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.

Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader-Willi syndrome.

PubMed

Radicioni, A F; Di Giorgio, G; Grugni, G; Cuttini, M; Losacco, V; Anzuini, A; Spera, S; Marzano, C; Lenzi, A; Cappa, M; Crinò, A

2012-01-01

Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear. To investigate the aetiology of hypothalamic-pituitary-gonadal axis dysfunction in PWS males. Clinical examination and blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in 34 PWS patients, age 5·1-42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years. Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near-significantly lower LH, testosterone, SHBG, inhibin B and higher FSH. PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH-inhibin B axis and central origin for LH-T axis). © 2011 Blackwell Publishing Ltd.

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

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.

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.

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.

Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe

PubMed Central

Travison, Thomas G.; Vesper, Hubert W.; Orwoll, Eric; Wu, Frederick; Kaufman, Jean Marc; Wang, Ying; Lapauw, Bruno; Fiers, Tom; Matsumoto, Alvin M.

2017-01-01

Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating assays to a reference method and standard. Population: The 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; and Male Sibling Study of Osteoporosis. Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control and Prevention (CDC). Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were used to generate harmonized values, which were used to derive standardized, age-specific reference ranges. Results: Harmonization procedure reduced intercohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19 to 39 years, harmonized 2.5th, 5th, 50th, 95th, and 97.5th percentile values were 264, 303, 531, 852, and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men. Conclusion: Harmonized normal range in a healthy nonobese population of European and American men, 19 to 39 years, is 264 to 916 ng/dL. A substantial proportion of intercohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator. PMID:28324103

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.

[Erectile dysfunction and obstructive sleep apnea syndrome].

PubMed

Zhuravlev, V N; Frank, M A; Gomzhin, A I

2008-01-01

Of 72 patients with obstructive sleep apnea syndrome (OSAS) 32 had erectile dysfunction (ED). OSAS patients with erectile dysfunction had hypogonadism in 24 cases, in 8 men testosterone level was normal. A polysomnographic investigation with monitoring of nocturnal spontaneous erections showed that 32 patients had severe sleep fragmentation with reduced or complete absence of REM and deep sleep phases. In nocturnal penile tumescencia quantitative and qualitative characteristics were abnormal suggesting organic nature of erectile dysfunction in these patients. Eight ED and OSAS patients with normal testosterone received standard OSAS therapy with administration of FDE-5 type inhibitors. Six months later improvement of the erectile function was observed in 6 patients. OSAS patients with hypogonadism were divided into 2 groups. Group 1 (n = 5) received CPAP therapy and group 2 (n = 19) received OSAS standard therapy. Group 2 was treated with inhibitors of FDE-5 type. Three months later improvement of erectile function was seen only in 8. Group 1 received the inhibitors and testosterone replacement. Three months later all 5 patients had no ED complaints, their testosterone was normal. It is recommended to perform monitoring of nocturnal spontaneous erections in the algorithm of examination of all men with OSAS. All patients with OSAS, ED and documented hypogonadism need testosterone replacement therapy if its level persists low despite adequate therapy of OSAS.

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.

Elevated testosterone and hypergonadotropism in active adolescents of normal weight with oligomenorrhea.

PubMed

Singer, K; Rosenthal, A; Kasa-Vubu, Josephine Z

2009-10-01

Oligomenorrhea in active adolescent females of normal weight is presumed to be related to hypoestrogenism secondary to physical activity and decreased fat mass. We hypothesized that active adolescents with oligomenorrhea would have lower estrogen levels than normal controls with similar levels of cardiovascular fitness. Twenty healthy participants between the ages of 16 and 20 years were recruited at least 2 years postmenarche. Adolescents reporting fewer than 9 cycles a year (n = 6) were compared to 14 controls with monthly menstrual cycles. Histories of eating disorder, hirsutism, severe acne, depression, or amenorrhea were cause for exclusion. Body composition and bone density were measured by total body dual x-ray absorpitometry. Cardiovascular fitness was evaluated by measuring oxygen consumption during exercise. Control subjects were matched by age, body mass index (BMI), and fitness level. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, progesterone, and estradiol were obtained. Statistical analysis was performed using SAS 9.1. Cardiovascular fitness in both groups was within normal limits for age. No significant differences in BMI, estradiol concentrations, or bone density were found, but trunk fat mass was lower in adolescents with oligomenorrhea who also reported more frequent exercise. Testosterone concentrations and LH/FSH ratios were significantly higher in participants with irregular menstrual cycles (P = 0.0018 and <0.001, respectively). Adolescents with oligomenorrhea were leaner, yet they had higher testosterone levels and a greater LH/FSH ratio than their BMI-matched, cyclic counterparts. We hypothesize that, in active adolescents of normal weight, elevated androgen and LH concentrations are linked to ovarian dysfunction, which can masquerade as exercise-induced oligomenorrhea.

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.

