of the particular formulation, reversibility if an adverse event should occur, convenience of use, cosmetic issues related to the preparation, and cost. In addition, potential adverse effects of testosterone therapy applicable to all forms of testosterone delivery, such as fluid retention, gynecomastia, polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or alterations in prostate health, need to be considered both prior to therapy and during treatment monitoring.

ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

PubMed

Han, Aijie; Zou, Lingyue; Gan, Xiaoqin; Li, Yu; Liu, Fangfang; Chang, Xuhong; Zhang, Xiaotian; Tian, Minmin; Li, Sheng; Su, Li; Sun, Yingbiao

2018-06-15

Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

Relating testosterone levels and free play social behavior in male and female preschool children.

PubMed

Sánchez-Martín, J R; Fano, E; Ahedo, L; Cardas, J; Brain, P F; Azpíroz, A

2000-11-01

This study assessed potential relationships between a series of behavioral measures seen in the interactions of preschool children with their peers (particularly aggressive behavior) and testosterone levels. 28 boys and 20 girls of preschool age were videotaped in free play interactions. Their behavior was then evaluated with particular emphasis on aggression and affiliation in play and social interactions. Testosterone levels were measured using radioimmunoassay in saliva samples. Correlation analysis revealed a positive relationship in boys between testosterone and giving and receiving aggression in the context of 'social interactions' (serious aggression), but not in the context of play (playful aggresstion). Testosterone can be a useful biological marker for serious aggression (and behavioral patterns reflecting different levels of sociability) in preschool boys.

Androgen replacement for women.

PubMed Central

Basson, R.

1999-01-01

OBJECTIVES: To determine whether a postmenopausal syndrome comprising specific changes in sexual desire and response associated with low free testosterone exists. To determine whether this syndrome is ameliorated by testosterone replacement. QUALITY OF EVIDENCE: Literature documenting that replacement of physiological levels of testosterone is beneficial and safe is scant. Only one randomized prospective blinded study examines sexual outcome in detail. MAIN MESSAGE: Testosterone is an important metabolic and sex hormone produced by the ovary throughout life. The variable reduction in ovarian testosterone production coincident with menopause is sometimes associated with a syndrome of specific changes in sexual desire and sexual response. Estrogen deficiency also impairs sexual response, but its replacement will not improve and might exacerbate sexual symptoms from androgen loss. Diagnosis of androgen deficiency is clinical, based on accurate assessment of a woman's sexual status before and after menopause and only confirmed (rather than diagnosed) by a low level of free testosterone. Partial androgen replacement restores much of the sexual response and facilitates sexual desire that is triggered by external cues. Avoiding supraphysiological levels of testosterone lessens risk of masculinization. Avoiding alkylated testosterone lessens hepatic or lipid impairment. CONCLUSION: Further prospective randomized studies of replacement of physiological levels of testosterone in women with androgen deficiency syndrome are needed, using formulations of testosterone available in Canada. The consistency of sexual changes, the associated personal and relationship distress, together with our clinical experience of the gratifying response to physiological replacement, make further studies urgently needed. PMID:10509222

Testosterone-related cortical maturation across childhood and adolescence.

PubMed

Nguyen, Tuong-Vi; McCracken, James; Ducharme, Simon; Botteron, Kelly N; Mahabir, Megan; Johnson, Wendy; Israel, Mimi; Evans, Alan C; Karama, Sherif

2013-06-01

Neuroendocrine theories of brain development hold testosterone as the predominant factor mediating sex-specific cortical growth and the ensuing lateralization of hemispheric function. However, studies to date have focussed on prenatal testosterone rather than pubertal changes in testosterone. Yet, animal studies have shown a high density of androgen-sensitive receptors in multiple key cortical areas, and puberty is known to coincide with both a significant rise in testosterone and the emergence of behavioral sex differences, suggesting peripubertal influences of testosterone on brain development. Here, we used linear mixed models to examine sex-specific cortical maturation associated with changes in testosterone levels in a longitudinal sample of developmentally healthy children and adolescents. A significant "sex by age by testosterone" interaction on cortical thickness (CTh) involving widespread areas of the developing brain was found. Testosterone levels were associated with CTh changes in regions of the left hemisphere in males and of the right hemisphere in females. In both sexes, the relationship between testosterone and CTh varied across the age span. These findings show the association between testosterone and CTh to be complex, highly dynamic, and to vary, depending on sex and age; they also suggest sex-related hemispheric lateralization effects of testosterone in humans.

The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials.

PubMed

Mohler, Emile R; Ellenberg, Susan S; Lewis, Cora E; Wenger, Nanette K; Budoff, Matthew J; Lewis, Michael R; Barrett-Connor, Elizabeth; Swerdloff, Ronald S; Stephens-Shields, Alisa; Bhasin, Shalender; Cauley, Jane A; Crandall, Jill P; Cunningham, Glenn R; Ensrud, Kristine E; Gill, Thomas M; Matsumoto, Alvin M; Molitch, Mark E; Pahor, Marco; Preston, Peter E; Hou, Xiaoling; Cifelli, Denise; Snyder, Peter J

2018-02-01

Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Double-blind, placebo-controlled trial. Twelve academic medical centers in the United States. In all, 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials. Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjusted mean difference, -6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, -2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, -2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, -1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, -0.6; P = 0.03). Testosterone did not change triglycerides, d-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Testosterone treatment of 1 year in older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes. Copyright © 2017 Endocrine Society

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

PubMed Central

2011-01-01

Background The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism. Methods Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires. Results All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment. Conclusions Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment. PMID:21439088

Relationship between testosterone levels and depressive symptoms in older men in Amirkola, Iran.

PubMed

Kheirkhah, Farzan; Hosseini, Seyed Reza; Hosseini, Seyyedeh Fatemeh; Ghasemi, Nafiseh; Bijani, Ali; G Cumming, Robert

2014-01-01

Testosterone may be an important factor causing depression in the elderly men. The purpose of this study was to determine the relationship between testosterone levels and depressive symptoms in older men in Amirkola, Iran. This cross- sectional study is a part of the Amirkola Health and Aging Project (AHAP) that involves people aged 60 and above living in Amirkola, a small town in northern Iran. The testosterone levels were measured using ELISA on morning blood samples (ngr / ml) and depressive symptoms were identified using Geriatric Depression Scale (GDS). The data were collected and analyzed. Eight hundred thirty elderly men with the mean age of 70.02±7.7 years were included. On the basis of GDS criteria, 593 individuals had no depressive symptoms and 237 had at least one of these symptoms. The mean serum testosterone level in men without symptoms of depression (4.94±4.22) ngr/ml and was higher than in those with such symptoms (4.19±3.65) ngr/ml (P=0.011). Also, there was a significant inverse correlation between the testosterone levels and number of depressive symptoms (P=0.015, r=-0.084). After adjusting with age and educational levels, and living alone (OR=2.6, 95% CI: 1.17-5.82, P=0.02), testosterone levels (OR=1.67, 95% CI: 1.03-2.72, P=0.038) had the greatest impact on the development of depression. The results of this study showed a significant inverse relationship between serum testosterone levels and depressive symptoms in elderly men.

Experimental increase of testosterone increases boldness and decreases anxiety in male African striped mouse helpers.

PubMed

Raynaud, Julien; Schradin, Carsten

2014-04-22

Males of many species can adjust their behaviors to environmental conditions by changing reproductive tactics. Testosterone surges in adult breeding males typically inhibit the expression of paternal care while facilitating the expression of aggression during environmental changes. Similarly, in non-breeding philopatric males of cooperatively breeding species, up-regulation of testosterone may inhibit alloparental care while facilitating dispersal, i.e. males might become bolder and more explorative. We tested this hypothesis in philopatric male African striped mice, Rhabdomys pumilio. Striped mouse males can either remain in their natal groups providing alloparental care or they can disperse seeking mating opportunities. Compared to philopatric males, dispersed males typically show higher testosterone levels and lower corticosterone levels, and more aggression toward pups and same sex conspecifics. We experimentally increased the testosterone levels of the philopatric males kept in their family groups when pups were present. Testosterone-treated males did not differ significantly from control males in alloparental care and in aggression toward same-sex conspecifics. Compared to the control males, testosterone treated males were bolder, more active, and less anxious; they also showed lower corticosterone levels. The philopatric males were sensitive to our testosterone treatment for dispersal- and anxiety-like behavior but insensitive for social behaviors. Our results suggest a role of testosterone in dispersal. Copyright © 2014. Published by Elsevier Inc.

NIH-Supported Trials Test Hormonal Therapy in Older Men with Low Testosterone Levels

MedlinePlus

... February 18, 2016 NIH-supported trials test hormonal therapy in older men with low testosterone levels Testosterone ... Hadley, M.D., director of NIA’s Division of Geriatrics and Clinical Gerontology. “In contrast, though, the results ...

Combination therapy with clomiphene citrate and anastrozole is a safe and effective alternative for hypoandrogenic subfertile men.

PubMed

Alder, Nathan J; Keihani, Sorena; Stoddard, Gregory J; Myers, Jeremy B; Hotaling, James M

2018-06-06

To assess the efficacy and safety of combination therapy with clomiphene citrate (CC) and anastrozole (AZ) for male hypoandrogenism. We identified patients treated with a combination of CC + AZ in the period 2014 to 2017. Data were gathered on patient characteristics and laboratory values at baseline. Total testosterone, bioavailable testosterone, oestradiol and testosterone:oestradiol ratio were measured before combination therapy (treatment with CC only) and at CC + AZ combination therapy follow-ups. Treatment side effects were recorded; prostatic-specific antigen and haematocrit levels were measured to assess safety after 6 months. As a secondary outcome, semen characteristics were compared at baseline and after at least 3 months of combination therapy when these data were available. Data were analysed using a paired t-test and Wilcoxon's signed-rank test. A total of 51 men were included, with a mean age of 35.4 ± 7.4 years and a mean body mass index of 35.0 ± 8.0 kg/m 2 . After CC treatment, total testosterone, bioavailable testosterone, and oestradiol levels all significantly increased. AZ was added in all patients with hyperoestrogenaemia (oestradiol >50 pg/mL) or a testosterone:oestradiol ratio <10. CC + AZ therapy maintained therapeutic total testosterone and bioavailable testosterone levels while also normalizing oestradiol levels and testosterone:oestradiol ratio. Eleven patients experienced side effects: anxiety/irritability, n = 5; decreased libido, n = 4; elevated (>54%) haematocrit, n = 2. Combination therapy with CC + AZ is an effective and safe alternative for patients with elevated oestradiol level or low testosterone:oestradiol ratio. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Changes in the Diurnal Rhythms during a 45-Day Head-Down Bed Rest

PubMed Central

Liang, Xiaodi; Zhang, Lin; Wan, Yufeng; Yu, Xinyang; Guo, Yiming; Chen, Xiaoping; Tan, Cheng; Huang, Tianle; Shen, Hanjie; Chen, Xianyun; Li, Hongying; Lv, Ke; Sun, Fei; Chen, Shanguang; Guo, Jinhu

2012-01-01

In spaceflight human circadian rhythms and sleep patterns are likely subject to change, which consequently disturbs human physiology, cognitive abilities and performance efficiency. However, the influence of microgravity on sleep and circadian clock as well as the underlying mechanisms remain largely unknown. Placing volunteers in a prone position, whereby their heads rest at an angle of −6° below horizontal, mimics the microgravity environment in orbital flight. Such positioning is termed head-down bed rest (HDBR). In this work, we analysed the influence of a 45-day HDBR on physiological diurnal rhythms. We examined urinary electrolyte and hormone excretion, and the results show a dramatic elevation of cortisol levels during HDBR and recovery. Increased diuresis, melatonin and testosterone were observed at certain periods during HDBR. In addition, we investigated the changes in urination and defecation frequencies and found that the rhythmicity of urinary frequency during lights-off during and after HDBR was higher than control. The grouped defecation frequency data exhibits rhythmicity before and during HDBR but not after HDBR. Together, these data demonstrate that HDBR can alter a number of physiological processes associated with diurnal rhythms. PMID:23110150

Effects of two dominance manipulations on the stress response: Cognitive and embodied influences.

PubMed

Deuter, Christian Eric; Schächinger, Hartmut; Best, Daniel; Neumann, Roland

2016-09-01

In response to stress, physiological and mental resources are allocated towards those systems that are needed for rapid responding in terms of fight or flight. On the other hand, long term regenerative processes such as growth, digestion and reproduction are attenuated. Levels of the sex steroid testosterone are reduced in participants that suffer from chronic stress. However, beyond its role for reproductive functions, testosterone plays an important role in the regulation of social status and dominance, testosterone levels increase during competition or when the social status is challenged. The Trier Social Stress Test (TSST), a laboratory stressor with a substantial social-evaluative component, can provoke an increase in salivary testosterone levels. Still, so far the reported findings regarding acute stress effects on testosterone are equivocal, possibly due to moderating effects. In this study we experimentally manipulated social dominance in 56 healthy participants (28m) by two independent manipulations (body posture and cognitive role taking) and subjected them to the TSST. We analyzed salivary testosterone and cortisol levels as dependent measures for the endocrine stress response. The role taking manipulation interacted with the testosterone response: we found the strongest increase when participants had to put themselves in a dominant (vs. submissive) role. Our results suggest that transient changes in testosterone levels during stress reflect a response to status threat that is affected by social dominance. Copyright © 2016 Elsevier B.V. All rights reserved.

Maternal salivary testosterone in pregnancy and fetal neuromaturation.

PubMed

Voegtline, Kristin M; Costigan, Kathleen A; DiPietro, Janet A

2017-11-01

Testosterone exposure during pregnancy has been hypothesized as a mechanism for sex differences in brain and behavioral development observed in the postnatal period. The current study documents the natural history of maternal salivary testosterone from 18 weeks gestation of pregnancy to 6 months postpartum, and investigates associations with fetal heart rate, motor activity, and their integration. Findings indicate maternal salivary testosterone increases with advancing gestation though no differences by fetal sex were detected. High intra-individual stability in prenatal testosterone levels extend into the postnatal period, particularly for pregnancies with male fetuses. With respect to fetal development, by 36 weeks gestation higher maternal prenatal salivary testosterone was significantly associated with faster fetal heart rate and less optimal somatic-cardiac integration. Measurement of testosterone in saliva is a useful tool for repeated-measures studies of hormonal concomitants of pregnancy. Moreover, higher maternal testosterone levels are associated with modest interference to fetal neurobehavioral development. © 2017 Wiley Periodicals, Inc.

Finasteride does not prevent bladder cancer: A secondary analysis of the Medical Therapy for Prostatic Symptoms Study.

PubMed

Sathianathen, Niranjan J; Fan, Yunhua; Jarosek, Stephanie L; Lawrentschuk, Nathan L; Konety, Badrinath R

2018-05-03

Preclinical models have demonstrated that androgen receptor modulation can influence bladder carcinogenesis with an inverse association observed between serum androgen levels and bladder cancer (BC) incidence. It is still unclear whether 5α-reductase inhibitors, by preventing the conversion of testosterone to dihydrotestosterone, have a similar effect. This study aims to evaluate whether dihydrotestosterone-mediated androgen activity has an impact on BC incidence in a cohort of men included in a clinical trial of finasteride vs. placebo with rigorous compliance monitoring. A secondary analysis was performed on all patients enrolled in the Medical Therapy for Prostatic Symptoms (MTOPS) Study and included in the biopsy substudy. Men were stratified into groups based on receiving finasteride and the incidence of BC compared between the groups. After exclusions for poor finasteride compliance (n = 338) and missing serum hormone results (n = 9), 2,700 men were eligible for analysis. In total, 0.8% (n = 18) of the cohort was diagnosed with BC during the trial period. There was no difference in the incidence of BC between men who received finasteride and those who did not (0.74% [n = 9] vs. 0.61% [n = 9], P = 0.67). Neither serum testosterone levels, prostate cancer diagnosis nor urinary bother (measured by International Prostate Symptom Score) demonstrated an association with BC diagnosis. These relationships were consistent in the subgroup of men in the biopsy substudy. There was no observable relationship between decreased dihydrotestosterone levels and BC diagnosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute thermal stressor increases glucocorticoid response but minimizes testosterone and locomotor performance in the cane toad (Rhinella marina).

PubMed

Narayan, Edward J; Hero, Jean-Marc

2014-01-01

Climatic warming is a global problem and acute thermal stressor in particular could be considered as a major stressor for wildlife. Cane toads (Rhinella marina) have expanded their range into warmer regions of Australia and they provide a suitable model species to study the sub-lethal impacts of thermal stressor on the endocrine physiology of amphibians. Presently, there is no information to show that exposure to an acute thermal stressor could initiate a physiological stress (glucocorticoid) response and secondly, the possible effects on reproductive hormones and performance. Answering these questions is important for understanding the impacts of extreme temperature on amphibians. In this study, we experimented on cane toads from Queensland, Australia by acclimating them to mildly warm temperature (25°C) and then exposing to acute temperature treatments of 30°, 35° or 40°C (hypothetical acute thermal stressors). We measured acute changes in the stress hormone corticosterone and the reproductive hormone testosterone using standard capture and handling protocol and quantified the metabolites of both hormones non-invasively using urinary enzyme-immunoassays. Furthermore, we measured performance trait (i.e. righting response score) in the control acclimated and the three treatment groups. Corticosterone stress responses increased in all toads during exposure to an acute thermal stressor. Furthermore, exposure to a thermal stressor also decreased testosterone levels in all toads. The duration of the righting response (seconds) was longer for toads that were exposed to 40°C than to 30°, 35° or 25°C. The increased corticosterone stress response with increased intensity of the acute thermal stressor suggests that the toads perceived this treatment as a stressor. Furthermore, the results also highlight a potential trade-off with performance and reproductive hormones. Ultimately, exposure acute thermal stressors due to climatic variability could impact amphibians at multiple eco-physiological levels through impacts on endocrine physiology, performance and potentially fitness traits (e.g. reproductive output).

Acute Thermal Stressor Increases Glucocorticoid Response but Minimizes Testosterone and Locomotor Performance in the Cane Toad (Rhinella marina)

PubMed Central

Narayan, Edward J.; Hero, Jean-Marc

2014-01-01

Climatic warming is a global problem and acute thermal stressor in particular could be considered as a major stressor for wildlife. Cane toads (Rhinella marina) have expanded their range into warmer regions of Australia and they provide a suitable model species to study the sub-lethal impacts of thermal stressor on the endocrine physiology of amphibians. Presently, there is no information to show that exposure to an acute thermal stressor could initiate a physiological stress (glucocorticoid) response and secondly, the possible effects on reproductive hormones and performance. Answering these questions is important for understanding the impacts of extreme temperature on amphibians. In this study, we experimented on cane toads from Queensland, Australia by acclimating them to mildly warm temperature (25°C) and then exposing to acute temperature treatments of 30°, 35° or 40°C (hypothetical acute thermal stressors). We measured acute changes in the stress hormone corticosterone and the reproductive hormone testosterone using standard capture and handling protocol and quantified the metabolites of both hormones non-invasively using urinary enzyme-immunoassays. Furthermore, we measured performance trait (i.e. righting response score) in the control acclimated and the three treatment groups. Corticosterone stress responses increased in all toads during exposure to an acute thermal stressor. Furthermore, exposure to a thermal stressor also decreased testosterone levels in all toads. The duration of the righting response (seconds) was longer for toads that were exposed to 40°C than to 30°, 35° or 25°C. The increased corticosterone stress response with increased intensity of the acute thermal stressor suggests that the toads perceived this treatment as a stressor. Furthermore, the results also highlight a potential trade-off with performance and reproductive hormones. Ultimately, exposure acute thermal stressors due to climatic variability could impact amphibians at multiple eco-physiological levels through impacts on endocrine physiology, performance and potentially fitness traits (e.g. reproductive output). PMID:24643017

What does testosterone do for red deer males?

PubMed Central

Malo, A.F.; Roldan, E.R.S.; Garde, J.J.; Soler, A.J.; Vicente, J.; Gortazar, C.; Gomendio, M.

2008-01-01

Testosterone has been proposed to have a dual effect, enhancing sexual traits while depressing parasite resistance in males. Here, we test this hypothesis in red deer, examining males from captive populations during the whole annual cycle and males from natural populations during the breeding season. We first explored the effects of body size, age and sampling date on testosterone to avoid confounding effects. Our results show that in captive populations seasonal changes in testosterone levels were mirrored by changes in testes size, and that during the rut there was a strong correlation between both. In natural populations, males with higher testosterone levels had larger testes, improved sperm quality, smaller burr diameter, stronger antlers, higher haematocrit levels, and increased nematode parasite load. By contrast, no significant relationship was found between testosterone and spleen size or tick parasite load. We conclude that testosterone (i) improves males' reproductive investment and physical stamina, (ii) improves antler strength but reduces burr diameter, and (iii) imposes a cost in terms of depressed parasite resistance. PMID:19129132

Relationships of Polychlorinated Biphenyls and Dichlorodiphenyldichloroethylene (p,p’-DDE) with Testosterone Levels in Adolescent Males

PubMed Central

Gallo, Mia V.; Deane, Glenn D.; Nelder, Kyrie R.; DeCaprio, Anthony P.; Jacobs, Agnes

2013-01-01

Background: Concern persists over endocrine-disrupting effects of persistent organic pollutants (POPs) on human growth and sexual maturation. Potential effects of toxicant exposures on testosterone levels during puberty are not well characterized. Objectives: In this study we evaluated the relationship between toxicants [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p´-DDE), hexachlorobenzene (HCB), and lead] and testosterone levels among 127 Akwesasne Mohawk males 10 to < 17 years of age with documented toxicant exposures. Methods: Data were collected between February 1996 and January 2000. Fasting blood specimens were collected before breakfast by trained Akwesasne Mohawk staff. Multivariable regression models were used to estimates associations between toxicants and serum testosterone, adjusted for other toxicants, Tanner stage, and potential confounders. Results: The sum of 16 PCB congeners (Σ16PCBs) that were detected in ≥ 50% of the population was significantly and negatively associated with serum testosterone levels, such that a 10% change in exposure was associated with a 5.6% decrease in testosterone (95% CI: –10.8, –0.5%). Of the 16 congeners, the more persistent ones (Σ8PerPCBs) were related to testosterone, whereas the less persistent ones, possibly reflecting more recent exposure, were not. When PCB congeners were subgrouped, the association was significant for the sum of eight more persistent PCBs (5.7% decrease; 95% CI: –11, –0.4%), and stronger than the sum of six less persistent congeners (3.1% decrease; 95% CI: –7.2, 0.9%). p,p´-DDE was positively but not significantly associated with serum testosterone (5.2% increase with a 10% increase in exposure; 95% CI: –0.5, 10.9%). Neither lead nor HCB was significantly associated with testosterone levels. Conclusions: Exposure to PCBs, particularly the more highly persistent congeners, may negatively influence testosterone levels among adolescent males. The positive relationship between p,p´-DDE and testosterone indicates that not all POPs act similarly. Citation: Schell LM, Gallo MV, Deane GD, Nelder KR, DeCaprio AP, Jacobs A; Akwesasne Task Force on the Environment. 2014. Relationships of polychlorinated biphenyls and dichlorodiphenyldichloroethylene (p,p´-DDE) with testosterone levels in adolescent males. Environ Health Perspect 122:304–309; http://dx.doi.org/10.1289/ehp.1205984 PMID:24398050

The relationship between sleep disorders and testosterone in men

PubMed Central

Wittert, Gary

2014-01-01

Plasma testosterone levels display circadian variation, peaking during sleep, and reaching a nadir in the late afternoon, with a superimposed ultradian rhythm with pulses every 90 min reflecting the underlying rhythm of pulsatile luteinizing hormone (LH) secretion. The increase in testosterone is sleep, rather than circadian rhythm, dependent and requires at least 3 h of sleep with a normal architecture. Various disorders of sleep including abnormalities of sleep quality, duration, circadian rhythm disruption, and sleep-disordered breathing may result in a reduction in testosterone levels. The evidence, to support a direct effect of sleep restriction or circadian rhythm disruption on testosterone independent of an effect on sex hormone binding globulin (SHBG), or the presence of comorbid conditions, is equivocal and on balance seems tenuous. Obstructive sleep apnea (OSA) appears to have no direct effect on testosterone, after adjusting for age and obesity. However, a possible indirect causal process may exist mediated by the effect of OSA on obesity. Treatment of moderate to severe OSA with continuous positive airway pressure (CPAP) does not reliably increase testosterone levels in most studies. In contrast, a reduction in weight does so predictably and linearly in proportion to the amount of weight lost. Apart from a very transient deleterious effect, testosterone treatment does not adversely affect OSA. The data on the effect of sleep quality on testosterone may depend on whether testosterone is given as replacement, in supratherapeutic doses, or in the context abuse. Experimental data suggest that testosterone may modulate individual vulnerability to subjective symptoms of sleep restriction. Low testosterone may affect overall sleep quality which is improved by replacement doses. Large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities of sleep duration and architecture. PMID:24435056

Testosterone regulates bone response to inflammation.

PubMed

Steffens, J P; Herrera, B S; Coimbra, L S; Stephens, D N; Rossa, C; Spolidorio, L C; Kantarci, A; Van Dyke, T E

2014-03-01

This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1β expression was increased in the L group (p<0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function. © Georg Thieme Verlag KG Stuttgart · New York.

The hormonal correlates of implicit power motivation

PubMed Central

Stanton, Steven J.; Schultheiss, Oliver C.

2009-01-01

Attempts to link testosterone to dominance dispositions using self-report measures of dominance have yielded inconsistent findings. Similarly, attempts to link testosterone changes to a situational outcome like winning or losing a dominance contest have yielded inconsistent findings. However, research has consistently shown that an indirect measure of an individual’s dominance disposition, implicit power motivation, is positively related to baseline testosterone levels and, in interaction with situational outcomes, predicts testosterone changes. We propose a hormonal model of implicit power motivation that describes how testosterone levels change as an interactive function of individuals’ implicit power motivation and dominance situations. We also propose that estradiol, and not testosterone, plays a key role in dominance motivation in women. PMID:20161646

Job strain variations in relation to plasma testosterone fluctuations in working men--a longitudinal study.

PubMed

Theorell, T; Karasek, R A; Eneroth, P

1990-01-01

Job strain, a high level of psychological demands combined with a low level of decision latitude, has been hypothesized to induce mobilization of energy and inhibition of anabolism. In the present project this hypothesis was tested using four repeated observations every third month in a group of 44 men working in six widely different occupations. On each occasion scores of self-reported demands and decision latitude were calculated for every participant. An earlier report has shown that systolic blood pressure during work hours--an indicator of mobilization of energy--increased with increasing job strain (ratio between demands and decision latitude). Blood samples were drawn in the morning at the work site. For each man the plasma testosterone levels--representing the general level of anabolic activity--on the two occasions with the worst strain (ratio between demands and decision latitude) were compared with the plasma testosterone levels on the two occasions with the least strain. The results indicated that total plasma testosterone (but not free testosterone) levels increased when strain diminished in sedentary but not in physically demanding work. Subjects with a family history of hypertension showed a greater decrease in testosterone levels than others when job strain increased.

External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer.

PubMed

Pompe, Raisa S; Karakiewicz, Pierre I; Zaffuto, Emanuele; Smith, Ariane; Bandini, Marco; Marchioni, Michele; Tian, Zhe; Leyh-Bannurah, Sami-Ramzi; Schiffmann, Jonas; Delouya, Guila; Lambert, Carole; Bahary, Jean-Paul; Beauchemin, Marie Claude; Barkati, Maroie; Ménard, Cynthia; Graefen, Markus; Saad, Fred; Tilki, Derya; Taussky, Daniel

2017-07-01

Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported. To examine testosterone kinetics in a large series of contemporary patients after EBRT. The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses. Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence. Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone < 8 nmol/L). Of all patients with testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence. EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism. We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study lacked information on health-related quality-of-life data. Our findings indicate that up to 75% of patients will have a profound testosterone decrease, with up to a 40% increase in rates of biochemical hypogonadism, although the latter events will leave biochemical recurrence unaffected. Pompe RS, Karakrewicz PI, Zaffuto E, et al. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer. J Sex Med 2017;14:876-882. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Testosterone and Haemosporidian Parasites Along a Tropical Elevational Gradient in Rufous-Collared Sparrows (Zonotrichia capensis).

PubMed

Escallón, Camilo; Weinstein, Nicole M; Tallant, James A; Wojtenek, Winfried; Rodríguez-Saltos, Carlos A; Bonaccorso, Elisa; Moore, Ignacio T

2016-10-01

Elevation has been proposed as a dominant ecological variable shaping life history traits and subsequently their underlying hormonal mechanisms. In an earlier meta-analysis of tropical birds, elevation was positively related to testosterone levels. Furthermore, parasitism by avian haemosporidians should vary with elevation as environmental conditions affect vector abundance, and while testosterone is needed for breeding, it is hypothesized to be immunosuppressive and thus could exacerbate haemosporidian infection. Our objective in this study was to examine the relationships between elevation, testosterone levels, and parasitism by avian haemosporidians. We surveyed breeding male rufous-collared sparrows (Zonotrichia capensis) across a wide elevational range along the equator. We measured baseline testosterone levels, haemosporidian infection at four elevations spanning the species' natural range in the Ecuadorian Andes (600, 1500, 2100, 3300 m). Testosterone levels from breeding males were not related to elevation, but there was high intrapopulation variability. Testosterone levels were not related to the probability of parasitism, but our results from one population suggested that the likelihood of being infected by haemosporidian parasites was greater when in breeding condition. In conclusion, even though there is variation in life history strategies among the studied populations, wider divergence in seasonality and life history traits would probably be needed to detect an effect of elevation on testosterone if one exists. Additionally, our results show that variation in testosterone is not related to infection risk of haemosporidians, thus other factors that take a toll on energetic resources, such as reproduction, should be looked at more closely. © 2016 Wiley Periodicals, Inc.

Increased Free Testosterone Levels in Men with Uncontrolled Type 2 Diabetes Five Years After Randomization to Bariatric Surgery.

PubMed

Pham, Nathan H; Bena, James; Bhatt, Deepak L; Kennedy, Laurence; Schauer, Philip R; Kashyap, Sangeeta R

2018-01-01

Hypogonadism frequently occurs in male patients with type 2 diabetes (T2DM) and is linked to insulin resistance and inflammation. Testosterone levels rise acutely in obese patients following bariatric surgery, though long-term changes have not been investigated in a randomized controlled trial. This study evaluated obese men with T2DM randomized to either bariatric surgery or medical therapy. Testosterone, gonadotropins, body composition, insulin sensitivity, and inflammatory markers were evaluated in 32 patients at baseline and at 5 years. Surgical patients had 47.4% increase in free testosterone compared to medical therapy patients who had 2.2% decrease (P = 0.013). Increase in free testosterone correlated with reduction in body weight, high-sensitivity C-reactive protein (hsCRP), and leptin levels. Prolonged improvements in testosterone levels after bariatric surgery in T2DM are found to be related to reduction in body weight and adipogenic inflammation.

Prevalence of androgen deficiency in men with erectile dysfunction.

PubMed

Köhler, Tobias S; Kim, Johnny; Feia, Kendall; Bodie, Josh; Johnson, Nick; Makhlouf, Antoine; Monga, Manoj

2008-04-01

Erectile dysfunction (ED) and androgen deficiency in aging men are two separate clinical entities that often overlap. Controversy exists regarding the most appropriate total testosterone level that defines androgen deficiency in aging men, and its prevalence in men with ED is still uncertain. We evaluated the prevalence and risk factors of low and low-normal testosterone levels in men presenting for an initial ED evaluation. The computerized charts from 1987 to 2002 of 2794 men aged 25 to 80 years and presenting with a primary complaint of ED who also had serum total testosterone levels measured were retrospectively reviewed. Multiple testosterone level cutpoints and a linear regression model (including age, diabetes, cholesterol, anemia, creatinine, and prostate-specific antigen) were used to analyze the factors that correlated with hypogonadism. The prevalence of androgen deficiency was 7%, 23%, 33%, and 47% for testosterone levels of less than 200, less than 300, less than 346, and less than 400 ng/dL, respectively. An abrupt increase in hypogonadism prevalence occurred in men aged 45 to 50, beyond which a plateau of prevalence was maintained until older than 80 years of age. Age, the presence of uncontrolled diabetes, high total cholesterol, and anemia all correlated with significantly decreased testosterone levels in men with ED. The prostate-specific antigen level and creatinine did not affect the testosterone levels. Androgen deficiency was quite common in men presenting with ED and correlated significantly with age, uncontrolled diabetes, hypercholesteremia, and anemia. Although additional prospective studies evaluating the effect of testosterone supplementation in this population are needed, clinicians, including urologists, should be keenly aware of the large overlap of patients with ED who might also have the entity, androgen deficiency in the aging male.

Association of admission testosterone level with ST-segment resolution in male patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PubMed

Separham, Ahmad; Ghaffari, Samad; Sohrabi, Bahram; Aslanabadi, Naser; Hadavi Bavil, Mozhgan; Lotfollahi, Hasanali

2017-01-01

Low level of testosterone may be associated with cardiovascular diseases in men, as some evidence suggests a protective role for testosterone in cardiovascular system. Little is known about the possible role of serum testosterone in response to reperfusion therapy in ST-elevation myocardial infarction (STEMI) and its relationship with ST-segment recovery. The present study was conducted to evaluate the association of serum testosterone levels with ST-segment resolution following primary percutaneous coronary intervention (PPCI) in male patients with acute STEMI. Forty-eight men (mean age 54.55 ± 12.20) with STEMI undergoing PPCI were enrolled prospectively. Single-lead ST segment resolution in the lead with maximum baseline ST-elevation was measured and patients were divided into two groups according to the degree of ST-segment resolution: complete (> or =50%) or incomplete (<50%). The basic and demographic data of all patients, their left ventricular ejection fraction (LVEF) and laboratory findings including serum levels of free testosterone and cardiac enzymes were recorded along with angiographic finding and baseline TIMI (Thrombolysis in Myocardial Infarction) flow and also in-hospital complications and then these variables were compared between two groups. A complete ST-resolution (≥50%) was observed in 72.9% of the patients. The serum levels of free testosterone ( P  = 0.04), peak cardiac troponin ( P  = 0.03) were significantly higher and hs-CRP ( P  = 0.02) were lower in patients with complete ST-resolution compared to those with incomplete ST-resolution. In-hospital complications were observed in 31.2% of patients. The patients with a lower baseline TIMI flow ( P  = 0.03) and those who developed complications ( P  = 0.04) had lower levels of free testosterone. A significant positive correlation was observed between the left ventricular function and serum levels of free testosterone ( P  = 0.01 and r = +0.362). This study suggests that in men with STEMI undergoing PPCI, higher serum levels of testosterone are associated with a better reperfusion response, fewer complications and a better left ventricular function.

Assessment of gonadotropins and testosterone hormone levels in regular Mitragyna speciosa (Korth.) users.

PubMed

Singh, Darshan; Murugaiyah, Vikneswaran; Hamid, Shahrul Bariyah Sahul; Kasinather, Vicknasingam; Chan, Michelle Su Ann; Ho, Eric Tatt Wei; Grundmann, Oliver; Chear, Nelson Jeng Yeou; Mansor, Sharif Mahsufi

2018-07-15

Mitragyna speciosa (Korth.) also known as kratom, is a native medicinal plant of Southeast Asia with opioid-like effects. Kratom tea/juice have been traditionally used as a folk remedy and for controlling opiate withdrawal in Malaysia. Long-term opioid use is associated with depletion in testosterone levels. Since kratom is reported to deform sperm morphology and reduce sperm motility, we aimed to clinically investigate the testosterone levels following long-term kratom tea/juice use in regular kratom users. A total of 19 regular kratom users were recruited for this cross-sectional study. A full-blood test was conducted including determination of testosterone level, follicle stimulating hormone (FSH) and luteinizing hormone (LH) profile, as well as hematological and biochemical parameters of participants. We found long-term kratom tea/juice consumption with a daily mitragynine dose of 76.23-94.15 mg did not impair testosterone levels, or gonadotrophins, hematological and biochemical parameters in regular kratom users. Regular kratom tea/juice consumption over prolonged periods (>2 years) was not associated with testosterone impairing effects in humans. Copyright © 2018 Elsevier B.V. All rights reserved.

Marriage and motherhood are associated with lower testosterone concentrations in women

PubMed Central

Barrett, Emily S.; Tran, Van; Thurston, Sally; Jasienska, Grazyna; Furberg, Anne-Sofie; Ellison, Peter T.; Thune, Inger

2012-01-01

Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes. PMID:23123222

Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes.

PubMed

Muraleedharan, Vakkat; Marsh, Hazel; Kapoor, Dheeraj; Channer, Kevin S; Jones, T Hugh

2013-12-01

Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone. A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years. mortality rates were compared between total testosterone 10.4nmol/l (300ng/dl; n=343) and testosterone 10.4nmol/l (n=238). the effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group. Mortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2-3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3-3.9, P=0.004). Low testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples.

PubMed

Bhongade, M B; Prasad, S; Jiloha, R C; Ray, P C; Mohapatra, S; Koner, B C

2015-04-01

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases. © 2014 Blackwell Verlag GmbH.

A herbal medicine, saikokaryukotsuboreito, improves serum testosterone levels and affects sexual behavior in old male mice.

PubMed

Zang, Zhi Jun; Ji, Su Yun; Dong, Wang; Zhang, Ya Nan; Zhang, Er Hong; Bin, Zhang

2015-06-01

Late-onset hypogonadism (LOH) is a clinical syndrome characterized with aging and declined serum testosterone levels. Sexual symptoms are also essential for the diagnosis of LOH. Testosterone replacement therapy is used widely to treat LOH. However, the side effects of it should not be ignored, such as fluid retention, hypertension and spermatogenic suppression. Therefore, alternate treatment modalities have been pursued. Herbal medicines used widely in China have achieved satisfying results with little side effects. Nonetheless, there are few pharmacological researches on them. In this study, 24-month-old mice were used as LOH animal models to explore the pharmacological effects of a herbal medicine, saikokaryukotsuboreito (SKRBT), on serum testosterone levels and sexual functions. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein, a kind of rate-limiting enzyme of testosterone synthesis, was also examined. As a result, SKRBT improved the serum testosterone levels of these mice at a dose of 300 and 450 mg/kg. Multiple measures of sexual behavior were enhanced. The expression of StAR was also increased. Therefore, this study suggested that SKRBT can improve the serum testosterone levels by activating the expression of StAR and might be a viable option to treat sexual symptoms caused by LOH.

Testosterone, territorial response, and song in seasonally breeding tropical and temperate stonechats.

PubMed

Apfelbeck, Beate; Mortega, Kim G; Flinks, Heiner; Illera, Juan Carlos; Helm, Barbara

2017-04-17

Testosterone facilitates physiological, morphological, and behavioral changes required for breeding in male vertebrates. However, testosterone concentrations and the link between its seasonal changes and those in reproductive behaviors vary greatly among species. To better understand the impact of tropical and temperate environments and life history factors on this variation, we have compared testosterone, territorial behavior and song performance across sequential stages of the breeding season in males of 16 closely related taxa of East African tropical and West European temperate stonechats (Saxicola spp), which all breed during a short breeding season, but differ in migratory behavior, seasonal territory-acquisition and pace of life. We found that generally, the profiles of testosterone and territorial behavior were similar across latitudes. African stonechats with a slow pace of life had equally high peak testosterone concentrations and responded as aggressively to an intruder as European stonechats with a fast pace of life. However, song performance at the beginning of the breeding season was lower in African than in European stonechats. The differences in song performance were not associated with variation in testosterone levels between tropical and temperate stonechats. The results suggest a very similar role for testosterone as a mediator of high intensity territorial aggression during the fertile period of females in tropical and temperate stonechats, which all are highly seasonal, locally synchronous breeders. A potential explanation may be high risk of extra-pair copulations which has been associated with synchronous breeding. Interestingly, an association was not consistent for song performance. Our data suggest that song performance can be disassociated from peak testosterone levels depending on its role in breeding behavior. Despite similar testosterone levels, European males, which early in the breeding season acquire territories and mates, showed greater song performance than African stonechats, which maintain year-round territories and pair-bonds. Taken together, our study comparing related taxa of old world songbirds suggests that short breeding seasons may be a major selective force for high peak testosterone levels during breeding regardless of latitude and pace of life, but that particular behaviors, in our case song, can be uncoupled from peak testosterone levels.

Basal testosterone, leadership and dominance: A field study and meta-analysis.

PubMed

van der Meij, Leander; Schaveling, Jaap; van Vugt, Mark

2016-10-01

This article examines the role of basal testosterone as a potential biological marker of leadership and hierarchy in the workplace. First, we report the result of a study with a sample of male employees from different corporate organizations in the Netherlands (n=125). Results showed that employees with higher basal testosterone levels reported a more authoritarian leadership style, but this relationship was absent among those who currently held a real management position (i.e., they had at least one subordinate). Furthermore, basal testosterone levels were not different between managers and non-managers, and testosterone was not associated with various indicators of status and hierarchy such as number of subordinates, income, and position in the organizational hierarchy. In our meta-analysis (second study), we showed that basal testosterone levels were not associated with leadership in men nor in women (9 studies, n=1103). Taken together, our findings show that basal testosterone is not associated with having a leadership position in the corporate world or related to leadership styles in leaders. We suggest that basal testosterone could play a role in acquiring leadership positions through dominant and authoritarian behavior. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dynamics of testosterone concentration in male steppe lemmings (Lagurus lagurus) in the reproductive cycle reflects the species-specific mating system.

PubMed

Potapova, O F; Potapov, M A; Kondratyuk, E Yu; Evsikov, V I

2016-05-01

In the blood of male steppe lemmings, relatively low background levels of testosterone were detected, this is characteristic of a monogamous species. A significant increase in testosterone level, more expressed in sexually active males, was observed at the initial stage of formation of reproductive couples. Apparently, in the future, the couple will exist in a stable relationship, and, hence, the maintenance of a high testosterone level becomes excessive. The decrease in, and the relative "normalization" of, the hormone level during the existence of the pair, including raising of the young, promotes higher expression of the male paternal care of the offspring at the species level.

Sexual Function and Testosterone Level in Men With Conservatively Treated Chronic Kidney Disease.

PubMed

Fugl-Meyer, Kerstin S; Nilsson, Marie; Hylander, Britta; Lehtihet, Mikael

2017-07-01

Sexual dysfunctions are common, but underrecognized, in patients with chronic kidney disease (CKD) and are inversely associated with the glomerular filtration rate (GFR). Sexual dysfunctions may affect quality of life in males with CKD. The aim of this study was to analyze the relationship among sex hormones, sexual function, and sexual satisfaction in a group of men between 18 and 50 years of age with CKD Stages 1 to 5 not treated with hemodialysis or peritoneal dialysis. Fasting blood samples for hemoglobin, testosterone, prolactin, and luteinizing hormone and questionnaire surveys (Sexual Complaints Screener for Men, International Index of Erectile Function, and Aging Male Symptom scale) were evaluated in 100consecutive men. Higher CKD stage (i.e., lower renal function) had a statistically significant ( p < .01) correlation with lower total testosterone, free testosterone, and hemoglobin levels, and higher luteinizing hormone and prolactin levels. Sexual function/dysfunctions were not significantly associated with CKD stage, even after adjustment for age and serum testosterone. The results indicate that CKD stage is a factor affecting testosterone levels in combination with age in men between 18 and 50 years of age at different stages of CKD but not treated with hemodialysis or peritoneal dialysis. Sexual dysfunctions are common but not strongly correlated to testosterone levels, prolactin levels, and survey (Sexual Complaints Screener for Men, International Index of Erectile Function, and Aging Male Symptom scale) responses in patients with CKD.

Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

PubMed Central

Barragry, J M; Makin, H L; Trafford, D J; Scott, D F

1978-01-01

Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG. PMID:569688

Effectiveness of testosterone therapy in obese men with low testosterone levels, for losing weight, controlling obesity complications, and preventing cardiovascular events: Protocol of a systematic review of randomized controlled trials.