Testosterone, aggression, and territoriality in male Western Screech-owls (Otus kennicottii): results from preliminary experiments

Treesearch

Brian L. Herting; James R. Belthoff

1997-01-01

Using a hormone implant protocol, we created treatment groups in which circulating levels of testosterone (T) were increased, decreased, or maintained at normal levels (controls) in male Western Screech-owls (Otus kennicottii). Owls were exposed to tape-recorded vocalizations of a conspecific, to which territory holders responded with aggression....

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.

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.

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.

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.

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.

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.

A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.

PubMed

Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J

1999-10-01

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.

Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

PubMed

Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

2004-08-01

Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at acute treatment but showed a gradual rise reflecting the stress imposed on the animals. The rise in cortisol levels was visualized to potentiate the cardiovascular and metabolic changes. The effects on insulin and thyroxin were similar to those of testosterone level showing normal or stimulatory effect with acute treatment followed by decreased levels of hormones with chronic treatment.

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.

Cardiovascular benefits and risks of testosterone replacement therapy in older men with low testosterone.

PubMed

Chrysant, Steven G; Chrysant, George S

2018-04-01

Many studies have shown that low testosterone (T) levels have been associated with increased risk for cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and strokes. In contrast, many other studies have demonstrated that normal T levels or the normalization of low T levels with testosterone replacement therapy (TRT) is associated with decreased incidence of CV events, T2DM, and strokes, besides improving sexual function and the quality of life. However, recent studies have indicated that TRT could lead to increased incidence of CV events and strokes. These latter studies have created a great controversy among physicians regarding these findings, who question the validity of their results. In order to get a better perspective on the current status of TRT in hypogonadal men, a focused Medline and EMBASE search of the English language literature was conducted between 2010 and 2017 using the terms hypogonadism, low Testosterone, cardiovascular disease, testosterone replacement therapy, benefits, risks, older men, mechanism of action, and 58 papers with pertinent information were selected and 48 papers were rejected. The selected papers will be discussed in this review. In conclusion, based on the current status of TRT, the majority of studies indicate that TRT is safe and is associated with prevention of CVD and strokes in hypogonadal men. However, the evidence is not uniform and the therefore, decision to administer TRT should be discussed with the patient till more definitive information becomes available.

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.

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

Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy.

PubMed

Davidiuk, Andrew J; Broderick, Gregory A

2016-12-01

Testosterone deficiency (TD) has become a growing concern in the field of men's sexual health, with an increasing number of men presenting for evaluation of this condition. Given the increasing demand for testosterone replacement therapy (TRT), a panel of experts met in August of 2015 to discuss the treatment of men who present for evaluation in the setting of low or normal gonadotropin levels and the associated signs and symptoms of hypogonadism. This constellation of factors can be associated with elements of both primary and secondary hypogonadism. Because this syndrome commonly occurs in men who are middle-aged and older, it was termed adult-onset hypogonadism (AOH). AOH can be defined by the following elements: low levels of testosterone, associated signs and symptoms of hypogonadism, and low or normal gonadotropin levels. Although there are significant benefits of TRT for patients with AOH, candidates also need to understand the potential risks. Patients undergoing TRT will need to be monitored regularly because there are potential complications that can develop with long-term use. This review is aimed at providing a deeper understanding of AOH, discussing the benefits and risks of TRT, and outlining each modality of TRT in use for AOH.

Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

PubMed

Atkins, Katelyn M; Chen, Ming-Hui; Wu, Jing; Renshaw, Andrew A; Loffredo, Marian; Kantoff, Philip W; Small, Eric J; D'Amico, Anthony V

2018-04-01

Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

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.

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

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

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.

Endocrine gland-derived vascular endothelial growth factor in rat pancreas: genetic expression and testosterone regulation.

PubMed

Morales, Angélica; Morimoto, Sumiko; Díaz, Lorenza; Robles, Guillermo; Díaz-Sánchez, Vicente

2008-05-01

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an endothelial cell mitogen, expressed essentially in steroidogenic cells. Recently, the expression of EG-VEGF in normal human pancreas and pancreatic adenocarcinoma has been demonstrated. Epidemiologically, pancreatic carcinogenesis is more frequent in males than females, and given that androgen receptors and testosterone biotransformation have been described in pancreas, we hypothesized that testosterone could participate in the regulation of EG-VEGF expression. In this study, we investigated the regulation of EG-VEGF gene expression by testosterone in normal rat pancreatic tissue and rat insulinoma cells (RINm5F). Total RNA was extracted from rat pancreas and cultured cells. Gene expression was studied by real-time PCR and protein detection by immunohistochemistry. Serum testosterone was quantified by RIA. Results showed that EG-VEGF is expressed predominantly in pancreatic islets and vascular endothelium, as well as in RINm5F cells. EG-VEGF gene expression was lower in the pancreas of rats with higher testosterone serum levels. A similar effect that was reverted by flutamide was observed in testosterone-treated RINm5F cells. In summary, testosterone down-regulated EG-VEGF gene expression in rat pancreatic tissue and RINm5F cells. This effect could be mediated by the androgen receptor. To our knowledge, this is the first time that a direct effect of testosterone on EG-VEGF gene expression in rat pancreas and RINm5F cells is demonstrated.