PubMed

Mangolim, Amanda S; Brito, Leonardo A R; Nunes-Nogueira, Vania S

2018-04-01

The use of testosterone replacement therapy in obese men with low testosterone levels has been controversial. This review aims to analyze the effectiveness of testosterone therapy for weight loss and preventing cardiovascular complications in obese men with low testosterone levels. We will perform a systematic review according to Cochrane Methodology of randomized studies, including crossover studies, wherein patients are allocated into one of the two groups: testosterone therapy and control (no treatment or placebo). The primary outcomes analyzed will be: weight loss, adverse events, quality of life, improvement of libido, control of obesity complications, frequency of cardiovascular events, and deaths. Four general and adaptive search strategies have been created for the following electronic health databases: Embase, Medline, LILACS, and CENTRAL. Two reviewers will independently select the eligible studies, assess the risk of bias, and extract the data from included studies. Similar outcomes measured in at least two trials will be plotted in the meta-analysis using Review Manager 5.3. The quality of evidence of the effect estimate of the intervention for the outcomes that could be plotted in the meta-analysis will be generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group. Although testosterone replacement seems to be an attractive treatment modality for obese men with low testosterone, its potential benefits has been refuted by some studies, whose results have not shown significant differences between treated and untreated patients. For obese men with low testosterone concentrations, the proposed systematic review aims to answer the following questions: When compared with no treatment or placebo: Is testosterone therapy safe? Is testosterone therapy effective in promoting weight loss, a sustained reduction in body weight and changes in body composition? Is testosterone effective in improving quality of life, libido, and erectile function? Is testosterone therapy effective in controlling obesity complications and in preventing cardiovascular events?

Association between age-related reductions in testosterone and risk of prostate cancer-An analysis of patients' data with prostatic diseases.

PubMed

Wang, Kai; Chen, Xinguang; Bird, Victoria Y; Gerke, Travis A; Manini, Todd M; Prosperi, Mattia

2017-11-01

The relationship between serum total testosterone and prostate cancer (PCa) risk is controversial. The hypothesis that faster age-related reduction in testosterone is linked with increased PCa risk remains untested. We conducted our study at a tertiary-level hospital in southeast of the USA, and derived data from the Medical Registry Database of individuals that were diagnosed of any prostate-related disease from 2001 to 2015. Cases were those diagnosed of PCa and had one or more measurements of testosterone prior to PCa diagnosis. Controls were those without PCa and had one or more testosterone measurements. Multivariable logistic regression models for PCa risk of absolute levels (one-time measure and 5-year average) and annual change in testosterone were respectively constructed. Among a total of 1,559 patients, 217 were PCa cases, and neither one-time measure nor 5-year average of testosterone was found to be significantly associated with PCa risk. Among the 379 patients with two or more testosterone measurements, 27 were PCa cases. For every 10 ng/dL increment in annual reduction of testosterone, the risk of PCa would increase by 14% [adjusted odds ratio, 1.14; 95% confidence interval (CI), 1.03-1.25]. Compared to patients with a relatively stable testosterone, patients with an annual testosterone reduction of more than 30 ng/dL had 5.03 [95% CI: 1.53, 16.55] fold increase in PCa risk. This implies a faster age-related reduction in, but not absolute level of serum total testosterone as a risk factor for PCa. Further longitudinal studies are needed to confirm this finding. © 2017 UICC.

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction

PubMed Central

Karabakan, Mehmet; Keskin, Ercument; Akdemir, Serkan; Bozkurt, Aliseydi

2017-01-01

ABSTRACT Objective To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS) in patients with erectile dysfunction. Materials and Methods A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5), intravaginal ejaculatory latency time (IELT) and international prostate symptoms scores (IPSS). After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were measured. The independent-samples t-test was used to compare the pre- and post-treatment scores of the patients. Results The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL-1, 188.7±29.6mg/dL-1,104 (80-360) mg dL-1, respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01). Conclusion A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time. PMID:27819758

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction.

PubMed

Karabakan, Mehmet; Keskin, Ercument; Akdemir, Serkan; Bozkurt, Aliseydi

2017-01-01

To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS) in patients with erectile dysfunction. A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5), intravaginal ejaculatory latency time (IELT) and international prostate symptoms scores (IPSS). After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol and total cholesterol were measured. The independentsamples t-test was used to compare the pre- and post-treatment scores of the patients. The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL-1, 188.7±29.6mg/dL-1,104 (80-360) mg dL-1, respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01). A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time. Copyright® by the International Brazilian Journal of Urology.

Atherosclerosis is associated with erectile function and lower urinary tract symptoms, especially nocturia, in middle-aged men.

PubMed

Tsujimura, Akira; Hiramatsu, Ippei; Aoki, Yusuke; Shimoyama, Hirofumi; Mizuno, Taiki; Nozaki, Taiji; Shirai, Masato; Kobayashi, Kazuhiro; Kumamoto, Yoshiaki; Horie, Shigeo

2017-06-01

Atherosclerosis is a systematic disease in which plaque builds up inside the arteries that can lead to serious problems related to quality of life (QOL). Lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and late-onset hypogonadism (LOH) are highly prevalent in aging men and are significantly associated with a reduced QOL. However, few questionnaire-based studies have fully examined the relation between atherosclerosis and several urological symptoms. The study comprised 303 outpatients who visited our clinic with symptoms of LOH. Several factors influencing atherosclerosis, including serum concentrations of triglyceride, fasting blood sugar, and total testosterone measured by radioimmunoassay, were investigated. We also measured brachial-ankle pulse wave velocity (baPWV) and assessed symptoms by specific questionnaires, including the Sexual Health Inventory for Men (SHIM), Erection Hardness Score (EHS), International Prostate Symptom Score (IPSS), QOL index, and Aging Male Symptoms rating scale (AMS). Stepwise associations between the ratio of measured/age standard baPWV and clinical factors including laboratory data and the scores of the questionnaires were compared using the Jonckheere-Terpstra test for trend. The associations between the ratio of measured/age standard baPWV and each IPSS score were assessed in a multivariate linear regression model after adjustment for serum triglyceride, fasting blood sugar, and total testosterone. Regarding ED, a higher level of the ratio of measured/age standard baPWV was associated with a lower EHS, whereas no association was found with SHIM. Regarding LUTS, a higher ratio of measured/age standard baPWV was associated with a higher IPSS and QOL index. However, there was no statistically significant difference between the ratio of measured/age standard baPWV and AMS. A multivariate linear regression model showed only nocturia to be associated with the ratio of measured/age standard baPWV for each IPSS score. Atherosclerosis is associated with erectile function and LUTS, especially nocturia.

Gonadal Status and physical performance in older men

PubMed Central

Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Metter, E. Jeffrey; Guralnik, Jack M.; Basaria, Shehzad; Cattabiani, Chiara; Luci, Michele; Dall'Aglio, Elisabetta; Vignali, Alessandro; Volpi, Riccardo; Valenti, Giorgio; Ferrucci, Luigi

2011-01-01

Background Male aging is characterized by a progressive decline in serum testosterone levels and physical performance. Low testosterone levels may be implicated in the decline of physical performance and consequent mobility disability that occurs with aging. During the recent years many consensus reports have advocated that one of the potential effects of testosterone supplementation is the improvement in mobility. However, to the best of our knowledge no study has fully investigated the relationship between gonadal status and objective measures of physical performance in older men and their determinants. Methods We evaluated 455 ≥ 65 year old male participants of InCHIANTI study a population based study in two municipalities of Tuscany, Italy with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance. Results According to baseline serum levels of total testosterone, three different groups of older men were created: 1) severely hypogonadal (N= 23),total testosterone levels ≤230 ng /dl; 2) moderately hypogonadal (N=88), total testosterone >230 and <350 ng/dL), and 3) eugonadal (N=344), testosterone levels ≥350 ng/dL. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in hemoglobin levels, hand grip strength and SPPB score (p for trend<0.001) among −3 groups, with severely hypogonadal men having lower values of hemoglobin, muscle strength and physical performance. We found no association between testosterone group assignment and calf muscle mass and 4 meter walking speed. In the multivariate analysis grip strength (p for trend=0.004) and haemoglobin (p for trend <0.0001) but not SPPB and other determinants of physical performance were significantly different between the 3 groups. Conclusions In older men, gonadal status is independently associated with some determinants (hemoglobin and muscle strength) of physical performance. PMID:20937007

Lowered testosterone in male obesity: mechanisms, morbidity and management

PubMed Central

Fui, Mark Ng Tang; Dupuis, Philippe; Grossmann, Mathis

2014-01-01

With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials. PMID:24407187

Lipophagy Contributes to Testosterone Biosynthesis in Male Rat Leydig Cells.

PubMed

Ma, Yi; Zhou, Yan; Zhu, Yin-Ci; Wang, Si-Qi; Ping, Ping; Chen, Xiang-Feng

2018-02-01

In recent years, autophagy was found to regulate lipid metabolism through a process termed lipophagy. Lipophagy modulates the degradation of cholesteryl esters to free cholesterol (FC), which is the substrate of testosterone biosynthesis. However, the role of lipophagy in testosterone production is unknown. To investigate this, primary rat Leydig cells and varicocele rat models were administered to inhibit or promote autophagy, and testosterone, lipid droplets (LDs), total cholesterol (TC), and FC were evaluated. The results demonstrated that inhibiting autophagy in primary rat Leydig cells reduced testosterone production. Further studies demonstrated that inhibiting autophagy increased the number and size of LDs and the level of TC, but decreased the level of FC. Furthermore, hypoxia promoted autophagy in Leydig cells. We found that short-term hypoxia stimulated testosterone secretion; however, the inhibition of autophagy abolished stimulated testosterone release. Hypoxia decreased the number and size of LDs in Leydig cells, but the changes could be largely rescued by blocking autophagy. In experimental varicocele rat models, the administration of autophagy inhibitors substantially reduced serum testosterone. These data demonstrate that autophagy contributes to testosterone biosynthesis at least partially through degrading intracellular LDs/TC. Our observations might reveal an autophagic regulatory mode regarding testosterone biosynthesis. Copyright © 2018 Endocrine Society.

[Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

PubMed

Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

2013-03-01

To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention).

PubMed

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Kreiberg, Michael; Oturai, Peter Sandor; Helge, Jørn Wulff; Daugaard, Gedske

2017-07-03

Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. This is a single-center, randomized, double-blind, placebo-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent will be obtained. Afterwards, a 52-weeks treatment period begins in which study participants will receive a daily dose of transdermal testosterone or placebo. Dose adjustment will be made three times during the initial 8 weeks of the study to a maximal daily dose of 40 mg of testosterone in the intervention arm. Evaluation of primary and secondary endpoints will be performed at baseline, 26 weeks post-randomization, at the end of treatment (52 weeks) and 3 months after completion of treatment (week 64). This study is the first to investigate the effect of testosterone substitution in testicular cancer survivors with mild Leydig cell insufficiency. If positive, it may change the clinical handling of testicular cancer survivors with borderline low levels of testosterone. ClinicalTrials.gov : NCT02991209 (November 25, 2016).

Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruheim, Kjersti; Svartberg, Johan; Department of Medicine, University Hospital of North Norway, Tromso

Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone bindingmore » globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.« less

EXOGENOUS TESTOSTERONE DOES NOT INDUCE OR EXACERBATE THE METABOLIC FEATURES ASSOCIATED WITH PCOS AMONG TRANSGENDER MEN.

PubMed

Chan, Kelly J; Liang, Jennifer J; Jolly, Divya; Weinand, Jamie D; Safer, Joshua D

2018-04-06

Polycystic ovarian syndrome (PCOS) is a complex condition which can include menstrual irregularity, metabolic derangement, and increased androgen levels. The mechanism of PCOS is unknown. Some suggest that excess production of androgens by the ovaries may cause or exacerbate the metabolic findings. The purpose of this study was to assess the role of increased testosterone on metabolic parameters on individuals presumed to be chromosomally female by examination of these parameters in hormone-treated transgender men. In 2015 and 2016, we asked all transgender men who visited the Endocrinology Clinic at Boston Medical Center treated with testosterone for consent for a retrospective anonymous chart review. Of the 36 men, 34 agreed (94%). Serum metabolic factors and body mass index levels for each patient were graphed over time, from initiation of therapy through 6 years of treatment. Bivariate analyses were conducted to analyze the impact of added testosterone. Regressions measuring the impact of testosterone demonstrated no significant change in levels of glycosylated hemoglobin, triglycerides, or low density lipoprotein cholesterol. There was a statistically significant decrease in BMI with increasing testosterone. There was also a statistically significant decrease in high density lipoprotein levels upon initiation of testosterone therapy. Testosterone therapy in transgender men across a wide range of doses and over many years did not result in the abnormalities in HbA1c or dyslipidemia seen with PCOS. Instead, treatment of transgender men with testosterone resulted only in a shift of metabolic biomarkers toward the average physiologic male body. This retrospective chart review of 34 transgender men found that testosterone therapy does not induce or exacerbate the metabolic features associated with PCOS.

Lower serum testosterone associated with elevated polychlorinated biphenyl concentrations in Native American men.

PubMed

Goncharov, Alexey; Rej, Robert; Negoita, Serban; Schymura, Maria; Santiago-Rivera, Azara; Morse, Gayle; Carpenter, David O

2009-09-01

Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05-0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06-0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men.

Low bioavailable testosterone levels predict future height loss in postmenopausal women.

PubMed

Jassal, S K; Barrett-Connor, E; Edelstein, S L

1995-04-01

The objective of this study was to examine the relation of endogenous sex hormones to subsequent height loss in postmenopausal women, in whom height loss is usually a surrogate for osteoporotic vertebral fractures. This was a prospective, community-based study. The site chosen was Rancho Bernardo, an upper middle class community in Southern California. A total of 170 postmenopausal women participated, aged 55-80 years. None of them were taking exogenous estrogen between 1972 and 1974. Plasma was obtained for sex hormone and sex hormone-binding globulin (SHBG) assays. Estradiol/SHBG and testosterone/SHBG ratios were used to estimate biologically available hormone levels; bioavailable (non-SHBG-bound) testosterone was measured directly in 60 women. Height loss was based on height measurements taken 16 years apart. Height loss was strongly correlated with age (p = 0.001). These women lost an average 0.22 cm/year in height. Neither estrone nor estradiol levels were significantly and independently related to height loss. Both estimated bioavailable testosterone (testosterone/SHBG ratio) and measured bioavailable testosterone levels predicted future height loss (p = 0.02 and 0.08, respectively) independent of age, obesity, cigarette smoking, alcohol intake, and use of thiazides and estrogen. We conclude that bioavailable testosterone is an independent predictor of height loss in elderly postmenopausal women. The reduced height loss is compatible with a direct effect of testosterone on bone mineral density or bone remodeling.

Testosterone and androgen receptor gene polymorphism are associated with confidence and competitiveness in men.

PubMed

Eisenegger, Christoph; Kumsta, Robert; Naef, Michael; Gromoll, Jörg; Heinrichs, Markus

2017-06-01

A contribution to a special issue on Hormones and Human Competition. Studies in non-human animals and humans have demonstrated the important role of testosterone in competitive interactions. Here, we investigated whether endogenous testosterone levels predict the decision to compete, in a design excluding spite as a motive underlying competitiveness. In a laboratory experiment with real monetary incentives, 181 men solved arithmetic problems, first under a noncompetitive piece rate, followed by a competition incentive scheme. We also assessed several parameters relevant to competition, such as risk taking, performance, and confidence in one's own performance. Salivary testosterone levels were measured before and 20min after the competition task using mass spectrometry. Participants were also genotyped for the CAG repeat polymorphism of the androgen receptor gene, known to influence the efficacy of testosterone signaling in a reciprocal relationship to the number of CAG repeats. We observed a significant positive association between basal testosterone levels and the decision to compete, and that higher testosterone levels were related to greater confidence in one's own performance. Whereas the number of CAG repeats was not associated with the choice to compete, a lower number of CAG repeats was related to greater confidence in those who chose to compete, but this effect was attributable to the polymorphism's effect on actual performance. An increase in testosterone levels was observed following the experiment, and this increase varied with self-reported high-school math grades. We expand upon the latest research by documenting effects of the androgen system in confidence in one's own ability, and conclude that testosterone promotes competitiveness without spite. Copyright © 2016 Elsevier Inc. All rights reserved.

Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

PubMed

Malan, Nicolaas T; von Känel, Roland; Schutte, Alta E; Huisman, Hugo W; Schutte, Rudolph; Smith, Wayne; Mels, Carina M; Kruger, Ruan; Meiring, Muriel; van Rooyen, Johannes M; Malan, Leoné

2013-10-12

Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; p<0.05). An interdependence between acute mental stress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels. © 2013.

Testosterone and cardiovascular disease in men

PubMed Central

Morris, Paul D; Channer, Kevin S

2012-01-01

Despite regional variations in the prevalence of coronary artery disease (CAD), men are consistently more at risk of developing and dying from CAD than women, and the gender-specific effects of sex hormones are implicated in this inequality. This ‘Perspectives' article reviews the current evidence regarding the cardiovascular effects of testosterone in men including an examination of the age-related decline in testosterone, the relationship between testosterone levels and coronary disease, coronary risk factors and mortality. We also review the vaso-active effects of testosterone, and discuss how these have been used in men with heart failure and angina. We discuss the ‘cause' versus ‘effect' controversy, regarding low testosterone levels in men with coronary heart disease, as well as concerns over the use of testosterone replacement therapy in middle aged and elderly men. The article concludes with a discussion regarding the future direction for work in this interesting area, including the relative merits of screening for, and treating hypogonadism with testosterone replacement therapy in men with heart disease. PMID:22522504

Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Zhao, Di; Ouyang, Pamela; de Boer, Ian H; Lutsey, Pamela L; Farag, Youssef M K; Guallar, Eliseo; Siscovick, David S; Post, Wendy S; Kalyani, Rita R; Billups, Kevin L; Michos, Erin D

2017-02-01

25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity. To examine associations of 25(OH)D concentrations with sex hormone levels. Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort. Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone. The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity. Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effects of saliva collection, handling and storage on salivary testosterone measurement.

PubMed

Durdiaková, Jaroslava; Fábryová, Helena; Koborová, Ivana; Ostatníková, Daniela; Celec, Peter

2013-12-20

Several endocrine parameters commonly measured in plasma, such as steroid hormones, can be measured in the oral fluid. However, there are several technical aspects of saliva sampling and processing that can potentially bias the validity of salivary testosterone measurement. The aim of this study was to evaluate the effects caused by repeated sampling; 5 min centrifugation (at 2000, 6000 or 10,000g); the stimulation of saliva flow by a cotton swab soaked in 2% citric acid touching the tongue; different storage times and conditions as well as the impact of blood contamination on salivary testosterone concentration measured using a commercially available ELISA kit. Fresh, unprocessed, unstimulated saliva samples served as a control. Salivary testosterone concentrations were influenced neither by repeated sampling nor by stimulation of salivary flow. Testosterone levels determined in samples stored in various laboratory conditions for time periods up to 1 month did not differ in comparison with controls. For both genders, salivary testosterone levels were substantially reduced after centrifugation (men F=29.1; women F=56.17, p<0.0001). Blood contamination decreased salivary testosterone levels in a dose-dependent manner (men F=6.54, p<0.01, F=5.01, p<0.05). Salivary testosterone can be considered A robust and stable marker. However, saliva processing and blood leakage can introduce bias into measurements of salivary testosterone using ELISA. Our observations should be considered in studies focusing on salivary testosterone. Copyright © 2013 Elsevier Inc. All rights reserved.

The female menstrual cycle does not influence testosterone concentrations in male partners.

PubMed

Strom, Jakob O; Ingberg, Edvin; Druvefors, Emma; Theodorsson, Annette; Theodorsson, Elvar

2012-01-03

The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation. Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis. In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05). Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.

The female menstrual cycle does not influence testosterone concentrations in male partners

PubMed Central

2012-01-01

Background The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation. Methods Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis. Results In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05). Conclusions Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level. PMID:22214343

Urinary androgens and cortisol metabolites in field-sampled bonobos (Pan paniscus).

PubMed

Dittami, John; Katina, Stanislav; Möstl, Erich; Eriksson, Jonas; Machatschke, Ivo H; Hohmann, Gottfried

2008-02-01

Urinary metabolites of androgens and cortisol were measured in free-living male and female bonobos. Sex differences and correlations between adrenal and gonadal steroid excretion were investigated. The immunoreactive concentrations of androgens were measured with two different androgen assays. One assay used a testosterone (T) antibody raised with a 17beta-hydroxy group, and the other employed an antibody raised against a reduced form, 5alpha-androstane-17alpha-ol-3-one-CM (17alpha) with cross reactivity for epitestosterone and 5alpha-androstanedione. Both assays have been used in bonobo and chimpanzee studies where non-invasive techniques were employed. The levels of 17alpha-androgen metabolites were 1.7- and 3-fold higher than those of T-metabolites in males and females. The two androgen assay results correlated in males but not females. There was a sex difference in the T-metabolites measured. Male levels were significantly higher. Levels of 17alpha in the two sexes were similar. Cortisol metabolite levels (CORT) were similar between the sexes. The T-metabolites were significantly correlated with CORT in males but not in females. In females, the 17alpha-androgen metabolites correlated with CORT. This suggests that either androgen secretion or metabolism differs between the sexes. A parsimonious interpretation of the androgen assay cortisol/androgen correlation differences would be that larger components of dehydroepiandrosterone (DHEA), androstenedione or epitestosterone from the adrenal androgens were being excreted and measured in the females. The CORT/T metabolite interactions in males may reflect male-specific social or metabolic endocrine conditions.

Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Weiping, E-mail: weiping.qin@mssm.edu; Department of Medicine, Mount Sinai School of Medicine, NY; Pan, Jiangping

Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis,more » REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the gastrocnemius muscle. Regulation of FOXO1, PGC-1{alpha} and p38 MAPK by testosterone may represent a novel mechanism by which this agent protects against dexamethasone-induced muscle atrophy.« less

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia.

PubMed

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-08-04

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca(2+)-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.

Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia

PubMed Central

Cha, Joo Young; Wee, Jungwon; Jung, Jooyoung; Jang, Yongwoo; Lee, Byeongjun; Hong, Gyu-Sang; Chang, Beom Chul; Choi, Yoon-La; Shin, Young Kee; Min, Hye-Young; Lee, Ho-Young; Na, Tae-Young; Lee, Mi-Ock; Oh, Uhtaek

2015-01-01

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca2+-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker or Ano1 small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH. PMID:26153424

Serum testosterone levels in non-dosed females after secondary exposure to 1.62% testosterone gel: effects of clothing barrier on testosterone absorption.

PubMed

Stahlman, Jodi; Britto, Margaret; Fitzpatrick, Sherahe; McWhirter, Cecilia; Testino, Samuel A; Brennan, John J; Zumbrunnen, Troy L

2012-02-01

To evaluate secondary exposure of testosterone transferred to females from a male partner, dosed with 1.62% testosterone gel after direct skin-to-skin contact with the application site, and to investigate the effect of wearing a t-shirt on testosterone transfer. Across three studies, a total of 72 healthy males applied 5.0 g 1.62% testosterone gel to their abdomen alone, upper arms/shoulders alone, or a combination of their upper arms/shoulders and abdomen (single dose or once daily for 7 days). Male-female contact occurred 2 or 12 hours after testosterone gel application, with males either wearing or not wearing a t-shirt. There were 15 minutes of supervised contact with the application site between the male and his female partner. Blood samples were collected over a 24 hour period in females for assessment of serum testosterone levels at baseline and after contact. Pharmacokinetic parameters included C(max) (maximum serum concentration), AUC(0-24) (area under the serum concentration-time curve from 0-24 hours), and C(av) (time-averaged concentration over the 24-hour period post-contact). Subjects were monitored for adverse events. CLINICAL TRIAL REGISTRATION NCT NUMBERS: Study 1 was not registered (first subject enrolled 8 March 2007); Study 2: 00998933; Study 3, 01130298. Testosterone levels (C(av) and C(max)) in females increased 86-185% from baseline after direct abdominal skin contact, although C(av) levels remained within female eugonadal range. Testosterone concentrations returned to baseline within 48 hours after last skin contact. A t-shirt barrier reduced testosterone transfer by approximately 40-48% when 5.0 g of testosterone gel was applied to the abdomen alone. A t-shirt barrier prevented transfer when 5.0 g of testosterone gel was applied to the upper arms and shoulders or to a combination of the upper arms and shoulders and the abdomen (C(max) and C(av) increased by approximately 5-11%). No major safety events were observed during the studies. There is a risk of testosterone transfer from males using 1.62% testosterone gel to others who come in contact with the application site for at least 12 hours after application. Secondary exposure can be mitigated by means of a t-shirt barrier. Women for these studies were not selected by menopausal status. The study designs were intended to simulate exaggerated conditions of transfer.

Testosterone concentrations in female athletes and ballet dancers with menstrual disorders.

PubMed

Łagowska, Karolina; Kapczuk, Karina

2016-01-01

Menstrual disorders are common among female athletes and ballet dancers. Endocrine changes, such as high testosterone (HT) levels and high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios, may suggest functional ovarian hyperandrogenism which may induce such dysfunction. The aim of this study was therefore to evaluate endocrine status in female athletes and ballet dancers with menstrual disorders. Their nutritional status and dietary habits were analysed in relation to the testosterone levels. In a cross-sectional approach, 31 female athletes (18.1 ± 2.6 years) and 21 ballerinas (17.1 ± 0.9) with menstrual disorders participated in the study. The levels of serum LH, FSH, progesterone (P), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone, testosterone (T) and sex hormone-binding globulinwere measured to assess hormonal status. In addition, the free androgen index (FAI) was calculated. Nutritional status, total daily energy expenditure and nutritional habits were evaluated. Girls were assigned to one of the following groups: low testosterone (LT) level, normal testosterone level or HT level. There were significant differences between ballerinas and other female athletes in terms of testosterone levels, FAI, age at the beginning of training, length of training period and age at menarche. The PRL level was lowest in the LT group while the FAI index was highest in the HT group. Daily energy and carbohydrate intakes were significantly lower in the HT group. T levels in the study subjects were found to be associated with nutritional factors, energy availability, age at the beginning of training and frequency of training. This is the first report of HT levels being associated with the status of a female ballet dancer, the age of menarche and the length of the training history. Further research is necessary to confirm the results in a larger study group.

Circulating testosterone and inhibin levels at different ages in the male beluga (Delphinapterus leucas).

PubMed

Katsumata, Etsuko; Ueda, Yoko; Arai, Kazutoshi; Katsumata, Hiroshi; Kishimoto, Miori; Watanabe, Gen; Taya, Kazuyoshi

2012-03-01

This study is the first report on circulating testosterone and inhibin levels in a species of whales, the beluga. Circulating testosterone and immunoreactive (ir-) inhibin levels in two captive male belugas ("Nack", originally from Canada and "Duke", from the Okhotsk Sea) were measured every month for 9 years between 1995 and 2003. Assuming that clearly increased testosterone levels in the circulation indicates that the belugas had reached sexual maturity, at the ages of 10 ("Nack") and 11 years old ("Duke"). Their testosterone levels before the significant increase (pre-pubertal) were 0.42 ± 0.07 ng/ml (n=18) and 0.35 ± 0.10 ng/ml (n=18) and, those of after the increase (maturity) were 1.65 ± 0.14 ng/m l (n=74) and 2.06 ± 0.14 ng/ml (n=74). Circulating ir-inhibin levels before sexual maturity were 0.78 ± 0.04 ng/ml (n=18) and 0.64 ± 0.04 ng/ml (n=15) and, after sexual maturity were 0.52 ± 0.02 ng/ml (n=56) and 0.43 ± 0.02 ng/ml (n=67). Seasonal changes were observed in the testosterone levels after sexual maturity and the levels increased during March and April in Canadian origin "Nack", and peaked in February in Okhotsk origin "Duke". Circulating ir-inhibin level gradually decreased as they aged. A negative correlation between the circulating testosterone and ir-inhibin was observed. No seasonal changes were observed in the ir-inhibin levels after sexual maturity. These data will surely correspond to clarification of endocrinology and the successful reproduction of the beluga.

Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population.

PubMed

Gustafsson, O; Norming, U; Gustafsson, S; Eneroth, P; Aström, G; Nyman, C R

1996-03-01

To investigate the possible relationship between serum levels of prostate specific antigen (PSA), dihydrotestosterone (DHT), testosterone, sexual-hormone binding globulin (SHBG) and tumour stage, grade and ploidy in 65 cases of prostate cancer diagnosed in a screening study compared to 130 controls from the same population. From a population of 26,602 men between the ages of 55 and 70 years, 2400 were selected randomly and invited to undergo screening for prostate cancer using a digital rectal examination, transrectal ultrasonography and PSA analysis. Among the 1782 attendees, 65 cases of prostate cancer were diagnosed. Each case was matched with two control subjects of similar age and prostate volume from the screening population. Frozen serum samples were analysed for PSA, DHT, testosterone and SHBG, and compared to the diagnosis and tumour stage, grade and ploidy. Comparisons between these variables, and multivariate and regression analyses were performed. There were significant differences in PSA level with all variables except tumour ploidy. DHT levels were slightly lower in patients with prostate cancer but the difference was not statistically significant. There was a trend towards lower DHT values in more advanced tumours and the difference for T-stages was close to statistical significance (P = 0.059). Testosterone levels were lower in patients with cancer than in the control group, but the differences were not significant. There was no correlation between testosterone levels, tumour stage and ploidy, but the differences in testosterone level in tumours of a low grade of differentiation compared to those with intermediate and high grade was nearly significant (P = 0.058). The testosterone/DHT ratio tended to be higher in patients with more advanced tumours. SHBG levels were lower in patients with cancer than in controls but the differences were not statistically significant. There were no systematic variations of tumour stage, grade and ploidy. Multivariate analysis showed that if the PSA level was known, then DHT, testosterone or SHBG added no further information concerning diagnosis, stage, grade or ploidy. Regression analysis on T-stage, PSA level and DHT showed an inverse linear relationship between PSA and DHT for stage T-3 (P = 0.035), but there was no relationship between PSA and testosterone. PSA was of value in discriminating between cases and controls and between various tumour stages and grades, but no statistically significant correlation was found for ploidy. If PSA level was known, no other variable added information in individual cases. Within a group, DHT levels tended to be lower among cases and in those with more advanced tumours. There was an inverse relationship between tumour volume, as defined by PSA level, and 5 alpha-reductase activity, as defined by DHT level, and the testosterone/DHT ratio. This trend was most obvious with T-stage. No systematic variation were found in the levels of testosterone or SHBG.

A systematic review of methods for quantifying serum testosterone in patients with prostate cancer who underwent castration.

PubMed

Comas, I; Ferrer, R; Planas, J; Celma, A; Regis, L; Morote, J

2018-03-01

The clinical practice guidelines recommend measuring serum testosterone in patients with prostate cancer (PC) who undergo castration. The serum testosterone concentration should be <50ng/dL, a level established by using a radioimmunoassay method. The use of chemiluminescent immunoassays (IA) has become widespread, although their metrological characteristics do not seem appropriate for quantifying low testosterone concentrations. The objective of this review is to analyse the methods for quantifying testosterone and to establish whether there is scientific evidence that justifies measuring it in patients with PC who undergo castration, through liquid chromatography attached to a mass spectrometry in tandem (LC-MSMS). We performed a search in PubMed with the following MeSH terms: measurement, testosterone, androgen suppression and prostate cancer. We selected 12 studies that compared the metrological characteristics of various methods for quantifying serum testosterone compared with MS detection methods. IAs are standard tools for measuring testosterone levels; however, there is evidence that IAs lack accuracy and precision for quantifying low concentrations. Most chemiluminescent IAs overestimate their concentration, especially below 100ng/dL. The procedures that use LC-MSMS have an adequate lower quantification limit and proper accuracy and precision. We found no specific evidence in patients with PC who underwent castration. LC-MSMS is the appropriate method for quantifying low serum testosterone concentrations. We need to define the level of castration with this method and the optimal level related to better progression of the disease. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Circulating testosterone and prostate-specific antigen in nipple aspirate fluid and tissue are associated with breast cancer.

PubMed Central

Sauter, Edward R; Tichansky, David S; Chervoneva, Inna; Diamandis, Eleftherios P

2002-01-01

Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects who underwent surgical resection for suspected disease. Women currently using birth control pills or hormone replacement therapy were excluded from the study. Controlling for age and menopausal status, serum testosterone was significantly increased in women with breast cancer (p = 0.002). NAF and serum testosterone levels were not associated. Neither NAF nor tissue testosterone was associated with breast cancer. Controlling for menopausal status and age, NAF PSA was significantly decreased in women with breast cancer (p < 0.001). We did not find serum PSA to be associated with breast cancer, although we found an indication that, in postmenopausal women, its levels were lower in women with cancer. Serum PSA was associated with NAF PSA in postmenopausal women (p < 0.001). PSA levels in cancerous tissue were significantly lower than in benign breast specimens from subjects without cancer (p = 0.011), whereas levels of PSA in histologically benign specimens from subjects with cancer were intermediate. Our results suggest that serum testosterone is increased and NAF PSA is decreased in women with breast cancer, with PSA expression being higher in normal than in cancerous breast tissues. NAF and serum PSA levels in postmenopausal women are correlated, suggesting that as laboratory assessment of PSA becomes more sensitive, serum PSA may become useful in identifying women with breast cancer. PMID:11882474

Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer.

PubMed

Breul, Jürgen; Lundström, Eija; Purcea, Daniela; Venetz, Werner P; Cabri, Patrick; Dutailly, Pascale; Goldfischer, Evan R

2017-02-01

Androgen deprivation therapy (ADT) is a mainstay of treatment against advanced prostate cancer (PC). As a treatment goal, suppression of plasma testosterone levels to <50 ng/dl has been established over decades. Evidence is growing though that suppression to even lower levels may add further clinical benefit. Therefore, we undertook a pooled retrospective analysis on the efficacy of 1-, 3-, and 6-month sustained-release (SR) formulations of the gonadotropin-releasing hormone (GnRH) agonist triptorelin to suppress serum testosterone concentrations beyond current standards. Data of 920 male patients with PC enrolled in 9 prospective studies using testosterone serum concentrations as primary endpoint were pooled. Patients aged 42-96 years had to be eligible for ADT and to be either naïve to hormonal treatment or have undergone appropriate washout prior to enrolment. Patients were treated with triptorelin SR formulations for 2-12 months. Primary endpoints of this analysis were serum testosterone concentrations under treatment and success rates overall and per formulation, based on a testosterone target threshold of 20 ng/dl. After 1, 3, 6, 9, and 12 months of treatment, 79%, 92%, 93%, 90%, and 91% of patients reached testosterone levels <20 ng/dl, respectively. For the 1-, 3-, and 6-month formulations success rates ranged from 80-92%, from 83-93%, and from 65-97% with median (interquartile range) serum testosterone values of 2.9 (2.9-6.5), 5.0 (2.9-8.7), and 8.7 (5.8-14.1) ng/dl at study end, respectively. In the large majority of patients, triptorelin SR formulations suppressed serum testosterone concentrations to even <20 ng/dl. Testosterone should be routinely monitored in PC patients on ADT although further studies on the clinical benefit of very low testosterone levels and the target concentrations are still warranted.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

PubMed

Sayyid, Rashid K; Sayyid, Abdallah K; Klaassen, Zachary; Fadaak, Kamel; Goldberg, Hanan; Chandrasekar, Thenappan; Ahmad, Ardalanejaz; Leao, Ricardo; Perlis, Nathan; Chadwick, Karen; Hamilton, Robert J; Kulkarni, Girish S; Finelli, Antonio; Zlotta, Alexandre R; Fleshner, Neil E

2018-01-01

We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats.

PubMed

Kataoka, Tomoya; Hotta, Yuji; Maeda, Yasuhiro; Kimura, Kazunori

2017-12-01

Testosterone is believed to mediate the penile erectile response by producing adequate nitric oxide; therefore, testosterone deficiency results in erectile dysfunction through decreased nitric oxide bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone deficiency remain unclear. To investigate the mechanism of endothelial dysfunction in a rat model of testosterone deficiency. Rats were distributed into 3 groups: castrated (Cast), castrated and supplemented with testosterone (Cast + T), and sham (Sham). In the Cast + T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats received only the vehicle. Erectile function using intracavernosal pressure and mean arterial pressure measurements after electrical stimulation of the cavernous nerve, endothelial function using isometric tension, asymmetric dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and tandem mass spectrometry, and inflammatory biomarker expression were performed 4 weeks after the operation. In the Cast group, the ratio of intracavernosal pressure to mean arterial pressure significantly decreased, acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and inflammation biomarker levels were significantly increased (P < .01). Testosterone injection significantly improved each of these parameters (P < .01). The present results provide scientific evidence of the effect of testosterone deficiency on erectile function and the effect of testosterone replacement therapy. This study provides evidence of the influence of testosterone deficiency on endothelial function by investigating ADMA and oxidative stress. A major limitation of this study is the lack of a direct link of increased ADMA by oxidative stress to inflammation. Testosterone deficiency increased not only ADMA levels but also oxidative stress and inflammation in castrated rats, which can cause damage to the corpus cavernosum, resulting in erectile dysfunction. Kataoka T, Hotta Y, Maeda Y, Kimura K. Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats. J Sex Med 2017;14:1540-1548. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

ACTN3 GENOTYPE IS ASSOCIATED WITH TESTOSTERONE LEVELS OF ATHLETES

PubMed Central

Donnikov, A.E.; Trofimov, D.Y.

2014-01-01

α-Actinin-3 (ACTN3) has been proposed to regulate skeletal muscle differentiation and hypertrophy through its interaction with the signalling protein calcineurin. Since the inhibition of calcineurin potentiates the production of testosterone, we hypothesized that α-actinin-3 deficiency (predicted from the ACTN3 XX genotype) may influence serum levels of testosterone of athletes. Objective: To investigate the association of ACTN3 gene R577X polymorphism with resting testosterone levels in athletes. Methods: A total of 209 elite Russian athletes from different sports (119 males, 90 females) were genotyped for ACTN3 gene R577X polymorphism by real-time PCR. Resting testosterone was examined in serum of athletes using enzyme immunoassay. Results: The mean testosterone levels were significantly higher in both males and females with the ACTN3 R allele than in XX homozygotes (males: RR: 24.9 (5.7), RX: 21.8 (5.5), XX: 18.6 (4.9) ng · mL-1, P = 0.0071; females: RR: 1.43 (0.6), RX: 1.21 (0.71), XX: 0.79 (0.66) ng · mL-1, P = 0.0167). Conclusions: We found that the ACTN3 R allele was associated with high levels of testosterone in athletes, and this may explain, in part, the association between the ACTN3 RR genotype, skeletal muscle hypertrophy and power athlete status. PMID:24899773

Testosterone Administration Inhibits Hepcidin Transcription and is Associated with Increased Iron Incorporation into Red Blood Cells

PubMed Central

Guo, Wen; Bachman, Eric; Li, Michelle; Roy, Cindy N.; Blusztajn, Jerzy; Wong, Siu; Chan, Stephen Y.; Serra, Carlo; Jasuja, Ravi; Travison, Thomas G.; Muckenthaler, Martina U.; Nemeth, Elizabeta; Bhasin, Shalender

2013-01-01

Testosterone administration increases hemoglobin levels and has been used to treat anemia of chronic disease. Erythrocytosis is the most frequent adverse event associated with testosterone therapy of hypogonadal men, especially older men. However, the mechanisms by which testosterone increases hemoglobin remain unknown. Testosterone administration in male and female mice was associated with a greater increase in hemoglobin and hematocrit, reticulocyte count, reticulocyte hemoglobin concentration, and serum iron and transferring saturation than placebo. Testosterone downregulated hepatic hepcidin mRNA expression, upregulated renal erythropoietin mRNA expression, and increased erythropoietin levels. Testosterone-induced suppression of hepcidin expression was independent of its effects on erythropoietin or hypoxia-sensing mechanisms. Transgenic mice with liver-specific constitutive hepcidin over-expression failed to exhibit the expected increase in hemoglobin in response to testosterone administration. Testosterone upregulated splenic ferroportin expression and reduced iron retention in spleen. After intravenous administration of transferrin-bound 58Fe, the amount of 58Fe incorporated into red blood cells was significantly greater in testosterone-treated mice than in placebo-treated mice. Serum from testosterone-treated mice stimulated hemoglobin synthesis in K562 erythroleukemia cells more than that from vehicle-treated mice. Testosterone administration promoted the association of androgen receptor (AR) with Smad1 and Smad4 to reduce their binding to BMP-response elements in hepcidin promoter in the liver. Ectopic expression of AR in hepatocytes suppressed hepcidin transcription; this effect was blocked dose-dependently by AR antagonist flutamide. Testosterone did not affect hepcidin mRNA stability. Conclusion: Testosterone inhibits hepcidin transcription through its interaction with BMP-Smad signaling. Testosterone administration is associated with increased iron incorporation into red blood cells. PMID:23399021

Effect of Testosterone Administration on Liver Fat in Older Men With Mobility Limitation: Results From a Randomized Controlled Trial

PubMed Central

2013-01-01

Background. Androgen receptor (AR) knockout male mice display hepatic steatosis, suggesting that AR signaling may regulate hepatic fat. However, the effects of testosterone replacement on hepatic fat in men are unknown. The aim of this study was to determine the effects of testosterone administration on hepatic fat in older men with mobility limitation and low testosterone levels who were participating in a randomized trial (the Testosterone in Older Men trial). Methods. Two hundred and nine men with mobility limitation and low total or free testosterone were randomized in the parent trial to either placebo or 10-g testosterone gel daily for 6 months. Hepatic fat was determined by magnetic resonance imaging in 73 men (36 in placebo and 37 in testosterone group) using the volumetric method. Insulin sensitivity (homeostatic model assessment–insulin resistance) was derived from fasting glucose and insulin. Results. Baseline characteristics were similar between the two groups, including liver volumes (1583±363 in the testosterone group vs 1522±271mL in the placebo group, p = .42). Testosterone concentrations increased from 250±72 to 632±363ng/dL in testosterone group but did not change in placebo group. Changes in liver volume during intervention did not differ significantly between groups (p = .5) and were not related to on-treatment testosterone concentrations. The change in homeostatic model assessment–insulin resistance also did not differ significantly between groups and was not related to either baseline or change in liver fat. Conclusion. Testosterone administration in older men with mobility limitation and low testosterone levels was not associated with a reduction in hepatic fat. Larger trials are needed to determine whether testosterone replacement improves liver fat in men with nonalcoholic hepatic steatosis. PMID:23292288

Association between serum total testosterone and Body Mass Index in middle aged healthy men

PubMed Central

Shamim, Muhammad Omar; Ali Khan, Farooq Munfaet; Arshad, Rabia

2015-01-01

Objective: To determine correlation of serum total testosterone with body mass index (BMI) and waist hip ratio (WHR) in healthy adult males. Methods: A cross sectional study was conducted on 200 nonsmoker healthy males (aged 30-50 years) university employees. They were selected by convenience sampling technique after a detailed medical history and clinical examination including BMI and Waist Hip Ratio (WHR) calculation. Blood sampling was carried out to measure serum total testosterone (TT) using facilities of Chemiluminescence assay (CLIA) technique in Dow Chemical Laboratory. Independent sample T test was used for mean comparisons of BMI and WHR in between low and normal testosterone groups. (Subjects having < 9.7 nmol/L of total testosterone in blood were placed in low testosterone group and subjects having ≥ 9.7 nmol/L of total testosterone in blood were placed in normal testosterone group). Correlation of testosterone with BMI and WHR was analyzed by Pearson Correlation. Results: Mean (± SD) age of the subjects included in this study was 38.7 (± 6.563) years mean (± SD) total testosterone was 15.92 (±6.322)nmol/L. The mean (± SD) BMI, and WHR were 24.95 (±3.828) kg/m2 and 0.946 (±0.0474) respectively. Statistically significant differences were observed in the mean values of BMI and WHR for the two groups of testosterone. Significant inverse correlation of serum total testosterone with BMI(r = -0.311, p = 0.000) was recorded in this study. However testosterone was not significantly correlated with waist/hip ratio.(r = -0.126, p = 0.076) Conclusion: Middle age men working at DUHS who have low level of serum total testosterone are more obese than individuals with normal total testosterone level. PMID:26101490

High-testosterone men reject low ultimatum game offers.

PubMed

Burnham, Terence C

2007-09-22

The ultimatum game is a simple negotiation with the interesting property that people frequently reject offers of 'free' money. These rejections contradict the standard view of economic rationality. This divergence between economic theory and human behaviour is important and has no broadly accepted cause. This study examines the relationship between ultimatum game rejections and testosterone. In a variety of species, testosterone is associated with male seeking dominance. If low ultimatum game offers are interpreted as challenges, then high-testosterone men may be more likely to reject such offers. In this experiment, men who reject low offers ($5 out of $40) have significantly higher testosterone levels than those who accept. In addition, high testosterone levels are associated with higher ultimatum game offers, but this second finding is not statistically significant.

Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components.

PubMed

Barone, Rosario; Pitruzzella, Alessandro; Marino Gammazza, Antonella; Rappa, Francesca; Salerno, Monica; Barone, Fulvio; Sangiorgi, Claudia; D'Amico, Daniela; Locorotondo, Nicola; Di Gaudio, Francesca; Cipolloni, Luigi; Di Felice, Valentina; Schiavone, Stefania; Rapisarda, Venerando; Sani, Gabriele; Tambo, Amos; Cappello, Francesco; Turillazzi, Emanuela; Pomara, Cristoforo

2017-08-01

The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography-mass spectrometry. Western blot analysis and quantitative real-time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression levels of the blood-testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein-1 (TJP1). ND stimulation deregulated metalloproteinase-9, metalloproteinase-2 (MMP-2) and the tissue inhibitor of MMP-2. Moreover, ND administration resulted in a mislocalization of mucin-1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP-2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The Effects of Fetal Gender on Serum Human Chorionic Gonadotropin and Testosterone in Normotensive and Preeclamptic Pregnancies

PubMed Central

Lorzadeh, Nahid; Kazemirad, Sirous

2012-01-01

Introduction. The aim of the present study was to evaluate the effects of fetal sex on serum human chorionic gonadotropin (hCG) and testosterone in normotensive and preeclamptic pregnancies. Materials and Methods. This is a cross-sectional study and 139 women with singleton pregnancies in the third trimester were studied. Seventy-one pregnancies were uncomplicated; among those were 35 male and 36 female fetuses. Sixty-eight pregnancies were complicated by preeclampsia; among those were 35 male and 33 female fetuses. Human chorionic gonadotropin and total testosterone were measured in maternal peripheral blood. Data analyzed by SPSS software. Results. In male-bearing pregnancies, maternal hCG and testosterone serum levels were significantly higher in preeclamptic than normotensive mothers (P < 0.001 and P < 0.001, resp.) in female-bearing pregnancies testosterone levels were significantly higher in preeclamptic than normotensive mothers (P < 0.001). Total testosterone levels were significantly higher in pregnancies with either gender and significantly higher in mlae-bearing than in female-bearing pregnancies. Conclusion. According to our results, there is a correlation between maternal serum hCG and testosterone levels and preeclampsia. Therefore these tests can be used as routine during 30–38 weeks of gestation. High maternal serum concentrations of these markers can predict preeclampsia. PMID:22518314

Salivary Testosterone Levels Under Psychological Stress and Its Relationship with Rumination and Five Personality Traits in Medical Students

PubMed Central

Afrisham, Reza; Sadegh-Nejadi, Sahar; SoliemaniFar, Omid; Kooti, Wesam; Ashtary-Larky, Damoon; Alamiri, Fatima; Najjar-Asl, Sedigheh; Khaneh-Keshi, Ali

2016-01-01

Objective The purpose of this study was to evaluate the salivary testosterone levels under psychological stress and its relationship with rumination and five personality traits in medical students. Methods A total of 58 medical students, who wanted to participate in the final exam, were selected by simple random sampling. Two months before the exam, in the basal conditions, the NEO Inventory short form, and the Emotional Control Questionnaire (ECQ) were completed. Saliva samples were taken from students in both the basal conditions and under exam stress. Salivary testosterone was measured by ELISA. Data was analyzed using multivariate analysis of variance with repeated measures, paired samples t-test, Pearson correlation and stepwise regression analysis. Results Salivary testosterone level of men showed a significant increase under exam stress (p<0.05). However, a non-significant although substantial reduction observed in women. A significant correlation was found between extroversion (r=-0.33) and openness to experience (r=0.30) with salivary testosterone (p<0.05). Extraversion, aggression control and emotional inhibition predicted 28% of variance of salivary testosterone under stress. Conclusion Salivary testosterone reactivity to stress can be determined by sexual differences, personality traits, and emotional control variables which may decrease or increase stress effects on biological responses, especially the salivary testosterone. PMID:27909455

Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response.

PubMed

White, Hillary D; Brown, Lin A J; Gyurik, Robert J; Manganiello, Paul D; Robinson, Thomas D; Hallock, Linda S; Lewis, Lionel D; Yeo, Kiang-Teck J

2015-08-01

To test our hypothesis that testosterone deficiency plays an important role in chronic pain, a Phase I/II pilot study was initiated with 12 fibromyalgia patients to verify that a daily dose for 28days with transdermal testosterone gel would 1) significantly and safely increase mean serum testosterone concentrations from low baseline levels to mid/high-normal levels, and 2) effectively treat the pain and fatigue symptoms of fibromyalgia. Pharmacokinetic data confirmed that serum free testosterone concentrations were raised significantly above baseline levels, by assessment of maximum hormone concentration (Cmax) and area under the curve (AUC) parameters: free testosterone Cmax was significantly raised from a mean of 2.64pg/mL to 3.91pg/mL (p<0.05), and 24hour free testosterone AUC was significantly raised from a mean of 35.0pg-hr/mL to 53.89pg-hr/mL. Assessment of the typical symptoms of fibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment. These results are consistent with the hypothesized ability of testosterone to relieve the symptoms of fibromyalgia. Symptoms not tightly related to fibromyalgia were not improved. Copyright © 2015. Published by Elsevier B.V.

Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway.

PubMed

Zhao, Jing; Liu, Ge-Li; Wei, Ying; Jiang, Li-Hong; Bao, Peng-Li; Yang, Qing-Yan

2016-09-01

The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high‑fat‑diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3‑kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate‑1 (IRS‑1), glucose transporter type 4 (GLUT‑4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high‑fat‑diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high‑dose testosterone treatment. Low‑dose testosterone induced upregulation in the levels of IRS‑1, AKT, GLUT‑4 protein, NF‑κB, TNF‑α and PI3K, compared with those in the animals fed a high‑fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT, GLUT‑4, NF‑κB, TNF‑α and PI3K. Compared with the rats in the high‑fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS‑1, AKT and GLUT‑4, and downregulation of the mRNA levels of NF‑κB, TNF‑α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT and GLUT‑4, and marked increases in the mRNA levels of NF‑κB, TNF‑α and PI3K, compared with the low dose group. Castration induced marked disorders of glucolipid metabolism and vascular injuries in the pubescent male rats. Low‑dose testosterone treatment was found to ameliorate the vascular damage caused by castration via the PI3K/AKT signaling pathway.

Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep.

PubMed

Veiga-Lopez, Almudena; Steckler, Teresa L; Abbott, David H; Welch, Kathleen B; MohanKumar, Puliyur S; Phillips, David J; Refsal, Kent; Padmanabhan, Vasantha

2011-01-01

Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ~147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64-66, 87-90, and 139-140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep.

Developmental Programming: Impact of Excess Prenatal Testosterone on Intrauterine Fetal Endocrine Milieu and Growth in Sheep1

PubMed Central

Veiga-Lopez, Almudena; Steckler, Teresa L.; Abbott, David H.; Welch, Kathleen B.; MohanKumar, Puliyur S.; Phillips, David J.; Refsal, Kent; Padmanabhan, Vasantha

2010-01-01

Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ∼147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64–66, 87–90, and 139–140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep. PMID:20739662

Consequences of elevating plasma testosterone in females of a socially monogamous songbird: evidence of constraints on male evolution?

PubMed

Clotfelter, Ethan D; O'Neal, Dawn M; Gaudioso, Jacqueline M; Casto, Joseph M; Parker-Renga, Ian M; Snajdr, Eric A; Duffy, Deborah L; Nolan, Val; Ketterson, Ellen D

2004-08-01

To explore whether selection for testosterone-mediated traits in males might be constrained by costs of higher testosterone to females, we examined the effects of experimental elevation of plasma testosterone on physiological, reproductive, and behavioral parameters in a female songbird, the dark-eyed junco (Junco hyemalis). We used subcutaneous implants to elevate testosterone (T) in captive and free-living female juncos. In captive birds, we measured the effects of high T on body mass, feather molt, and brood patch formation. In the field, we monitored its effects on the timing of egg laying, clutch size, egg size, egg steroid levels, incubation, and nest-defense behavior. Females implanted with testosterone (T-females) had significantly higher circulating levels of testosterone than did control females (C-females). Captive T-females had lower body mass, were less likely to develop brood patches, and delayed feather molt relative to C-females. Among free-living females, the interval between nest completion and appearance of the first egg was longer for T-females than for C-females and egg yolk concentrations of testosterone were higher, but there were no significant differences in estradiol levels, clutch size, or egg size. Incubation and nest defense behavior were also similar between T- and C-females. Our results suggest that selection on males for higher testosterone might initially lead to a correlated response in females producing changes in body mass and feather molt, both of which could be detrimental. Other possible female responses would be delayed onset of reproduction, which might reduce reproductive success, and higher yolk testosterone, which might have either positive or negative effects on offspring development. We found no reason to expect reduced parental behavior by females as a negative fitness consequence of selection for higher testosterone in males.

Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism

PubMed Central

Reimers, Luise; Diekhof, Esther K.

2015-01-01

The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner's dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject's own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism. PMID:26124701

Testosterone is associated with cooperation during intergroup competition by enhancing parochial altruism.

PubMed

Reimers, Luise; Diekhof, Esther K

2015-01-01

The steroid hormone testosterone is widely associated with negative behavioral effects, such as aggression or dominance. However, recent studies applying economic exchange tasks revealed conflicting results. While some point to a prosocial effect of testosterone by increasing altruistic behavior, others report that testosterone promotes antisocial tendencies. Taking into account additional factors such as parochial altruism (i.e., ingroup favoritism and outgroup hostility) might help to explain this contradiction. First evidence for a link between testosterone and parochial altruism comes from recently reported data of male soccer fans playing the ultimatum game. In this study high levels of endogenous testosterone predicted increased altruistic punishment during outgroup interactions and at the same time heightened ingroup generosity. Here, we report findings of another experimental task, the prisoner's dilemma, applied in the same context to examine the role of testosterone on parochial tendencies in terms of cooperation. In this task, 50 male soccer fans were asked to decide whether or not they wanted to cooperate with partners marked as either fans of the subject's own favorite team (ingroup) or fans of other teams (outgroups). Our results show that high testosterone levels were associated with increased ingroup cooperation during intergroup competition. In addition, subjects displaying a high degree of parochialism during intergroup competition had significantly higher levels of testosterone than subjects who did not differentiate much between the different groups. In sum, the present data demonstrate that the behavioral effects of testosterone are not limited to aggressive and selfish tendencies but may imply prosocial aspects depending on the context. By this means, our results support the previously reported findings on testosterone-dependent intergroup bias and indicate that this social hormone might be an important factor driving parochial altruism.

Testosterone, territoriality, and the 'home advantage'.

PubMed

Neave, Nick; Wolfson, Sandy

2003-02-01

The consistently better performance seen by teams in various sporting contexts when playing at home is referred to as the 'home advantage'. Various explanations have been put forward to account for this robust phenomenon, though none has yet focussed on possible hormonal factors. In an initial study, we showed that salivary testosterone levels in soccer players were significantly higher before a home game than an away game.In a second study involving a different group of soccer players, this finding was replicated over two home games, two away games, and three training sessions. Perceived rivalry of the opposing team was important as testosterone levels were higher before playing an 'extreme' rival than a 'moderate' rival. Self-reported measures of mood in both studies were not linked to testosterone level. The present results corroborate and extend earlier findings on the relationships between testosterone, territoriality, and dominance in human competitive encounters and further suggest an important role for testosterone in the home advantage seen in various team sports.

Analysis of seminal plasma from brown bear (Ursus arctos) during the breeding season: Its relationship with testosterone levels.

PubMed

Anel-López, L; Ortega-Ferrusola, C; Martínez-Rodríguez, C; Álvarez, M; Borragán, S; Chamorro, C; Peña, F J; Anel, L; de Paz, P

2017-01-01

Seminal plasma (SP) plays an important role in the motility, viability and maintenance of the fertilizing capacity of mammalian spermatozoa. This study is the first on brown bear (Ursus arctos) SP components, and has two main objectives: 1) to define the SP composition in bear ejaculate and 2) to identify variations in SP composition in relation to high and low levels of testosterone in serum during the breeding season. Forty-eight sperm samples from 30 sexually mature male brown bears (Ursus arctos) were obtained by electroejaculation, and their serum testosterone levels were assessed to sort the animals into 2 groups (high and low testosterone levels, threshold 5 ng/dl). The biochemical and protein compositions of the SP samples were assessed, and sperm motility was analyzed. We found that lactate dehydrogenase was significantly higher in the low-serum-testosterone samples, while concentrations of lipase and Mg+ values were significantly higher in the high-serum-testosterone samples. In contrast, sperm motility did not significantly differ (P>0.05) between the testosterone level groups (total motility: 74.42.8% in the high-level group vs. 77.1±4.7% in the low-level group). A reference digital model was constructed since there is no information for this wild species. To do this, all gel images were added in a binary multidimensional image and thirty-three spots were identified as the most-repeated spots. An analysis of these proteins was done by qualitative equivalency (isoelectric point and molecular weight) with published data for a bull. SP protein composition was compared between bears with high and low serum testosterone, and three proteins (binder of sperm and two enzymes not identified in the reference bull) showed significant (P<0.05) quantitative differences. We conclude that male bears with high or low serum testosterone levels differs only in some properties of their SP, differences in enzyme LDIP2, energy source LACT2, one protein (similar to BSP1) and Mg ion were identified between these two groups. These data may inform the application of SP to improve bear semen extenders.

Pharmacological effects of saw palmetto extract in the lower urinary tract

PubMed Central

Suzuki, Mayumi; Ito, Yoshihiko; Fujino, Tomomi; Abe, Masayuki; Umegaki, Keizo; Onoue, Satomi; Noguchi, Hiroshi; Yamada, Shizuo

2009-01-01

Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic remedy for urinary dysfunction due to benign prostatic hyperplasia (BPH) in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5α-reductase. Today, α1-adrenoceptor antagonists and muscarinic cholinoceptor antagonists are commonly used in the treatment of men with voiding symptoms secondary to BPH. The improvement of voiding symptoms in patients taking SPE may arise from its binding to pharmacologically relevant receptors in the lower urinary tract, such as α1-adrenoceptors, muscarinic cholinoceptors, 1,4-dihyropyridine receptors and vanilloid receptors. Furthermore, oral administration of SPE has been shown to attenuate the up-regulation of α1-adrenoceptors in the rat prostate induced by testosterone. Thus, SPE at clinically relevant doses may exert a direct effect on the pharmacological receptors in the lower urinary tract, thereby improving urinary dysfunction in patients with BPH and an overactive bladder. SPE does not have interactions with co-administered drugs or serious adverse events in blood biochemical parameters, suggestive of its relative safety, even with long-term intake. Clinical trials (placebo-controlled and active-controlled trials) of SPE conducted in men with BPH were also reviewed. This review should contribute to the understanding of the pharmacological effects of SPE in the treatment of patients with BPH and associated lower urinary tract symptoms (LUTS). PMID:19262550

Pharmacological effects of saw palmetto extract in the lower urinary tract.

PubMed

Suzuki, Mayumi; Ito, Yoshihiko; Fujino, Tomomi; Abe, Masayuki; Umegaki, Keizo; Onoue, Satomi; Noguchi, Hiroshi; Yamada, Shizuo

2009-03-01

Saw palmetto extract (SPE), an extract from the ripe berries of the American dwarf palm, has been widely used as a therapeutic remedy for urinary dysfunction due to benign prostatic hyperplasia (BPH) in Europe. Numerous mechanisms of action have been proposed for SPE, including the inhibition of 5alpha-reductase. Today, alpha(1)-adrenoceptor antagonists and muscarinic cholinoceptor antagonists are commonly used in the treatment of men with voiding symptoms secondary to BPH. The improvement of voiding symptoms in patients taking SPE may arise from its binding to pharmacologically relevant receptors in the lower urinary tract, such as alpha(1)-adrenoceptors, muscarinic cholinoceptors, 1,4-dihyropyridine receptors and vanilloid receptors. Furthermore, oral administration of SPE has been shown to attenuate the up-regulation of alpha(1)-adrenoceptors in the rat prostate induced by testosterone. Thus, SPE at clinically relevant doses may exert a direct effect on the pharmacological receptors in the lower urinary tract, thereby improving urinary dysfunction in patients with BPH and an overactive bladder. SPE does not have interactions with co-administered drugs or serious adverse events in blood biochemical parameters, suggestive of its relative safety, even with long-term intake. Clinical trials (placebo-controlled and active-controlled trials) of SPE conducted in men with BPH were also reviewed. This review should contribute to the understanding of the pharmacological effects of SPE in the treatment of patients with BPH and associated lower urinary tract symptoms (LUTS).

Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function: a Systematic Review of Human Evidence.

PubMed

Høyer, Birgit Bjerre; Lenters, Virissa; Giwercman, Aleksander; Jönsson, Bo A G; Toft, Gunnar; Hougaard, Karin S; Bonde, Jens Peter E; Specht, Ina Olmer

2018-03-01

The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.

Triptorelin embonate (6-month formulation).

PubMed

Keating, Gillian M

2010-02-12

A 6-month formulation of the gonadotropin-releasing hormone agonist triptorelin embonate (designed to deliver 22.5 mg of triptorelin over a 6-month period) has been developed for use in the treatment of advanced prostate cancer. Following intramuscular administration of the 6-month formulation of triptorelin embonate 22.5 mg to men with advanced prostate cancer (subset of 15 patients from the pivotal clinical trial), serum testosterone levels initially increased, followed by a rapid, sustained decrease. Castrate serum testosterone levels (i.e. < or =1.735 nmol/L) were achieved in a geometric mean time of 18.8 days. The 6-month formulation of triptorelin embonate achieved and maintained castrate serum testosterone levels in patients with advanced prostate cancer (n = 120), according to the results of the pivotal, noncomparative, multicentre trial (patients received intramuscular triptorelin embonate 22.5 mg on day 1 and at month 6 [week 24]). By day 29, 97.5% of patients had castrate serum testosterone levels. Castrate serum testosterone levels were maintained from months 2 to 12 in 93.0% of patients. Prior to the second injection at month 6, 98.3% of patients had castrate serum testosterone levels, and 98.3% of patients had castrate serum testosterone levels at study completion. The 6-month formulation of triptorelin embonate 22.5 mg was generally well tolerated in patients with advanced prostate cancer; adverse events were of mild severity in the majority of patients. Drug-related adverse events (e.g. hot flushes) were consistent with the pharmacological action of triptorelin. Injection-site reactions occurred in 6.7% of triptorelin embonate recipients.

Age related testosterone level changes and male andropause syndrome.

PubMed

Wu, C Y; Yu, T J; Chen, M J

2000-06-01

Much like the menopause syndrome occurring among older women, a similar condition has been defined among men. Testosterone production increases rapidly at the onset of puberty, then dwindles quickly after age 50 to become 20 to 50% of the peak level by age 80. Many men older than age 50 have experienced frailty syndrome, which includes decrease of libido, easy fatigue, mood disturbance, accelerated osteoporosis, and decreased muscle strength. We investigated serum total testosterone levels and andropause syndrome in men. Serum total testosterone levels were measured in 53 symptomatic men older than age 50 and in 48 men younger than age 40 for a control group. We also analyzed andropause symptoms among the 53 men older than age 50. The mean serum total testosterone level in the symptomatic men older than age 50 (mean: 2.68 +/- 0.51 ng/ml, range: 1.21 to 4.13 ng/ml) was significantly lower than that in the control group (mean: 7.01 +/- 0.82 ng/ml, range: 5.53 ng/ml to 8.14 ng/ml). Male frailty syndrome in these men older than 50 included: decreased libido (91%), lack of energy (89%), erection problems (79%), falling asleep after dinner (77%), memory impairment (77%), loss of pubic hair (70%), sad or grumpy mood changes (68%), decrease in endurance (66%), loss of axillary hair (55%), and deterioration in work performance (51%). The serum total testosterone level showed a decline with aging, especially in the men older than age 50. Low serum testosterone levels were also associated with the symptoms of male andropause syndrome.

Testosterone during Pregnancy and Gender Role Behavior of Preschool Children: A Longitudinal, Population Study.

ERIC Educational Resources Information Center

Hines, Melissa; Golombok, Susan; Rust, John; Johnston, Katie J.; Golding, Jean

2002-01-01

Related blood levels of testosterone and sex hormone-binding globulin in pregnant women to gender role behavior among 342 male and 337 female offspring at 3.5 years. Found that testosterone levels related linearly to girls' gender role behavior. Neither hormone related to boys' gender role behavior. Other factors, including older brothers or…

Blood Test: Testosterone

MedlinePlus

... test measures the blood level of the male sex hormone testosterone. Testosterone, which plays an important role in sexual development, is produced mainly by the testes in boys and in much smaller amounts by the ovaries ...

Testosterone and Child and Adolescent Adjustment: The Moderating Role of Parent-Child Relationships.

ERIC Educational Resources Information Center

Booth, Alan; Johnson, David R.; Granger, Douglas A.; Crouter, Ann C.; McHale, Susan

2003-01-01

In a sample of families with 6- to 18-year-olds, this study found that sons' and daughters' testosterone levels showed little direct connection to risk behavior or depressive symptoms. As parent-child relationship quality increased, testosterone-related adjustment problems were less evident. When relationship quality decreased, testosterone-linked…

Testosterone treatment and the risk of aggressive prostate cancer in men with low testosterone levels.

PubMed

Walsh, Thomas J; Shores, Molly M; Krakauer, Chloe A; Forsberg, Christopher W; Fox, Alexandra E; Moore, Kathryn P; Korpak, Anna; Heckbert, Susan R; Zeliadt, Steven B; Kinsey, Chloe E; Thompson, Mary Lou; Smith, Nicholas L; Matsumoto, Alvin M

2018-01-01

Testosterone treatment of men with low testosterone is common and, although relatively short-term, has raised concern regarding an increased risk of prostate cancer (CaP). We investigated the association between modest-duration testosterone treatment and incident aggressive CaP. Retrospective inception cohort study of male Veterans aged 40 to 89 years with a laboratory-defined low testosterone measurement from 2002 to 2011 and recent prostate specific antigen (PSA) testing; excluding those with recent testosterone treatment, prostate or breast cancer, high PSA or prior prostate biopsy. Histologically-confirmed incident aggressive prostate cancer or any prostate cancer were the primary and secondary outcomes, respectively. Of the 147,593 men included, 58,617 were treated with testosterone. 313 aggressive CaPs were diagnosed, 190 among untreated men (incidence rate (IR) 0.57 per 1000 person years, 95% CI 0.49-0.65) and 123 among treated men (IR 0.58 per 1000 person years; 95% CI 0.48-0.69). After adjusting for age, race, hospitalization during year prior to cohort entry, geography, BMI, medical comorbidities, repeated testosterone and PSA testing, testosterone treatment was not associated with incident aggressive CaP (HR 0.89; 95% CI 0.70-1.13) or any CaP (HR 0.90; 95% CI 0.81-1.01). No association between cumulative testosterone dose or formulation and CaP was observed. Among men with low testosterone levels and normal PSA, testosterone treatment was not associated with an increased risk of aggressive or any CaP. The clinical risks and benefits of testosterone treatment can only be fully addressed by large, longer-term randomized controlled trials.

Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by orchidectomy and testosterone replacement.

PubMed

Ibebunjo, Chikwendu; Eash, John K; Li, Christine; Ma, QiCheng; Glass, David J

2011-02-01

Declines in skeletal muscle size and strength, often seen with chronic wasting diseases, prolonged or high-dose glucocorticoid therapy, and the natural aging process in mammals, are usually associated with reduced physical activity and testosterone levels. However, it is not clear whether the decline in testosterone and activity are causally related. Using a mouse model, we found that removal of endogenous testosterone by orchidectomy results in an almost complete cessation in voluntary wheel running but only a small decline in muscle mass. Testosterone replacement restored running behavior and muscle mass to normal levels. Orchidectomy also suppressed the IGF-I/Akt pathway, activated the atrophy-inducing E3 ligases MuRF1 and MAFBx, and suppressed several energy metabolism pathways, and all of these effects were reversed by testosterone replacement. The study also delineated a distinct, previously unidentified set of genes that is inversely regulated by orchidectomy and testosterone treatment. These data demonstrate the necessity of testosterone for both speed and endurance of voluntary wheel running in mice and suggest a potential mechanism for declined activity in humans where androgens are deficient.

High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

PubMed

Liu, Tao; Cui, Yu-qian; Zhao, Han; Liu, Hong-bin; Zhao, Shi-dou; Gao, Yuan; Mu, Xiao-li; Gao, Fei; Chen, Zi-jiang

2015-10-01

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

Free testosterone as marker of adaptation to medium-intensive exercise.

PubMed

Shkurnikov, M U; Donnikov, A E; Akimov, E B; Sakharov, D A; Tonevitsky, A G

2008-09-01

A 4-week study of adaptation reserves of the body was carried out during medium intensive exercise (medium intensive training: 60-80% threshold anaerobic metabolism). Two groups of athletes were singled out by the results of pulsometry analysis: with less than 20% work duration at the level above the 80% threshold anaerobic metabolism and with more than 20% work duration at the level above 80% threshold anaerobic metabolism. No appreciable differences between the concentrations of total testosterone, growth hormone, and cortisol before and after exercise in the groups with different percentage of anaerobic work duration were detected. In group 1 the concentrations of free testosterone did not change throughout the period of observation in comparison with the levels before training. In group 2, the level of free testosterone increased in comparison with the basal level: from 0.61+/-0.12 nmol/liter at the end of week 1 to 0.98+/-0.11 nmol/liter at the end of week 4 (p<0.01). The results indicate that the level of free testosterone can be used for evaluating the degree of athlete's adaptation to medium intensive exercise.

Homocysteine induced cardiovascular events: a consequence of long term anabolic‐androgenic steroid (AAS) abuse

PubMed Central

Graham, M R; Grace, F M; Boobier, W; Hullin, D; Kicman, A; Cowan, D; Davies, B; Baker, J S

2006-01-01

Objectives The long term effects (>20 years) of anabolic‐androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self‐prescribing bodybuilders. Methods Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non‐drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10). Results HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = −0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels. Conclusions With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events. PMID:16488899

Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China.

PubMed

Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

2006-11-01

Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.

Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

PubMed Central

Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken

2006-01-01

Background Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Objective Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. Methods We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Results Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). Conclusion We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers. PMID:17107847

Decision-making, financial risk aversion, and behavioral biases: The role of testosterone and stress.

PubMed

Nofsinger, John R; Patterson, Fernando M; Shank, Corey A

2018-05-01

We examine the relation between testosterone, cortisol, and financial decisions in a sample of naïve investors. We find that testosterone level is positively related to excess risk-taking, whereas cortisol level is negatively related to excess risk-taking (correlation coefficient [r]: 0.75 and -0.21, respectively). Additionally, we find support for the dual-hormone hypothesis in a financial context. Specifically, the testosterone-to-cortisol ratio is significantly related to loss aversion. Individuals with a higher ratio are 3.4 times more likely to sell losing stocks (standard error [SE]: 1.63). Furthermore, we find a positive feedback loop between financial success, testosterone, and cortisol. Specifically, financial success is significantly related to higher post-trial testosterone and cortisol by a factor of 0.53 (SE: 0.14). Finally, we find that in a competitive environment, testosterone level increases significantly, leading to greater risk-taking than in noncompetitive environment. Overall, this study underscores the importance of the endocrine system on financial decision-making. The results of this study are relevant to a broad audience, including investors looking to optimize financial performance, industry human resources, market regulators, and researchers. Copyright © 2018 Elsevier B.V. All rights reserved.

Towards more physiological manipulations of hormones in field studies: comparing the release dynamics of three kinds of testosterone implants, silastic tubing, time-release pellets and beeswax.

PubMed

Quispe, Rene; Trappschuh, Monika; Gahr, Manfred; Goymann, Wolfgang

2015-02-01

Hormone manipulations are of increasing interest in the areas of physiological ecology and evolution, because hormones are mediators of complex phenotypic changes. Often, however, hormone manipulations in field settings follow the approaches that have been used in classical endocrinology, potentially using supra-physiological doses. To answer ecological and evolutionary questions, it may be important to manipulate hormones within their physiological range. We compare the release dynamics of three kinds of implants, silastic tubing, time-release pellets, and beeswax pellets, each containing 3mg of testosterone. These implants were placed into female Japanese quail, and plasma levels of testosterone measured over a period of 30 days. Testosterone in silastic tubing led to supraphysiological levels. Also, testosterone concentrations were highly variable between individuals. Time-release pellets led to levels of testosterone that were slightly supraphysiological during the first days. Over the period of 30 days, however, testosterone concentrations were more consistent. Beeswax implants led to a physiological increase in testosterone and a relatively constant release. The study demonstrated that hormone implants in 10mm silastic tubing led to a supraphysiological peak in female quail. Thus, the use of similar-sized or even larger silastic implants in males or in other smaller vertebrates needs careful assessment. Time-release pellets and beeswax implants provide a more controlled release and degrade within the body. Thus, it is not necessary to recapture the animal to remove the implant. We propose beeswax implants as an appropriate procedure to manipulate testosterone levels within the physiological range. Hence, such implants may be an effective alternative for field studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Testosterone Treatment on Adipokines and Gut Hormones in Obese Men on a Hypocaloric Diet.

PubMed

Ng Tang Fui, Mark; Hoermann, Rudolf; Grossmann, Mathis

2017-04-01

In obese men with lowered testosterone levels, testosterone treatment augments diet-associated loss of body fat. We hypothesized that testosterone treatment modulates circulating concentrations of hormonal mediators of fat mass and energy homeostasis in obese men undergoing a weight loss program. Prespecified secondary analysis of a randomized, double-blind, placebo-controlled trial. Tertiary referral center. Obese men (body mass index ≥30 kg/m 2 ) with a repeated total testosterone level ≤12 nmol/L. One hundred participants mean age 53 years (interquartile range 47 to 60 years) receiving 10 weeks of a very low-energy diet followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (cases, n = 49) or matching placebo (controls, n = 51). Eighty-two men completed the study. Between-group differences in leptin, adiponectin, ghrelin, glucagon like peptide-1, gastric inhibitory polypeptide, peptide YY, pancreatic polypeptide, and amylin levels. At study end, compared with controls, cases had greater reductions in leptin [mean adjusted difference (MAD), -3.6 ng/mL (95% CI, -5.3 to -1.9); P < 0.001]. The change in leptin levels between cases and controls was dependent on baseline fat mass, as the between-group difference progressively increased with increasing fat mass [MAD, -0.26 ng/mL (95% CI, -0.31 to -0.26); P = 0.001 per 1 kg of baseline fat mass]. Weight loss-associated changes in other hormones persisted during the weight maintenance phase but were not modified by testosterone treatment. Testosterone treatment led to reductions in leptin beyond those achieved by diet-associated weight loss. Testosterone treatment may reduce leptin resistance in obese men.

Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study

PubMed Central

Glaser, RL; Dimitrakakis, C; Messenger, AG

2012-01-01

Background Androgens are thought to have an adverse effect on female scalp hair growth. However, our clinical experience of androgen replacement therapy in women with androgen deficiency, in which hair loss was seldom reported, led us to question this concept. Objectives To evaluate the effect of subcutaneous testosterone therapy on scalp hair growth in female patients. Methods A total of 285 women, treated for a minimum of 1 year with subcutaneous testosterone implants for symptoms of androgen deficiency, were asked to complete a survey that included questions on scalp and facial hair. Age, body mass index (BMI) and serum testosterone levels were examined. Results Out of the 285 patients, 76 (27%) reported hair thinning prior to treatment; 48 of these patients (63%) reported hair regrowth on testosterone therapy (responders). Nonresponders (i.e. no reported hair regrowth on therapy) had significantly higher BMIs than responders (P = 0·05). Baseline serum testosterone levels were significantly lower in women reporting hair loss prior to therapy than in those who did not (P = 0·0001). There was no significant difference in serum testosterone levels, measured 4 weeks after testosterone implantation, between responders and nonresponders. No patient in this cohort reported scalp hair loss on testosterone therapy. A total of 262 women (92%) reported some increase in facial hair growth. Conclusions Subcutaneous testosterone therapy was found to have a beneficial effect on scalp hair growth in female patients treated for symptoms of androgen deficiency. We propose this is due to an anabolic effect of testosterone on hair growth. The fact that no subject complained of hair loss as a result of treatment casts doubt on the presumed role of testosterone in driving female scalp hair loss. These results need to be confirmed by formal measurements of hair growth. PMID:21967243

Three and six grams supplementation of d-aspartic acid in resistance trained men.

PubMed

Melville, Geoffrey W; Siegler, Jason C; Marshall, Paul Wm

2015-01-01

Although abundant research has investigated the hormonal effects of d-aspartic acid in rat models, to date there is limited research on humans. Previous research has demonstrated increased total testosterone levels in sedentary men and no significant changes in hormonal levels in resistance trained men. It was hypothesised that a higher dosage may be required for experienced lifters, thus this study investigated the effects of two different dosages of d-aspartic acid on basal hormonal levels in resistance trained men and explored responsiveness to d-aspartic acid based on initial testosterone levels. Twenty-four males, with a minimum of two years' experience in resistance training, (age, 24.5 ± 3.2 y; training experience, 3.4 ± 1.4 y; height, 178.5 ± 6.5 cm; weight, 84.7 ± 7.2 kg; bench press 1-RM, 105.3 ± 15.2 kg) were randomised into one of three groups: 6 g.d(-1) plain flour (D0); 3 g.d(-1) of d-aspartic acid (D3); and 6 g.d(-1) of d-aspartic acid (D6). Participants performed a two-week washout period, training four days per week. This continued through the experimental period (14 days), with participants consuming the supplement in the morning. Serum was analysed for levels of testosterone, estradiol, sex hormone binding globulin, albumin and free testosterone was determined by calculation. D-aspartic acid supplementation revealed no main effect for group in: estradiol; sex-hormone-binding-globulin; and albumin. Total testosterone was significantly reduced in D6 (P = 0.03). Analysis of free testosterone showed that D6 was significantly reduced as compared to D0 (P = 0.005), but not significantly different to D3. Analysis did not reveal any significant differences between D3 and D0. No significant correlation between initial total testosterone levels and responsiveness to d-aspartic acid was observed (r = 0.10, P = 0.70). The present study demonstrated that a daily dose of six grams of d-aspartic acid decreased levels of total testosterone and free testosterone (D6), without any concurrent change in other hormones measured. Three grams of d-aspartic acid had no significant effect on either testosterone markers. It is currently unknown what effect this reduction in testosterone will have on strength and hypertrophy gains.

Testosterone reduces conscious detection of signals serving social correction: implications for antisocial behavior.

PubMed

van Honk, Jack; Schutter, Dennis J L G

2007-08-01

Elevated levels of testosterone have repeatedly been associated with antisocial behavior, but the psychobiological mechanisms underlying this effect are unknown. However, testosterone is evidently capable of altering the processing of facial threat, and facial signals of fear and anger serve sociality through their higher-level empathy-provoking and socially corrective properties. We investigated the hypothesis that testosterone predisposes people to antisocial behavior by reducing conscious recognition of facial threat. In a within-subjects design, testosterone (0.5 mg) or placebo was administered to 16 female volunteers. Afterward, a task with morphed stimuli indexed their sensitivity for consciously recognizing the facial expressions of threat (disgust, fear, and anger) and nonthreat (surprise, sadness, and happiness). Testosterone induced a significant reduction in the conscious recognition of facial threat overall. Separate analyses for the three categories of threat faces indicated that this effect was reliable for angry facial expressions exclusively. This testosterone-induced impairment in the conscious detection of the socially corrective facial signal of anger may predispose individuals to antisocial behavior.

High serum oxytocin is associated with metabolic syndrome in older men - The MINOS study.

PubMed

Szulc, Pawel; Amri, Ez Zoubir; Varennes, Annie; Panaia-Ferrari, Patricia; Fontas, Eric; Goudable, Joëlle; Chapurlat, Roland; Breuil, Véronique

2016-12-01

Oxytocin regulates food intake, carbohydrate and lipid metabolism, and urinary sodium excretion. We assessed the association between serum oxytocin levels and presence of metabolic syndrome (MetS) in older men. Cross-sectional study was performed in 540 volunteer men aged 50-85yrs from the MINOS cohort. Oxytocin was measured in fasting serum by radioimmunoassay (Oxytocin RIA, Phoenix Pharmaceuticals). MetS was diagnosed using the harmonized definition. Serum oxytocin was higher in 166 men with MetS vs. controls (p<0.005). After adjustment for confounders including leptin, higher oxytocin was associated with higher odds of MetS (OR=1.38 per SD, 95%CI: 1.10-1.71, p<0.005). Men with serum oxytocin >0.74pg/mL (median) had higher odds of MetS vs. men with oxytocin ⩽0.74pg/mL (OR=2.06, 95%CI: 1.33-3.18, p<0.005). Higher oxytocin levels and low testosterone levels (total or free) were significantly associated with higher odds of MetS jointly and independently of each other. Men having oxytocin >0.74pg/mL and total testosterone <300ng/dL (<10.4nmol/L) had higher odds of MetS vs. men without these characteristics (OR=3.95, 95%CI: 1.65-9.46, p<0.005). Men having 25-hydroxycholecalciferol levels <30ng/mL and oxytocin >0.74pg/mL had higher odds of MetS vs. men without these characteristics (OR=2.86, 95%CI: 1.47-5.58, p<0.01). Men having oxytocin >0.74pg/mL and osteocalcin levels <14.6ng/mL (lowest quartile) had higher odds of MetS vs. men without these characteristics (OR=4.12, 95%CI: 2.07-8.20, p<0.001). In older men, higher serum oxytocin levels are associated with higher odds of MetS regardless of potential confounders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle.

PubMed

Di Fiore, Maria M; Lamanna, Claudia; Assisi, Loredana; Botte, Virgilio

2008-07-04

D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis. By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels. IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited. Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.

Diminished androgen and estrogen receptors and aromatase levels in hypogonadal diabetic men: reversal with testosterone.

PubMed

Ghanim, Husam; Dhindsa, Sandeep; Abuaysheh, Sanaa; Batra, Manav; Kuhadiya, Nitesh D; Makdissi, Antoine; Chaudhuri, Ajay; Dandona, Paresh

2018-03-01

One-third of males with type 2 diabetes (T2DM) have hypogonadism, characterized by low total and free testosterone concentrations. We hypothesized that this condition is associated with a compensatory increase in the expression of androgen receptors (AR) and that testosterone replacement reverses these changes. We also measured estrogen receptor and aromatase expression. This is a randomized double-blind placebo-controlled trial. Thirty-two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men were randomized to receive intramuscular testosterone or saline every 2 weeks for 22 weeks. We measured AR, ERα and aromatase expression in peripheral blood mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and eugonadal males with T2DM at baseline and after 22 weeks of treatment in those with hypogonadism. The mRNA expression of AR, ERα (ESR1) and aromatase in adipose tissue from hypogonadal men was significantly lower as compared to eugonadal men, and it increased significantly to levels comparable to those in eugonadal patients with T2DM following testosterone treatment. AR mRNA expression was also significantly lower in MNC from hypogonadal patients compared to eugonadal T2DM patients. Testosterone administration in hypogonadal patients also restored AR mRNA and nuclear extract protein levels from MNC to that in eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are lower in men with hypogonadism. Testosterone treatment restored AR expression levels to that comparable to levels in eugonadal men. We conclude that, contrary to our hypothesis, the expression of AR, ERα and aromatase is significantly diminished in hypogonadal men as compared to eugonadal men with type 2 diabetes. Following testosterone replacement, there is a reversal of these deficits. © 2018 European Society of Endocrinology.

Testosterone, DHEA and DHEA-S in patients with schizophrenia: A systematic review and meta-analysis.

PubMed

Misiak, Błażej; Frydecka, Dorota; Loska, Olga; Moustafa, Ahmed A; Samochowiec, Jerzy; Kasznia, Justyna; Stańczykiewicz, Bartłomiej

2018-03-01

Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) might play an important role in the pathophysiology of schizophrenia. Therefore, we performed a systematic review and meta-analysis of studies comparing the levels of testosterone, DHEA and DHEA-S in patients with schizophrenia and healthy controls. We searched electronic databases from their inception until Oct 29, 2017. Effect size (ES) estimates were calculated as Hedges' g. Data analysis was performed using random-effects models. Our analysis included 34 eligible studies, representing 1742 patients and 1604 controls. Main analysis revealed elevated DHEA-S levels in the whole group of patients (ES = 0.75, 95%CI: 0.23-1.28, p = 0.005). In subgroup analyses, patients with first-episode psychosis (FEP) had significantly higher levels of free testosterone (ES = 1.21, 95%CI: 0.30-2.12, p = 0.009) and DHEA-S (ES = 1.19, 95%CI: 0.66-1.71, p < 0.001). Acutely relapsed schizophrenia patients presented significantly higher levels of total testosterone (ES = 0.50, 95%CI: 0.21-0.70, p < 0.001). Total testosterone levels were also elevated in stable multi-episode schizophrenia (sMES) females (ES = 0.56, 95%CI: 0.33-0.80, p < 0.001) and reduced in sMES males (ES = -0.62, 95%CI: -1.07 to 0.18, p = 0.006). Increased levels of biologically active, free testosterone and DHEA-S in FEP suggest that these alterations might appear as a response to stress that becomes blunted during subsequent exacerbations of schizophrenia. Differential changes in total testosterone levels in male and female sMES patients might represent medication effects related to prolactin-releasing effects of antipsychotics. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Association of Free Testosterone Levels in Men and Lifestyle Factors and Chronic Disease Status: A North Texas Healthy Heart Study.

PubMed

Cardarelli, Roberto; Singh, Meharvan; Meyer, Jason; Balyakina, Elizabeth; Perez, Oscar; King, Michael

2014-07-01

Hypogonadism is highly prevalent in men older than 45 years and is associated with an increased risk of chronic diseases, including obesity, metabolic syndrome, diabetes, and cardiovascular disease. The objective of this study was to determine whether lifestyle factors such as smoking, diet, and exercise are associated with reduced testosterone levels. In this cross-sectional study, 147 men older than 44 years were recruited from a collaborative network of primary care clinics in the Dallas/Fort Worth, Texas, metropolitan area. Free testosterone levels were measured in plasma samples via an enzyme-linked immunosorbent assay-based method, and analyzed by simple and multiple linear regression in relationship to age, race/ethnicity, smoking, diet, exercise, obesity, diabetes, hypertension, and dyslipidemia. The participants had a mean free testosterone level of 3.1 ng/mL (standard deviation [SD] = 1.5) and mean age of 56.8 years (SD = 7.9). In simple regression analysis, free testosterone levels were associated with increased age (β = -0.04; P = .02), diet (β = -0.49; P = .05), diabetes (β = -0.9; P = .003), and hypertension (β = -0.55; P = .03) but not with race/ethnicity, smoking, exercise, obesity, or dyslipidemia. In multiple regression analysis, free testosterone values were significantly associated only with age (β = -0.05; P = .01) and diet (β = -0.72; P = .01). This study implicates diet, in addition to advanced age as a possible risk factor in the development of reduced testosterone levels. © The Author(s) 2014.

Provider and Site-Level Determinants of Testosterone Prescribing in the Veterans Healthcare System.

PubMed

Jasuja, Guneet K; Bhasin, Shalender; Rose, Adam J; Reisman, Joel I; Hanlon, Joseph T; Miller, Donald R; Morreale, Anthony P; Pogach, Leonard M; Cunningham, Francesca E; Park, Angela; Wiener, Renda S; Gifford, Allen L; Berlowitz, Dan R

2017-09-01

Testosterone prescribing rates have increased substantially in the past decade. However, little is known about the context within which such prescriptions occur. We evaluated provider- and site-level determinants of receipt of testosterone and of guideline-concordant testosterone prescribing. This study was cross-sectional in design. This study was conducted at the Veterans Health Administration (VA). Study participants were a national cohort of male patients who had received at least one outpatient prescription within the VA during fiscal year (FY) 2008 to FY 2012. A total of 38,648 providers and 130 stations were associated with these patients. This study measured receipt of testosterone and guideline-concordant testosterone prescribing. Providers ranging in age from 31 to 60 years, with less experience in the VA [all adjusted odds ratio (AOR), <2; P < 0.01] and credentialed as medical doctors in endocrinology (AOR, 3.88; P < 0.01) and urology (AOR, 1.48; P < 0.01) were more likely to prescribe testosterone compared with older providers, providers of longer VA tenure, and primary care providers, respectively. Sites located in the West compared with the Northeast [AOR, 1.75; 95% confidence interval (CI), 1.45-2.11] and care received at a community-based outpatient clinic compared with a medical center (AOR, 1.22; 95% CI, 1.20-1.24) also predicted testosterone use. Although they were more likely to prescribe testosterone, endocrinologists were also more likely to obtain an appropriate workup before prescribing compared with primary care providers (AOR, 2.14; 95% CI, 1.54-2.97). Our results highlight the opportunity to intervene at both the provider and the site levels to improve testosterone prescribing. This study also provides a useful example of how to examine contributions to prescribing variation at different levels of the health care system. Copyright © 2017 Endocrine Society

Lower Serum Testosterone Associated with Elevated Polychlorinated Biphenyl Concentrations in Native American Men

PubMed Central

Goncharov, Alexey; Rej, Robert; Negoita, Serban; Schymura, Maria; Santiago-Rivera, Azara; Morse, Gayle; Carpenter, David O.

2009-01-01

Background Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. Objective We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. Methods We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Results Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05–0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06–0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Conclusions Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men. PMID:19750113

How do we love? Romantic love style in men is related to lower testosterone levels.

PubMed

Babková Durdiaková, J; Celec, P; Koborová, I; Sedláčková, T; Minárik, G; Ostatníková, D

2017-09-22

Testosterone has been widely investigated in associations with many aspects of social interactions, emotions and behavior. No research has been conducted on its contribution to the variability of love styles in human. The aim of this paper was to uncover the possible relationship between not only the actual plasma testosterone levels, but also the prenatal testosterone level (expressed as 2D:4D ratio) and the sensitivity of androgen receptor and love typology in young healthy men. There are six love styles which are primary including Eros (passionate romantic love), Ludus (playful) and Storge (friendly) and secondary love consisting of Mania (obsessive), Pragma (practical realistic) and Agape (altruistic). Our results pointed out that low testosterone concentrations are associated with higher score for Eros, Ludus, Pragma, Mania love style. No significant association was proved for other tested parameters of androgenicity (2D:4D, sensitivity of androgen receptor) and love style after correction was applied. Different attitudes and behavior in relationships do have a biological foundation related to endogenous testosterone levels in plasma. Future studies should address questions about the family and social background of participants to differentiate here between moral rules or/and social-conventional rules.

Effects of Unripe Musa Paradisiaca on the Histochemistry of the Testis and Testosterone Levels in Adult Albino Rats.

PubMed

Alabi, A S; Omotosho, G O; Tagoe, C N B; Akinola, O B; Enaibe, B U

2017-06-30

This study was aimed at determining the effects of the unripe fruit of Musa paradisiaca on the testis andtestosterone levels in male Wistar rats. The animals were grouped into three, comprising a control, and 2 treatment groupsadministered with different doses (500 mg/kg and 1000 mg/kg) daily of the fruit flour over 28 days. Histochemical evaluationof the testes was done using Haematoxylin and Eosin, Periodic acid Schiff's (PAS) and Feulgen staining techniques, whilethe serum and homogenised testicular tissue were evaluated for testosterone levels using Accu-Bind ELISA Kit. The testisof the treated groups showed more rapidly dividing cells and more population of sperm cells compared to the control group,and also showed more positivity for Feulgen staining and PAS reaction. Both serum and testicular testosterone levels werehowever reduced. Serum testosterone was significantly lowered in the animals given the low dose (0.67 ± 0.03 ng/ml),compared to those given high dose (0.85 ± 0.02 ng/ml) and the control animals (1.88 ± 0.15 ng/ml) (p < 0.05). Changes intesticular testosterone were not statistically significant. The study suggests that M. paradisiaca fruit has reproductiveenhancing potential when consumed moderately, but this benefit may not be related to testosterone levels.

Plasma Testosterone and the Course of Major Depressive Disorder in Older Men and Women.

PubMed

Giltay, Erik J; van der Mast, Roos C; Lauwen, Esther; Heijboer, Annemieke C; de Waal, Margot W M; Comijs, Hannie C

2017-04-01

To investigate associations between testosterone levels and major depressive disorder (MDD) in older men and women. In a cross-sectional, 2-year prospective analyses within the Netherlands Study on Depression in Older persons cohort study, 469 participants comprised 350 patients with MDD and 119 nondepressed participants in the comparison group (mean age 70.5 ± 7.3 years; 166 [35.4%] men). MDD was assessed by the Composite International Diagnostic Interview. Baseline plasma total testosterone and sex hormone binding globulin (SHBG) were assessed to calculate free testosterone. The Inventory of Depressive Symptomatology was assessed every 6 months. Whereas SHBG levels did not differ between the depressed/nondepressed groups (F(1,149) = 0.075, p = 0.78), men with MDD had lower mean total and free testosterone levels than the comparison group in the multivariate adjusted analyses (F(1,150) = 7.249, p = 0.008, Cohen's d = 0.51; and F(1,149) = 8.548, p = 0.004 Cohen's d = 0.55, respectively). This could be ascribed to lower testosterone in men with "pure" MDD and not in men with MDD and comorbid anxiety. Nine men (5.4%) had a total testosterone level < 8 nmol/L, of whom 8 suffered from MDD. In women, hormone levels showed no significant difference between the groups. In men (using all five measurement points during follow-up) baseline free testosterone was inversely associated with depression severity in the adjusted analyses (β = -0.15, t(151) = -2.15, p = 0.03). Testosterone levels were lower in men with MDD compared with healthy men after adjustment for confounders, such as body mass index. No significant associations were found in women. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Relationships among Musical Aptitude, Digit Ratio and Testosterone in Men and Women

PubMed Central

Borniger, Jeremy C.; Chaudhry, Adeel; Muehlenbein, Michael P.

2013-01-01

Circulating adult testosterone levels, digit ratio (length of the second finger relative to the fourth finger), and directional asymmetry in digit ratio are considered sexually dimorphic traits in humans. These have been related to spatial abilities in men and women, and because similar brain structures appear to be involved in both spatial and musical abilities, neuroendocrine function may be related to musical as well as spatial cognition. To evaluate relationships among testosterone and musical ability in men and women, saliva samples were collected, testosterone concentrations assessed, and digit ratios calculated using standardized protocols in a sample of university students (N = 61), including both music and non-music majors. Results of Spearman correlations suggest that digit ratio and testosterone levels are statistically related to musical aptitude and performance only within the female sample: A) those females with greater self-reported history of exposure to music (p = 0.016) and instrument proficiency (p = 0.040) scored higher on the Advanced Measures of Music Audiation test, B) those females with higher left hand digit ratio (and perhaps lower fetal testosterone levels) were more highly ranked (p = 0.007) in the orchestra, C) female music students exhibited a trend (p = 0.082) towards higher testosterone levels compared to female non-music students, and D) female music students with higher rank in the orchestra/band had higher testosterone levels (p = 0.003) than lower ranked students. None of these relationships were significant in the male sample, although a lack of statistical power may be one cause. The effects of testosterone are likely a small part of a poorly understood system of biological and environmental stimuli that contribute to musical aptitude. Hormones may play some role in modulating the phenotype of musical ability, and this may be the case for females more so than males. PMID:23520475

Testosterone therapy in microphallic hypospadias: topical or parenteral?

PubMed

Chalapathi, G; Rao, K L N; Chowdhary, S K; Narasimhan, K L; Samujh, Ram; Mahajan, J K

2003-02-01

Local or systemic application of testosterone is reported to stimulate penile growth. Intramuscular testosterone has been found to be effective in 50% of patients; however, variable results have been reported with topical testosterone. The current study is an attempt to compare the efficacy of intramuscular versus topical testosterone application. A total of 26 consecutive patients with hypospadias and small penis (<2SD for given age) were studied prospectively. These patients were recruited alternately into group A or group B. Each group consisted of 13 patients. In group A, penile growth was accomplished by topical application of testosterone (Testoviron, oily solution containing testosterone propionate, 25 mg, and testosterone enanthate, 110 mg, equivalent to about 100 mg of testosterone, Schering, Germany) with a dose of 2 mg/kg/wk, for 3 weeks. While in group B, testosterone (same preparation as above) was administered by intramuscular injection weekly for 3 consecutive weeks. Penile length, diameter, and secondary effects were recorded before, during, and 3 weeks after the therapy by a single observer. Significant penile growth (P <.01) was noticed in both the groups of patients when compared with pretherapy with maximum response observed during the third week of therapy (reaching from an average pretherapy length of 2.0 cm and 1.8 cm to 3.18 cm and 3.11 cm posttherapy in group A and B patients, respectively). Seven patients in each group had growth of at least 50% compared with the initial size. The basal serum testosterone was within the normal range in both the groups. During therapy the serum testosterone was elevated above the basal level in all patients, but within the normal range except in 2 patients of group A. In these 2 children the serum testosterone level crossed the normal range. Linear growth did not alter significantly for the chronological age. Two patients of group A went on to have pubic hair, one of them had elevated testosterone level above the normal range. There was a surge in serum testosterone in all children, although significant penile enlargement was observed in 60% children in group A and 75% in group B. Although the desired therapeutic effect of testosterone was achieved in both the groups, this study failed to show any significant difference between the 2 routes of administration. However, in group A, (topical) serum testosterone crossed the normal range in 15% of patients and was associated with significant reversible side effects. Copyright 2003, Elsevier Science (USA). All rights reserved.

No Evidence for a Relationship Between Hair Testosterone Concentrations and 2D:4D Ratio or Risk Taking

PubMed Central

Ronay, Richard; van der Meij, Leander; Oostrom, Janneke K.; Pollet, Thomas V.

2018-01-01

Using a recently developed alternative assay procedure to measure hormone levels from hair samples, we examined the relationships between testosterone, cortisol, 2D:4D ratio, overconfidence and risk taking. A total of 162 (53 male) participants provided a 3 cm sample of hair, a scanned image of their right and left hands from which we determined 2D:4D ratios, and completed measures of overconfidence and behavioral risk taking. While our sample size for males was less than ideal, our results revealed no evidence for a relationship between hair testosterone concentrations, 2D:4D ratios and risk taking. No relationships with overconfidence emerged. Partially consistent with the Dual Hormone Hypothesis, we did find evidence for the interacting effect of testosterone and cortisol on risk taking but only in men. Hair testosterone concentrations were positively related to risk taking when levels of hair cortisol concentrations were low, in men. Our results lend support to the suggestion that endogenous testosterone and 2D:4D ratio are unrelated and might then exert diverging activating vs. organizing effects on behavior. Comparing our results to those reported in the existing literature we speculate that behavioral correlates of testosterone such as direct effects on risk taking may be more sensitive to state-based fluctuations than baseline levels of testosterone. PMID:29556180

When is a varicocele repair indicated: the dilemma of hypogonadism and erectile dysfunction?

PubMed

Dabaja, Ali A; Goldstein, Marc

2016-01-01

In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogonadism is controversial and debated. Recently, multiple reports in the literature have suggested that varicocele is associated with hypogonadism and varicocele repair can increase testosterone levels. Men with hypogonadal symptoms should have at least two serum testosterone levels. Microsurgical varicocelectomy may be beneficial for men with clinically palpable varicoceles with documented hypogonadism. In this review, we summarize the most recent literature linking varicocele to hypogonadism and sexual dysfunction and the impact of repair on serum testosterone levels. We performed a search of the published English literature. The key words used were "varicocele and hypogonadism" and "varicocele surgery and testosterone." We included published studies after 1998. We, also, evaluated the effect of surgery on the changes in the serum testosterone level regardless of the indication for the varicocele repair.

Annual cycle of plasma luteinizing hormone and sex hormones in male and female mallards (Anas platyrhynchos)

USGS Publications Warehouse

Donham, R.S.

1979-01-01

Comparisons between 'wild'and 'game farm' mallards (Anas platyrhynchos) were made to assess the differences in the temporal changes of plasma hormones. Seasonal variation in the levels of immunoreactive luteinizing hormone (LH), testosterone, 5 -dihydrotestosterone (DHT), estrone, estradiol-17i?? and progesterone were measured in male and female mallards. In all birds there was a vernal increase in the concentrations of LH and testosterone in plasma which were correlated with the development of the testes and ovaries prior to and during the nesting season. The concentrations of estrogens in the plasma of the females were, in general, slightly higher during the nesting season but were much lower than the levels of testosterone. The highest levels of LH and testosterone in the females coincided precisely with the period of egg laying which occurred approximately one month earlier in game farm females than in wild females. The concentrations of LH and testosterone in the plasma of females decreased rapidly during incubation. In wild males, the decline in levels of these hormones temporally coincided with that of females. In contrast, plasma levels of LH and testosterone of males of the game farm stock remained elevated after the beginning of incubation in females to which they were paired. On the basis of these results and an examination of the literature, it appears that domestication results in: 1) increased reproductive potential through earlier initiation of nesting and by delay of the termination of reproduction until later in the summer; and 2) a decrease in the synchronization of the hormonal events supporting reproduction between the male and female of a pair. Testicular weights and plasma levels of testosterone become higher in game farm and domestic males than in the wild stock but levels of LH are similar.

Puberty timing and fluid intelligence: a study of correlations between testosterone and intelligence in 8- to 12-year-old Chinese boys.

PubMed

Shangguan, Fangfang; Shi, Jiannong

2009-08-01

Sex hormone such as testosterone was recently recognized as an important contributor of spatial cognition and intelligence during development, but the relationship between puberty timing and intelligence especially in children is largely unknown. Here in this study, we investigated the potential relationship between the level of sex hormones in saliva and fluid intelligence in 8- to 12-year-old Chinese boys. Fluid intelligence was measured by the Cattell's Culture Fair Intelligence Test. 1600 children aged 8-12 years were included in the Cattell's Culture Fair Intelligence Test and saliva samples were collected thereafter from 166 boys with normal intelligence distribution, composed of 49, 54 and 63 boys in 8-, 10- and 12-year-old group respectively. The level of salivary testosterone and estradiol was measured with enzyme-immunoassay technique. Data of BMI and age were collected. The relationship between the level of salivary sex hormones and fluid intelligence was analysed by correlation test. There was no significant correlation between salivary testosterone level and fluid intelligence in 8-year-old boys, whereas there was a significant positive correlation in 10-year-old boys and a significant negative correlation in 12-year-old boys between those two variable. To verify the correlation, we performed stepwise multivariate linear regression and discriminant analysis, with both the age and BMI of the boys and their parents, and salivary estradiol level considered. The results showed that the level of testosterone and intelligence was correlated, and the correlation was much stronger when the level of salivary testosterone was higher than 14 pg/ml. In summary, the study suggests that the relationship of testosterone and intelligence varies from late childhood to early adolescence, and the puberty timing is closely related with fluid intelligence.

Low testosterone levels and increased inflammatory markers in patients with cancer and relationship with cachexia.

PubMed

Burney, Basil O; Hayes, Teresa G; Smiechowska, Joanna; Cardwell, Gina; Papusha, Victor; Bhargava, Peeyush; Konda, Bhavana; Auchus, Richard J; Garcia, Jose M

2012-05-01

Male cancer patients suffer from fatigue, sexual dysfunction, and decreased functional performance and muscle mass. These symptoms are seen in men with hypogonadism and/or inflammatory conditions. However, the relative contribution of testosterone and inflammation to symptom burden in cancer has not been well-established. The aim of this study was to measure testosterone levels in male cancer patients and determine the relationship between testosterone, inflammation, and symptom burden. This cross-sectional study enrolled patients from a tertiary-care center. SUBJECTS/OUTCOME MEASURES: Subjects included males with cancer-cachexia (CC; n = 45) and cancer without cachexia (CNC; n = 50), as well as noncancer controls (CO; n = 45). Total testosterone (TT), bioavailable testosterone, C-reactive protein (CRP), and IL-6 were measured in plasma. Functional performance was assessed by the ECOG (Eastern Cooperative Oncology Group) and KPS (Karnofsky Performance Scales), and sexual function was assessed by the IIEF (International Index of Erectile Function). Low testosterone levels were seen in more than 70% of CC cases. TT was lower in CC compared to CNC (P < 0.05). Also, CC had lower bioavailable testosterone, grip strength, IIEF scores, appendicular lean body mass, and fat mass and higher IL-6 and CRP compared to controls (P ≤ 0.05). ECOG and KPS were lower in CC and CNC compared to controls (P ≤ 0.05). On multiple regression analysis, TT, albumin, and CRP predicted symptoms differentially in cancer patients. CC patients have higher inflammation and lower testosterone, grip strength, functional status, erectile function, fat mass, and appendicular lean body mass. Inflammation, TT, and albumin are associated with heavier symptom burden in this population. Interventional trials are needed to determine whether testosterone replacement and/or antiinflammatory agents benefit cancer patients.

Testosterone related to age and life-history stages in male baboons and geladas

PubMed Central

Beehner, Jacinta C.; Gesquiere, Laurence; Seyfarth, Robert M.; Cheney, Dorothy L.; Alberts, Susan C.; Altmann, Jeanne

2013-01-01

Despite significant advances in our knowledge of how testosterone mediates life-history trade-offs, this research has primarily focused on seasonal species. We know comparatively little about the relationship between testosterone and life-history stages for non-seasonally breeding species. Here we examine testosterone profiles across the lifespan of males from three non-seasonally breeding primates: yellow baboons (Papio cynocephalus or P. hamadryas cynocephalus), chacma baboons (Papio ursinus or P. h. ursinus), and geladas (Theropithecus gelada). First, we predict that testosterone profiles will track the reproductive profiles of each taxon across their respective breeding years. Second, we evaluate age-related changes in testosterone to determine whether several life-history transitions are associated with these changes. Subjects include males (>2.5 years) from wild populations of each taxon from whom we had fecal samples for hormone determination. Although testosterone profiles across species were broadly similar, considerable variability was found in the timing of two major changes: (1) the attainment of adult levels of testosterone, and (2) the decline in testosterone after the period of maximum production. Attainment of adult testosterone levels was delayed by one year in chacmas compared with yellows and geladas. With respect to the decline in testosterone, geladas and chacmas exhibited a significant drop after three years of maximum production, while yellows declined so gradually that no significant annual drop was ever detected. For both yellows and chacmas, increases in testosterone production preceded elevations in social dominance rank. We discuss these differences in the context of ecological and behavioral differences exhibited by these taxa. PMID:19712676

Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

NASA Astrophysics Data System (ADS)

Kusuma, R.; Siregar, Y.; Mardianto

2018-03-01

Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous measurement of salivary testosterone and cortisol in healthy men for utilization in the diagnosis of late-onset hypogonadism in males.

PubMed

Matsui, Futoshi; Koh, Eitetsu; Yamamoto, Kenrou; Sugimoto, Kazuhiro; Sin, Ho-Su; Maeda, Yuji; Honma, Seijiro; Namiki, Mikio

2009-01-01

It is well known that late-onset hypogonadism in males can cause a variety of symptoms, and the differential diagnosis is relatively difficult, including psychological disorders, stress, and mood disturbances. The level of serum cortisol can be measured to reflect a patient's level of stress. Salivary hormones facilitate the evaluation of physiological hormonal actions based on free hormone assay. For the simultaneous measurement of testosterone and cortisol levels in saliva, we validate a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Concerning accuracy and precision, the lower limit of quantification of salivary testosterone and cortisol were established as 5 and 10 pg/mL, respectively. Testosterone and cortisol in saliva is stable for 2 days, 14 days, and 28 days at room temperature, refrigeration and frozen, respectively. Freezing and thawing for 3 cycles and stimulation of salivation with gum chewing do not alter the measured values of testosterone and cortisol. Total, bioavailable, and free serum testosterone showed slight diurnal changes, but total and bioavailable serum cortisol showed marked diurnal changes. Salivary testosterone levels negatively correlate with age, regardless of the time of saliva collection (r=0.64, p<0.05). However, there is no relationship between salivary cortisol and age (r=0033, p>0.05). LC-MS/MS allows rapid, simultaneous, sensitive, and accurate quantification of testosterone and cortisol in saliva for the diagnosis late-onset hypogonadism or other hormone related disease.

Delivering enhanced testosterone replacement therapy through nanochannels.

PubMed

Ferrati, Silvia; Nicolov, Eugenia; Bansal, Shyam; Zabre, Erika; Geninatti, Thomas; Ziemys, Arturas; Hudson, Lee; Ferrari, Mauro; Goodall, Randal; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

2015-02-18

Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Salivary testosterone as a potential indicator for risky behaviour associated with smoking-related peer pressure in adolescents.

PubMed

Idris, Adi; Ghazali, Nur B; Said, Nadzirah M; Steele, Michael; Koh, David; Tuah, Nik A

2016-04-09

Early smoking is considered an indicator for risky behaviour in adolescents. Although social indicators predicting adolescent smoking are known, biological indicators have not been defined. This study aimed to establish whether salivary testosterone could be used as a "predictive biomarker" for smoking-associated peer pressure. Saliva samples were collected from Bruneian adolescents (aged 13-17 years) by the passive drool method. Salivary testosterone concentration was determined by enzyme-linked immunosorbent assay. Salivary testosterone concentration and smoking-associated peer pressure indicators were compared between adolescent males and females and statistical significance was determined by an independent samples t-test. A significant positive relationship between smoking-associated peer pressure and salivary testosterone levels in adolescents was found. However, this relationship was not significant when males and females were considered separately. Our data suggest that students who have tried cigarette smoking and have friends who are cigarette smokers have higher salivary testosterone levels.

Effects of prolonged physical exercise and fasting upon plasma testosterone level in rats.

PubMed

Guezennec, C Y; Ferre, P; Serrurier, B; Merino, D; Pesquies, P C

1982-01-01

Prolonged physical exercise and fasting in male rats were studied to determine the effect of these two treatments on plasma testosterone level. Blood and tissue samples were drawn after 1 h, 3 h, 5 h, and 7 h treadmill running, and after 24 h, 48 h, and 72 h of fasting. Both treatments resulted in a significant fall in plasma testosterone, plasma luteinizing hormone (LH), plasma Insulin (IRI) and in liver and muscle glycogen stores. In the course of these two treatments the injection of a supra maximal dose of Human Chorionic Gonadotropin (HCG) produced a rise in plasma testosterone similar to that in control rats. This indicates that the decrease of plasma LH may be responsible for the decrease in plasma testosterone, which is time-related with the decrease in glycogen stores. The possible metabolic role of the decrease in plasma testosterone is discussed.

Hormone-Diversity Fit: Collective Testosterone Moderates the Effect of Diversity on Group Performance.

PubMed

Akinola, Modupe; Page-Gould, Elizabeth; Mehta, Pranjal H; Liu, Zaijia

2018-03-01

Prior research has found inconsistent effects of diversity on group performance. The present research identifies hormonal factors as a critical moderator of the diversity-performance connection. Integrating the diversity, status, and hormone literatures, we predicted that groups collectively low in testosterone, which orients individuals less toward status competitions and more toward cooperation, would excel with greater group diversity. In contrast, groups collectively high in testosterone, which is associated with a heightened status drive, would be derailed by diversity. Analysis of 74 randomly assigned groups engaged in a group decision-making exercise provided support for these hypotheses. The findings suggest that diversity is beneficial for performance, but only if group-level testosterone is low; diversity has a negative effect on performance if group-level testosterone is high. Too much collective testosterone maximizes the pains and minimizes the gains from diversity.

Disturbance of DNA conformation by the binding of testosterone-based platinum drugs via groove-face and intercalative interactions: a molecular dynamics simulation study

PubMed Central

2013-01-01

Background To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. It was reported that the monofunctional testosterone-based platinum(II) agents present the high anticancer activity. Moreover, it was also found that the testosterone-based platinum agents could cause the DNA helix to undergo significant unwinding and bending over the non-testosterone-based platinum agents. However, the interaction mechanisms of these platinum agents with DNA at the atomic level are not yet clear so far. Results In the present work, we used molecular dynamics (MD) simulations and DNA conformational dynamics calculations to study the DNA distortion properties of the testosterone-based platinum + DNA, the improved testosterone-based platinum + DNA and the non-testosterone-based platinum + DNA adducts. The results show that the intercalative interaction of the improved flexible testosterone-based platinum agent with DNA molecule could cause larger DNA conformational distortion than the groove-face interaction of the rigid testosterone-based platinum agent with DNA molecule. Further investigations for the non-testosterone-based platinum agent reveal the occurrence of insignificant change of DNA conformation due to the absence of testosterone ligand in such agent. Based on the DNA dynamics analysis, the DNA base motions relating to DNA groove parameter changes and hydrogen bond destruction of DNA base pairs were also discussed in this work. Conclusions The flexible linker in the improved testosterone-based platinum agent causes an intercalative interaction with DNA in the improved testosterone-based platinum + DNA adduct, which is different from the groove-face interaction caused by a rigid linker in the testosterone-based platinum agent. The present investigations provide useful information of DNA conformation affected by a testosterone-based platinum complex at the atomic level. PMID:23517640

The effects of chronic testosterone administration on body weight, food intake, and fat weight were age-dependent.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yiliyasi, Mayila; Yano, Kiyohito; Irahara, Minoru

2017-11-01

Previously, we showed that chronic testosterone administration increased body weight (BW) and food intake (FI), but did not alter fat weight, in young female rats. To examine our hypothesis that the effects of androgens on BW, FI and body composition might be age-dependent, the effects of chronic testosterone administration were evaluated in rats of different ages; i.e., young and middle-aged rats. Although chronic testosterone administration increased BW gain, FI, and feed efficiency in both young and middle-aged rats, it increased visceral fat weight in middle-aged rats, but not in young rats. Therefore, it is possible that testosterone promotes the conversion of energy to adipose tissue and exacerbates fat accumulation in older individuals. In addition, although the administration of testosterone increased the serum leptin level, it did not alter hypothalamic neuropeptide Y mRNA expression in middle-aged rats. On the contrary, the administration of testosterone did not affect the serum leptin levels of young rats. Thus, testosterone might induce hypothalamic leptin resistance, which could lead to fat accumulation in older individuals. Testosterone might disrupt the mechanisms that protect against adiposity and hyperphagia and represent a risk factor for excessive body weight and obesity, especially in older females. Copyright © 2017 Elsevier Inc. All rights reserved.

[Testosterone and psyche].

PubMed

Leiber, C; Wetterauer, U; Berner, M

2010-01-01

Testosterone, like other steroid hormones, crosses the blood-brain barrier, and the androgen receptor is present in most parts of the human brain. Therefore, testosterone has many effects on the psyche, mainly in men but also in women. Most often discussed is its influence on sexuality, especially on desire and sexual fantasies, spontaneous nighttime erections, sexual activity, and the number of orgasms and ejaculations. Mood and energy are also testosterone related. Testosterone deficiency in male patients can lead to depressive disorders. In the past, elevated testosterone levels were seen as responsible for strongly aggressive behaviour. Some cognitive functions (spatial and mathematical sense, verbal skills) are, at least to a certain point, testosterone related. Due to the extremely complex functioning of the human brain, a scientifically exact statement regarding the true relationship between testosterone and human behaviour is not possible. On the one hand, the cause is definitively multifactorial, but on the other, testosterone is metabolised in the brain, and the metabolites act by themselves. Furthermore, a bidirectional relationship exists between hormones and human behaviour: Human behaviour is influenced by hormones, and human behaviour also has a direct influence on the levels of many hormones in the human body. Finally, much data in this field are derived from animal studies; studies on humans cannot be conducted because of ethical reasons or scientific and technical problems.

Pharmacokinetics and pharmacodynamics of injectable testosterone undecanoate in castrated cynomolgus monkeys (Macaca fascicularis) are independent of different oil vehicles.

PubMed

Wistuba, Joachim; Marc Luetjens, C; Kamischke, Axel; Gu, Yi-Qun; Schlatt, Stefan; Simoni, Manuela; Nieschlag, Eberhard

2005-08-01

Testosterone undecanoate (TU) dissolved in soybean oil was developed in China to improve the pharmacokinetics of this testosterone ester in comparison with TU in castor or tea seed oil. As a pre-clinical primate model, three groups of five castrated cynomolgus macaques received either a single intramuscular injection of 10 mg/kg body weight TU in soybean oil, in tea seed oil, or in castor oil (equals 6.3 mg pure T/kg body weight for all preparations). Testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone as well as prostate volume, body weight and ejaculate weight were evaluated. After injection supraphysiological testosterone levels were induced. There were no significant differences in the pharmacokinetics of the three TU preparations for testosterone and estradiol. The gonadotropin levels showed a high individual variation. Prostate volumes increased equally in all groups after administration and declined to castrate level afterwards. The results suggest that TU in soybean oil produces similar effects as TU in the other vehicles. This study in non-human primates provides no objection to testing of this new preparation in humans.

The association of total antioxidant capacity with sex hormones.

PubMed

Demirbag, Recep; Yilmaz, Remzi; Erel, Ozcan

2005-07-01

Although sex hormones have potential cardioprotective effects, their effects on total antioxidant capacity (TAC) are not very well known. The aim of the study was to evaluate TAC in men who have decreased and normal testosterone levels and in women in menopausal and premenopausal period. Ninety-seven subjects with similar age intervals, men aged <45 years and female aged <50 years, were divided into four groups: 1) 10 men with normal testosterone levels, as control, 2) 36 men with decreased testosterone, 3) 19 women in menopause, surgically induced, and 4) 32 women in premenopausal period. Testosterone and estrogen levels were measured by chemiluminescence assay and TAC were measured by using a more recently developed automated measurement method. The TAC was significantly lower in Group 2 and Group 3 than those of Group 1 and Group 4 (ANOVA, p<0.001). A strong correlation between TAC, and testosterone and estrogen were found (r=0.807, p<0.001; r=0.685, p<0.001, testosterone and estrogen respectively). The observed relationship between sex hormones and TAC may have a role in mechanism of their cardioprotective effect.

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG.

PubMed

Maggio, Marcello; Nicolini, Francesco; Cattabiani, Chiara; Beghi, Cesare; Gherli, Tiziano; Schwartz, Robert S; Valenti, Giorgio; Ceda, Gian Paolo

2012-07-01

Testosterone levels decrease with age. This decline is steeper during "critical illnesses". Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as "acute postoperative frailty". We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Associations of Maternal and Infant Testosterone and Cortisol Levels With Maternal Depressive Symptoms and Infant Socioemotional Problems

PubMed Central

Cho, June; Su, Xiaogang; Phillips, Vivien; Holditch-Davis, Diane

2015-01-01

This study examined the associations of testosterone and cortisol levels with maternal depressive symptoms and infant socioemotional (SE) problems that are influenced by infant gender. A total of 62 mothers and their very-low-birth weight (VLBW) infants were recruited from a neonatal intensive care unit at a tertiary medical center in the southeast United States. Data were collected at three time points (before 40 weeks’ postmenstrual age [PMA] and at 3 months and 6 months of age corrected for prematurity). Measures included infant medical record review, maternal interview, biochemical assays of salivary hormone levels in mother-VLBWinfant pairs, and standard questionnaires. Generalized estimating equations with separate analyses for boys and girls showed that maternal testosterone level was negatively associated with depressive symptoms in mothers of boys, whereas infant testosterone level was negatively associated with maternal report of infant SE problems in girls after controlling for characteristics of mothers and infants and number of days post birth of saliva collection. Not surprisingly, the SE problems were positively associated with a number of medical complications. Mothers with more depressive symptoms reported that their infants had more SE problems. Mothers with higher testosterone levels reported that girls, but not boys, had fewer SE problems. In summary, high levels of testosterone could have a protective role for maternal depressive symptoms and infant SE problems. Future research need to be directed toward clinical application of these preliminary results. PMID:25954021

Associations of Maternal and Infant Testosterone and Cortisol Levels With Maternal Depressive Symptoms and Infant Socioemotional Problems.

PubMed

Cho, June; Su, Xiaogang; Phillips, Vivien; Holditch-Davis, Diane

2016-01-01

This study examined the associations of testosterone and cortisol levels with maternal depressive symptoms and infant socioemotional (SE) problems that are influenced by infant gender. A total of 62 mothers and their very-low-birth weight (VLBW) infants were recruited from a neonatal intensive care unit at a tertiary medical center in the southeast United States. Data were collected at three time points (before 40 weeks' postmenstrual age [PMA] and at 3 months and 6 months of age corrected for prematurity). Measures included infant medical record review, maternal interview, biochemical assays of salivary hormone levels in mother-VLBWinfant pairs, and standard questionnaires. Generalized estimating equations with separate analyses for boys and girls showed that maternal testosterone level was negatively associated with depressive symptoms in mothers of boys, whereas infant testosterone level was negatively associated with maternal report of infant SE problems in girls after controlling for characteristics of mothers and infants and number of days post birth of saliva collection. Not surprisingly, the SE problems were positively associated with a number of medical complications. Mothers with more depressive symptoms reported that their infants had more SE problems. Mothers with higher testosterone levels reported that girls, but not boys, had fewer SE problems. In summary, high levels of testosterone could have a protective role for maternal depressive symptoms and infant SE problems. Future research need to be directed toward clinical application of these preliminary results. © The Author(s) 2015.

Cortisol and testosterone increase financial risk taking and may destabilize markets.

PubMed

Cueva, Carlos; Roberts, R Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N; Herbert, Joe; Rustichini, Aldo

2015-07-02

It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders' financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways.

Cortisol and testosterone increase financial risk taking and may destabilize markets

PubMed Central

Cueva, Carlos; Roberts, R. Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N.; Herbert, Joe; Rustichini, Aldo

2015-01-01

It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders’ financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID:26135946

Dominance and testosterone in women.

PubMed

Grant, V J; France, J T

2001-09-01

Fifty-two young women completed the Simple Adjective Test (a questionnaire designed to measure dominance) and at the same time provided 5 ml blood for testosterone assay. Higher dominance scores were associated with higher serum testosterone levels (t-test P<0.008).

Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

PubMed

Pandit, S; Biswas, S; Jana, U; De, R K; Mukhopadhyay, S C; Biswas, T K

2016-06-01

Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained. © 2015 The Authors. Andrologia Published by Blackwell Verlag GmbH.

Review of the pathophysiological aspects involved in urological disease associated with metabolic syndrome.

PubMed

Sáenz Medina, J; Carballido Rodríguez, J

2016-06-01

Metabolic syndrome is a constellation of disorders that includes insulin resistance, central obesity, arterial hypertension and hyperlipidaemia. These disorders can have implications for the genitourinary apparatus. To conduct a review on the pathophysiological aspects that explain the relationship between metabolic syndrome and sexual dysfunction, lower urinary tract syndrome, prostate cancer and stone disease. We performed a qualitative, narrative literature review through a literature search on PubMed of articles published between 1997 and 2015, using the terms pathophysiology, metabolic syndrome, endothelial dysfunction, lipotoxicity, mitochondrial dysfunction, kidney stones, hypogonadism, erectile dysfunction, lower urinary tract syndrome and prostate cancer. Metabolic syndrome constitutes an established complex of symptoms, defined as the presence of insulin resistance, central obesity, hypertension and hyperlipidaemia. Endothelial dysfunction secondary to lipotoxicity generates an inflammatory state, which involves renal cell metabolism, vascularisation of the pelvis and androgen production. These facts explain the relationship between metabolic syndrome, nephrolithiasis, lower urinary tract syndrome, hypogonadism and erectile dysfunction in men. Strategies such as proper diet, regular exercise, insulin treatment, testosterone-replacement therapy, therapy with antioxidants and free-radical inhibitors and urological treatments classically used for lower urinary tract syndrome have shown promising results in this syndrome. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Hormonal studies and physical maturation in adolescent gynecomastia.

PubMed

Biro, F M; Lucky, A W; Huster, G A; Morrison, J A

1990-03-01

As part of a 3-year longitudinal study of lipid and hormonal changes during puberty, 536 boys aged 10 to 15 years were prospectively followed every 6 months to assess development of gynecomastia. The overall prevalence of gynecomastia in the 377 with complete data was 48.5% (51% of white subjects and 46% of black subjects). In the majority of subjects, gynecomastia developed during mid-puberty. Gynecomastia was bilateral in 55% of subjects, on the left side in 19%, and on the right in 26%. Gynecomastia was documented for only one visit in the majority of subjects. When subjects were matched at the onset of gynecomastia for race, visit number, and pubertal rating, there were no significant differences between those with or without gynecomastia in serum estradiol level, testosterone level, estrogen/testosterone, ratio, or dehydroepiandrosterone-sulfate level. However, free testosterone level, weight, and Quetelet index were all significantly lower, and the testosterone-estrogen binding globulin level was significantly greater, in those with gynecomastia. We conclude that approximately half of adolescent boys have transient gynecomastia, usually lasting less than 1 year; those with gynecomastia enter mid-puberty at an earlier age, have a lower Quetelet index, and have lower serum free testosterone levels.

The Relationship between Hot Flashes and Testosterone Recovery after 12 Months of Androgen Suppression for Men with Localised Prostate Cancer in the ASCENDE-RT Trial.

PubMed

Dosani, M; Morris, W J; Tyldesley, S; Pickles, T

2017-10-01

This study describes the proportion of men who experienced hot flashes (flashes), and the testosterone level at onset, peak frequency and cessation of flashes after 12 months of androgen deprivation therapy (ADT) in men undergoing curative-intent external beam radiation therapy (± brachytherapy boost). We also aimed to characterise testosterone recovery in this population. This was a pre-specified secondary analysis of the ASCENDE-RT clinical trial. Three hundred and ninety-eight men were randomised. All received 12 months of ADT. The presence and frequency of flashes were patient reported. Cessation of flashes was defined as the first date a patient reported resolution of this symptom. Testosterone recovery was defined as any single serum testosterone above the threshold of 5, 7.5 or 10 nmol/l. The median age and follow-up were 68 years and 6.1 years. Flashes were reported in 93% of men. Flashes began and reached peak frequency at a median time of 4.0 months from the first luteinizing hormone-releasing hormone injection when testosterone levels had fallen to castrate. The median time to cessation of flashes was 7.6 months after the cessation of ADT (last injection + 3 months), when the median testosterone had risen to 5.7 nmol/l. A resolution of flashes was reported in 99% of patients. Baseline testosterone was available in 338 patients (85%). The median baseline testosterone was 13.2 nmol/l. The median (95% confidence interval) time of testosterone recovery to thresholds of 5 nmol/l, 7.5 nmol/l and 10 nmol/l were 9 (9-10) months, 13 (10-15) months and 18 (17-19) months from the cessation of ADT. At the time of censor, 96, 94 and 91% of patients had recovered testosterone to thresholds of 5, 7.5 and 10 nmol/l. Flashes occur at castrate levels of testosterone, with cessation of hot flashes antedating full recovery of testosterone in most patients. Rates of testosterone recovery after 12 months of ADT exceed 90%, although it can be delayed. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Testosterone deficiency: a determinant of aortic stiffness in men.

PubMed

Vlachopoulos, Charalambos; Ioakeimidis, Nikolaos; Miner, Martin; Aggelis, Athanassios; Pietri, Panagiota; Terentes-Printzios, Dimitrios; Tsekoura, Dorothea; Stefanadis, Christodoulos

2014-03-01

Low testosterone levels and increased aortic stiffness are predictors of cardiovascular events. The influence of androgen level on the age- and blood pressure-related increase in aortic stiffness is unknown. From January 2007 to June 2011 we enrolled 455 consecutive men with no evidence of cardiovascular disease from a large cohort followed in our Department for arterial function studies. Their total testosterone (TT) levels were measured and carotid-femoral pulse wave velocity (PWVc-f) was measured as an index of aortic stiffness. In multivariable analysis, PWVc-f values were inversely correlated to TT after adjustment for confounders (β = -0.365, P < 0.001). In younger age categories (<50 yrs and 50-59 yrs), patients with testosterone deficiency (TD) had higher blood pressure-adjusted PWVc-f (P < 0.001 and P = 0.005, respectively) compared to subjects with normal TT, indicating an "aging effect" of 10 years, whereas in older age categories such a difference was not observed. Furthermore, in men with a higher mean pressure (102-108 mmHg and >108 mmHg), patients with TD had higher age-adjusted PWVc-f (P < 0.001) compared to subjects with normal TT, indicating a synergistic unfavorable effect of testosterone deficiency and blood pressure on aortic stiffness. TT levels are independently associated with aortic stiffening. The effect of low testosterone concentration on aortic stiffness is more prominent in young men and in subjects with higher blood pressure levels. These findings identify testosterone as a marker of arterial damage with special emphasis on young and hypertensive individuals and support its role as predictor of events. Copyright © 2014. Published by Elsevier Ireland Ltd.

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

PubMed Central

Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A.

2012-01-01

Abstract Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation. PMID:22208735

Associations of lead and cadmium with sex hormones in adult males

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kresovich, Jacob K., E-mail: jkreso2@uic.edu; Argos, Maria; Turyk, Mary E.

Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999–2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood leadmore » was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. - Highlights: • We used a nationally representative dataset (NHANES) and employed sample weighting. • We examined associations between lead and cadmium with sex-hormone levels. • Blood lead level was positively associated with serum testosterone and SHBG levels. • Blood cadmium level was positively associated with SHBG levels, modified by lead. • Diabetes, smoking and cadmium modified lead and testosterone association.« less

Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury.

PubMed

Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A; Cardozo, Christopher P

2012-05-20

Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation.

Sex-specific associations of testosterone with prefrontal-hippocampal development and executive function.

PubMed

Nguyen, Tuong-Vi; Lew, Jimin; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Fonov, Vladimir S; Collins, D Louis; Ducharme, Simon; McCracken, James T

2017-02-01

Testosterone is thought to play a crucial role in mediating sexual differentiation of brain structures. Examinations of the cognitive effects of testosterone have also shown beneficial and potentially sex-specific effects on executive function and mnemonic processes. Yet these findings remain limited by an incomplete understanding of the critical timing and brain regions most affected by testosterone, the lack of documented links between testosterone-related structural brain changes and cognition, and the difficulty in distinguishing the effects of testosterone from those of related sex steroids such as of estradiol and dehydroepiandrosterone (DHEA). Here we examined associations between testosterone, cortico-hippocampal structural covariance, executive function (Behavior Rating Inventory of Executive Function) and verbal memory (California Verbal Learning Test-Children's Version), in a longitudinal sample of typically developing children and adolescents 6-22 yo, controlling for the effects of estradiol, DHEA, pubertal stage, collection time, age, handedness, and total brain volume. We found prefrontal-hippocampal covariance to vary as a function of testosterone levels, but only in boys. Boys also showed a specific association between positive prefrontal-hippocampal covariance (as seen at higher testosterone levels) and lower performance on specific components of executive function (monitoring the action process and flexibly shifting between actions). We also found the association between testosterone and a specific aspect of executive function (monitoring) to be significantly mediated by prefrontal-hippocampal structural covariance. There were no significant associations between testosterone-related cortico-hippocampal covariance and verbal memory. Taken together, these findings highlight the developmental importance of testosterone in supporting sexual differentiation of the brain and sex-specific executive function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression

PubMed Central

Zou, Zhiran; Wang, Dan; Lu, Yapeng; Dong, Zhangji; Zhu, Li

2017-01-01

Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis. PMID:28146428

Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

PubMed Central

Surampudi, Prasanth N.; Wang, Christina; Swerdloff, Ronald

2012-01-01

Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men. PMID:22505891

Basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality.

PubMed

Devkota, Bhuminand; Takahashi, Ken-Ichi; Matsuzaki, Shigenori; Matsui, Motozumi; Miyamoto, Akio; Yamagishi, Norio; Osawa, Takeshi; Hashizume, Tsutomu; Izaike, Yoshiaki; Miyake, Yoh-Ichi

2011-06-01

The present study investigated the basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality. On the basis of semen parameters, bulls (n=5) having poor semen quality were selected as experimental bulls, and good semen quality bulls (n=4) were used as control bulls. Both groups were treated intramuscularly once with GnRH (250 µg of fertirelin acetate). Blood samples were collected at -1 day (d), -30 min and 0 h (treatment) followed by every 30 min for 5 h and 1, 3 and 5 d post-GnRH treatment (PGT), and LH, testosterone and estradiol-17β (E(2)) concentrations were measured. The pretreatment concentrations were used as basal levels. The percentage increments based on the 0-h levels were calculated per bull for each sampling time until 5 h PGT, and differences were compared between the experimental and control groups. The PGT concentrations of testosterone and basal and PGT concentrations of E(2) were significantly lower in the experimental group. The testosterone increment in the experimental group was delayed and significantly lower from 1 to 5 h PGT than those in the control group. It can be suggested that bulls with poor semen quality have delayed and lower GnRH-induced testosterone response and may also have lower estrogen levels.

Rosa Damascena oil improved sexual function and testosterone in male patients with opium use disorder under methadone maintenance therapy-results from a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Farnia, Vahid; Tatari, Faeze; Alikhani, Mostafa; Shakeri, Jalal; Taghizadeh, Moshen; Karbasizadeh, Hassan; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

2017-07-01

Some patients with opioid use disorder (OUD) are treated with methadone maintenance therapy (MMT). However, as with opioids, methadone has major side-effects; sexual dysfunction is a particularly distressing such effect. Rosa Damascena oil has been shown to reduce subjective sexual dysfunction in patients with major depressive disorders, but its influence on testosterone has not so far been tested. The aim of the present study was to investigate the influence of Rosa Damascena oil on sexual dysfunction and testosterone levels among male patients with OUD and undergoing MMT. A total of 50 male patients (mean age: 40 years) diagnosed with OUD and receiving MMT were randomly assigned either to the Rosa Damascena oil (drops) or a placebo condition. At baseline, and four and eight weeks later, patients completed questionnaires covering sexual and erectile function. Blood samples to assess testosterone levels were taken at baseline and eight weeks later on completion of the study. Over time sexual dysfunction decreased, and testosterone increased in the Rosa Damascena oil, but not in the placebo condition. Sexual dysfunction scores and testosterone levels were not consistently related. Results from this double-blind, randomized, and placebo-controlled clinical trial showed that Rosa Damascena oil improved sexual function and testosterone levels among males with OUD and undergoing MMT. Copyright © 2017 Elsevier B.V. All rights reserved.

Testosterone and cortisol release among Spanish soccer fans watching the 2010 World Cup final.

PubMed

van der Meij, Leander; Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; Ijzerman, Hans; van Lange, Paul A M; Salvador, Alicia

2012-01-01

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem.

Testosterone and Cortisol Release among Spanish Soccer Fans Watching the 2010 World Cup Final

PubMed Central

van der Meij, Leander; Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; IJzerman, Hans; van Lange, Paul A. M.; Salvador, Alicia

2012-01-01

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem. PMID:22529940

The Impact of Exogenic Testosterone and Nortestosterone-Decanoate Toxicological Evaluation Using a Rat Model

PubMed Central

Cristina, Romeo Teodor; Hanganu, Flavia; Dumitrescu, Eugenia; Muselin, Florin; Butnariu, Monica; Constantin, Adriana; Chiurciu, Viorica

2014-01-01

The impact of exogenic testosterone (T): 1.5 and 3.0 mg/kg.bw) and 19-nortestosterone 17-decanoate (ND): 1.5 and 7.5 mg/kg.bw) in castrated male rats was evaluated based on: (a) weight increase of the androgen target tissues, respecting the Hershberger methodology; (b) the 17α and β-testosterone, 17 α and β-estradiol and 17 α and β-nortestosterone levels using the GC-MS/MS technique; and (c) observation of the serum free thyroxine levels (T4). Results revealed that T and ND significantly increased the weight of androgen target tissues as follows: ND was more influential on seminal vesicles, levator ani-bulbocavernosus muscle (LABC) and Cowper's glands and T (at a dose of 3.0 mg/kg.bw) influenced the weight of the ventral prostate and glans penis. Serum samples analyzed for steroid hormone levels showed the presence of 17β-testosterone, 17β-estradiol and 17β-nor-testosterone, in castrated male rats injected with testosterone and nortestosterone, but no significant differences were found between thyroid responses and thyroid hormone levels. The results of this research proved the disrupting activity of T and ND when administered in high doses and the useful application of the Hershberger bioassay in the case of ND. PMID:25302584

The Correlation among Neural Dynamic Processing of Conflict Control, Testosterone and Cortisol Levels in 10-Year-Old Children.

PubMed

Shangguan, Fangfang; Liu, Tongran; Liu, Xiuying; Shi, Jiannong

2017-01-01

Cognitive control is related to goal-directed self-regulation abilities, which is fundamental for human development. Conflict control includes the neural processes of conflict monitoring and conflict resolution. Testosterone and cortisol are essential hormones for the development of cognitive functions. However, there are no studies that have investigated the correlation of these two hormones with conflict control in preadolescents. In this study, we aimed to explore whether testosterone, cortisol, and testosterone/cortisol ratio worked differently for preadolescent's conflict control processes in varied conflict control tasks. Thirty-two 10-year-old children (16 boys and 16 girls) were enrolled. They were instructed to accomplish three conflict control tasks with different conflict dimensions, including the Flanker, Simon, and Stroop tasks, and electrophysiological signals were recorded. Salivary samples were collected from each child. The testosterone and cortisol levels were determined by enzyme-linked immunosorbent assay. The electrophysiological results showed that the incongruent trials induced greater N2/N450 and P3/SP responses than the congruent trials during neural processes of conflict monitoring and conflict resolution in the Flanker and Stroop tasks. The hormonal findings showed that (1) the testosterone/cortisol ratio was correlated with conflict control accuracy and conflict resolution in the Flanker task; (2) the testosterone level was associated with conflict control performance and neural processing of conflict resolution in the Stroop task; (3) the cortisol level was correlated with conflict control performance and neural processing of conflict monitoring in the Simon task. In conclusion, in 10-year-old children, the fewer processes a task needs, the more likely there is an association between the T/C ratios and the behavioral and brain response, and the dual-hormone effects on conflict resolution may be testosterone-driven in the Stroop and Flanker tasks.

Testosterone Regulates NUCB2 mRNA Expression in Male Mouse Hypothalamus and Pituitary Gland

PubMed Central

Seon, Sojeong; Jeon, Daun; Kim, Heejeong; Chung, Yiwa; Choi, Narae; Yang, Hyunwon

2017-01-01

ABSTRACT Nesfatin-1/NUCB2 is known to take part in the control of the appetite and energy metabolism. Recently, many reports have shown nesfatin-1/NUCB2 expression and function in various organs. We previously demonstrated that nesfatin-1/NUCB2 expression level is higher in the pituitary gland compared to other organs and its expression is regulated by 17β-estradiol and progesterone secreted from the ovary. However, currently no data exist on the expression of nesfatin-1/NUCB2 and its regulation mechanism in the pituitary of male mouse. Therefore, we examined whether nesfatin-1/NUCB2 is expressed in the male mouse pituitary and if its expression is regulated by testosterone. As a result of PCR and western blotting, we found that a large amount of nesfatin-1/NUCB2 was expressed in the pituitary and hypothalamus. The NUCB2 mRNA expression level in the pituitary was decreased after castration, but not in the hypothalamus. In addition, its mRNA expression level in the pituitary was increased after testosterone treatment in the castrated mice, whereas, the expression level in the hypothalamus was significantly decreased after the treatment with testosterone. The in vitro experiment to elucidate the direct effect of testosterone on NUCB2 mRNA expression showed that NUCB2 mRNA expression was significantly decreased with testosterone in cultured hypothalamus tissue, but increased with testosterone in cultured pituitary gland. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the male mouse pituitary and was regulated by testosterone. This data suggests that reproductive-endocrine regulation through hypothalamus-pituitary-testis axis may contribute to NUCB2 mRNA expression in the mouse hypothalamus and pituitary gland. PMID:28484746

The effects of competition and implicit power motive on men's testosterone, emotion recognition, and aggression.

PubMed

Vongas, John G; Al Hajj, Raghid

2017-06-01

A contribution to a special issue on Hormones and Human Competition. We investigated the effects of competition on men's testosterone levels and assessed whether androgen reactivity was associated with subsequent emotion recognition and reactive and proactive aggression. We also explored whether personalized power (p Power) moderated these relationships. In Study 1, 84 males competed on a number tracing task and interpreted emotions from facial expressions. In Study 2, 72 males competed on the same task and were assessed on proactive and reactive aggression. In both studies, contrary to the biosocial model of status (Mazur, 1985), winners' testosterone levels decreased significantly while losers' levels increased, albeit not significantly. Personalized power moderated the effect of competition outcome on testosterone change in both studies. Using the aggregate sample, we found that the effect of decreased testosterone levels among winners (compared to losers) was significant for individuals low in p Power but not for those with medium or high p Power. Testosterone change was positively related to emotion recognition, but unrelated to either aggression subtype. The testosterone-mediated relationship between winning and losing and emotion recognition was moderated by p Power. In addition, p Power moderated the direct (i.e., non-testosterone mediated) path between competition outcome and emotion recognition and both types of aggression: high p-Power winners were more accurate at deciphering others' emotions than high p-Power losers. Finally, among high p-Power men, winners aggressed more proactively than losers, whereas losers aggressed more reactively than winners. Collectively, these studies highlight the importance of implicit power motivation in modulating hormonal, cognitive, and behavioral outcomes arising from human competition. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of testosterone administration on liver structure and function in aging rats.

PubMed

Nucci, Ricardo Aparecido Baptista; Teodoro, Ana Caroline de Souza; Krause Neto, Walter; Silva, Wellington de Assis; de Souza, Romeu Rodrigues; Anaruma, Carlos Alberto; Gama, Eliane Florencio

2017-06-01

Aging males have a decrease in testosterone levels, by which the testosterone treatment may influence in a negatively fashion the liver. This study aimed to analyze the effects of aging with or without testosterone administration on the liver components of animals. Wistar rats were divided into three groups: 20 months' group (G20), 24 months' group (G24), group treated with testosterone for 16 weeks (GT). All groups were sacrificed at 24 months except for G20 that was sacrificed at 20 months. Aging and testosterone treatment alters the body weight (BW), liver weight (LW) and relative liver weight. Besides, testosterone increased the mitogen capacity of hepatocytes. Nonetheless, we reinforce the negative effects of testosterone on old animals' liver as chronic hepatic congestion and/or cholestasis. In addition, we observed that testosterone plays an important role on hepatic glycogen stores. Our study showed many implications for the knowledge about the effects of aging with or without testosterone administration on old animals' liver.

Testosterone and Jamaican Fathers : Exploring Links to Relationship Dynamics and Paternal Care.

PubMed

Gray, Peter B; Reece, Jody; Coore-Desai, Charlene; Dinall, Twana; Pellington, Sydonnie; Samms-Vaughan, Maureen

2017-06-01

This paper investigates relationships between men's testosterone and family life in a sample of approximately 350 Jamaican fathers of children 18-24 months of age. The study recognizes the role of testosterone as a proximate mechanism coordinating and reflecting male life history allocations within specific family and cultural contexts. A sample of Jamaican fathers and/or father figures reported to an assessment center for an interview based on a standardized questionnaire and provided a saliva sample for measuring testosterone level. Outcomes measured include subject demographics such as age and relationship status as well as partnership quality and sexuality and paternal attitudes and behavior. The variation in these fathers' relationship status (e.g., married co-residential fathers, fathers in new non-residential relationships) was not associated with men's testosterone. Too few stepfathers participated to enable a direct test of the prediction that stepfathers would have higher testosterone than biological fathers, although fathers who reported living with partners' (but not his own) children did not have higher testosterone than fathers not reporting residing with a non-biological child. Fathers' relationship quality was negatively related to their testosterone. Measures of paternal attitudes and behavior were not related to fathers' testosterone. Consistent with previous ethnography, this sample of Jamaican fathers exhibited variable life history profiles, including residential status. We discuss why fathers' relationship quality was found to be negatively related to their testosterone level, but other predictions were not upheld.

The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response.

PubMed

Roberts, Mark L; Buchanan, Katherine L; Evans, Matthew R; Marin, Raul H; Satterlee, Daniel G

2009-10-01

The immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birds' humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.

The role of fructose‑1,6‑bisphosphatase 1 in abnormal development of ovarian follicles caused by high testosterone concentration.

PubMed

Liu, Tao; Zhao, Han; Wang, Jianfeng; Shu, Xin; Gao, Yuan; Mu, Xiaoli; Gao, Fei; Liu, Hongbin

2017-11-01

The present study aimed to identify the molecular mechanisms underlying the effects of the fructose‑1,6‑bisphosphatase 1 (FBP1) signaling pathway within normal follicle development and in hyperandrogenism‑induced abnormal follicle growth. To achieve this, murine primary follicles, granulosa cells (GCs) and theca‑interstitial cells (TICs) were isolated, cultured in vitro and treated with a high concentration of androgens. A concentration of 1x10‑5 mol/l testosterone was considerable to induce hyperandrogenism by MTT assay. All cells were divided into four groups, as follows: Control group, testosterone group, androgen receptor antagonist‑flutamide group and flutamide + testosterone group. Flutamide was used in the present study as it blocks the effects of the androgen receptor. The mRNA expression levels of FBP1 were detected using reverse transcription‑quantitative polymerase chain reaction. The expression levels and localization of FBP1 were analyzed by western blot analysis and immunofluorescence staining. The experimental results demonstrated that androgen presence stimulated follicle development, whereas excessive testosterone inhibited development. FBP1 was identified as being mainly expressed in follicles; FBP1 protein was significantly expressed in GCs of the 14‑day‑cultured follicle, as well as in the cytoplasm and nuclei of GCs and TICs in vitro. Testosterone increased FBP1 expression during a specific range of testosterone concentrations. Testosterone increased the expression of FBP1 within GCs. Furthermore, FBP1 and phosphoenolpyruvate carboxykinase 1 (PCK1) mRNA expression was increased in GCs treated with testosterone, whereas forkhead box protein O1 (FOXO1) and peroxisome proliferator‑activated receptor γ coactivator‑1α mRNA expression was significantly decreased in the testosterone group. In TICs, testosterone and flutamide inhibited the mRNA expression levels of FOXO1 and glucose‑6‑phosphatase enzyme, and promoted the expression of PCK1. These results suggested that the FBP1 signaling pathway may serve an important role in normal follicle growth and hyperandrogenism‑induced abnormal development, which may be associated with abnormal glucose metabolism induced by high concentrations of testosterone.

Parenting styles and hormone levels as predictors of physical and indirect aggression in boys and girls.

PubMed

Pascual-Sagastizabal, Eider; Azurmendi, Aitziber; Braza, Francisco; Vergara, Ana I; Cardas, Jaione; Sánchez-Martín, José R

2014-01-01

This study examines the relationship between parenting style, androgen levels, and measures of physical and indirect aggression. Peer ratings of aggression were obtained from 159 eight-year-old children (89 boys and 70 girls). Parenting styles (authoritative, authoritarian or permissive) were assessed using the Parenting Styles and Dimensions Questionnaire (PSDQ).Saliva samples were obtained from children and assayed for testosterone and androstenedione concentrations. A regression analysis revealed that high testosterone levels were associated with a higher level of physical aggression in boys with authoritarian mothers. Testosterone was also found to moderate the relationship between father's authoritarian parenting and physical aggression in girls, with both moderate and high levels being significant. In relation to indirect aggression, moderate and high levels of testosterone were associated with higher levels of this type of aggression in girls with permissive mothers. Our results highlight the importance of taking into account the interaction of biological and psychosocial variables when investigating aggressive behavior. © 2014 Wiley Periodicals, Inc.

Effect of caricapryl-99 seed alkaloid extract on the serum levels of sex hormones and pituitary gonadotrophins in male albino rats.

PubMed

Udoh, P B; Udoh, F V; Umoren, E B; James, U W; Okeke, C P; Agwu, B

2009-06-01

Activity of alkaloid extract of caricapryl-99 seeds [Carica papaya Linn seeds] on the serum levels of steroid hormones was studied in adult male albino rats. Three tolerated doses obtained from the graph of percentage toxicity [10, 50 and 150 mg/kg] were separately administered orally, daily for three days to three groups of male rats [n=5] while group four of 5 rats received the vehicle [corn oil] as control. The results showed that 10 mg/kg/d caused increase serum levels of FSH and estrogen but decrease in the serum levels of LH and testosterone compared to control; 50 mg/kg/d elevated the serum levels of FSH, estrogen but inhibited testosterone; while 150 mg/kg/d pretreatments caused a significant decrease [p<0.01] in the serum levels of FSH, LH and testosterone. The results suggest that caricapryl-99 treatment inhibited the serum level of the androgen, testosterone which might result in a male infertility.

Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

PubMed

Eriksson, C J P; Etelälahti, T J; Apter, S J

2017-06-01

A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational stress than to intrinsic factors. In further studies, it should be investigated, whether the present results also apply to stress and human alcohol drinking. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of parenteral testosterone in hypospadias: A study from a teaching hospital in India

PubMed Central

Ahmad, Reyaz; Chana, Rajendra Singh; Ali, Syed Manazir; Khan, Shehtaj

2011-01-01

Objectives: To evaluate the effect of parenteral testosterone on penile length, preputial skin and side effects in patients with hypospadias. Materials and Methods: 23 patients with hypospadias were included in this study. An oily solution, each ml of which contained testosterone propionate 25 mg, and testosterone enanthate 110 mg, equivalent to 100 mg of testosterone was given deep intramuscularly 4, 3 and 2 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Increase in penile length, transverse preputial diameter, and diameter at the base of penis were noted. Basal testosterone levels were obtained before the institution of therapy and on the day of operation. In addition, side effect such as development of pubic hair and delay in bone age was noted. Results: Following parenteral testosterone administration, the mean increase in penile length, transverse preputial diameter and diameter at the base of penis was 1.35±0.40 cm (P<0.001), 1.40±0.47 cm (P<0.001), and 0.72±0.47 cm (P<0.001), respectively. Serum testosterone level after injection was well within normal range for that age. Minimal side effects were noted in form of development of fine pubic hair. Conclusion: We conclude that parenteral testosterone can be safely used to improve the surgical outcome of hypospadias repair. PMID:21976926

Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study.

PubMed

Safarinejad, Mohammad Reza

2005-01-01

To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Prostatic- Specific Antigen (PSA), testosterone levels, and prostate size. At the end of 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. 558 patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention- to-treat analysis, at the end of 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drug than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica dioica and from 19.2 to 17.7 with placebo (P = 0.002). Peak flow rates improved by 3.4 mL/s for placebo recipients and by 8.2 mL/s for treated patients (P < 0.05). In Urtica dioica group, PVR decreased from an initial value of 73 to 36 mL (P < 0.05). No appreciable change was seen in the placebo group. Serum PSA and testosterone levels were unchanged in both groups. A modest decrease in prostate size as measured by transrectal ultrasonography (TRUS) was seen in Urtica dioica group (from 40.1 cc initially to 36.3 cc; P < 0.001). There was no change in the prostate volume at the end of study with placebo. At 18-month follow-up, only patients who continued therapy, had a favorable treatment variables value. No side effects were identified in either group. In the present study, Urtica dioica have beneficial effects in the treatment of symptomatic BPH. Further clinical trials should be conducted to confirm these results before concluding that Urtica dioica is effective.

Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice

PubMed Central

Zang, Zhi-Jun; Tang, Hong-Feng; Tuo, Ying; Xing, Wei-Jie; Ji, Su-Yun; Gao, Yong; Deng, Chun-Hua

2016-01-01

Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg−1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo. PMID:26608944

Correlation Between Resting Testosterone/Cortisol Ratio and Sound-Induced Vasoconstriction at Fingertip in Men

PubMed Central

Ooishi, Yuuki

2018-01-01

A sound-induced sympathetic tone has been used as an index for orienting responses to auditory stimuli. The resting testosterone/cortisol ratio is a biomarker of social aggression that drives an approaching behavior in response to environmental stimuli, and a higher testosterone level and a lower cortisol level can facilitate the sympathetic response to environmental stimuli. Therefore, it is possible that the testosterone/cortisol ratio is correlated with the sound-induced sympathetic tone. The current study investigated the relationship between the resting testosterone/cortisol ratio and vasoconstriction induced by listening to sound stimuli. Twenty healthy males aged 29.0 ± 0.53 years (mean ± S.E.M) participated in the study. They came to the laboratory for 3 days and listened to one of three types of sound stimuli for 1 min on each day. Saliva samples were collected for an analysis of salivary testosterone and cortisol levels on the day of each experiment. After the collecting the saliva sample, we measured the blood volume pulse (BVP) amplitude at a fingertip. Since vasoconstriction is mediated by the activation of the sympathetic nerves, the strength of the reduction in BVP amplitude at a fingertip was called the BVP response (finger BVPR). No difference was observed between the sound-induced finger BVPR for the three types of sound stimuli (p = 0.779). The correlation coefficient between the sound-induced finger BVPR and the salivary testosterone/cortisol ratio within participants was significantly different from no correlation (p = 0.011) and there was a trend toward a significance in the correlation between the sound-induced finger BVPR and the salivary testosterone/cortisol ratio between participants (r = 0.39, p = 0.088). These results suggest that the testosterone/cortisol ratio affects the difference in the sound-evoked sympathetic response. PMID:29559922

Correlation Between Resting Testosterone/Cortisol Ratio and Sound-Induced Vasoconstriction at Fingertip in Men.

PubMed

Ooishi, Yuuki

2018-01-01

A sound-induced sympathetic tone has been used as an index for orienting responses to auditory stimuli. The resting testosterone/cortisol ratio is a biomarker of social aggression that drives an approaching behavior in response to environmental stimuli, and a higher testosterone level and a lower cortisol level can facilitate the sympathetic response to environmental stimuli. Therefore, it is possible that the testosterone/cortisol ratio is correlated with the sound-induced sympathetic tone. The current study investigated the relationship between the resting testosterone/cortisol ratio and vasoconstriction induced by listening to sound stimuli. Twenty healthy males aged 29.0 ± 0.53 years (mean ± S.E.M) participated in the study. They came to the laboratory for 3 days and listened to one of three types of sound stimuli for 1 min on each day. Saliva samples were collected for an analysis of salivary testosterone and cortisol levels on the day of each experiment. After the collecting the saliva sample, we measured the blood volume pulse (BVP) amplitude at a fingertip. Since vasoconstriction is mediated by the activation of the sympathetic nerves, the strength of the reduction in BVP amplitude at a fingertip was called the BVP response (finger BVPR). No difference was observed between the sound-induced finger BVPR for the three types of sound stimuli ( p = 0.779). The correlation coefficient between the sound-induced finger BVPR and the salivary testosterone/cortisol ratio within participants was significantly different from no correlation ( p = 0.011) and there was a trend toward a significance in the correlation between the sound-induced finger BVPR and the salivary testosterone/cortisol ratio between participants ( r = 0.39, p = 0.088). These results suggest that the testosterone/cortisol ratio affects the difference in the sound-evoked sympathetic response.

Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice.

PubMed

Zang, Zhi-Jun; Tang, Hong-Feng; Tuo, Ying; Xing, Wei-Jie; Ji, Su-Yun; Gao, Yong; Deng, Chun-Hua

2016-01-01

Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3β-HSD) and the following promotion of testosterone synthesis in vivo.

The interaction of serum testosterone levels and androgen receptor CAG repeat polymorphism on the risk of erectile dysfunction in aging Taiwanese men.

PubMed

Liu, C C; Lee, Y C; Tsai, V F S; Cheng, K H; Wu, W J; Bao, B Y; Huang, C N; Yeh, H C; Tsai, C C; Wang, C J; Huang, S P

2015-09-01

Testosterone has been found to play important roles in men's sexual function. However, the effects of testosterone can be modulated by androgen receptor (AR) CAG repeat polymorphism. It could also contribute to the risk of erectile dysfunction (ED). The aim of this study is to evaluate the interaction of serum testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging Taiwanese men. This cross-sectional data of Taiwanese men older than 40 years were collected from a free health screening held between August 2010 and August 2011 in Kaohsiung city, Taiwan. All participants completed a health questionnaires included five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptoms Score, received a detailed physical examination and provided 20 cm3 whole blood samples for biochemical and genetic evaluation. The IIEF-5 was used to evaluate ED. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Finally, 478 men with the mean age of 55.7 ± 4.8 years were included. When TT levels were above 330 ng/dL, the effect of testosterone level on erectile function seemed to reach a plateau and a significantly negative correlation between AR CAG repeat length and the score of IIEF-5 was found (r = -0.119, p = 0.034). After adjusting for other covariates, the longer AR CAG repeat length was still an independent risk factor for ED in subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or below. In conclusion, both serum testosterone levels and AR CAG repeat polymorphism can influence erectile function concomitantly. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing ED. © 2015 American Society of Andrology and European Academy of Andrology.

Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy.

PubMed

Hadji, P; Kauka, A; Bauer, T; Tams, J; Hasenburg, A; Kieback, D G

2012-10-01

The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.

AB19. Testosterone replacement therapy: how safe is it?

PubMed Central

Goldenberg, Larry

2014-01-01

Testosterone has a ubiquitous role in the male body and the importance of a decline in testosterone levels has wide ranging impact on: regulation of gonadal function, prostate development and growth, libido, cerebral function, behavior, mood, muscle mass, liver function, lipid regulation, bone formation, atherogenesis, erythropoiesis, hair growth and immune function. What the minimum required level of serum testosterone for the optimal health of each of these areas, nor whether each organ system’s biological response to increasing or decreasing testosterone levels follows a ‘dose-response’, ‘threshold’ or other behaviour is unclear. Late-onset hypogonadism (also known as age-associated testosterone deficiency syndrome) is a syndrome associated with advancing age and characterized by a spectrum of symptoms and a biochemical deficiency in serum testosterone levels below the young healthy adult male reference range (280-300 ng/dL; 9.8-10.4 nmol/L- Note: this level may vary in different laboratories). The decrease in serum testosterone levels seems to be a gradual, age-related process resulting in an approximate 1-2% annual decline after age 30 years, with a steep decline in bioavailable and free testosterone levels. The findings Baltimore Longitudinal Study of Aging demonstrated that 30% of men in their eighth have total testosterone values in the hypogonadal range (that is between 200 and 400 ng/dL), and 50% have low free testosterone values (5-9 ng/dL; 0.17-0.31 nmol/L). An estimated 500,000 new cases of late-onset hypogonadism occur annually in the USA, with similar levels reported worldwide. Testosterone deficiency has marked physiological and clinical effects on men in middle age and beyond. With subnormal testosterone levels, the potential positive benefits of TRT on factors such as muscle mass, libido or erectile function are likely a dose-response phenomena, and should be considered differently than the threshold impact on the prostate. The controversies surrounding testosterone replacement therapy (TRT) have been addressed in the past few years. Although the androgenic effects of TRT on normal and malignant prostate cells have been studied for over 70 years, little clinical prospective research exists on the physiological responses of prostate tissues to a wide range of serum testosterone levels. The early, well-designed in vivo studies formed the basis of the concept that testosterone has a threshold or saturation level in all types of androgen-dependent prostate cells. That is, the stimulatory effects of androgens on the prostate reach a point within physiological serum levels above which they no longer have any proliferative effect and serum levels of testosterone and dihydrotestosterone can decrease substantially in both the eugonadal and hypogonadal states without affecting the amount of androgen within the nucleus of the cell. At a certain threshold level (possibly ‘castrate’ level), the intranuclear level of androgen will begin to decrease and the appropriate physiological changes will be triggered. Questions remain as to whether results from experimental studies in the rat can be extrapolated to the situation in humans. Is the human prostate subject to the same homeostatic constraints as has been so well defined in animal experiments, and if so, what is the threshold or saturation level for maximal intracellular androgens and physiological responses in man? The sensitivity of an individual to varying levels of testosterone is also influenced by his genetic makeup, particularly polymorphisms in the androgen receptor, and other upstream signaling and downstream metabolic events, including diabetes mellitus and obesity. Despite decades of research, no compelling evidence exists that increasing testosterone beyond this threshold level has a causative role in prostate cancer, or indeed changes the biology of the disease. Notwithstanding this, the reluctance to utilize testosterone replacement has been incorporated into urological dogma and is largely responsible for the US FDA’s continuing caution about the relationship between therapy and initiation or progression of prostate cancer. Recent international concern has arisen on the potential negative impact of TRT on the cardiovascular system, specifically MI and CVA. This is based on the results of a clinical trial and two observational studies. The first study to identify an association was the Testosterone in Older Men (TOM) trial designed to evaluate the effect of a T gel on muscle strength and functionality in an elderly population. The study did show an increase in upper and lower limb strength but was terminated prematurely due to an increased cardiovascular event rate in men receiving T. But because of the low event rate, the fact that many men reached supraphysiologic levels of serum T and the fact that the study was not designed with any specific cardiovascular endpoints in mind, it is difficult to conclude from this study that T therapy places men at increased risk of CVS disease. The next publication by Vigen et al. was a retrospective, non-randomized, observational analysis of 8,709 men, 61 to 64 years, who had undergone coronary angiography in the VA system with a low serum total testosterone (<300 ng/dL), looking at the CV events after having filled a prescription for TRT, comparing to untreated patients. The actual CVS event rate was twice as high for the untreated men (21.2% vs. 10.1%) but after complex statistical modeling the number of events in the treated men tripled. This study has been widely discredited because of serious flaws. For example, many of the treated men did not achieve normal levels, most men did not fill their scripts for the full 4-year duration of the study, and almost 3,000 men who received TRT prior to angiography were excluded so all men began in the ‘no TRT’ group. Most importantly, the authors inexplicably excluded 1,132 men who suffered stroke or heart attack prior to receiving a testosterone prescription. These men all had events during the study period and all should have been included in the no-testosterone group. This would have increased the rate of events in the no-testosterone group by 71%, likely reversing the results. It is impossible to conclude from this study that testosterone prescriptions increase rates of cardiovascular events. In a third population-based retrospective, non-randomized, observational study (insurance claims) of a cohort of 55,593 men, Finkle and colleagues evaluated the rate of non fatal MI in the three months after either having filled a first prescription for TRT or a PDE5i and compared this rate to the rate of non fatal MI in the preceding year. The authors concluded that the risk of MI is increased in older men and in younger men with pre-existing known heart disease who received testosterone prescriptions. Unfortunately, this study also has flaws in that it is impossible from the design to distinguish whether any observed difference was due to the underlying condition (T deficiency) or to its treatment (T prescription). Also the shorter the exposure time for a drug, the less likely it is responsible for an observed difference and though the authors had long term data (12 months) they did not report, raising a concern that the observed difference no longer persisted over time. Contrary to these three studies, new retrospective studies reveal no CVS dangers of TRT, and in fact suggest a possible protective mechanism. One trial suggests a 7-fold decrease in risk of MI. These studies would support multiple previous publications that suggest that men with normal T levels actually have longer life expectancies than hypogonadal men and that both low and high T levels have negative physiologic impact on male health. In summary, “expert views” from all walks of life (endocrinologists, epidemiologists, gerontologists, public health experts and urologists; lay press and regulatory agencies; pharmaceutical and film industry) is resulting in a cacophony of opinions creating much confusion and detriment to patients and physicians alike. A properly funded and implemented longitudinal study, similar to the Women’s Health Initiative, is required before we can address the true prostate and cardiovascular safety of TRT in the hypogonadal man. Until then, the application of this therapy should be personalized to the needs of the individual.

Serum sex hormone and growth arrest-specific protein 6 levels in male patients with coronary heart disease.

PubMed

Zhao, Rui; Li, Yan; Dai, Wen

2016-01-01

Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease. Moreover, the tyrosine kinase receptor Axl, the ligand of which is growth arrest-specific protein 6 (GAS6), is expressed in the vasculature, and serum GAS6 levels are associated with endothelial dysfunction and cardiovascular events. Testosterone regulates GAS6 gene transcription directly, which inhibits calcification of vascular smooth muscle cells and provides a mechanistic insight into the cardioprotective action of androgens. This study was designed to determine the correlation between serum GAS6 and testosterone levels in male patients with coronary heart disease (CHD). We recruited 225 patients with CHD and 102 apparently healthy controls. Serum concentrations of GAS6 and soluble Axl were quantified by an enzyme-linked immunosorbent assay. Levels of high-sensitivity C-reactive protein, testosterone, estradiol, and other routine biochemical markers were also measured. Testosterone decreased from 432.69 ± 14.40 to 300.76 ± 6.23 ng dl-1 (P < 0.001) and GAS6 decreased from 16.20 ± 0.31 to 12.51 ± 0.19 ng ml-1 (P < 0.001) in patients with CHD, compared with control subjects. Multiple linear regression analysis showed that serum testosterone and GAS6 levels were positively associated in male patients with CHD. Alterations in GAS6 levels may influence the development of CHD. Downregulation of GAS6/Axl signaling in the presence of low sex hormone levels during disease progression is a potential mechanism by which GAS6 affects CHD. This study provides novel results regarding the influence of sex hormones on serum GAS6 levels in patients with CHD.

Seasonal changes in testosterone and corticosterone levels in four social classes of a desert dwelling sociable rodent.

PubMed

Schradin, Carsten

2008-04-01

Animals have to adjust their physiology to seasonal changes, in response to variation in food availability, social tactics and reproduction. I compared basal corticosterone and testosterone levels in free ranging striped mouse from a desert habitat, comparing between the sexes, breeding and philopatric non-breeding individuals, and between the breeding and the non-breeding season. I expected differences between breeders and non-breeders and between seasons with high and low food availability. Basal serum corticosterone was measured from 132 different individuals and serum testosterone from 176 different individuals of free living striped mice. Corticosterone and testosterone levels were independent of age, body weight and not influenced by carrying a transmitter. The levels of corticosterone and testosterone declined by approximately 50% from the breeding to the non-breeding season in breeding females as well as non-breeding males and females. In contrast, breeding males showed much lower corticosterone levels during the breeding season than all other classes, and were the only class that showed an increase of corticosterone from the breeding to the non-breeding season. As a result, breeding males had similar corticosterone levels as other social classes during the non-breeding season. During the breeding season, breeding males had much higher testosterone levels than other classes, which decreased significantly from the breeding to the non-breeding season. My results support the prediction that corticosterone decreases during periods of low food abundance. Variation in the pattern of hormonal secretion in striped mice might assist them to cope with seasonal changes in energy demand in a desert habitat.

Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment.

PubMed

Resnick, Susan M; Matsumoto, Alvin M; Stephens-Shields, Alisa J; Ellenberg, Susan S; Gill, Thomas M; Shumaker, Sally A; Pleasants, Debbie D; Barrett-Connor, Elizabeth; Bhasin, Shalender; Cauley, Jane A; Cella, David; Crandall, Jill P; Cunningham, Glenn R; Ensrud, Kristine E; Farrar, John T; Lewis, Cora E; Molitch, Mark E; Pahor, Marco; Swerdloff, Ronald S; Cifelli, Denise; Anton, Stephen; Basaria, Shehzad; Diem, Susan J; Wang, Christina; Hou, Xiaoling; Snyder, Peter J

2017-02-21

Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to -26), executive function (Trail-Making Test B minus A; range, -290 to 290), and spatial ability (Card Rotation Test; score range, -80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, -0.07 [95% CI, -0.92 to 0.79]; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (-0.28 [95% CI, -0.76 to 0.19]; P = .24), executive function (-5.51 [95% CI, -12.91 to 1.88]; P = .14), or spatial ability (-0.12 [95% CI, -1.89 to 1.65]; P = .89). Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions. clinicaltrials.gov Identifier: NCT00799617.

Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men.

PubMed

Clague, J E; Wu, F C; Horan, M A

1999-08-01

Muscle wasting in older men may be related to androgen deficiency. We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older (age > 60 years) men with blood testosterone levels < 14 nmol/L. Subjects (n = 7 per group) received testosterone enanthate 200 mg i.m. or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks. A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group. Total body mass, haemoglobin and packed cell volume also increased significantly (p < 0.05). No improvements in handgrip strength, isometric strength of knee flexors and extensors or leg extensor power were seen in either group. Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function.

Effects of a GnRH administration on testosterone profile, libido and semen parameters of dromedary camel bulls.

PubMed

Monaco, Davide; Fatnassi, Meriem; Padalino, Barbara; Aubé, Lydiane; Khorchani, Touhami; Hammadi, Mohamed; Lacalandra, Giovanni Michele

2015-10-01

GnRH treatment has been suggested to increase testosterone levels temporarily and to stimulate libido in stallions, but its use has not fully ascertained in dromedary camels. The aim of this work was to study the effects of administering 100 μg of GnRH on testosterone profile, libido and semen parameters in dromedary camels. The same bulls were used as self-controls and experimental group. Blood samples were collected every 20 min (T0-T12) for 4h, and semen collections were performed over a 2-hour period after T12. GnRH was administered immediately after T0. In GnRH-treated bulls, testosterone levels showed an upward trend, peaking after 140 min, and then slowly decreasing. GnRH administration also led to a decrease in mating time and an increase in spermatozoa concentration. Overall, it seems that administration of 100 μg GnRH might increase testosterone levels temporarily and enhance camel reproduction performance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Late-Onset Hypogonadism and Testosterone Replacement in Older Men.

PubMed

Bhattacharya, Rajib K; Bhattacharya, Shelley B

2015-11-01

Late-onset hypogonadism is an underdiagnosed and easily treated condition defined by low serum testosterone levels in men older than 65 years. When treated, a significant improvement in quality of life may be reached in this rapidly rising sector of the population. During the evaluation, laboratory tests and a full medication review should be performed to exclude other illnesses or adverse effects from medications. The major goal of treatment in this population is treating the symptoms related to hypogonadism. There has not been clear evidence supporting universally giving older men with low serum testosterone levels and hypogonadal symptoms testosterone replacement therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Estradiol and inflammatory markers in older men.

PubMed

Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Metter, E Jeffrey; Artoni, Andrea; Gatti, Elisa; Ruggiero, Carmelinda; Guralnik, Jack M; Valenti, Giorgio; Ling, Shari M; Basaria, Shehzad; Ferrucci, Luigi

2009-02-01

Aging is characterized by a mild proinflammatory state. In older men, low testosterone levels have been associated with increasing levels of proinflammatory cytokines. It is still unclear whether estradiol (E2), which generally has biological activities complementary to testosterone, affects inflammation. We analyzed data obtained from 399 men aged 65-95 yr enrolled in the Invecchiare in Chianti study with complete data on body mass index (BMI), serum E2, testosterone, IL-6, soluble IL-6 receptor, TNF-alpha, IL-1 receptor antagonist, and C-reactive protein. The relationship between E2 and inflammatory markers was examined using multivariate linear models adjusted for age, BMI, smoking, physical activity, chronic disease, and total testosterone. In age-adjusted analysis, log (E2) was positively associated with log (IL-6) (r = 0.19; P = 0.047), and the relationship was statistically significant (P = 0.032) after adjustments for age, BMI, smoking, physical activity, chronic disease, and serum testosterone levels. Log (E2) was not significantly associated with log (C-reactive protein), log (soluble IL-6 receptor), or log (TNF-alpha) in both age-adjusted and fully adjusted analyses. In older men, E2 is weakly positively associated with IL-6, independent of testosterone and other confounders including BMI.

Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women.

PubMed

Karolczak, Kamil; Konieczna, Lucyna; Kostka, Tomasz; Witas, Piotr J; Soltysik, Bartlomiej; Baczek, Tomasz; Watala, Cezary

2018-05-02

The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no ex vivo studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the ex vivo part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively associated with platelet activation and reactivity. These observations were confirmed in an in vitro model: testosterone and dihydrotestosterone significantly inhibited platelet aggregation triggered by arachidonate or collagen. Our findings indicate that testosterone and dihydrotestosterone are significant haemostatic steroids with inhibitory action on blood platelets in older people.

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

PubMed

Kulin, H E; Finkelstein, J W; D'Arcangelo, M R; Susman, E J; Chinchilli, V; Kunselman, S; Schwab, J; Demers, L; Lookingbill, G

1997-01-01

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

Testosterone and Occupational Achievement.

ERIC Educational Resources Information Center

Dabbs, James M., Jr.

1992-01-01

Archival data on 4,462 military veterans linked higher levels of serum testosterone to lower-status occupations. A structural equation model was supported in which higher testosterone, mediated through lower intellectual ability, greater antisocial behavior, and lower education, leads away from white-collar occupations. Contains 49 references.…

Determination of free and deconjugated testosterone and epitestosterone in urine using SPME and LC-MS/MS.

PubMed

Zhan, Yanwei; Musteata, Florin M; Basset, Fabien A; Pawliszyn, Janusz

2011-01-01

A thin sheet of polydimethylsilosane membrane was used as an extraction phase for solid-phase microextraction. Compared with fiber or rod solid-phase microextraction geometries, the thin film exhibited much higher extraction capacity without sacrificing extraction time due to its higher area-to-volume ratio. The analytical method involved direct extraction of unconjugated testosterone (T) and epitestosterone (ET) followed by separation on a C18 column and detection by selected reaction monitoring in positive ionization mode. The limit of detection was 1 ng/l for both T and ET. After method validation, free (unconjugated) T and ET were extracted and quantified in real samples. Since T and ET are extensively metabolized, the proposed method was also applied to extract the steroids after enzymatic deconjugation of urinary-excreted steroid glucuronides. The proposed method allows quantification of both conjugated and unconjugated steroids, and revealed that there was a change in the ratio of T to ET after enzymatic deconjugation, indicating different rates of metabolism.

Testosterone regulates erectile function and Vcsa1 expression in the corpora of rats.

PubMed

Chua, Rowena G; Calenda, Giulia; Zhang, Xinhua; Siragusa, Joseph; Tong, Yuehong; Tar, Moses; Aydin, Memduh; DiSanto, Michael E; Melman, Arnold; Davies, Kelvin P

2009-05-06

Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4 ng/ml to <0.04 ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2 mg in 100ml sesame oil every 4 days for 2 weeks) restored average levels of testosterone to 2 ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls.

Salivary testosterone and cortisol are jointly related to pro-environmental behavior in men.

PubMed

Sollberger, Silja; Bernauer, Thomas; Ehlert, Ulrike

2016-10-01

Recently, cortisol has been suggested to moderate the positive relationship between testosterone and antisocial behavior. More precisely, high testosterone levels have been found to be related to aggressive or dominant behavior especially when cortisol levels were low. In the present study, we aimed to extend these findings to pro-environmental behavior as an indicator of prosocial behavior. In a first step, 147 male participants provided information on their everyday pro-environmental behavior by completing an online questionnaire on various energy-saving behaviors. In a second step, subjects provided two saliva samples for the assessment of testosterone and cortisol on two subsequent mornings after awakening. We found that testosterone was negatively related to pro-environmental behavior, but only in men with low cortisol. In conclusion, our findings provide first evidence for the joint association of testosterone and cortisol with everyday pro-environmental behavior. These results further reinforce the importance of considering interdependent hormone systems simultaneously rather than focusing on a single hormone.

Testosterone administration decreases generosity in the ultimatum game.

PubMed

Zak, Paul J; Kurzban, Robert; Ahmadi, Sheila; Swerdloff, Ronald S; Park, Jang; Efremidze, Levan; Redwine, Karen; Morgan, Karla; Matzner, William

2009-12-16

How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72); 95% CI T: (.98, 2.30)). This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT). Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially.

Testosterone Administration Decreases Generosity in the Ultimatum Game

PubMed Central

Zak, Paul J.; Kurzban, Robert; Ahmadi, Sheila; Swerdloff, Ronald S.; Park, Jang; Efremidze, Levan; Redwine, Karen; Morgan, Karla; Matzner, William

2009-01-01

How do human beings decide when to be selfish or selfless? In this study, we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design. We also confirmed participants' testosterone levels before and after treatment through blood draws. Using the Ultimatum Game from behavioral economics, we find that men with artificially raised T, compared to themselves on placebo, were 27% less generous towards strangers with money they controlled (95% CI placebo: (1.70, 2.72); 95% CI T: (.98, 2.30)). This effect scales with a man's level of total-, free-, and dihydro-testosterone (DHT). Men in the lowest decile of DHT were 560% more generous than men in the highest decile of DHT. We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them. Our results continue to hold after controlling for altruism. We conclude that elevated testosterone causes men to behave antisocially. PMID:20016825

Uncarboxylated Osteocalcin and Gprc6a Axis Produce Intratumoral Androgens in Castration-Resistant Prostate Cancer

DTIC Science & Technology

2016-05-01

multiple pathways, despite castrate levels of testosterone . One such adaptive mechanism is the “intracrine” production of androgens in the primary...despite castrate levels of testosterone . One such adaptive mechanism is the “intracrine” production of androgens in the primary tumor and/or at... testosterone . Thus, just as the skeleton regulates fertility in an endocrine fashion, and it may also promote bone metastasis via an “intracrine” mechanism

Evidence of boldenone, nandrolone, 5(10)-estrene-3β-17α-diol and 4-estrene-3,17-dione as minor metabolites of testosterone in equine.

PubMed

Wong, Jenny K Y; Leung, David K K; Curl, Peter; Schiff, Peter J; Lam, Kenneth K H; Wan, Terence S M

2017-09-01

The detection of boldenone, nandrolone, 5(10)-estrene-3β,17α-diol, and 4-estrene-3,17-dione in a urine sample collected from a gelding having been treated with testosterone (500 mg 'Testosterone Suspension 100', single dose, injected intramuscularly) in 2009 led the authors' laboratory to suspect that these 'testicular' steroids could be minor metabolites of testosterone in geldings. Administration trials on six castrated horses with Testosterone Suspension 100 confirmed that low levels of boldenone, nandrolone, 5(10)-estrene-3β,17α-diol, and 4-estrene-3,17-dione could indeed be detected and confirmed in the early post-administration urine samples from all six geldings. Although boldenone has been reported to be present in urine after testosterone administration, there has been no direct evidence reported that boldenone, nandrolone, 5(10)-estrene-3β,17α-diol, and 4-estrene-3,17-dione are metabolites of testosterone in geldings. Subsequent in vitro experiments involving the incubation of testosterone with horse liver microsomes, liver, adipose and muscle tissues, and adrenal cortex homogenates failed to provide evidence that these four substances are minor metabolites of testosterone. An administration trial using 'Testosterone Suspension 100' supplemented with 13 C-labelled testosterone (500 mg, 1:1 ratio, injected intramuscularly) was performed. The similarities of the excretion curves of 12 C-testosterone and 13 C-testosterone in urine suggest that there was minimal kinetic isotope effect. 13 C-Labelled boldenone, nandrolone and 4-estrene-3,17-dione were detected but not 5(10)-estrene-3β,17α-diol and its 13 C-counterpart. This is the first unequivocal evidence of boldenone, nandrolone and 4-estrene-3,17-dione being metabolites of testosterone in geldings. In view of these results, caution should be exercised when interpreting findings of boldenone, nandrolone and/or 4-estrene-3,17-dione together with a relatively high level of testosterone in gelding urine. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Testosterone in human studies: Modest associations between plasma and salivary measurements.

PubMed

de Wit, A E; Bosker, F J; Giltay, E J; de Kloet, C S; Roelofs, K; van Pelt, J; Penninx, B W J H; Schoevers, R A

2018-02-01

Testosterone is involved in many processes like aggression and mood disorders. As it may easily diffuse from blood into saliva, salivary testosterone is thought to reflect plasma free testosterone level. If so, it would provide a welcome noninvasive and less stressful alternative to blood sampling. Past research did not reveal consensus regarding the strength of the association, but sample sizes were small. This study aimed to analyse the association in a large cohort. In total, 2,048 participants (age range 18-65 years; 696 males and 1,352 females) were included and saliva (using cotton Salivettes) and plasma were collected for testosterone measurements. Levels were determined by enzyme-linked immunosorbent assay and radioimmunoassay respectively. Free testosterone was calculated by the Vermeulen algorithm. Associations were determined using linear regression analyses. Plasma total and free testosterone showed a significant association with salivary testosterone in men (adjusted β = .09, p = .01; and β = .15, p < .001, respectively) and in women (adjusted β = .08, p = .004; and crude β = .09, p = .002 respectively). The modest associations indicate that there are many influencing factors of both technical and biological origin. © 2017 Blackwell Verlag GmbH.

Effects of Testosterone Therapy on Muscle Performance and Physical Function in Older Men with Mobility Limitations (The TOM Trial): Design and Methods

PubMed Central

LeBrasseur, Nathan K.; Lajevardi, Newsha; Miciek, Renee; Mazer, Norman; Storer, Thomas W.; Bhasin, Shalender

2010-01-01

The TOM study is the first, single-site, placebo-controlled, randomized clinical trial designed to comprehensively determine the effects of testosterone administration on muscle strength and physical function in older men with mobility limitations. A total of 252 community dwelling individuals aged 65 and older with low testosterone levels and self-reported limitations in mobility and short physical performance battery (SPPB) score between 4 and 9 will be randomized to receive either placebo or testosterone therapy for 6 months. The primary objective is to determine whether testosterone therapy improves maximal voluntary muscle strength as quantified by the one repetition maximum. Secondary outcomes will include measures of physical function (walking, stair climbing and a lifting and lowering task), habitual physical activity and self-reported disability. The effects of testosterone on affect, fatigue and sense of well being will also be assessed. Unique aspects of the TOM Trial include selection of men with self-reported as well as objectively demonstrable functional limitations, community-based screening and recruitment, adjustment of testosterone dose to ensure serum testosterone levels in the target range while maintaining blinding, and inclusion of a range of self-reported and performance-based physical function measures as outcomes. Clinicaltrials.gov identifier: NCT00240981. PMID:18996225

Effects of testosterone therapy on muscle performance and physical function in older men with mobility limitations (The TOM Trial): design and methods.

PubMed

LeBrasseur, Nathan K; Lajevardi, Newsha; Miciek, Renee; Mazer, Norman; Storer, Thomas W; Bhasin, Shalender

2009-03-01

The TOM study is the first, single-site, placebo-controlled, randomized clinical trial designed to comprehensively determine the effects of testosterone administration on muscle strength and physical function in older men with mobility limitations. A total of 252 community dwelling individuals aged 65 and older with low testosterone levels and self-reported limitations in mobility and short physical performance battery (SPPB) scores between 4 and 9 will be randomized to receive either placebo or testosterone therapy for 6 months. The primary objective is to determine whether testosterone therapy improves maximal voluntary muscle strength as quantified by the one repetition maximum. Secondary outcomes will include measures of physical function (walking, stair climbing and a lifting and lowering task), habitual physical activity and self-reported disability. The effects of testosterone on affect, fatigue and sense of well being will also be assessed. Unique aspects of the TOM Trial include selection of men with self-reported as well as objectively demonstrable functional limitations, community-based screening and recruitment, adjustment of testosterone dose to ensure serum testosterone levels in the target range while maintaining blinding, and inclusion of a range of self-reported and performance-based physical function measures as outcomes. Clinicaltrials.gov identifier: NCT00240981.

Prediabetes Is Associated with an Increased Risk of Testosterone Deficiency, Independent of Obesity and Metabolic Syndrome

PubMed Central

Ho, Chen-Hsun; Yu, Hong-Jeng; Wang, Chih-Yuan; Jaw, Fu-Shan; Hsieh, Ju-Ton; Liao, Wan-Chung; Pu, Yeong-Shiau; Liu, Shih-Ping

2013-01-01

Objective The association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency. Methods This study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen’s formula. Prediabetes was defined by impaired fasting glucose (IFG), impaired postprandial glucose (IPG), or glycated hemoglobin (HbA1c) 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR) for subnormal total testosterone (<300 ng/dL) or free testosterone (<6 ng/dL) in prediabetic and diabetic men compared with normoglycemic individuals, while adjusting for age, BMI, waist circumference, and metabolic syndrome (MetS). Results Normoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%), 543 (41.6%), and 186 (14.2%) men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54). The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50). IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses. Conclusions Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in men with prediabetes. PMID:24069277

Testosterone and aggressive behavior in man.

PubMed

Batrinos, Menelaos L

2012-01-01

Atavistic residues of aggressive behavior prevailing in animal life, determined by testosterone, remain attenuated in man and suppressed through familial and social inhibitions. However, it still manifests itself in various intensities and forms from; thoughts, anger, verbal aggressiveness, competition, dominance behavior, to physical violence. Testosterone plays a significant role in the arousal of these behavioral manifestations in the brain centers involved in aggression and on the development of the muscular system that enables their realization. There is evidence that testosterone levels are higher in individuals with aggressive behavior, such as prisoners who have committed violent crimes. Several field studies have also shown that testosterone levels increase during the aggressive phases of sports games. In more sensitive laboratory paradigms, it has been observed that participant's testosterone rises in the winners of; competitions, dominance trials or in confrontations with factitious opponents. Aggressive behavior arises in the brain through interplay between subcortical structures in the amygdala and the hypothalamus in which emotions are born and the prefrontal cognitive centers where emotions are perceived and controlled. The action of testosterone on the brain begins in the embryonic stage. Earlier in development at the DNA level, the number of CAG repeats in the androgen receptor gene seems to play a role in the expression of aggressive behavior. Neuroimaging techniques in adult males have shown that testosterone activates the amygdala enhancing its emotional activity and its resistance to prefrontal restraining control. This effect is opposed by the action of cortisol which facilitates prefrontal area cognitive control on impulsive tendencies aroused in the subcortical structures. The degree of impulsivity is regulated by serotonin inhibiting receptors, and with the intervention of this neurotransmitter the major agents of the neuroendocrine influence on the brain process of aggression forms a triad. Testosterone activates the subcortical areas of the brain to produce aggression, while cortisol and serotonin act antagonistically with testosterone to reduce its effects.

Effects of testosterone treatment on bone mineral density in men with testosterone deficiency syndrome.

PubMed

Rodriguez-Tolrà, J; Torremadé, J; di Gregorio, S; Del Rio, L; Franco, E

2013-07-01

The decline in testosterone levels found in men with testosterone deficiency syndrome (TDS) is associated with a decrease in bone mineral density (BMD). To study the safety profile and efficacy of testosterone treatment on BMD in patients with TDS. In this 2-year prospective open-label study, patients were administered 50 mg of testosterone gel daily (adjustable after 3 months up to 75-100 mg or down to 25 mg) for 12 months, followed by treatment with 1000 mg of testosterone undecanoate every 2-3 months from months 12-24. Outcome measures were as follows: (i) Changes in clinical chemistry safety parameters and total testosterone, sex hormone binding globulin and calculated free testosterone (cFT) levels; (ii) Changes in Aging Males' Symptoms Scale (AMS) and International Prostate Symptom Score scores; and (iii) Changes in lumbar spine and hip BMD. A total of 50 men aged 50-65 years with TDS (AMS >26 and cFT <0.250 nmol/mL) took part in the study. There was no significant impact of testosterone on safety. Prostate-specific antigen and haematopoietic parameters increased significantly, although the changes were not clinically significant. Total and cFT increased significantly after 3 months (p < 0.001) and there were significant improvements after 3 months in AMS scores (p < 0.001). BMD improved significantly in L2-L4 (2.90 and 4.5%), total femur (0.74 and 3%) and trochanter (1.09 and 3.2%) at 12 and 24 months respectively. Testosterone treatment in men with TDS has a good safety profile, leads to significant improvement in lumbar spine and hip BMD, and improves symptoms, as assessed by the AMS questionnaire. © 2013 American Society of Andrology and European Academy of Andrology.

Differential neural responses to child and sexual stimuli in human fathers and non-fathers and their hormonal correlates

PubMed Central

Mascaro, Jennifer S.; Hackett, Patrick D.; Rilling, James K.

2015-01-01

Despite the well-documented importance of paternal caregiving for positive child development, little is known about the neural changes that accompany the transition to fatherhood in humans, or about how changes in hormone levels affect paternal brain function. We compared fathers of children aged 1–2 with non-fathers in terms of hormone levels (oxytocin and testosterone), neural responses to child picture stimuli, and neural responses to visual sexual stimuli. Compared to non-fathers, fathers had significantly higher levels of plasma oxytocin and lower levels of plasma testosterone. In response to child picture stimuli, fathers showed stronger activation than non-fathers within regions important for face emotion processing (caudal middle frontal gyrus [MFG]), mentalizing (temporo-parietal junction [TPJ]) and reward processing (medial orbitofrontal cortex [mOFC]). On the other hand, non-fathers had significantly stronger neural responses to sexually provocative images in regions important for reward and approach-related motivation (dorsal caudate and nucleus accumbens). Testosterone levels were negatively correlated with responses to child stimuli in the MFG. Surprisingly, neither testosterone nor oxytocin levels predicted neural responses to sexual stimuli. Our results suggest that the decline in testosterone that accompanies the transition to fatherhood may be important for augmenting empathy toward children. PMID:24882167

The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50 years or older.

PubMed

Kim, Hye-Jung; Koo, Hyung Suk; Kim, Young-Sang; Kim, Moon Jong; Kim, Kwang-Min; Joo, Nam-Seok; Haam, Ji-Hee

2017-11-01

Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for the maintenance of bone health in men. However, the results for the association of testosterone and IGF-1 with bone parameters were not consistent in prior studies. We evaluated the relationship of testosterone, sex hormone-binding globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover markers (BTMs) in Korean men. We enrolled 1227 men aged ≥50 years in this cross-sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX) were measured. Free testosterone (FT) was calculated using Vermeulen's method. BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1, the association between TT and BTMs was significant (β = -0.139 for osteocalcin and β = -0.204 for CTX). SHBG levels were negatively associated with lumbar BMD, and positively associated with BTMs in all models. As SHBG level increased, the prevalence of osteopenia or osteoporosis defined by BMD significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly related with BMD, but not with BTMs. Meanwhile, FT levels were positively associated with BMD and negatively associated with BTMs. In conclusion, SHBG levels were independently related with bone parameters and osteopenia in men aged ≥50 years. IGF-1 levels were positively associated with BMD, but not with BTMs. SHBG may play a role in regulating age-related bone loss in men after middle-age.

Positive association of personal distress with testosterone in opiate-addicted patients.

PubMed

Stange, Katrin; Krüger, Mathias; Janke, Eva; Lichtinghagen, Ralf; Bleich, Stefan; Hillemacher, Thomas; Heberlein, Annemarie

2017-01-01

Clinical studies report that substance addictions are associated with sociocognitive impairments. Regarding opiate-addicted patients, the few existing studies point to deficits in empathic abilities. Previous research suggests that testosterone might be a relevant biomarker of these impairments. The authors aimed to investigate whether opiate-addicted patients show specific impairments in emotional (empathic concern, personal distress) and cognitive empathy compared to healthy controls. Furthermore, the authors aimed to assess possible associations of testosterone levels with impaired empathic abilities in the patients' group. In this cross-sectional study, 27 opiate-addicted, diacetylmorphine-maintained patients (21 males, age mean 41.67 years, standard deviation 8.814) and 31 healthy controls (23 males, age mean 40.77 years, standard deviation 8.401) matched in age, sex, and educational level were examined. Cognitive and emotional empathy were measured via the German version of the Interpersonal Reactivity Index and salivary testosterone levels were assessed. The authors found higher personal distress scores (p < 0.01, d = 0.817) and higher testosterone (p < 0.001, d = 1.093) in the patients' group compared to controls. Moreover, a positive correlation was found between testosterone and personal distress among the patients' group (r = 0.399, p < 0.05). Opiate-addicted patients show specific impairments in emotional empathy, namely higher personal distress, which has clinical implications regarding social cognition rehabilitation and relapse prevention. The current data point toward testosterone as a possible biomarker for these sociocognitive impairments and suggest that high personal distress and high testosterone during withdrawal are possible markers for severe opiate addiction.

A Low-Testosterone State Associated with Endometrioma Leads to the Apoptosis of Granulosa Cells

PubMed Central

Ono, Yoshihiro J.; Tanabe, Akiko; Nakamura, Yoko; Yamamoto, Hikaru; Hayashi, Atsushi; Tanaka, Tomohito; Sasaki, Hiroshi; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

2014-01-01

Although endometriosis is suspected to be a cause of premature ovarian insufficiency (POI), the mechanism(s) underlying this process have not been elucidated. Recently, androgens were shown to promote oocyte maturation and to play a role in folliculogenesis. In addition, several reports have documented low testosterone levels in the follicular fluid obtained from endometriosis patients. We therefore examined whether the low levels of serum testosterone are associated with the apoptosis of granulosa cells in follicles obtained from endometriosis patients. Serum samples were collected from 46 patients with endometriosis and from 62 patients without endometriosis who received assisted reproductive therapy. Specimens of the ovaries obtained from 10 patients with endometrioma were collected using laparoscopy. The mean serum testosterone concentration in the patients with endometriosis was significantly lower than that observed in the patients without endometriosis. Furthermore, high expression of a pro-apoptotic Bcl-2 member, BimEL, in the follicles was found to be associated with a low serum testosterone level. We clarified the underlying mechanisms using a basic approach employing human immortalized granulosa cells derived from a primary human granulosa cell tumor, the COV434 cell line. The in vitro examination demonstrated that testosterone inhibited apoptosis induced by sex steroids depletion via the PI3K/Akt-FoxO3a pathway in the COV434 cells. In conclusion, we elucidated the mechanism underlying the anti-apoptotic effects of testosterone on granulosa cells, and found that a low-testosterone status is a potentially important step in the development of premature ovarian insufficiency in patients with endometriosis. PMID:25536335

Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring

PubMed Central

Dasinger, John Henry; Fahling, Joel M.; Backstrom, Miles A.; Alexander, Barbara T.

2017-01-01

Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants. Using a rat model of low birth weight, we previously reported that placental insufficiency induces a significant increase in circulating testosterone in male intrauterine growth-restricted offspring (mIUGR) in early adulthood that is lost by 12 months of age. Numerous studies indicate testosterone has a positive effect on glucose metabolism in men. Female growth-restricted littermates exhibit glucose intolerance at 6 months of age. Thus, the aim of this paper was to determine whether mIUGR develop impaired glucose metabolism, and whether a decrease in elevated testosterone levels plays a role in its onset. Male growth-restricted offspring were studied at 6 and 12 months of age. No impairment in glucose tolerance was observed at 6 months of age when mIUGR exhibited a 2-fold higher testosterone level compared to age-matched control. Fasting blood glucose was significantly higher and glucose tolerance was impaired with a significant decrease in circulating testosterone in mIUGR at 12 compared with 6 months of age. Castration did not additionally impair fasting blood glucose or glucose tolerance in mIUGR at 12 months of age, but fasting blood glucose was significantly elevated in castrated controls. Restoration of elevated testosterone levels significantly reduced fasting blood glucose and improved glucose tolerance in mIUGR. Thus, our findings suggest that the endogenous increase in circulating testosterone in mIUGR is protective against impaired glucose homeostasis. PMID:29145418

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, R. Charles, E-mail: rnichols@floridaproton.org; University of Florida Proton Therapy Institute, Jacksonville, FL; Morris, Christopher G.

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. Themore » pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.« less

The use of testosterone as a male contraceptive.

PubMed

Amory, J K; Bremner, W J

1998-10-01

Testosterone functions as a contraceptive by suppressing secretion of the pituitary gonadotropins luteinizing hormone and follicle stimulating hormone. Low levels of these hormones decrease endogenous testosterone secretion from the testis and deprive developing sperm of the signals required for normal maturation. Interference with sperm maturation causes a decline in sperm production and can lead to reversible infertility in men, raising the possibility that testosterone could be utilized in a commercially available contraceptive. To this end, testosterone has been studied alone and in combination with either gonadotropin releasing hormone analogues or progestins in efforts to improve its contraceptive efficacy. In this chapter, we will review efforts to use testosterone to create a safe, convenient, efficacious contraceptive method for men.

The association of latent toxoplasmosis and level of serum testosterone in humans.

PubMed

Zouei, Nima; Shojaee, Saeedeh; Mohebali, Mehdi; Keshavarz, Hossein

2018-06-08

Latent toxoplasmosis modifies various hormones and behaviors in infected hosts and possibly involves in etiology of different neurologic and psychiatric disorders. The aim of the current study was to assess possible associations between latent toxoplasmosis and testosterone concentration in Toxoplasma infected and free subjects. Briefly, 18-49 year-old participated in the study. After collected blood samples, sera were analyzed for the detection of anti-Toxoplasma IgG antibody. Totally, 76 positive sera were selected as study group (38 from men and 38 from women) and a same number of negative sera as control group. Comparison of testosterone concentrations and control groups showed that testosterone concentration in study group was higher than that in control group with statistically significant difference (P = 0.024 and P = 0.043 for men and women, respectively). Significant differences were found in testosterone concentrations and anti-Toxoplasma IgG antibody levels in study and control groups (P < 0.05). Toxoplasmosis can affect the mean concentration of serum testosterone in human. Alteration of testosterone during latent toxoplasmosis can result in alterations in behavioral, physiologic and immunological parameters in long time.

Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors.

PubMed

Wu, Yue; Godoy, Alejandro; Azzouni, Faris; Wilton, John H; Ip, Clement; Mohler, James L

2013-09-01

Blocking 5α-reductase-mediated testosterone conversion to dihydrotestosterone (DHT) with finasteride or dutasteride is the driving hypothesis behind two prostate cancer prevention trials. Factors affecting intracellular androgen levels and the androgen receptor (AR) signaling axis need to be examined systematically in order to fully understand the outcome of interventions using these drugs. The expression of three 5α-reductase isozymes, as determined by immunohistochemistry and qRT-PCR, was studied in five human prostate cancer cell lines. Intracellular testosterone and DHT were analyzed using mass spectrometry. A luciferase reporter assay and AR-regulated genes were used to evaluate the modulation of AR activity. Prostate cancer cells were capable of accumulating testosterone to a level 15-50 times higher than that in the medium. The profile and expression of 5α-reductase isozymes did not predict the capacity to convert testosterone to DHT. Finasteride and dutasteride were able to depress testosterone uptake in addition to lowering intracellular DHT. The inhibition of AR activity following drug treatment often exceeded the expected response due to reduced availability of DHT. The ability to maintain high intracellular testosterone might compensate for the shortage of DHT. The biological effect of finasteride or dutasteride appears to be complex and may depend on the interplay of several factors, which include testosterone turnover, enzymology of DHT production, ability to use testosterone and DHT interchangeably, and propensity of cells for off-target AR inhibitory effect. © 2013 Wiley Periodicals, Inc.

Salivary testosterone may not serve as a screening test in the diagnosis of biochemical hyperandrogenism.

PubMed

Ambroziak, Urszula; Kuryłowicz, Alina; Kępczyńska-Nyk, Anna; Kondracka, Agnieszka; Gajda, Sylvia; Sieńko, Damian

2018-06-01

The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism. © 2018 Japan Society of Obstetrics and Gynecology.

Marijuana use and serum testosterone concentrations among U.S. males.

PubMed

Thistle, J E; Graubard, B I; Braunlin, M; Vesper, H; Trabert, B; Cook, M B; McGlynn, K A

2017-07-01

Marijuana has been reported to have several effects on the male reproductive system. Marijuana has previously been linked to reduced adult testosterone, however, a study in Denmark reported increased testosterone concentrations among marijuana users. This study was performed to estimate the effect of marijuana use on testosterone in U.S. males. Data on serum testosterone, marijuana use, and covariates for 1577 men from the 2011-2012 U.S. National Health and Nutrition Examination Survey (NHANES) were analyzed. Information on marijuana use was collected by a self-administered computer-assisted questionnaire. Serum testosterone was determined using isotope dilution liquid chromatography tandem mass spectrometry. The effects of marijuana use on serum testosterone concentrations were examined by frequency, duration, and recency of use. Adjusted means and 95% confidence intervals (CI) of serum testosterone across levels of marijuana use were estimated using multiple linear regression weighted by the survey weights. The majority (66.2%) of the weighted study population reported ever using marijuana with 26.6% reporting current marijuana use. There was no difference in serum testosterone between ever users (adjusted mean = 3.69 ng/mL, 95% CI: 3.46, 3.93) and never users (adjusted mean = 3.70 ng/mL, 95% CI: 3.45, 3.98) upon multivariable analysis. However, serum testosterone was inversely associated with time since last regular use of marijuana (p-value for trend = 0.02). When restricted to men aged 18-29 years, this relationship strengthened (p-value for trend <0.01), and serum testosterone was also inversely associated with time since last use (p-value for trend <0.01), indicating that recency of use, and not duration or frequency, had the strongest relationship with testosterone levels. Serum testosterone concentrations were higher in men with more recent marijuana use. Studies are needed to determine the extent to which circulating testosterone concentrations mediate the relationship of marijuana use with male reproductive outcomes. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

PubMed Central

Khairullah, Ammar; Cousino Klein, Laura; Ingle, Suzanne M.; May, Margaret T.; Whetzel, Courtney A.; Susman, Elizabeth J.; Paus, Tomáš

2014-01-01

Purpose Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development. Methods We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant’s testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years. Results The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty. Conclusions The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics. PMID:25268961

Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels.

PubMed

Morgentaler, Abraham; Polzer, Paula; Althof, Stanley; Bolyakov, Alexander; Donatucci, Craig; Ni, Xiao; Patel, Ankur B; Basaria, Shehzad

2017-09-01

Although delayed ejaculation (DE) is typically characterized as a persistently longer than anticipated or desired time to ejaculation (or orgasm) during sexual activity, a timing-based definition of DE and its association with serum testosterone has not been established in a large cohort. To examine in an observational study estimated intravaginal ejaculatory latency time (IELT) and masturbatory ejaculation latency time (MELT) in men self-reporting DE, assess the association of IELT and MELT with serum testosterone levels, and determine whether correlation with demographic and sexual parameters exist. Men who resided in the United States, Canada, and Mexico were enrolled from 2011 to 2013. Self-estimated IELT and MELT were captured using an Ejaculatory Function Screening Questionnaire in a sample of 988 men screened for possible inclusion in a randomized clinical trial assessing testosterone replacement therapy for ejaculatory dysfunction (EjD) and who self-reported the presence or absence of DE and symptoms of hypogonadism. Additional comorbid EjDs (ie, anejaculation, perceived decrease in ejaculate volume, and decreased force of ejaculation) were recorded. Men with premature ejaculation were excluded from this analysis. IELT and MELT were compared between men self-reporting DE and men without DE. The associations of IELT and MELT with serum testosterone were measured. IELT, MELT, and total testosterone levels. Sixty-two percent of screened men self-reported DE with or without comorbid EjDs; 38% did not report DE but did report at least one of the other EjDs. Estimated median IELTs were 20.0 minutes for DE vs 15 minutes for no DE (P < .001). Estimated median MELTs were 15.0 minutes for DE vs 8.0 minutes for no DE (P < .001). Ejaculation time was not associated with serum testosterone levels. Younger men and those with less severe erectile dysfunction had longer IELTs and MELTs. Estimated ejaculation times during vaginal intercourse and/or masturbation were not associated with serum testosterone levels in this study; thus, routine androgen evaluation is not indicated in these men. This large systematic analysis attempted to objectively assess the ejaculation latency in men with self-reported DE. Limitations were that ejaculation time estimates were self-reported and were queried only once; the questionnaire did not distinguish between failure to achieve orgasm and ejaculation; and assessment of DE was limited to heterosexual vaginal intercourse and masturbation. IELT and MELT were longer in men with DE, and there was no association of ejaculation times with serum testosterone levels in this study population. Morgentaler A, Polzer P, Althof S, et al. Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels. J Sex Med 2017;14:1116-1124. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Endocrine events associated with spawning behavior in the sea lamprey (Petromyzon marinus)

USGS Publications Warehouse

Linville, Jane E.; Hanson, Lee H.; Sower, Stacia A.

1987-01-01

Levels of estradiol, progesterone, and testosterone were determined in plasma of sea lamprey (Petromyzon marinus) undergoing certain behaviors associated with spawning in natural and artifical stream environments. Significantly higher levels of estradiol, progesterone, and testosterone were found in males than in females. In the artifical spawning channel, levels of estradiol were significantly higher in females exhibiting resting and swimming behaviors than in fanning, nest building, and spawning behaviors. No significant correlation was found with either progesterone or testosterone levels and the various reproductive behaviors. The data presented are the first experimental evidence that suggest gonadal steroids may be correlated with certain reproductive behaviors in the sea lamprey.

Demographic and Clinical Correlates of Patient-Reported Improvement in Sex Drive, Erectile Function, and Energy With Testosterone Solution 2.

PubMed

Wu, Frederick; Zitzmann, Michael; Heiselman, Darell; Donatucci, Craig; Knorr, Jack; Patel, Ankur B; Kinchen, Kraig

2016-08-01

Evidence from well-designed studies documenting the benefit of testosterone replacement therapy as a function of patient demographic and clinical characteristics is lacking. To determine demographic and clinical predictors of treatment outcomes in hypogonadal men with low sex drive, low energy, and/or erectile dysfunction. Post hoc analysis of a randomized, multicenter, double-blinded, placebo-controlled, 16-week study of 715 hypogonadal men (mean age = 55.3 years, age range = 19-92 years) presenting with low sex drive and/or low energy who received placebo or testosterone solution 2% for 12 weeks. Two levels defined patient-reported improvement (PRI) in sex drive or energy: level 1 was at least "a little better" and level 2 was at least "much better" in energy or sex drive on the Patient Global Impression of Improvement at study end point. PRI in erectile function was stratified by erectile dysfunction severity at baseline as measured by the erectile function domain of the International Index for Erectile Function: mild at baseline (change of 2), moderate at baseline (change of 5), and severe at baseline (change of 7). Associations of demographic and clinical characteristics with PRI were calculated with stepwise forward multiple logistic regression analysis. Odds ratios represented the likelihood of PRI in symptoms among variable categories. Higher levels of end-point testosterone were associated with higher rates of PRI (at levels 1 and 2) in sex drive and energy (P < .001 for the two comparisons). Lower baseline testosterone levels were associated with higher rates of level 1 PRI in sex drive (P = .028); and classic hypogonadism (vs non-classic hypogonadism) was associated with higher rates of level 2 PRI in sex drive (P = .005) and energy (P = .006). When assessing the potential for improvements in men with testosterone deficiency using patient-reported outcome questionnaires, possible predictors of treatment outcomes to consider include the etiology of hypogonadism and testosterone levels (baseline and end point). Copyright © 2016. Published by Elsevier Inc.

Reduction of spermatogonia and testosterone in rat testes flown on Space Lab-3

NASA Technical Reports Server (NTRS)

Philpott, Delbert E.; Stevenson, J.; Black, S.; Sapp, W.; Williams, C.

1986-01-01

The effects of space flight on rat testes were investigated. The weight, spermatogonial cell count, and testosterone levels in six rats flown on Space Lab-3 were measured. It is observed that compared to ground control rats the average weight loss was 7.1 percent and the spermatogonial cell count decreased by 7.5 percent. The data reveal that the testosterone level for large control rats was 9.13 ng/ml and 0.31 ng/ml for flight rats; and 2.54 ng/ml and 0.233 ng/ml for smaller control and flight rats, respectively. It is noted that spermatogenesis and testosterone production are reduced during spaceflight.

Influence of testosterone gel treatment on spermatogenesis in men with hypogonadism.

PubMed

George, Mskhalaya; Yulia, Tishova; Svetlana, Kalinchenko

2014-10-01

The prevalence of androgen deficiency in reproductive-aged men is increasing and needs new approach to long-term hypogonadism treatment that can preserve fertility. An open non-controlled pilot study included 18 men with eugonadotropic hypogonadism, who received transdermal testosterone gel treatment for 3 months. Sperm analysis was made before treatment and after 3 month of testosterone therapy. Testosterone level was normalized in all patients, but no negative effect was observed on spermatogenesis. Testosterone gel therapy may be a therapy of choice in hypogonadal men of reproductive age but further studies are needed.

Sexual dysfunction and neuroendocrine correlates of posttraumatic stress disorder in combat veterans: Preliminary findings.

PubMed

Lehrner, Amy; Flory, Janine D; Bierer, Linda M; Makotkine, Iouri; Marmar, Charles R; Yehuda, Rachel

2016-01-01

Sexual dysfunction is not a symptom of PTSD but is a common clinical complaint in trauma survivors with this disorder. In that there are biological parallels in the neuroendocrine processes underlying both PTSD and sexual behavior, we conducted an exploratory investigation of the relationship of PTSD and related neuroendocrine indicators with sexual dysfunction in armed service veterans. Major Depressive Disorder, highly comorbid with PTSD and sexual dysfunction, was also assessed. In veterans with PTSD, sexual problems were associated with plasma DHEA and cortisol, urinary catecholamines, and glucocorticoid sensitivity, even when controlling for the effects of comorbid depression. In a subsample analysis, testosterone levels did not distinguish PTSD or sexual dysfunction, suggesting that sexual problems reported by veterans in this sample were not the result of organic disorder. PTSD did predict higher dihydrotestosterone (DHT) levels, which were associated with sexual problems. More detailed assessment of sexual dysfunction in biologically informed studies of PTSD is warranted to clarify the relationships of PTSD symptomatology and related neurobiology with sexual dysfunction. Published by Elsevier Ltd.

Prospective Analysis on the Effect of Botanical Medicine (Tribulus terrestris) on Serum Testosterone Level and Semen Parameters in Males with Unexplained Infertility.

PubMed

Roaiah, Mohamed Farid; Elkhayat, Yasser Ibrahim; Saleh, Sameh Fayek GamalEl Din; Abd El Salam, Mohamed Ahmed

2016-06-23

We evaluated the role of Tribulus terrestris in males with unexplained infertility and its effect on serum testosterone and semen parameters. Thirty randomized male patients presenting to Andrology outpatient clinic complaining of idiopathic infertility were selected. They were given Tribulus terrestris (750 mg) in three divided doses for three months. The effect of Tribulus terrestris on serum testosterone (total and free) and luteinizing hormone (LH), as well as its impact on semen parameters in those patients, was studied. No statistically significant difference was observed in the levels of testosterone (total and free) and LH and semen parameters (sperm concentration or motility, or abnormal forms) before and after the treatment. In addition, no statistically significant correlations were observed between testosterone (free and total) and LH and semen parameters before and after the treatment. Tribulus terrestris was ineffective in the treatment of idiopathic infertility.

Abnormal pituitary-gonadal axis may be responsible for rat decreased testicular function under simulated microgravity

NASA Astrophysics Data System (ADS)

Zhou, Yi; Tan, Xin; Zhu, Bao-an; Qi, Meng-di; Ding, Su-ling

Space flight and simulated microgravity lead to suppression of mammalian spermatogenesis and decreased plasma testosterone level. In order to explain the mechanism behind the depression, we used rat tail-suspended model to simulate weightless conditions. To prevent cryptorchidism caused by tail-suspension, some experimental animals received inguinal canal ligation. The results showed that mass of testis decreased significantly and seminiferous tubules became atrophied in rats after tail-suspension. The levels of plasma testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in tail-suspended rats with or without inguinal canal ligation decreased significantly compared with controls, and an increased level of plasma estradiol (E) was revealed in tail-suspended rats. The results indicate that besides the direct influence of fluid shift upon testis under short-term simulated microgravity, the pituitary function is also disturbed as a result of either immobilization stress or weight loss during tail-suspension treatment, which is responsible to some extent for the decreased testosterone secretion level and the atrophia of testis. The conversion of testosterone into E under simulated microgravity is another possible cause for the decline of plasma testosterone.

Pilot Study on the Effect of Botanical Medicine (Tribulus terrestris) on Serum Testosterone Level and Erectile Function in Aging Males With Partial Androgen Deficiency (PADAM).

PubMed

Roaiah, Mohamed Farid; El Khayat, Yasser Ibrahim; GamalEl Din, Sameh Fayek; Abd El Salam, Mohamed Ahmed

2016-05-18

This study was conducted on 30 consecutive male patients presenting to Kasr-Al Ainy Andrology outpatient clinic complaining of manifestations of partial androgen deficiency in aging males (PADAM). In this study (750 mg/day) of Tribulus terrestris in 3 divided doses, each of 250 mg, as an endogenous testosterone enhancer had been tried for a duration of 3 months and the evaluation of its effect had been monitored for each patient concerning its effect on serum testosterone (total and free) and luteinizing hormone (LH), as well as its impact on erectile function, which was evaluated by the International Index of Erectile Function-5 (IIEF-5) questionnaire for those patients. Results showed a statistically significant difference in the level of testosterone (total and free) and IIEF-5, but no statistically significant difference in the level of LH before and after treatment. Also, the study showed statistically significant correlation between testosterone (total and free) and IIEF-5, but no statistically significant correlation between the level of LH and the IIEF-5 before and after treatment.

Allo-parental care in Damaraland mole-rats is female biased and age dependent, though independent of testosterone levels.

PubMed

Zöttl, Markus; Vullioud, Philippe; Goddard, Katy; Torrents-Ticó, Miquel; Gaynor, David; Bennett, Nigel C; Clutton-Brock, Tim

2018-05-02

In Damaraland mole-rats (Fukomys damarensis), non-breeding subordinates contribute to the care of offspring born to the breeding pair in their group by carrying and retrieving young to the nest. In social mole-rats and some cooperative breeders, dominant females show unusually high testosterone levels and it has been suggested that high testosterone levels may increase reproductive and aggressive behavior and reduce investment in allo-parental and parental care, generating age and state-dependent variation in behavior. Here we show that, in Damaraland mole-rats, allo-parental care in males and females is unaffected by experimental increases in testosterone levels. Pup carrying decreases with age of the non-breeding helper while the change in social status from non-breeder to breeder has contrasting effects in the two sexes. Female breeders were more likely than female non-breeders to carry pups but male breeders were less likely to carry pups than male non-breeders, increasing the sex bias in parental care compared to allo-parental care. Our results indicate that testosterone is unlikely to be an important regulator of allo-parental care in mole-rats. Copyright © 2018. Published by Elsevier Inc.

Optimal diagnostic measures and thresholds for hypogonadism in men with HIV/AIDS: comparison between 2 transdermal testosterone replacement therapy gels.

PubMed

Blick, Gary

2013-03-01

To determine the incidence of hypogonadism in men with human immunodeficiency virus (HIV)/acquired immunodeficiency virus (AIDS), the most useful serum testosterone measurement and threshold for diagnosing hypogonadism, and the comparative efficacy of 2 testosterone replacement therapy (TRT) 1% gels (AndroGel® [Abbott Laboratories] and Testim® [Auxilium Pharmaceuticals, Inc.]). This was a 2-stage observational study. In stage 1, patient records from 2 medical practices specializing in HIV/AIDS were reviewed. Eligible patients were aged ≥ 18 years; had HIV-seropositive status confirmed by enzyme-linked immunosorbent assay and western blot test or HIV-1 viremia confirmed by HIV-1 RNA polymerase chain reaction; and had prior baseline testosterone assessments for hypogonadism (ie, presence of signs/symptoms of hypogonadism as well as total testosterone [TT] and free testosterone [FT] level measurements). Stage 2 included the evaluation of patients from stage 1 who were treated with 5 to 10 g/day of TRT. The stage 2 inclusion criteria were a diagnosis of low testosterone (defined as TT level < 300 ng/dL and/or FT level < 50 pg/mL, as per The Endocrine Society guidelines and presence/absence of hypogonadal signs and symptoms); ≥ 12 months of evaluable sign and symptom assessments and TT/FT level measurements while on TRT with either Testim® or AndroGel®; and ≥ 4 weeks on initial TRT if the initial TRT was switched or discontinued. Four hundred one of 422 patients met the stage 1 inclusion criteria and 167 of 401 patients (AndroGel®, n = 92; Testim®, n = 75) met the stage 2 inclusion criteria. Total testosterone level < 300 ng/dL alone identified 24% (94 of 390) of patients as hypogonadal, but failed to diagnose an additional 111 patients (67.7%) with FT levels < 100 pg/mL and hypogonadal symptoms. Through month 12, AndroGel® increased mean TT levels by +42.8% and FT levels by +66.9%, compared with +178.7% (P = 0.017) and +191% (P = 0.039), respectively, for Testim®. Patients treated with Testim® showed significantly greater improvements in libido, sexual performance, nighttime energy, focus/concentration, and abdominal girth, and trends for greater improvement in fatigue and erectile dysfunction than patients treated with AndroGel®. No patients discontinued therapy due to adverse events. The most useful serum testosterone measurement and threshold for diagnosing hypogonadism in men with HIV/AIDS was FT level < 100 pg/mL, which identified 64% of men as hypogonadal with the presence of ≥ 1 hypogonadal symptom. This is above currently accepted thresholds. Criteria using TT level < 300 ng/dL and FT level < 50 pg/mL only diagnosed 24% and 19% of patients, respectively, as having hypogonadism. Testim® was more effective than AndroGel® in increasing TT and FT levels and improving hypogonadal symptoms.

Quantitative trait loci that control body weight in DDD/Sgn and C57BL/6J inbred mice.

PubMed

Suto, Jun-Ichi; Kojima, Misaki

2017-02-01

Inbred DDD/Sgn mice are heavier than inbred C57BL/6J mice. In the present study, we performed quantitative trait loci (QTL) mapping for body weight using R/qtl in reciprocal F 2 male populations between the two strains. We identified four significant QTL on Chrs 1, 2, 5, and 17 (proximal region). The DDD/Sgn allele was associated with increased body weight at QTL on Chrs 1 and 5, and the DDD/Sgn allele was associated with decreased body weight at QTL on Chrs 2 and 17. A multiple regression analysis indicated that the detected QTL explain 30.94 % of the body weight variation. Because DDD/Sgn male mice have extremely high levels of circulating testosterone relative to other inbred mouse strains, we performed QTL mapping for plasma testosterone level to examine the effect of testosterone levels on body weight. We identified one suggestive QTL on Chr 5, which overlapped with body weight QTL. The DDD/Sgn allele was associated with increased testosterone level. Thus, we confirmed that there was a genetic basis for the changes in body weight and testosterone levels in male mice. These findings provide insights into the genetic mechanism by which body weight is controlled in male mice.

Low testosterone levels in elderly men with dysthymic disorder.

PubMed

Seidman, Stuart N; Araujo, Andre B; Roose, Steven P; Devanand, D P; Xie, Shan; Cooper, Thomas B; McKinlay, John B

2002-03-01

A decline in hypothalamic-pituitary-gonadal (HPG) axis function is often seen in elderly men, and dysthymic disorder is common. Symptoms of both HPG axis hypofunction and dysthymic disorder include dysphoria, fatigue, and low libido. The authors compared total testosterone levels in three groups of elderly men. Total testosterone levels were measured in subjects who met DSM-IV criteria for major depressive disorder (N=13) or dysthymic disorder (N=32) and a comparison group (N=175) who had participated in an epidemiological study of male aging and had scored below the median on the Center for Epidemiologic Studies Depression Scale, a well-validated, self-report depression symptom inventory. There were no differences among the three groups in measured demographic variables, including age and weight. Median testosterone levels varied for those with dysthymic disorder (295 ng/dl), major depressive disorder (425 ng/dl), and no depression (423 ng/dl). A test for differences in central tendency showed a statistically significant difference among the three groups. Post hoc pairwise comparisons revealed statistically significant differences between those with dysthymic disorder and those with major depressive disorder and no depression. Total testosterone levels were lower in elderly men with dysthymic disorder than in men with major depressive disorder and men without depressive symptoms. Dysthymic disorder in elderly men may be related to HPG axis hypofunction.

Synthesis of novel β-cyclodextrin functionalized S, N codoped carbon dots for selective detection of testosterone.

PubMed

Luo, Mai; Hua, Yifan; Liang, Yiran; Han, Jiajun; Liu, Donghui; Zhao, Wenting; Wang, Peng

2017-12-15

A novel functionalized carbon dot has been synthesized by covalently linking β-cyclodextrin to the surface of N, S codoped carbon dots (β-CD-CDs). The characterization was confirmed by transmission electron microscopy, X-ray photoelectron spectroscopy, infrared spectra, ultraviolet-visible, and fluorescence emission spectra. On the basis of this carbon dot and (ferrocenylmethyl) trimethylammonium iodide (Fc + ), a photo-induced electron transfer (PET) fluorescent probe system was developed to determine the concentration of testosterone in water and identify testosterone in cell by fluorescence imaging as a visible biomarker. Under the optimum condition, the fluorescent intensity of the probe system linearly responded to the concentration of testosterone from 0μM to 280μM and the limit of detection was 0.51μM. This probe system also performed well at determining testosterone in groundwater with average recoveries of testosterone ranging from 96% to 107% at spiking levels of 0.5-100μM, and the relative standard deviation remained below 13%, which provided a reliable, rapid and easy method to determine testosterone in environmental water. Furthermore, the low cytotoxicity, high anti-interference ability, and excellent biocompatibility of β-CD-CDs made this probe system successfully used in cell fluorescence imaging to monitor levels of testosterone in the cytoplasm of cells with a promising application value in medical research. Copyright © 2017 Elsevier B.V. All rights reserved.

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

PubMed

Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun; Jakobsen, Marianne Antonius; Brusgaard, Klaus; Tan, Qihua; Gaster, Michael

2014-09-05

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Testosterone affects language areas of the adult human brain.

PubMed

Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

2016-05-01

Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Urinary excretion of LH and testosterone from male rats during exposure to increased gravity: post-spaceflight and centrifugation

NASA Technical Reports Server (NTRS)

Ortiz, R. M.; Wade, C. E.; Morey-Holton, E.

2000-01-01

A dissociation between plasma luteinizing hormone (LH) and testosterone (T) appears to exist during exposure to altered gravity. The pulsatile nature of LH release and the diurnal variability of T secretion may mask or bias the effects of altered gravity on the pituitary-gonadal axis when analyzing plasma concentrations. Therefore, we examined the relationship between the excretion of urinary LH and T in male Sprague-Dawley rats during exposure to increased gravity upon return to Earth following a 14-day spaceflight (n = 6) and by 12 days of centrifugation at 2g (n = 8). Excreted LH and T were elevated on the first 3 days postflight. Excreted T was elevated between Days 1 and 8 of centrifugation; however, excreted LH was reduced on Days 2 and 3 compared with control animals. Excreted LH and T were significantly correlated (R = 0.731 and 0.706, respectively) in postspaceflight and centrifuged animals. Correlation curves had similar slopes (0.0213 and 0.023, respectively), but different y-intercepts (-1.43 and 3.32, respectively). The sustained increase in excreted T during centrifugation suggests that the pituitary-gonadal axis in postspaceflight animals may adapt quicker to increased gravity. The upward shift in the correlation curve exhibited by the centrifuged animals suggests that the sensitivity of LH-induced T release is increased in these animals. The previous dissociation between plasma LH and T during altered gravity was not observed in the present study in which excreted LH and T were measured.

Is testosterone important in LUT function in men and women? ICI-RS 2015.

PubMed

Badawi, Jasmin Katrin; Bosch, Ruud; Djurhuus, Jens Christian; Hanna-Mitchell, Ann T

2017-04-01

This review article is a collaborative report based upon the Authors' presentations and Group discussion on the role of testosterone (T) in the male and female lower urinary tract (LUT) which took place at the 6th International Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in Bristol, UK (September 8-10, 2015). It comprises overviews and opinions on both the current state of knowledge of the role of T in LUT function and dysfunction in both sexes. Results from animal studies suggest that T treatment may be beneficial for disorders of the LUT in women including urinary incontinence and pelvic organ prolapse. The need for clinical studies to evaluate the effect of T treatment in peri- and post-menopausal women, taking into account the type of applied androgen, the application form, timing and dosage, is especially emphasized. In males, findings on the impact of T on the male external urethral sphincter underscores that there is still much to learn about its role in male LUT physiology. The important topic of the use of T therapy in the treatment of enuresis in the young, both sexes, is also discussed. The importance of understanding the steroidogenic pathways linking T with estradiol is discussed as being of paramount importance in researching the unique actions of T in the LUT. The overall conclusion is that further research into the role of T in LUT function and dysfunction across genders and age groups (young to old) is extremely important. Neurourol. Urodynam. 36:859-862, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Androgen and androgen metabolite levels in serum and urine of East African chimpanzees (Pan troglodytes schweinfurthii): comparison of EIA and LC-MS analyses.

PubMed

Preis, Anna; Mugisha, Lawrence; Hauser, Barbara; Weltring, Anja; Deschner, Tobias

2011-12-01

The primary male androgen testosterone (T) is often used as an endocrinological marker to investigate androgen-behaviour interactions in males. In chimpanzees and bonobos, studies investigating the relationship between T levels and dominance rank or aggressive behaviour have revealed contradictory results. The immunoassays used in these studies were originally developed for the measurement of steroids in serum. Their application to non-invasively collected samples, however, can lead to methodological problems due to cross-reacting metabolites, which might occur in urine or faeces but not in blood. The overall aim of this study, therefore, is to clarify whether a T enzyme immunoassay (EIA) is an applicable method to monitor testicular function in adult male chimpanzees. To estimate the impact of cross-reacting androgens on the used T EIA, we compared the results of an EIA measurement with a set of androgen metabolite levels measured by LC-MS. In urine from male chimpanzees, cross-reactivities appear to exist mainly with T and its exclusive metabolites, 5α-dihydrotestosterone (5α-DHT) and 5α-androstanediol (androstanediol). Both urinary and serum T levels of male chimpanzees were significantly higher than female T levels when measured with the T EIA, indicating a reliable measurement of testicular androgens and their exclusive metabolites with the used EIA. In urine from female chimpanzees, the comparison between LC-MS and T EIA results indicated a higher impact of cross-reactions with adrenal androgen metabolites. Therefore, the investigation of urinary T levels in female chimpanzees with a T EIA seems to be problematic. Overall our results show that a T EIA can be a reliable method to monitor testicular function in male chimpanzee urine and that LC-MS is a valuable tool for the validation of immunoassays. Copyright © 2011 Elsevier Inc. All rights reserved.

Estradiol and Inflammatory Markers in Older Men

PubMed Central

Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Metter, E. Jeffrey; Artoni, Andrea; Gatti, Elisa; Ruggiero, Carmelinda; Guralnik, Jack M.; Valenti, Giorgio; Ling, Shari M.; Basaria, Shehzad; Ferrucci, Luigi

2009-01-01

Background: Aging is characterized by a mild proinflammatory state. In older men, low testosterone levels have been associated with increasing levels of proinflammatory cytokines. It is still unclear whether estradiol (E2), which generally has biological activities complementary to testosterone, affects inflammation. Methods: We analyzed data obtained from 399 men aged 65–95 yr enrolled in the Invecchiare in Chianti study with complete data on body mass index (BMI), serum E2, testosterone, IL-6, soluble IL-6 receptor, TNF-α, IL-1 receptor antagonist, and C-reactive protein. The relationship between E2 and inflammatory markers was examined using multivariate linear models adjusted for age, BMI, smoking, physical activity, chronic disease, and total testosterone. Results: In age-adjusted analysis, log (E2) was positively associated with log (IL-6) (r = 0.19; P = 0.047), and the relationship was statistically significant (P = 0.032) after adjustments for age, BMI, smoking, physical activity, chronic disease, and serum testosterone levels. Log (E2) was not significantly associated with log (C-reactive protein), log (soluble IL-6 receptor), or log (TNF-α) in both age-adjusted and fully adjusted analyses. Conclusions: In older men, E2 is weakly positively associated with IL-6, independent of testosterone and other confounders including BMI. PMID:19050054

Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females

PubMed Central

Shulman, Leanne M.; Spritzer, Mark D.

2014-01-01

Male rat sexual behavior has been intensively studied over the past 100 years, but few studies have examined how sexual behavior changes over the course of several days of interactions. In this experiment, adult male rats (n = 12) were given daily access to estrus females for 30 min per day for 15 consecutive days and control males did not interact with females. Ovariectomized females were induced into estrus with hormonal injections, and males interacted with a different female each day. The amount of sexual activity (mounts, intromissions, and ejaculations) was found to cycle with a period of approximately 4 days in most male rats. Additionally, blood was collected every other day following sexual interactions to assess serum testosterone levels. Testosterone was found to peak on the first day of interaction and then fell back to near the level of control rats that did not interact with females. Following the initial peak, testosterone concentrations fluctuated less in males exposed to females than in controls. Sexual activity was not found to predict testosterone concentration. We conclude that when male rats have daily sexual interactions, sexual behavior tends to show cyclic changes and testosterone is significantly elevated only on the first day of interactions. PMID:24813700

A practical guide to male hypogonadism in the primary care setting

PubMed Central

Dandona, P; Rosenberg, M T

2010-01-01

There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue. Diagnosis of the condition requires the presence of low serum testosterone levels and the presence of hypogonadal symptoms. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Restoration of testosterone levels to the normal range improves libido, sexual function, and mood; reduces fat body mass; increases lean body mass; and improves bone mineral density. Testosterone treatment is contraindicated in subjects with prostate cancer or benign prostate hyperplasia and risks of treatment are perceived to be high by many physicians. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment. PMID:20518947

Male song sparrows have elevated testosterone in response to neighbors versus strangers.

PubMed

Moser-Purdy, Christopher; MacDougall-Shackleton, Scott A; Bonier, Frances; Graham, Brendan A; Boyer, Andrea C; Mennill, Daniel J

2017-07-01

Upon hearing a conspecific signal, animals must assess their relationship with the signaller and respond appropriately. Territorial animals usually respond more aggressively to strangers than neighbors in a phenomenon known as the "dear enemy effect". This phenomenon likely evolved because strangers represent a threat to an animal's territory tenure and parentage, whereas neighbors only represent a threat to an animal's parentage because they already possess a territory (providing territory boundaries are established and stable). Although the dear enemy effect has been widely documented using behavioral response variables, little research has been conducted on the physiological responses of animals to neighbors versus strangers. We sought to investigate whether the dear enemy effect is observed physiologically by exposing territorial male song sparrows (Melospiza melodia) to playback simulating a neighbor or a stranger, and then collecting blood samples to measure plasma testosterone levels. We predicted that song sparrows would exhibit increased testosterone levels after exposure to stranger playback compared to neighbor playback, due to the role testosterone plays in regulating aggression. Contrary to our prediction, we found that song sparrows had higher testosterone levels after exposure to neighbor playback compared to stranger playback. We discuss several explanations for our result, notably that corticosterone may regulate the dear enemy effect in male song sparrows and this may inhibit plasma testosterone. Future studies will benefit from examining corticosterone in addition to testosterone, to better understand the hormonal underpinnings of the dear enemy effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex hormones and the risk of type 2 diabetes mellitus: A 9-year follow up among elderly men in Finland.

PubMed

Salminen, Marika; Vahlberg, Tero; Räihä, Ismo; Niskanen, Leo; Kivelä, Sirkka-Liisa; Irjala, Kerttu

2015-05-01

To analyze whether sex hormone levels predict the incidence of type2 diabetes among elderly Finnish men. This was a prospective population-based study, with a 9-year follow up period. The study population in the municipality of Lieto, Finland, consisted of elderly (age ≥64 years) men free of type 2 diabetes at baseline in 1998-1999 (n = 430). Body mass index and cardiovascular disease-adjusted hazard ratios and their 95% confidence intervals for type 2 diabetes predicted by testosterone, free testosterone, sex hormone-binding globulin, luteinizing hormone, and testosterone/luteinizing hormone were estimated. A total of 30 new cases of type 2 diabetes developed during the follow-up period. After adjustment, only higher levels of testosterone (hazard ratio for one-unit increase 0.93, 95% confidence interval 0.87-0.99, P = 0.020) and free testosterone (hazard ratio for 10-unit increase 0.96, 95% confidence interval 0.91-1.00, P = 0.044) were associated with a lower risk of incident type 2 diabetes during the follow up. These associations (0.94, 95% confidence interval 0.87-1.00, P = 0.050 and 0.95, 95% confidence interval 0.90-1.00, P = 0.035, respectively) persisted even after additional adjustment of sex hormone-binding globulin. Higher levels of testosterone and free testosterone independently predicted a reduced risk of type 2 diabetes in the elderly men. © 2014 Japan Geriatrics Society.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management.

PubMed

Grossmann, Mathis; Matsumoto, Alvin M

2017-03-01

Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic-pituitary-testicular axis pathology but have functional hypogonadism that is potentially reversible. Literature review from 1970 to October 2016. Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency-like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy.

Devices for home evaluation of women's health concerns.

PubMed

Scolaro, Kelly L; Lloyd, Kimberly Braxton; Helms, Kristen L

2008-02-15

Devices used for home evaluation of fertility, pregnancy, menopause, colon cancer, breast cancer, and urinary-tract and vaginal yeast infections are discussed. Ovulation-prediction devices monitor natural changes in a woman's body during the menstrual cycle, including changes in basal body temperature, urinary luteinizing hormone, and urinary estrone-3-glucuronide concentrations. Also available are devices that identify changes in the content of sodium chloride and other electrolytes in saliva and cervical-vaginal mucus. Home pregnancy tests are designed to detect human chorionic gonadotropin in the urine. Both urine and saliva tests are available for home evaluation of menopause; the most common devices use urine to measure follicle-stimulating hormone. The saliva tests measure estradiol, progesterone, and testosterone. Devices for home screening for colon cancer use either the guaiac test or the fecal immunochemical test. For aid in breast self-examination, patients may use a simulated-breast product designed to train them to detect lumps or a thin, silicone-containing pad intended to increase the sensitivity of the fingers to abnormalities. Urine-dipstick tests can be used to screen for urinary-tract infection, and a swab or panty liner can be used to detect vaginal pH changes indicative of vaginal yeast infection. Home-based tests may be convenient and economical but also have limitations; pharmacists can help educate patients and clinicians. Many devices are available to help evaluate women's health concerns at home.

The Correlation among Neural Dynamic Processing of Conflict Control, Testosterone and Cortisol Levels in 10-Year-Old Children

PubMed Central

Shangguan, Fangfang; Liu, Tongran; Liu, Xiuying; Shi, Jiannong

2017-01-01

Cognitive control is related to goal-directed self-regulation abilities, which is fundamental for human development. Conflict control includes the neural processes of conflict monitoring and conflict resolution. Testosterone and cortisol are essential hormones for the development of cognitive functions. However, there are no studies that have investigated the correlation of these two hormones with conflict control in preadolescents. In this study, we aimed to explore whether testosterone, cortisol, and testosterone/cortisol ratio worked differently for preadolescent’s conflict control processes in varied conflict control tasks. Thirty-two 10-year-old children (16 boys and 16 girls) were enrolled. They were instructed to accomplish three conflict control tasks with different conflict dimensions, including the Flanker, Simon, and Stroop tasks, and electrophysiological signals were recorded. Salivary samples were collected from each child. The testosterone and cortisol levels were determined by enzyme-linked immunosorbent assay. The electrophysiological results showed that the incongruent trials induced greater N2/N450 and P3/SP responses than the congruent trials during neural processes of conflict monitoring and conflict resolution in the Flanker and Stroop tasks. The hormonal findings showed that (1) the testosterone/cortisol ratio was correlated with conflict control accuracy and conflict resolution in the Flanker task; (2) the testosterone level was associated with conflict control performance and neural processing of conflict resolution in the Stroop task; (3) the cortisol level was correlated with conflict control performance and neural processing of conflict monitoring in the Simon task. In conclusion, in 10-year-old children, the fewer processes a task needs, the more likely there is an association between the T/C ratios and the behavioral and brain response, and the dual-hormone effects on conflict resolution may be testosterone-driven in the Stroop and Flanker tasks. PMID:28690571

Effects of gendered behavior on testosterone in women and men.

PubMed

van Anders, Sari M; Steiger, Jeffrey; Goldey, Katherine L

2015-11-10

Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to "sex differences" in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology.

Sex-Specific Associations between Umbilical Cord Blood Testosterone Levels and Language Delay in Early Childhood

ERIC Educational Resources Information Center

Whitehouse, Andrew J. O.; Mattes, Eugen; Maybery, Murray T.; Sawyer, Michael G.; Jacoby, Peter; Keelan, Jeffrey A.; Hickey, Martha

2012-01-01

Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time-points. Methods: Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When…

Nestling immunocompetence and testosterone covary with brood size in a songbird.

PubMed Central

Naguib, Marc; Riebel, Katharina; Marzal, Alfonso; Gil, Diego

2004-01-01

The social and ecological conditions that individuals experience during early development have marked effects on their developmental trajectory. In songbirds, brood size is a key environmental factor affecting development, and experimental increases in brood size have been shown to have negative effects on growth, condition and fitness. Possible causes of decreased growth in chicks from enlarged broods are nutritional stress, crowding and increased social competition, i.e. environmental factors known to affect adult steroid levels (especially of testosterone and corticosteroids) in mammals and birds. Little, however, is known about environmental effects on steroid synthesis in nestlings. We addressed this question by following the development of zebra finch (Taeniopygia guttata) chicks that were cross-fostered and raised in different brood sizes. In line with previous findings, nestling growth and cell-mediated immunocompetence were negatively affected by brood size. Moreover, nestling testosterone levels covaried with treatment: plasma testosterone increased with experimental brood size. This result provides experimental evidence that levels of circulating testosterone in nestlings can be influenced by their physiological response to environmental conditions. PMID:15255102

Testosterone Regulates Erectile Function and Vcsa1 Expression in the Corpora of Rats

PubMed Central

Chua, Rowena G.; Calenda, Giulia; Zhang, Xinhua; Siragusa, Joseph; Tong, Yuehong; Tar, Moses; Aydin, Memduh; DiSanto, Michael E.; Melman, Arnold; Davies, Kelvin P.

2009-01-01

Summary Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4ng/ml to <0.04ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2mg in 100ml sesame oil every 4 days for two weeks) restored average levels of testosterone to 2ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls. PMID:19428993

A Testosterone-Related Structural Brain Phenotype Predicts Aggressive Behavior From Childhood to Adulthood

PubMed Central

Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N.; Hudziak, James J; Ducharme, Simon

2015-01-01

Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6 to 22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. PMID:26431805

Winning isn't everything: mood and testosterone regulate the cortisol response in competition.

PubMed

Zilioli, Samuele; Watson, Neil V

2013-01-01

Dominance contests are recurrent and widespread causes of stress among mammals. Studies of activation of the stress axis in social defeat - as reflected in levels of adrenal glucocorticoid, cortisol - have generated scattered and sometimes contradictory results, suggesting that biopsychological individual differences might play an important mediating role, at least in humans. In the context of a larger study of the regulation of endocrine responses to competition, we evaluated the notion that mood states, such as self-assurance and hostility, may influence cortisol reactivity to dominance cues via an interplay with baseline testosterone, considered as a potential marker of individual differences in dominance. Seventy healthy male university students (mean age 20.02, range 18-26) provided saliva samples before and after competing for fifteen minutes on a rigged computer task. After a winner was determined, all participants were assessed on their mood states through a standardized psychometric instrument (PANAS-X). Among winners of a rigged videogame competition, we found a significant interaction between testosterone and self-assurance in relation to post-competition cortisol. Specifically, self-assurance was associated with lower post-competition cortisol in subjects with high baseline testosterone levels, but no such relationship was observed in subjects with lower baseline testosterone levels. In losers of the competition no interaction effect between basal testosterone and hostility was observed. However, in this subgroup a significant negative relationship between basal testosterone and post-competition cortisol was evident. Overall, these findings provide initial support for the novel hypothesis that biological motivational predispositions (i.e. basal testosterone) and state (i.e. mood changes) may interact in regulating the hypothalamic-pituitary-adrenal axis activation after a social contest.

A testosterone-related structural brain phenotype predicts aggressive behavior from childhood to adulthood.

PubMed

Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Ducharme, Simon

2016-01-01

Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here, we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6-22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Androgen deficiency in male patients diagnosed with ANCA-associated vasculitis: a cause of fatigue and reduced health-related quality of life?

PubMed

Tuin, Janneke; Sanders, Jan-Stephan F; Buhl, Birgit M; van Beek, André P; Stegeman, Coen A

2013-01-01

Low testosterone levels in men are associated with fatigue, limited physical performance and reduced health-related quality of life (HRQOL); however, this relationship has never been assessed in patients with anti-neutrophil cytoplasmic antibodies (ANCA) -associated vasculitides (AAV). The aim of this study was to assess the prevalence of androgen deficiency and to investigate the role of testosterone in fatigue, limited physical condition and reduced HRQOL in men with AAV. Male patients with AAV in remission were included in this study. Fatigue and HRQOL were assessed by the multi-dimensional fatigue inventory (MFI)-20 and RAND-36 questionnaires. Seventy male patients with a mean age of 59 years (SD 12) were included. Scores of almost all subscales of both questionnaires were significantly worse in patients compared to controls. Mean total testosterone and free testosterone levels were 13.8 nmol/L (SD 5.6) and 256 pmol/L (SD 102), respectively. Androgen deficiency (defined according to Endocrine Society Clinical Practice Guidelines) was present in 47% of patients. Scores in the subscales of general health perception, physical functioning and reduced activity were significantly worse in patients with androgen deficiency compared to patients with normal androgen levels. Testosterone and age were predictors for the RAND-36 physical component summary in multiple linear regression analysis. Testosterone, age, vasculitis damage index (VDI) and C-reactive protein (CRP) were associated with the MFI-20 subscale of general fatigue. This study showed that androgen deficiency was present in a substantial number of patients with AAV. Testosterone was one of the predictors for physical functioning and fatigue. Testosterone may play a role in fatigue, reduced physical performance and HRQOL in male patients with AAV.

The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houghton, E.; Dumasia, M.C.; Teale, P.

1990-10-01

Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. (16,16(-2)H2)Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicularmore » minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize (2H5)testosterone to (2H4)estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine.« less

Are total prostate-specific antigen serum levels in cirrhotic men different from those in normal men?

PubMed

Vicentini, Fabio C; Botelho, Luiz A A; Hisano, Marcelo; Ebaid, Gustavo X; Lucon, Marcos; Lucon, Antonio M; Srougi, Miguel

2009-05-01

To determine the serum total prostate-specific antigen (tPSA) levels in cirrhotic men and compare them with those in noncirrhotic men. We prospectively evaluated 113 cirrhotic patients listed for liver transplantation using the serum tPSA, total testosterone level, and Child-Pugh liver function score according to age and severity of liver disease. The tPSA levels were compared with those of 661 healthy men. The Mann-Whitney U test was used for statistical analysis, with a significance level of .05. The median age of the cirrhotic and noncirrhotic patients was 55 years (range 28-70) and 58 years (range 46-70), respectively (P < .01). However, when stratified by age group (<49, 50-59, and >60 years), this difference was not significant. The median serum tPSA level was 0.3 ng/mL (range 0.04-9.9) and 1.3 ng/mL (range 0.04-65.8) in the cirrhotic and noncirrhotic group, respectively (P < .0001). Stratifying both groups according to age, the cirrhotic patients had significantly lower tPSA levels than did the noncirrhotic patients. According to the Child-Pugh score (A, B, and C), Child-Pugh class C patients had significantly lower tPSA levels than did Child-Pugh class A patients and also had lower testosterone levels than did Child-Pugh class A and B patients. The tPSA levels correlated significantly with the testosterone levels in the cirrhotic patients (P = .028). The results of our study have shown that cirrhotic patients have approximately 4 times lower serum tPSA levels than noncirrhotic men. Patients with more severe liver disease have lower tPSA and testosterone levels than patients less affected. The tPSA levels in cirrhotic men are affected by the total testosterone levels.

Leptin inhibits testosterone secretion from adult rat testis in vitro.

PubMed

Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

1999-05-01

Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed adult rats. In addition, 10(-9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries from fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the state of sexual maturation, is able to inhibit testosterone secretion acting at the testicular level. Furthermore, the present data suggest that the actions of leptin on the reproductive system are complex and are probably carried out at different levels of the hypothalamic-pituitary-gonadal axis.

Benzo[a]pyrene Reduces Testosterone Production in Rat Leydig Cells via a Direct Disturbance of Testicular Steroidogenic Machinery

PubMed Central

Chung, Jin-Yong; Lee, Seung Gee; Park, Ji-Eun; Yoon, Yong-Dal; Yoo, Ki Soo; Yoo, Young Hyun

2011-01-01

Background: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells. Objective: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins. Results: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[a]P can negatively target 3β-HSD, which is required for testosterone production. Conclusions: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs. PMID:21737371

Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

PubMed Central

Szulc, Pawel

2011-01-01

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT) decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts), then decrease (slowdown of bone turnover). Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men. PMID:22220284

Cortisol, testosterone and mood state variation during an official female football competition.

PubMed

Casanova, Natalina; Palmeira-DE-Oliveira, Ana; Pereira, Ana; Crisóstomo, Luís; Travassos, Bruno; Costa, Aldo M

2016-06-01

Endogenous hormones are essential on the control of physiological reactions and adaptations during sport performance. This study aims to compare the mood state and the salivary levels of cortisol and testosterone during an official female association football tournament. Twenty female football players (22.85±4.2 years) from the Portuguese women's national team were included in the study. Mood, salivary cortisol and testosterone levels were examined in five moments over the championship (M1, neutral measures; M2-M5, on every match day). Saliva samples were collected before breakfast and immediately after each match. Mood was measured by the profile of mood states questionnaire (POMS); hormone levels were measure by immunoassay methods. Iceberg Profiles of POMS were observed during all the moments of evaluation (M2-M5), showing a decrease in vigor and an increase in tension and depression in both team defeats (M2 and M5). There is no relationship between the hormones levels and the outcome of the competition, once cortisol and testosterone decrease from pre-match to post-match in both wins (M2 and M5) and defeats (M3 and M4). For testosterone the observed decrease is significantly different (P<0.05) before and after all matches. Our results show a pattern in mood states behavior. Cortisol and testosterone decrease after match and throughout the tournament, independently of the match outcome. The absence of hormone fluctuations related to competition performance points out that top-level professional football players training systematically and regularly seem to be very well adapted to competition stress effect.

Visceral Adipose Tissue and Leptin Hyperproduction Are Associated With Hypogonadism in Men With Chronic Kidney Disease.

PubMed

Cobo, Gabriela; Cordeiro, Antonio C; Amparo, Fernanda Cassulo; Amodeo, Celso; Lindholm, Bengt; Carrero, Juan Jesús

2017-07-01

Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population. Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5. A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m 2 ). In them, serum levels of total testosterone, estrogen, sex hormone binding globulin, and leptin were quantified, together with visceral adipose tissue (VAT) by thoracic and abdominal CT scan. None, observational study. Total testosterone, hypogonadism. The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction, was strongly and independently associated with the prevalence of hypogonadism in multivariable regression analyses. Visceral adiposity independently associated with lower testosterone levels among men with CKD stage 3-5 nondialysis. The observed link between hyperleptinemia and hypogonadism is in line with previous evidence on direct effects of leptin on testosterone production. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model.

PubMed

Son, Seung-Wan; Lee, Jin-Seok; Kim, Hyeong-Geug; Kim, Dong-Woon; Ahn, Yo-Chan; Son, Chang-Gue

2016-01-01

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions. Unlike estrogen, the effects of testosterone on the brain have not been thoroughly investigated. In order to investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. Orchiectomy markedly augmented the restraint stress-induced elevation of serum corticosterone and adrenaline levels as well as oxidative alterations in brain tissues, especially in the hippocampus. These findings are the first evidence that testosterone depletion makes the brain prone to oxidative injury. © 2015 International Society for Neurochemistry.

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization.

PubMed

Ren, Xiaojiao; Fu, Xiaojian; Zhang, Xinhua; Chen, Shiqiang; Huang, Shuguang; Yao, Lun; Liu, Guoquan

2017-09-15

Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS)-induced M1 polarization, but has no direct effect on adipocyte differentiation. Cellular signaling studies indicate that testosterone regulates macrophage polarization through the inhibitory regulative G-protein (Gαi) mainly, rather than via androgen receptors, and phosphorylation of Akt. Moreover, testosterone inhibits pre-adipocyte differentiation induced by M1 macrophage medium. Lowering of serum testosterone in mice by injecting a luteinizing hormone receptor (LHR) peptide increases epididymal white adipose tissue. Testosterone supplementation reverses this effect. Therefore, our findings indicate that testosterone inhibits pre-adipocyte differentiation by switching macrophages to M2 polarization through the Gαi and Akt signaling pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Aggressive behavior and change in salivary testosterone concentrations predict willingness to engage in a competitive task.

PubMed

Carré, Justin M; McCormick, Cheryl M

2008-08-01

The current study investigated relationships among aggressive behavior, change in salivary testosterone concentrations, and willingness to engage in a competitive task. Thirty-eight male participants provided saliva samples before and after performing the Point Subtraction Aggression Paradigm (a laboratory measure that provides opportunity for aggressive and defensive behavior while working for reward; all three involve pressing specific response keys). Baseline testosterone concentrations were not associated with aggressive responding. However, aggressive responding (but not point reward or point protection responding) predicted the pre- to post-PSAP change in testosterone: Those with the highest aggressive responding had the largest percent increase in testosterone concentrations. Together, aggressive responding and change in testosterone predicted willingness to compete following the PSAP. Controlling for aggression, men who showed a rise in testosterone were more likely to choose to compete again (p=0.03) and controlling for testosterone change, men who showed the highest level of aggressive responding were more likely to choose the non-competitive task (p=0.02). These results indicate that situation-specific aggressive behavior and testosterone responsiveness are functionally relevant predictors of future social behavior.

An update on male hypogonadism therapy

PubMed Central

Surampudi, Prasanth; Swerdloff, Ronald S; Wang, Christina

2014-01-01

Introduction Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Areas covered Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Expert opinion Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men. PMID:24758365

An update on male hypogonadism therapy.

PubMed

Surampudi, Prasanth; Swerdloff, Ronald S; Wang, Christina

2014-06-01

Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.

Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis.

PubMed

Macció, Daniela R; Calfa, Gastón; Roth, German A

2005-01-01

Considering that sex steroids can influence the immune system, we studied the development of experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of the central nervous system, and the concomitant cell-mediated immunity in gonadally intact and gonadectomized male Wistar rats given testosterone supplementation. Sham-operated rats and surgically castrated animals were orally self-administered with vehicle or testosterone added in the water bottle for 20 days before EAE induction. The androgenic effect of oral testosterone self-administration was evidenced by changes in body weight, and in the weights of androgen-dependent testes and seminal vesicles. Testosterone administration reduced the incidence of clinical signs of EAE in sham-operated animals and reversed the clinical symptoms of the disease associated with castrated EAE animals. The clinical signs observed in the different groups correlated with changes in delayed-type hypersensitivity and mononuclear cell-proliferative responses to the encephalitogenic myelin basic protein. Moreover, testosterone but not cholesterol supplementation in vitro suppressed the proliferative response of mononuclear cells to myelin basic protein suggesting that testosterone may affect specific immune functions through direct actions on immune cells. Finally, self-administration of testosterone induced also elevated corticosterone levels that in sham-operated rats correlated with the low incidence of the disease and in gonadectomized animals could be involved in the remission of clinical symptoms of EAE. These results suggest that orally self-administered testosterone can modulate specific cellular immune responses and serum corticosterone levels leading to changes in the development of EAE. Copyright 2005 S. Karger AG, Basel.

Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women.

PubMed

Hermans, Erno J; Bos, Peter A; Ossewaarde, Lindsey; Ramsey, Nick F; Fernández, Guillén; van Honk, Jack

2010-08-01

Correlational evidence in humans shows that levels of the androgen hormone testosterone are positively related to reinforcement sensitivity and competitive drive. Structurally similar anabolic-androgenic steroids (AAS) are moreover widely abused, and animal studies show that rodents self-administer testosterone. These observations suggest that testosterone exerts activational effects on mesolimbic dopaminergic pathways involved in incentive processing and reinforcement regulation. However, there are no data on humans supporting this hypothesis. We used functional magnetic resonance imaging (fMRI) to investigate the effects of testosterone administration on neural activity in terminal regions of the mesolimbic pathway. In a placebo-controlled double-blind crossover design, 12 healthy women received a single sublingual administration of .5 mg of testosterone. During MRI scanning, participants performed a monetary incentive delay task, which is known to elicit robust activation of the ventral striatum during reward anticipation. Results show a positive main effect of testosterone on the differential response in the ventral striatum to cues signaling potential reward versus nonreward. Notably, this effect interacted with levels self-reported intrinsic appetitive motivation: individuals with low intrinsic appetitive motivation exhibited larger testosterone-induced increases but had smaller differential responses after placebo. Thus, the present study lends support to the hypothesis that testosterone affects activity in terminal regions of the mesolimbic dopamine system but suggests that such effects may be specific to individuals with low intrinsic appetitive motivation. By showing a potential mechanism underlying central reinforcement of androgen use, the present findings may moreover have implications for our understanding of the pathophysiology of AAS dependency. Copyright 2010 Elsevier Inc. All rights reserved.

Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Sahin, Cagdas; Majidi-Zolbin, Masoumeh; Ge, Guanghao; Mani, Arya; Taylor, Hugh S

2018-02-01

The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no preclinical research has assessed atherosclerosis risk after XHT. We examined the effects of testosterone XHT after ovariectomy on atherosclerosis plaque formation in female mice and evaluated whether adding low-dose estradiol to cross-sex testosterone treatments after ovariectomy reduced lesion formation. Six-week-old female ApoE-/- C57BL/6 mice underwent ovariectomy and began treatments with testosterone, estradiol, testosterone with low-dose estradiol, or vehicle alone until euthanized at 23 weeks of age. Atherosclerosis lesion progression was measured by Oil Red O stain and confirmed histologically. We found reduced atherosclerosis in the estradiol- and combined testosterone/estradiol-treated mice compared with those treated with testosterone or vehicle only in the whole aorta (-75%), aortic arch (-80%), and thoracic aorta (-80%). Plaque size was similarly reduced in the aortic sinus. These reductions in lesion size after combined testosterone/estradiol treatment were comparable to those obtained with estrogen alone. Testosterone/estradiol combined therapy resulted in less atherosclerosis plaque formation than either vehicle or testosterone alone after ovariectomy. Testosterone/estradiol therapy was comparable to estradiol replacement alone, whereas mice treated with testosterone only fared no better than untreated controls after ovariectomy. Adding low-dose estrogen to cross-sex testosterone therapy after oophorectomy could improve cardiovascular outcomes for transgender patients. Additionally, these results contribute to understanding of the effects of estrogen and testosterone on atherosclerosis progression. Copyright © 2018 Endocrine Society.

Social status strategy in early adolescent girls: Testosterone and value-based decision making.

PubMed

Cardoos, Stephanie L; Ballonoff Suleiman, Ahna; Johnson, Megan; van den Bos, Wouter; Hinshaw, Stephen P; Dahl, Ronald E

2017-07-01

There has been strong interest, spanning several disciplines, in understanding adolescence as a developmental period of increased risk-taking behavior. Our goals focus on one line of investigation within this larger developmental risk framework. Specifically, we examined levels of pubertal hormones in girls in relation to their willingness to take greater financial risks to gain social status. To this end, we tested the hypothesis that higher levels of testosterone during the ages of pubertal maturation are associated with a greater willingness to sacrifice money for social admiration. Sixty-three girls ages 10-14 (M age =12.74) participated in laboratory measures and completed at-home saliva sample collection. The Pubertal Development Scale (PDS) and basal hormone levels (testosterone, estradiol, DHEA) measured pubertal maturation. We made use of a developmentally appropriate version of an Auction Task in which adolescents could take financial risks in order to gain socially motivated outcomes (social status). PDS and testosterone were each associated with overall levels of financial risk taking over the course of the Auction Task. In hierarchical models, PDS and testosterone were predictors of the slope of overbidding over the course of the task. Results provide evidence for the role of testosterone and pubertal maturation in girls' motivations to engage in costly decision making in order to gain social status. Findings contribute to our understanding of the developmental underpinnings of some interesting aspects of adolescent risk behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

A systematic review on the herbal extract Tribulus terrestris and the roots of its putative aphrodisiac and performance enhancing effect.

PubMed

Qureshi, Ahmed; Naughton, Declan P; Petroczi, Andrea

2014-03-01

Tribulus terrestris (TT) is a dicotyledonous herbal plant of the Zygophyllaceae family. In ancient medicine, extracts of the aerial parts and fruits have been used for its diuretic, tonic, and aphrodisiac properties. Today, TT is widely used by athletes and bodybuilders based on the belief, fueled by claims in marketing information, that it can enhance testosterone concentrations. To assess TT's effect on testosterone levels in human and animals, an electronic literature search out using seven databases and the patent database up to August 2013 was carried out. Randomized control trials, which included healthy human subjects ingesting TT as sole or combined supplement, along with animal studies with TT as a sole treatment across a number of species were included. Eleven studies met the inclusion criteria, including one patent application. The results showed that trials varied in duration, dosage and supplementation with TT as sole or combined treatment, rendering meta-analysis impossible. A limited number of animal studies displayed a significant increase in serum testosterone levels after TT administration, but this effect was only noted in humans when TT was part of a combined supplement administration. Literature available for the effectiveness of TT on enhancing testosterone concentrations is limited. Evidence to date suggests that TT is ineffective for increasing testosterone levels in humans, thus marketing claims are unsubstantiated. The nitric oxide release effect of TT may offer a plausible explanation for the observed physiological responses to TT supplementation, independent of the testosterone level.

Fresh onion juice enhanced copulatory behavior in male rats with and without paroxetine-induced sexual dysfunction.

PubMed

Allouh, Mohammed Z; Daradka, Haytham M; Al Barbarawi, Mohammed M; Mustafa, Ayman G

2014-02-01

Onion (Allium cepa) is one of the most commonly cultivated species of the family Liliaceae, and has long been used in dietary and therapeutic applications. Treatment with fresh onion juice has been reported to promote testosterone production in male rats. Testosterone is the male sex hormone responsible for enhancing sexual libido and potency. This study aimed to investigate the effects of onion juice on copulatory behavior of sexually potent male rats and in male rats with paroxetine-induced sexual dysfunction. Sexually experienced male rats were divided into seven groups: a control group, three onion juice-treated groups, a paroxetine-treated group, and two groups treated with paroxetine plus different doses of onion juice. At the end of the treatments, sexual behavior parameters and testosterone levels were measured and compared among the groups. Administration of onion juice significantly reduced mount frequency and latency and increased the copulatory efficacy of potent male rats. In addition, administration of onion juice attenuated the prolonged ejaculatory latency period induced by paroxetine and increased the percentage of ejaculating rats. Serum testosterone levels increased significantly by onion juice administration. However, a significant reduction in testosterone because of paroxetine therapy was observed. This reduction was restored to normal levels by administration of onion juice. This study conclusively demonstrates that fresh onion juice improves copulatory behavior in sexually potent male rats and in those with paroxetine-induced sexual dysfunction by increasing serum testosterone levels.

Effect of ascorbic acid and alpha tocopherol supplementation on acute restraint stress induced changes in testosterone, corticosterone and nor epinephrine levels in male Sprague Dawley rats.

PubMed

Lodhi, Ghulam Mustafa; Latif, Rabia; Hussain, Muhammad Mazhar; Naveed, Abdul Khaliq; Aslam, Muhammad

2014-01-01

Stress of various origins suppresses male reproductive functions through releasing stress hormones. Antioxidant like ascorbic acid (AA) and alpha tocopherol (AT) have been thought to protect the body against stress induced damage. Whether, these antioxidants confer protection against the stress induced increased levels of corticosterone and nor-epinephrine, and decreased testosterone secretion have been investigated in this study. This quasi experimental study was carried out at the Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March to September 2009. Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group-I served as the control without stress while group-II was exposed to restraint stress for 6 hours, group-III was administered AA, group-IVAT and group-V was supplemented with both the antioxidants along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for 6 hours. Immediately after the stress episode, blood sample was obtained for the assay of serum testosterone, serum corticosterone by EIA and plasma nor-epinephrine levels by ELISA. Data were analyzed on SPSS-13 and p-value less than 0.05 was considered significant. Acute restraint stress resulted in a statistically significant rise in corticosterone and nor-epinephrine levels and fall in serum testosterone levels. AA supplementation for one month revealed insignificant changes in stress induced hormonal parameters. AT alone and in combination with ascorbic acid prevented the fall in testosterone level as well as rise in corticosterone, however nor-epinephrine levels remained unchanged. Supplementation with AT alone or in combination with AA prevent reduction in testosterone and rise in corticosterone levels while keeping the nor-epinephrine levels unchanged after acute restraint stress in Sprague Dawley rats.

Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

PubMed

Saggese, G; Cesaretti, G; Franchi, G; Startari, L

1996-08-01

Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chronological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and < 0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.

Stress-induced suppression of testosterone secretion in male alligators.

PubMed

Lance, V A; Elsey, R M

1986-08-01

In order to test the effect of acute stress on gonadal hormone secretion in reptiles, six mature male alligators were captured, and a blood sample was taken within 5 min of capture. Additional blood samples were taken at timed intervals for up to 41 hr, and plasma testosterone and corticosterone were measured by radioimmunoassay. Plasma testosterone declined to 50% of the initial value by 4 hr and dropped to less than 10% of initial by 24 hr. Plasma corticosterone increased during the first 12 hr, declined at 24 hr, and rose again at 40 hr. Blood samples from male alligators collected in North and South Carolina, south Florida, and in south Louisiana in two consecutive breeding seasons were also assayed for testosterone and corticosterone. In these populations there were significant differences in mean plasma testosterone and corticosterone levels. Elevated corticosterone levels were consistently seen in alligators caught in traps and from which a blood sample was taken several hours later. Plasma testosterone, although consistently lower in trapped alligators, did not show a negative correlation with plasma corticosterone. Farm-reared alligators bled once, released, and bled again at 24 hr also showed a highly significant suppression of testosterone secretion. These results demonstrate that stress has a rapid and dramatic effect on testicular steroid secretion in both farm-reared and wild alligators.

Testosterone and androstanediol glucuronide among men in NHANES III.

PubMed

Duan, Chuan Wei; Xu, Lin

2018-03-09

Most of the androgen replacement therapies were based on serum testosterone and without measurements of total androgen activities. Whether those with low testosterone also have low levels of androgen activity is largely unknown. We hence examined the association between testosterone and androstanediol glucuronide (AG), a reliable measure of androgen activity, in a nationally representative sample of US men. Cross-sectional analysis was based on 1493 men from the Third National Health and Nutrition examination Survey (NHANES III) conducted from 1988 to 1991. Serum testosterone and AG were measured by immunoassay. Kernel density was used to estimate the average density of serum AG concentrations by quartiles of testosterone. Testosterone was weakly and positively correlated with AG (correlation coefficient = 0.18). The kernel density estimates show that the distributions are quite similar between the quartiles of testosterone. After adjustment for age, the distributions of AG in quartiles of testosterone did not change. The correlation between testosterone and AG was stronger in men with younger age, lower body mass index, non-smoking and good self-rated health and health status. Serum testosterone is weakly correlated with total androgen activities, and the correlation is even weaker for those with poor self-rated health. Our results suggest that measurement of total androgen activity in addition to testosterone is necessary in clinical practice, especially before administration of androgen replacement therapy.

Alternatives to Testosterone Therapy: A Review.

PubMed

Lo, Eric M; Rodriguez, Katherine M; Pastuszak, Alexander W; Khera, Mohit

2018-01-01

Although testosterone therapy (TTh) is an effective treatment for hypogonadism, recent concerns regarding its safety have been raised. In 2015, the US Food and Drug Administration issued a warning about potential cardiovascular risks resulting from TTh. Fertility preservation is another reason to search for viable alternative therapies to conventional TTh, and in this review we evaluate the literature examining these alternatives. To review the role and limitations of non-testosterone treatments for hypogonadism. A literature search was conducted using PubMed to identify relevant studies examining medical and non-medical alternatives to TTh. Search terms included hypogonadism, testosterone replacement therapy, testosterone therapy, testosterone replacement alternatives, diet and exercise and testosterone, varicocele repair and testosterone, stress reduction and testosterone, and sleep apnea and testosterone. Review of peer-reviewed literature. Medical therapies examined include human chorionic gonadotropins, aromatase inhibitors, and selective estrogen receptor modulators. Non-drug therapies that are reviewed include lifestyle modifications including diet and exercise, improvements in sleep, decreasing stress, and varicocele repair. The high prevalence of obesity and metabolic syndrome in the United States suggests that disease modification could represent a viable treatment approach for affected men with hypogonadism. These alternatives to TTh can increase testosterone levels and should be considered before TTh. Lo EM, Rodriguez KM, Pastuszak AW, Khera M. Alternatives to Testosterone Therapy: A Review. Sex Med Rev 2018;6:106-113. Copyright © 2017. Published by Elsevier Inc.

[The importance of testosterone in the treatment of metabolic syndrome in men].

PubMed

Kempisty-Zdebik, Ewa; Zdebik, Aleksander

2012-01-01

Testosterone deficiency syndrome is being seen in increasing percentage of men with middle and old age. Besides the typical deterioration of sexual function there is predisposition to metabolic syndrome and increased risk of cardiovascular diseases. The similarity of the effects of testosterone substitution and the dietary treatment led the authors to a retrospective analysis of patient data treated for testosterone deficiency syndrome. Data on 341 patients aged over 45 years with metabolic syndrome and diabetes, meeting criteria for the diagnosis of testosterone deficiency syndrome were divided into 5 groups: T--testosterone substitution without additional diet, T-Low-Carb--testosterone and low carbohydrate diet, T-Fat-Low--testosterone and low fat diet, Carb-Low--only low carbohydrate diet, Fat-Low--only low fat diet. We analyzed change in body weight, waist circumference, blood pressure, fasting glucose, HbAlc, HDL cholesterol and triglyceride levels within 6 months from the start of observation. The best results of all investigated parameters were obtained in patients treated with testosterone and low-carbohydrate diet and in the group treated with testosterone and low-fat diet. Slightly worse results in the group received the same diets and the worst in the group treated only with testosterone. The improvement obtained in the total testosterone therapy and diet was much greater than the simple sum of the effects of both methods witch suggests the existence of synergies.

Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

PubMed

Singh, Gurmeet K S; Balzer, Ben W R; Desai, Reena; Jimenez, Mark; Steinbeck, Katharine S; Handelsman, David J

2015-11-01

Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable. © The Author(s) 2015.

Associations among dehydration, testosterone and stress hormones in terms of body weight loss before competition.

PubMed

İrfan, Yldrm

2015-08-01

In weight class sports, such as judo, taekwondo and wrestling, reducing body weight before competitions is common. However, it is recommended that weight loss per week should not exceed 1.5% of total body weight otherwise, athletes' metabolism and endocrine parameters are negatively affected, which will deteriorate their physiology and psychology and thus decrease their performance. The aim of this study was to determine weight loss and hydration levels after weight loss before competitions among the elite wrestlers and to explore the association between hydration levels, and stress and testosterone. This was an observational study. The study was undertaken with 56 voluntary athletes who participated in wrestling championship. With blood samples taken from the wrestlers, glucose, blood urea nitrogen, sodium (Na), cortisol, prolactin and testosterone hormone analyses were evaluated by a specialist at a biochemical laboratory. It was found out that according to plasma osmolarity levels, there were significant differences between those dehydrated and those who maintained euhydration in terms of cortisol and total testosterone levels (P < 0.001). It was detected that an association was present between plasma osmolarity, and cortisol (r = 0.667) and total testosterone levels (r = -0.627) among the elite wrestlers. It was discovered that elite wrestlers were subjected to quick and high level of weight losses before competitions in a very short time (1-5 days). It was seen that their hydration levels differed due to the weight loss, which was explored to be causing acute dehydration among the wrestlers.

Recent trends in the treatment of testosterone deficiency syndrome.

PubMed

Hong, Bum Sik; Ahn, Tai Young

2007-11-01

Testosterone deficiency syndrome (TDS) is defined as a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels. TDS is a result of the interaction of hypothalamo-pituitary and testicular factors. Now, treatment of TDS with testosterone is still controversial due to a lack of large, controlled clinical trials on efficacy. The risks of treatment with testosterone appear to be minimal, although long-term studies on the safety of testosterone therapy are lacking. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Newer testosterone patches seem not to cause severe skin irritation. Testosterone gels minimize the skin irritation while providing flexibility in dosing and a low discontinuation rate. Oral testosterone undecanoate (TU) is free of liver toxicity. Recent formulation of oral TU markedly increased shelf-live, a major drawback in the older preparation. Producing swings in testosterone levels rising rapidly to the supraphysiological range is not the case with the new injectable long-acting preparation of TU. To be able to rapidly react and stop treatment in cases where side-effects and contraindications are detected, the short-acting transdermal and oral delivery modes have certain advantages. However, there is no evidence that the use of an injectable long-acting TU in men with TDS has limitations in clinical application for this reason. The use of dehydroepiandrosterone is still controversial because of a lack of well designed long-term trials, although some recent studies suggest positive effects on various body systems. Only a few studies have been carried out to investigate the effect of hCG (human chorionic gonadotropin) in TDS with some positive results on various body systems.

EFFICACY AND SAFETY OF A NEW TOPICAL TESTOSTERONE REPLACEMENT GEL THERAPY FOR THE TREATMENT OF MALE HYPOGONADISM.

PubMed

Cunningham, Glenn; Belkoff, Laurence; Brock, Gerald; Efros, Mitchell; Gittelman, Marc; Carrara, Dario; Neijber, Anders; Ando, Masakazu; Mitchel, Jules

2017-05-01

Testosterone replacement therapy is indicated for male hypogonadism. This study aimed to evaluate the efficacy and safety of testosterone gel 2% (Tgel) over 90 days. This phase 3, open-label, noncomparator study was conducted in adult hypogonadal men (2 consecutive fasting serum testosterone values <300 ng/dL and >86% subjects with symptoms consistent with testosterone deficiency). Subjects applied Tgel 23 mg/day (single pump-actuation using a hands-free cap applicator). The dose was uptitrated to 46 mg/day after 2 weeks if the 4-hour serum total testosterone level was <500 ng/dL. The dose could be further up- or downtitrated to 23, 46, and 69 mg on Days 21, 42, and 63. The primary endpoint included the percentage of subjects with average testosterone concentration (C ave (0-24) ) between 300 and 1,050 ng/dL on Day 90. Safety endpoints were adverse events (AEs), laboratory parameters, and vital signs. Of the 159 who enrolled, 139 men completed the study. Approximately three-quarters (76.1%) of subjects met C ave criteria on Day 90. Most AEs were mild to moderate. There were 5 serious AEs, and 1 (myocardial infarction) was judged as possibly related to Tgel. Confirmed excessive increases in prostate-specific antigen or hematocrit levels were rare. Tgel had a favorable local skin tolerability profile. Overall, 76% of subjects achieved C ave between 300 and 1,050 ng/dL with Tgel. Symptoms of testosterone deficiency improved with few safety concerns. AE = adverse event C ave(0-24) = average testosterone concentration CI = confidence interval C max = maximum concentration IIEF = International Index of Erectile Function MAF = Multidimensional Assessment of Fatigue PK = pharmacokinetic PSA = prostate-specific antigen SAE = serious adverse event SF-12 = Short Form 12 Health Survey Tgel = testosterone gel 2% T max = time to achieve maximum concentration TRT = testosterone replacement therapy.

Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men.

PubMed

Kjaer, Thomas Nordstrøm; Ornstrup, Marie Juul; Poulsen, Morten Møller; Jørgensen, Jens Otto Lunde; Hougaard, David Michael; Cohen, Arieh Sierra; Neghabat, Shadman; Richelsen, Bjørn; Pedersen, Steen Bønløkke

2015-09-01

Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasing in relation to the management of benign prostate hyperplasia (BPH) and prostate cancer. So far, no human trials have evaluated the effects of resveratrol on circulating androgens, prostate size, or biochemical markers of prostate size. In a randomized placebo controlled clinical study using two doses of resveratrol (150 mg or 1,000 mg resveratrol daily) for 4 months, we evaluated the effects on prostate size, prostate specific antigen (PSA) and sex steroid hormones in 66 middle-aged men suffering from the metabolic syndrome(MetS). At baseline, prostate size and PSA were positively correlated (R = 0.34, P < 0.007) as was prostate size and age (R = 0.37, P < 0.003). Prostate size did not correlate with testosterone, free testosterone, dihydrotestosterone (DHT), or any other androgen precursor at baseline. The highest dose of resveratrol lowered the serum level of androstenedione 24% (P = 0.052), dehydroepiandrosterone (DHEA) 41% (P < 0.01), and dehydroepiandrosterone-sulphate (DHEAS) 50% (p<0.001), compared to the control group. However, prostate size and levels of PSA, testosterone, free testosterone and DHT remained unchanged. In this population of middle-aged men suffering from MetS, high dose resveratrol (1,000 mg daily) administration for 4 months significantly lowered serum levels of the androgen precursors androstenedione, DHEA and DHEAS, whereas prostate size and circulating levels of PSA, testosterone, free testosterone, and dihydrotestosterone were unaffected. The present study suggests that resveratrol does not affect prostate volume in healthy middle-aged men as measured by PSA levels and CT acquired prostate volumes. Consequently, we find no support for the use of resveratrol in the treatment of benign prostate hyperplasia. © 2015 Wiley Periodicals, Inc.

Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea

PubMed Central

Miller, K. K.; Lawson, E. A.; Mathur, V.; Wexler, T. L.; Meenaghan, E.; Misra, M.; Herzog, D. B.; Klibanski, A.

2011-01-01

Context Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting We conducted a cross-sectional study at a general clinical research center. Study Participants A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women. PMID:17284620

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

PubMed

Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

2007-04-01

Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether oral contraceptive use, mediated by reductions in endogenous androgen levels, is deleterious to skeletal health in such women.

Changes in estradiol and testosterone levels in postmenopausal women after changes in body mass index.

PubMed

Jones, Michael E; Schoemaker, Minouk; Rae, Megan; Folkerd, Elizabeth J; Dowsett, Mitch; Ashworth, Alan; Swerdlow, Anthony J

2013-07-01

Endogenous sex hormones are risk factors for postmenopausal breast cancer. A potential route for favorable hormonal modification is weight loss. The objective of the study was to measure change in plasma estradiol and testosterone levels in postmenopausal women in relation to change in body mass index (BMI) and plasma leptin. The setting was a cohort study of over 100,000 female volunteers from the general population, United Kingdom. The participants were a sample of 177 postmenopausal women aged over 45 years who provided blood samples during 2004-2005 and again during 2010-2011. Outcomes were percentage change in plasma estradiol and testosterone levels per 1 kg/m² change in BMI and per 1 ng/mL change in plasma leptin. Among women with reduction in BMI, estradiol decreased 12.7% (95% confidence interval: [6.4%, 19.5%]; P < .0001) per kg/m² and among women with increased BMI estradiol increased 6.4% [0.2%, 12.9%] (P = .042). The corresponding figures for testosterone were 10.7% [3.0%, 19.0%] (P = .006) and 1.9% [-5.4%, 9.7%] (P = .61) per kg/m². For women with decreases and increases in leptin, estradiol decreased by 3.6% [1.3%, 6.0%] (P = .003) per ng/mL and increased by 1.7% [-0.3%, 3.6%] (P = .094), respectively. The corresponding figures for testosterone were 4.8% [2.0%, 7.8%] (P = .009) and 0.3% [-2.0%, 2.6%] (P = .82) per ng/mL. In postmenopausal women, changes in BMI and plasma leptin occurring over several years are associated with changes in estradiol and testosterone levels. The results suggest that fat loss by an individual can result in substantial decreases in postmenopausal estradiol and testosterone levels and provides support for weight management to lessen breast cancer risk.

Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study.

PubMed

Rasmussen, Jon Jarløv; Selmer, Christian; Østergren, Peter Busch; Pedersen, Karen Boje; Schou, Morten; Gustafsson, Finn; Faber, Jens; Juul, Anders; Kistorp, Caroline

2016-01-01

Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. Former AAS abusers exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH and inhibin B indicative of impaired spermatogenesis.

Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an associationmore » between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response does not seem related to temporal testosterone changes.« less

Effects of gendered behavior on testosterone in women and men

PubMed Central

van Anders, Sari M.; Steiger, Jeffrey; Goldey, Katherine L.

2015-01-01

Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to “sex differences” in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology. PMID:26504229

American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update.

PubMed

Petak, Steven M; Nankin, Howard R; Spark, Richard F; Swerdloff, Ronald S; Rodriguez-Rigau, Luis J

2002-01-01

In these clinical practice guidelines, specific recommendations are made for determining the most effective methods of diagnosing and treating hypogonadism in adult male patients. The target populations for these guidelines include the following: (1) men with primary testicular failure requiring testosterone replacement (hypergonadotropic hypogonadism); (2) male patients with gonadotropin deficiency or dysfunction who may have received testosterone replacement therapy or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men with symptoms relating to testosterone deficiency who could benefit from testosterone replacement therapy. Initial hormonal evaluation generally consists of a testosterone determination, in conjunction with a free testosterone or sex hormone-binding globulin level, inpatients with clear symptoms and signs but normal-range total testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels. Other possible tests include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography,testicular biopsy, and specialized hormonal dynamic testing. Therapeutic options generally consist of testosterone replacement by injections, patches, or topically applied gel in hypergonadotropic patients and in hypogonadotropic patients not interested in fertility. In hypogonadotropic patients interested in fertility, gonadal stimulation option scan be considered, including human chorionic gonadotropin stimulation therapy with or without human menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin-releasing hormone pump therapy. These therapies may be combined with assisted reproductive technologies such as in vitro fertilization with intracytoplasmic sperm injection, which may allow pregnancy to occur with very low numbers of sperm.

Interactive effects of dehydroepiandrosterone and testosterone on cortical thickness during early brain development.

PubMed

Nguyen, Tuong-Vi; McCracken, James T; Ducharme, Simon; Cropp, Brett F; Botteron, Kelly N; Evans, Alan C; Karama, Sherif

2013-06-26

Humans and the great apes are the only species demonstrated to exhibit adrenarche, a key endocrine event associated with prepubertal increases in the adrenal production of androgens, most significantly dehydroepiandrosterone (DHEA) and to a certain degree testosterone. Adrenarche also coincides with the emergence of the prosocial and neurobehavioral skills of middle childhood and may therefore represent a human-specific stage of development. Both DHEA and testosterone have been reported in animal and in vitro studies to enhance neuronal survival and programmed cell death depending on the timing, dose, and hormonal context involved, and to potentially compete for the same signaling pathways. Yet no extant brain-hormone studies have examined the interaction between DHEA- and testosterone-related cortical maturation in humans. Here, we used linear mixed models to examine changes in cortical thickness associated with salivary DHEA and testosterone levels in a longitudinal sample of developmentally healthy children and adolescents 4-22 years old. DHEA levels were associated with increases in cortical thickness of the left dorsolateral prefrontal cortex, right temporoparietal junction, right premotor and right entorhinal cortex between the ages of 4-13 years, a period marked by the androgenic changes of adrenarche. There was also an interaction between DHEA and testosterone on cortical thickness of the right cingulate cortex and occipital pole that was most significant in prepubertal subjects. DHEA and testosterone appear to interact and modulate the complex process of cortical maturation during middle childhood, consistent with evidence at the molecular level of fast/nongenomic and slow/genomic or conversion-based mechanisms underlying androgen-related brain development.

A Perspective on Middle-Aged and Older Men With Functional Hypogonadism: Focus on Holistic Management

PubMed Central

Matsumoto, Alvin M.

2017-01-01

Abstract Context: Middle-aged and older men (≥50 years), especially those who are obese and suffer from comorbidities, not uncommonly present with clinical features consistent with androgen deficiency and modestly reduced testosterone levels. Commonly, such men do not demonstrate anatomical hypothalamic–pituitary–testicular axis pathology but have functional hypogonadism that is potentially reversible. Evidence Acquisition: Literature review from 1970 to October 2016. Evidence Synthesis: Although definitive randomized controlled trials are lacking, evidence suggests that in such men, lifestyle measures to achieve weight loss and optimization of comorbidities, including discontinuation of offending medications, lead to clinical improvement and a modest increase in testosterone. Also, androgen deficiency–like symptoms and end-organ deficits respond to targeted treatments (such as phosphodiesterase-5 inhibitors for erectile dysfunction) without evidence that hypogonadal men are refractory. Unfortunately, lifestyle interventions remain difficult and may be insufficient even if successful. Testosterone therapy should be considered primarily for men who have significant clinical features of androgen deficiency and unequivocally low testosterone levels. Testosterone should be initiated either concomitantly with a trial of lifestyle measures, or after such a trial fails, after a tailored diagnostic work-up, exclusion of contraindications, and appropriate counseling. Conclusions: There is modest evidence that functional hypogonadism responds to lifestyle measures and optimization of comorbidities. If achievable, these interventions may have demonstrable health benefits beyond the potential for increasing testosterone levels. Therefore, treatment of underlying causes of functional hypogonadism and of symptoms should be used either as an initial or adjunctive approach to testosterone therapy. PMID:28359097

Possible role of serum testosterone, gonadotropins and prolactin in patients with premature ejaculation.

PubMed

Abu El-Hamd, M; Farah, A

2018-02-01

Premature ejaculation (PE) is the most common male sexual dysfunction. This study aimed to investigate the role of serum testosterone, gonadotropins and prolactin in patients with PE. In a prospective a case-controlled study, it was conducted on 90 male patients with PE and 90 male healthy participants as controls. Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT). Patients with mean IELT values ≤60 s and PEDT total scores ≥11 were considered to have PE. Serum levels of total testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE and controls. There was no statistically significant difference between patients with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p value ˃.05). There was no significant correlation between the sex hormones levels (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT scores of the patients; p value ˃.05). This study concluded that there was no disturbance in serum levels of testosterone, gonadotropins and prolactin in patients with PE and controls. These hormones could not relate to pathogenesis of PE. © 2017 Blackwell Verlag GmbH.

Digit ratio (2D:4D) as an indicator of body size, testosterone concentration and number of children in human males.

PubMed

Klimek, Magdalena; Galbarczyk, Andrzej; Nenko, Ilona; Alvarado, Louis Calistro; Jasienska, Grazyna

2014-01-01

The 2nd to 4th digit ratio (2D:4D) is thought to reflect exposure to androgens during foetal development. This study examined the relationship between low (more masculine) and high (more feminine) 2D:4D and body size at different stages of the life course, adult testosterone levels and number of children among males. Five hundred and fifty-eight men from rural Poland at the Mogielica Human Ecology Study Site participated in this study. Life history data and anthropometric measurements were collected. Salivary morning and evening testosterone levels among 110 men from the same population were measured. Low 2D:4D was related to higher birth weight (p = 0.04), higher birth length (p = 0.01), higher body mass during childhood and adolescence (p = 0.01), higher BMI (borderline significance, p = 0.06), higher number of children among fathers (p = 0.04) and higher testosterone levels during adulthood (p = 0.04). This study shows, for the first time in a single population, that digit ratio is related to sub-adult body size at different stages of the life course, adult testosterone levels and number of children. The observed results suggest that digit ratio might be a valuable predictor of male body size and reproductive characteristics.

Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus)

PubMed Central

Burger, D.; Dolivo, G.; Marti, E.; Sieme, H.; Wedekind, C.

2015-01-01

Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies. PMID:25904670

Low Testosterone Correlates with Delayed Development in Male Orangutans

PubMed Central

Emery Thompson, Melissa; Zhou, Amy; Knott, Cheryl D.

2012-01-01

Male orangutans (Pongo spp.) display an unusual characteristic for mammals in that some adult males advance quickly to full secondary sexual development while others can remain in an adolescent-like form for a decade or more past the age of sexual maturity. Remarkably little is understood about how and why differences in developmental timing occur. While fully-developed males are known to produce higher androgen levels than arrested males, the longer-term role of steroid hormones in male life history variation has not been examined. We examined variation in testosterone and cortisol production among 18 fully-developed (“flanged”) male orangutans in U.S. captive facilities. Our study revealed that while testosterone levels did not vary significantly according to current age, housing condition, and species origin, males that had undergone precocious development had higher testosterone levels than males that had experienced developmental arrest. While androgen variation had previously been viewed as a state-dependent characteristic of male developmental status, our study reveals that differences in the physiology of early and late developing males are detectable long past the developmental transition and may instead be trait-level characteristics associated with a male’s life history strategy. Further studies are needed to determine how early in life differences in testosterone levels emerge and what consequences this variation may have for male behavioral strategies. PMID:23077585

Caffeine intake is not associated with serum testosterone levels in adult men: cross-sectional findings from the NHANES 1999-2004 and 2011-2012.

PubMed

Lopez, David S; Advani, Shailesh; Qiu, Xueting; Tsilidis, Konstantinos K; Khera, Mohit; Kim, Jeri; Canfield, Steven

2018-04-25

The association of caffeine intake with testosterone remains unclear. We evaluated the association of caffeine intake with serum testosterone among American men and determined whether this association varied by race/ethnicity and measurements of adiposity. Data were analyzed for 2581 men (≥20 years old) who participated in the cycles of the NHANES 1999-2004 and 2011-2012, a cross-sectional study. Testosterone (ng/mL) was measured by immunoassay among men who participated in the morning examination session. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable weighted linear regression models were conducted. We identified no linear relationship between caffeine intake and testosterone levels in the total population, but there was a non-linear association (p nonlinearity  < .01). Similarly, stratified analysis showed nonlinear associations among Mexican-American and Non-Hispanic White men (p nonlinearity  ≤ .03 both) and only among men with waist circumference <102 cm and body mass index <25 kg/m 2 (p nonlinearity  < .01, both). No linear association was identified between levels of caffeine intake and testosterone in US men, but we observed a non-linear association, including among racial/ethnic groups and measurements of adiposity in this cross-sectional study. These associations are warranted to be investigated in larger prospective studies.

Effect of testosterone replacement on the alteration of steroid metabolism in the hypothalamic-preoptic area of male hamsters treated with melatonin.

PubMed

Petterborg, L J; West, D A; Rudeen, P K; Ganjam, V K

1991-11-01

Adult male hamsters were maintained under 14 hours of light per day and randomly assigned to groups that received daily afternoon melatonin (25 micrograms) or vehicle injections. Animals from both groups were killed following 4, 8, and 12 weeks of treatment. By 12 weeks, the melatonin-treated hamsters had significant reductions in the weights of the testes and seminal vesicles, serum testosterone levels, and activities did not differ between groups. In a second experiment, hamsters were hypothalamic-preoptic area (HPOA) aromatase activities. Hypothalamic-preoptic area 5 alpha-reductase activities did not differ between groups. In a second experiment, hamsters were again treated with melatonin or vehicle for 12 weeks prior to being killed. After 10 weeks of treatment, groups of melatonin-treated animals received subcutaneous silastic capsules (5, 10, or 20 mm) filled with testosterone. Animals in two other groups were given blank implants or no implants at all. Two weeks later, at autopsy, reproductive organ weights, serum testosterone levels, and HPOA aromatase activities were significantly suppressed by melatonin administration. 5 alpha-Reductase activity in the HPOA was not affected. Hamsters that had been given the 10- and 20-mm testosterone implants exhibited normal seminal vesicle weights and HPOA aromatase activities. These results suggest that melatonin-induced reduction of HPOA aromatase activity is mediated by decreased circulating levels of testosterone.

Protection of male reproductive toxicity in rats exposed to di-n-butyl phthalate during embryonic development by testosterone.

PubMed

Giribabu, Nelli; Reddy, Pamanji Sreenivasula

2017-03-01

Di-n-butyl phthalate (DBP) widely spread industrial chemical that made drastic alteration in male reproductive system. The present study elucidates the protective role of testosterone on reproductive toxicity in prenatal DBP exposed adult male rats. Pregnant rats were injected with corn oil or 100 and 500mg/kg body weight of DBP on gestation day (GD) 1, 7 and 14. F1 male rats were weaned, injected with either testosterone or vehicle. On postnatal day (PND) 100 F1 adult male rats were cohabited with untreated female rats. Then rats were sacrificed and analyzed for other reproductive end points. Prenatal DBP exposed male rat testes, seminal vesicle weight, sperm count, motility, viability and HOS tail coiled sperm were significantly decreased with increased sperm morphological abnormalities. The levels of testicular 3β, 17βHSD, serum testosterone were significantly decreased with increased FSH, LH levels in experimental rats. The fertility studies revealed that increased pre, post-implantation losses and resorptions in normal females cohabited with experimental rats. Higher testicular LPO with lower SOD, CAT and GPx activity levels in experimental rats. Administration of testosterone to prenatal DBP treated male rats showed significant protection in above all parameters. In conclusions, testosterone deteriorates prenatal DBP induced reproductive and fertility toxicity by decreased oxidative stress and increased testicular antioxidant enzymes. Copyright © 2016. Published by Elsevier Masson SAS.

Cynanchum wilfordii Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase and Androgen Receptor Activities in a Rat Model

PubMed Central

Lee, Gyuok; Shin, Jawon; Choi, Hakjoon; Jo, Ara; Pan, SangO; Bae, Donghyuck; Lee, Yongwook; Choi, Chulyung

2017-01-01

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats. PMID:28953224

Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel.

PubMed

Kaminetsky, Jed; Werner, Michael; Fontenot, Greg; Wiehle, Ronald D

2013-06-01

Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75-334 × 10(6) /mL range. The gel was ineffective in raising sperm counts above 20 × 10(6) /mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts. Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic-pituitary-testicular axis. © 2013 Repros Therapeutics. Journal of Sexual Medicine © 2013 International Society for Sexual Medicine.

The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2015-02-01

For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small. The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Enclomiphene Citrate for the Treatment of Secondary Male Hypogonadism

PubMed Central

Rodriguez, Katherine M.; Pastuszak, Alexander W.; Lipshultz, Larry I.

2016-01-01

Introduction Hypogonadism is a growing concern in an aging male population. Historically treated using exogenous testosterone, concerns about possible adverse effects of testosterone have led physicians to seek alternative treatment approaches. Areas Covered Enclomiphene citrate is the trans isomer of clomiphene citrate, a non-steroidal estrogen receptor antagonist that is FDA-approved for the treatment of ovarian dysfunction in women. Clomiphene citrate has also been used off-label for many years to treat secondary male hypogonadism, particularly in the setting of male infertility. Here we review the literature examining the efficacy and safety of enclomiphene citrate in the setting of androgen deficiency. Expert Opinion Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option. PMID:27337642

Effect of Benincasa hispida fruits on testosterone-induced prostatic hypertrophy in albino rats

PubMed Central

Nandecha, Chetan; Nahata, Alok; Dixit, Vinod Kumar

2010-01-01

Background: Benincasa hispida Cogn. has been used traditionally in India for the management of urinary disorders. The fruit of B hispida is used as a diuretic and the seeds have been reported to possess antiangiogenic effects in prostate cells. Objective: The aim of the present study was to examine the effect of petroleum ether extract, ethanolic extract, and B hispida seed oil on hyperplasia of the prostate induced by the subcutaneous administration of testosterone in rats. Methods: In vitro studies were performed to determine the 5α-reductase inhibitory potential of the extracts. The results of those studies paved the way for the pharmacologic screening of the extracts to assess their potential against testosterone-induced hyperplasia in rats. Nine groups containing 10 rats per group were created for this study. Hyperplasia was induced by administration of testosterone (3 mg/kg SC) for 14 days in all the groups except the vehicle-treated group. Simultaneous administration of petroleum ether extract (100 or 200 mg/kg PO), ethanolic extract (100 or 200 mg/kg PO), and B hispida seed oil (20 or 40 mg/kg PO) was conducted. A standard 5α-reductase inhibitor (ie, finasteride) was used as a positive control. The weight of the rats was recorded on day 0 (ie, day 1 of the study) and on day 14, and the influence of testosterone and test extracts on the weight of the rats was determined. On day 14, rats were euthanized; prostates were dissected out, and weighed. The rats' prostate/body weight (P/BW) ratio was then determined. Histologic examinations were performed on prostates from each group. Results: The petroleum ether extract as well as B hispida seed oil exhibited inhibition of 5α-reductase activity in in vitro studies. Ethanolic extract did not exhibit significant inhibitory potential in vitro. Further in vivo study found that testosterone treatment significantly increased the rats' P/BW ratio in all the groups except the vehicle-treated rats, and this increase in weight was significantly inhibited in rats administered petroleum ether extract (100 and 200 mg/kg PO) and B hispida seed oil (20 and 40 mg/kg PO). Ethanolic extract did not exhibit any significant activity. Conclusions: Petroleum ether extract and B hispida seed oil inhibited testosterone-induced hyperplasia of the prostate in these rats. Further studies are needed to evaluate its effect in humans with benign prostatic hyperplasia. PMID:24688153

Endocrine and reproductive dysfunction in men associated with occupational inorganic lead intoxication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cullen, M.R.; Kayne, R.D.; Robins, J.M.

In an attempt to define a postulated effect of lead on male endocrine function, seven men with symptomatic occupational lead intoxication (maximum whole blood lead levels 66-139 ..mu..g/dl) underwent in-patient endocrine evaluation at the time of diagnosis. Defects in thyroid function probably of central origin, were present in three patients. Six patients had subnormal glucocorticoid production measured by 24-hr urinary 17-hydroxy-corticosteroids and plasma cortisol responses to vasopressin- and/or insulin-induced hypoglycemia. Although serum testosterone concentration was normal in six patients, five had defects in spermatogenesis, including two with ologospermia and two with azoospermia. Repeat examinations after chelation therapy showed only partialmore » improvement. It is concluded that heavy occupational exposure to lead, sufficient to cause clinical poisoning, may be associated with diffuse disturbances of endocrine and reproductive functions in men which are not rapidly reversible with standard treatment. Since men without overt poisoning have not been studied, these results cannot yet be included as sequelae of low-dose exposures.« less

New Paradigms for Advanced Prostate Cancer

PubMed Central

Petrylak, Daniel P

2007-01-01

In men with metastatic hormone-refractory prostate cancer, androgen blockade produces dramatic and rapid declines in prostate-specific antigen (PSA), bone pain, and urinary tract obstruction. Nevertheless, there have been limited options with at best palliative results for patients who progress despite a castrate testosterone level. This paradigm changed in 2004 with the publication of 2 randomized clinical trials that demonstrated a 20% to 24% survival benefit for docetaxel-based therapy when compared to mitoxantrone and prednisone, data that supported US Food and Drug Administration approval of docetaxel-based therapy for the treatment of metastatic hormone-refractory prostate cancer. This article reviews the preliminary data and the timing and sequencing implications of ongoing clinical trials. Studies are evaluating the combination of docetaxel with agents that target bone, tumor vasculature, and the vitamin D receptor as well as second-line agents, such as satraplatin. The role of immune therapy is also evolving, and further studies will define the optimal timing of chemotherapy with immune therapy. PMID:17554403

The effect of high level tennis matches on urine steroid profiles in professional tennis players.

PubMed

Muñoz, D; Toribio, F; Timón, R; Olcina, G; Maynar, J I; Maynar, M

2010-12-01

Modern day, tennis matches are characterized by shorter and more intense efforts with players enduring great physical and psychological stress. The aim of this study was to evaluate acute changes in the urinary steroid profile of elite tennis players following professional tournament matches. Eight professional male tennis players participated in this study. Urine samples were collected before and after tennis matches corresponding to the quarter finals of the Spanish Tennis Masters. After the match, there was a significant fall (P<0.05) in testosterone, androsterone, etiocholanolone, and dehydroepiandrosterone (DHEA). Cortisone increased whereas tetrahydrocortisone (THE) decreased. The anabolic/catabolic hormone ratio also decreased, although only the fall in total suprarenal androgen (TSA)/total corticosteroid (TC) and DHEA/(THE+THF) ratios had a significant decrease (P<0.05). These results indicate that a professional tennis match modifies the urine steroid profiles of players, increasing corticosteroid and decreasing androgen excretion in urine, suggesting an important adrenal activation.

High serum testosterone levels during postpartum period are associated with postpartum depression.

PubMed

Aswathi, A; Rajendiren, Soundravally; Nimesh, Archana; Philip, R Ravi; Kattimani, Shivanand; Jayalakshmi, D; Ananthanarayanan, P H; Dhiman, Pooja

2015-10-01

In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score ≥10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD. Copyright © 2015 Elsevier B.V. All rights reserved.

Klinefelter syndrome

MedlinePlus

... hormone levels including: Estradiol, a type of estrogen Follicle stimulating hormone Luteinizing hormone Testosterone Treatment Testosterone therapy may be prescribed. This can help: Grow body hair Improve appearance of muscles Improve concentration Improve mood ...

Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function.

PubMed

Jayaraman, Anusha; Lent-Schochet, Daniella; Pike, Christian J

2014-09-16

Low testosterone and obesity are independent risk factors for dysfunction of the nervous system including neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate the independent and cooperative interactions of testosterone and diet-induced obesity on metabolic, inflammatory, and neural health indices in the central and peripheral nervous systems. Male C57B6/J mice were maintained on normal or high-fat diet under varying testosterone conditions for a four-month treatment period, after which metabolic indices were measured and RNA isolated from cerebral cortex and sciatic nerve. Cortices were used to generate mixed glial cultures, upon which embryonic cerebrocortical neurons were co-cultured for assessment of neuron survival and neurite outgrowth. Peripheral nerve damage was determined using paw-withdrawal assay, myelin sheath protein expression levels, and Na+,K+-ATPase activity levels. Our results demonstrate that detrimental effects on both metabolic (blood glucose, insulin sensitivity) and proinflammatory (cytokine expression) responses caused by diet-induced obesity are exacerbated by testosterone depletion. Mixed glial cultures generated from obese mice retain elevated cytokine expression, although low testosterone effects do not persist ex vivo. Primary neurons co-cultured with glial cultures generated from high-fat fed animals exhibit reduced survival and poorer neurite outgrowth. In addition, low testosterone and diet-induced obesity combine to increase inflammation and evidence of nerve damage in the peripheral nervous system. Testosterone and diet-induced obesity independently and cooperatively regulate neuroinflammation in central and peripheral nervous systems, which may contribute to observed impairments in neural health. Together, our findings suggest that low testosterone and obesity are interactive regulators of neuroinflammation that, in combination with adipose-derived inflammatory pathways and other factors, increase the risk of downstream disorders including type 2 diabetes and Alzheimer's disease.

Preliminary evidence that acute stress moderates basal testosterone's association with retaliatory behavior.

PubMed

Prasad, Smrithi; Narayanan, Jayanth; Lim, Vivien K G; Koh, Gerald C H; Koh, David S Q; Mehta, Pranjal H

2017-06-01

A contribution to a special issue on Hormones and Human Competition. Testosterone is theorized to increase retaliation after social provocation. However, empirical evidence in support of these theories is mixed. The present research investigated whether acute stress causally suppresses testosterone's association with retaliation. We also explored sex differences in behavioral responses to acute stress. Thirty-nine participants (51.28% male) were randomly assigned to a high- or low-stress condition. Then participants engaged in 20 one-shot rounds of the ultimatum game, which was used to assess retaliatory behavioral responses to unfair treatment. Participants provided two saliva samples to measure testosterone and cortisol concentrations - one sample before the stress manipulation, and the second after the ultimatum game (20minutes post-stressor). Results revealed a positive association between basal testosterone and retaliation in the low-stress condition, but not in the high-stress condition. Further, cortisol concentrations increased in the high- compared to the low-stress condition, and these cortisol changes moderated the association between basal testosterone and retaliation. The associations between basal testosterone and retaliation under varying levels of stress were similar in men and women. However, there was a sex difference in behavioral responses to the stress manipulation that was independent of testosterone. In women, the high-stress condition reduced retaliation compared to the low-stress condition, whereas in men the opposite pattern emerged. Collectively, this study (i) provides preliminary evidence that experimentally manipulated stress blocks basal testosterone's association with retaliation, and (ii) reveals a sex difference in retaliation under varying levels of stress. Discussion focuses on mechanisms, limitations, and the need for follow-up studies with larger sample sizes. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in androgen receptor, estrogen receptor alpha, and sexual behavior with aging and testosterone in male rats.

PubMed

Wu, Di; Gore, Andrea C

2010-07-01

Reproductive aging in males is characterized by a diminution in sexual behavior beginning in middle age. We investigated the relationships among testosterone, androgen receptor (AR) and estrogen receptor alpha (ERalpha) cell numbers in the hypothalamus, and their relationship to sexual performance in male rats. Young (3months) and middle-aged (12months) rats were given sexual behavior tests, then castrated and implanted with vehicle or testosterone capsules. Rats were tested again for sexual behavior. Numbers of AR and ERalpha immunoreactive cells were counted in the anteroventral periventricular nucleus and the medial preoptic nucleus, and serum hormones were measured. Middle-aged intact rats had significant impairments of all sexual behavior measures compared to young males. After castration and testosterone implantation, sexual behaviors in middle-aged males were largely comparable to those in the young males. In the hypothalamus, AR cell density was significantly (5-fold) higher, and ERalpha cell density significantly (6-fold) lower, in testosterone- than vehicle-treated males, with no age differences. Thus, restoration of serum testosterone to comparable levels in young and middle-aged rats resulted in similar preoptic AR and ERalpha cell density concomitant with a reinstatement of most behaviors. These data suggest that age-related differences in sexual behavior cannot be due to absolute levels of testosterone, and further, the middle-aged brain retains the capacity to respond to exogenous testosterone with changes in hypothalamic AR and ERalpha expression. Our finding that testosterone replacement in aging males has profound effects on hypothalamic receptors and behavior has potential medical implications for the treatment of age-related hypogonadism in men. Copyright 2010 Elsevier Inc. All rights reserved.

The effect of food composition on serum testosterone levels after oral administration of Andriol® Testocaps®

PubMed Central

Schnabel, Peter G; Bagchus, Wilma; Lass, Holger; Thomsen, Torben; Geurts, T B Paul

2007-01-01

Objective Andriol® Testocaps® is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. Design An open-label, single-centre, four-way crossover study. With a washout period of 6–7 days, 80 mg TU was administered in the morning 5 min after consuming each of four different meals in a randomized order (A: 230 kcal, 0·6 g lipid; B: 220 kcal, 5 g lipid; C: 474 kcal, 19 g lipid; D: 837 kcal, 44 g lipid). Patients Twenty-four postmenopausal volunteers. Measurements Serial blood samples were collected until 24 h after dosing to determine testosterone and dihydrotestosterone (DHT) by gas chromatography-mass spectroscopy (GC-MS). Results The bioavailability of testosterone after a low-calorie meal containing 0·6 g lipid or 5 g lipid was relatively low, the area under the concentration–time curve (AUC0–tlast) for testosterone being 30·7 and 43·5 nmol h/l, respectively. The bioavailability of testosterone after a meal containing 19 g lipid was considerably higher (AUC0–tlast = 146 nmol h/l), whereas increasing the lipid content to 44 g lipid did not further increase the bioavailability of testosterone (AUC0–tlast = 154 nmol h/l). Conclusion Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU. PMID:17371478

Paternal and Maternal Testosterone in Parents of NICU Infants Transitioning Home.

PubMed

Garfield, Craig F; Simon, Clarissa D; Rutsohn, Joshua; Lee, Young S

Lower testosterone during the transition to new parenthood is considered beneficial to help parents better engage with their infants. No data currently exist studying salivary testosterone of parents with infants in neonatal intensive care units (NICUs) during the transition to home. We examine testosterone levels for parents of very low-birth-weight infants, including links between salivary testosterone and infant factors (such as breast-feeding), psychosocial stress, and changes over time.Testosterone salivary samples were assayed after self-collection by 86 parents (43 fathers and 43 mothers) with NICU infants at wakeup and bedtime prior to discharge and at 3 additional times at home. Self-reported survey measures, including psychosocial reports, were also collected at these times.Using multilevel modeling approaches, we report significant associations between paternal testosterone by time and psychosocial adjustment and between both paternal and maternal testosterone and infant feeding mode (P < .05). Results were significant after accounting for covariates. Our study is the first to examine the time course of diurnal testosterone for parents of premature infants over the transition home; as such, we suggest further research into better understanding parental physiology in this vulnerable parent population.

[A case of locally advanced prostate cancer with low serum testosterone associated with intake of an androgenic medicine].

PubMed

Sakura, Mizuaki; Tsukamoto, Tetsurou; Yonese, Junji; Nakaishi, Masayuki; Maezawa, Takuya; Takimoto, Keita; Fukui, Iwao

2003-05-01

A 74-year-old man was referred to our clinic for the work-up of digitally hard and irregularly surfaced prostate and elevated serum prostate-specific antigen (PSA). His serum PSA was elevated to 41 ng/ml, but testosterone and LH level were decreased to 23.5 ng/dl and 0.5 mIU/ml, respectively. He had a history of taking an androgenic medicine containing methyl-testosterone 2 to 3 times a week for 2 year and 6 months. Transrectal sextant prostatic biopsy revealed moderately differentiated adenocarcinoma (Gleason score: 3 + 4) in 6 of 6 specimens and CT scan of the abdomen showed an enlarged obturator lymph-node (15 mm), resulting in the diagnosis of stage D1 (T3aN1M0) prostate cancer. Since serum testosterone level seemed to recover around the normal level after discontinuation of the exogenous androgen, we treated him with combination androgen blockade with LHRH agonist and bicaltamide, although his testosterone level was very low. Indeed, serum PSA decreased to 0.09 ng/ml and the right obturator node was markedly reduced by the hormone treatment. After the neoadjuvant therapy of 6 months duration, radical prostatectomy and limited pelvic lymph node dissection was carried out. Histologically, viable cancer cells were not found in any of resected lymph nodes, but they remained in bilateral lobes of the prostate (pT2bN0). The histological effect of the neoadjuvant hormone therapy according to General rule for Clinical and Pathological Studies on Prostate Cancer (3rd ed.) was grade 2. The patient has been well with undetectable PSA and no evidence of clinical failure for more than 12 months, though serum testosterone level recovered to near normal (288 ng/dl) 8 months after the cessation of the hormone treatment following the operation. Combination androgen blockade or non-steroidal anti-androgen agent appears to be effective for the treatment of prostatic cancer patients who takes exogenous androgenic medicine, even with a suppressed low serum testosterone level.

Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation.

PubMed

Sharma, Rishi; Oni, Olurinde A; Gupta, Kamal; Sharma, Mukut; Sharma, Ram; Singh, Vikas; Parashara, Deepak; Kamalakar, Surineni; Dawn, Buddhadeb; Chen, Guoqing; Ambrose, John A; Barua, Rajat S

2017-05-09

Atrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone. Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score-weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post-TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81-0.99, P =0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70-0.89, P =0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78- 1.0009, P =0.0675) in incidence of AF. These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Hair and urine testing to assess drugs of abuse consumption in couples undergoing assisted reproductive technology (ART).

PubMed

Pichini, Simona; De Luca, Roberto; Pellegrini, Manuela; Marchei, Emilia; Rotolo, Maria Concetta; Spoletini, Roberta; D'Aloja, Paola; Pacifici, Roberta; Mortali, Claudia; Scaravelli, Giulia

2012-05-10

For the first time in Europe hair and urine testing have been applied to assess drugs of abuse consumption in couples undergoing assisted reproductive technology and the eventual association of toxic habits with other lifestyle, health status and sociodemographic factors was also investigated. Couples attending five assisted reproduction centers in Rome were invited to join the study. When they presented at the Centre for the visit, they were asked to answer a structured questionnaire concerning sociodemographic characteristics and lifestyle habits, and at the same time to provide hair and urine samples. Hair and urine testing for drugs of abuse, urinary profile of principal endogenous steroids involved in fertility process (testosterone, epitestosterone, androsterone, etiocholanolone and dehydroepiandrosterone) and of alcohol and tobacco smoke biomarkers were performed with validated methodologies. Of the 594 enrolled individuals (297 couples), 352 (164 couples and 24 single individuals from the couple) completed the questionnaire and gave both hair and urine samples, apart from 3 bald men, who only gave urine samples. Urine testing showed an overall 4.8% (17 individuals) positivity to drugs of abuse: 4.2% to cannabinoids, 1.4% to cocaine and 0.85% to both drugs. Results of 4cm segment hair samples testing matched those from urine samples. Thus, taking together, results of urine and hair testing confirmed repeated use of cannabis, cocaine and both drugs in 3.7, 0.85 and 0.57% examined individuals, respectively. Drug consumers were in a statistically higher percentage active smokers and alcohol drinkers, less prone to physical activity and with a trend towards higher weight than non consumers. Finally, repeated drug consumption was associated with significant lower concentration of urinary testosterone in males and of urinary dehydroepiandrosterone in females. The findings of the present study confirm the suitability of urine testing to disclose recent drugs of abuse consumption and of hair analysis to verify repeated consumption. Association between different toxic habits and sedentary lifestyle is also substantiated by the obtained results in our cohort of couples attending assisted reproduction centers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Exploring the role of testosterone in the cerebellum link to neuroticism: From adolescence to early adulthood.

PubMed

Schutter, Dennis J L G; Meuwese, Rosa; Bos, Marieke G N; Crone, Eveline A; Peper, Jiska S

2017-04-01

Previous research has found an association between a smaller cerebellar volume and higher levels of neuroticism. The steroid hormone testosterone reduces stress responses and the susceptibility to negative mood. Together with in vitro studies showing a positive effect of testosterone on cerebellar gray matter volumes, we set out to explore the role of testosterone in the relation between cerebellar gray matter and neuroticism. Structural magnetic resonance imaging scans were acquired, and indices of neurotic personality traits were assessed by administering the depression and anxiety scale of the revised NEO personality inventory and Gray's behavioural avoidance in one hundred and forty-nine healthy volunteers between 12 and 27 years of age. Results demonstrated an inverse relation between total brain corrected cerebellar volumes and neurotic personality traits in adolescents and young adults. In males, higher endogenous testosterone levels were associated with lower scores on neurotic personality traits and larger cerebellar gray matter volumes. No such relations were observed in the female participants. Analyses showed that testosterone significantly mediated the relation between male cerebellar gray matter and measures of neuroticism. Our findings on the interrelations between endogenous testosterone, neuroticism and cerebellar morphology provide a cerebellum-oriented framework for the susceptibility to experience negative emotions and mood in adolescence and early adulthood. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats.

PubMed

Ohta, Y; Yoshida, K; Kamiya, S; Kawate, N; Takahashi, M; Inaba, T; Hatoya, S; Morii, H; Takahashi, K; Ito, M; Ogawa, H; Tamada, H

2016-04-01

Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol. © 2015 Blackwell Verlag GmbH.

Testosterone affects language areas of the adult human brain

PubMed Central

Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

2016-01-01

Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

Diagnosis and management of testosterone deficiency.

PubMed

McBride, James A; Carson, Culley C; Coward, Robert M

2015-01-01

Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.

Diagnosis and management of testosterone deficiency

PubMed Central

McBride, James A; Carson, Culley C; Coward, Robert M

2015-01-01

Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD. PMID:25532575