[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.

Does Calculated Free Testosterone Overcome Total Testosterone in Protecting From Sexual Symptom Impairment? Findings of a Cross-Sectional Study.

PubMed

Boeri, Luca; Capogrosso, Paolo; Ventimiglia, Eugenio; Cazzaniga, Walter; Pederzoli, Filippo; Moretti, Donatella; Dehò, Federico; Montanari, Emanuele; Montorsi, Francesco; Salonia, Andrea

2017-12-01

Although erectile dysfunction (ED) has been associated with low circulating total testosterone (TT) levels, the utility of free testosterone (FT) over TT is debatable. To assess the relative impact of low TT and low calculated FT (cFT) on androgen-related sexual symptoms in men with ED. Data from 485 men were analyzed. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF) and the Beck Inventory for Depression (BDI). Descriptive statistics tested differences between patients with normal TT levels (>3 ng/mL) and normal cFT levels (>65 pg/mL; group 1) and men with normal TT and low cFT (group 2), low TT and normal cFT (group 3), and low TT and low cFT (group 4). Linear regression models tested the association between clinical predictors and sexual function impairment. We assessed the impact of different hormonal categories on androgen-related symptoms and the clinical utility of measuring cFT in men with ED. Groups 1, 2, 3, and 4 were composed of 338 (69.6%), 44 (9.1%), 34 (7.0%), and 69 (14.3%) patients, respectively. Compared with group 1, patients in group 2 were older (P < .001), had a higher body mass index (P < .01), and had a larger proportion with CCI scores of at least 1 (P = .006). Likewise, group 2 presented lower scores for the IIEF erectile function (P = .07), sexual desire (P = .04), and orgasmic function (P = .007) domains and lower BDI scores (P = .02) than group 1. Similar findings were found for group 4 vs 1. Conversely, patients in group 3 had similar scores on the questionnaires to those in group 1. Low cFT and normal or low TT achieved independent predictor status for pathologic IIEF domains and BDI scores after accounting for age, CCI, and body mass index. Conversely, low TT and normal cFT status was not associated with pathologic scores on the questionnaires. The inclusion of cFT in the first-line assessment of hypogonadal symptoms in men with ED has major clinical utility. This is the first study evaluating the concomitant impact of TT and cFT on men with ED using well-validated instruments to assess patients' sexuality and depressive symptoms. Limitations are the retrospective nature of the study and lack of physical function data and bone ultrasound measurements. Although normal cFT was not associated with signs and symptoms suggestive of testosterone deficiency, even when concomitant with low TT or low cFT irrespective of TT values, it was indicative of poorer clinical profiles and impaired sexual and depressive parameters compared with normal TT and normal cFT in a cohort of patients with ED. Boeri L, Capogrosso P, Ventimiglia E, et al. Does Calculated Free Testosterone Overcome Total Testosterone in Protecting From Sexual Symptom Impairment? Findings of a Cross-Sectional Study. J Sex Med 2017;14:1549-1557. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice.

PubMed

Kelly, Daniel M; Nettleship, Joanne E; Akhtar, Samia; Muraleedharan, Vakkat; Sellers, Donna J; Brooke, Jonathan C; McLaren, David S; Channer, Kevin S; Jones, T Hugh

2014-07-30

Non-alcoholic fatty liver disease and its precursor hepatic steatosis is common in obesity and type-2 diabetes and is associated with cardiovascular disease (CVD). Men with type-2 diabetes and/or CVD have a high prevalence of testosterone deficiency. Testosterone replacement improves key cardiovascular risk factors. The effects of testosterone on hepatic steatosis are not fully understood. Testicular feminised (Tfm) mice, which have a non-functional androgen receptor (AR) and very low serum testosterone levels, were used to investigate testosterone effects on high-cholesterol diet-induced hepatic steatosis. Hepatic lipid deposition was increased in Tfm mice and orchidectomised wild-type littermates versus intact wild-type littermate controls with normal androgen physiology. Lipid deposition was reduced in Tfm mice receiving testosterone treatment compared to placebo. Oestrogen receptor blockade significantly, but only partially, reduced the beneficial effects of testosterone treatment on hepatic lipid accumulation. Expression of key regulatory enzymes of fatty acid synthesis, acetyl-CoA carboxylase alpha (ACACA) and fatty acid synthase (FASN) were elevated in placebo-treated Tfm mice versus placebo-treated littermates and Tfm mice receiving testosterone treatment. Tfm mice on normal diet had increased lipid accumulation compared to littermates but significantly less than cholesterol-fed Tfm mice and demonstrated increased gene expression of hormone sensitive lipase, stearyl-CoA desaturase-1 and peroxisome proliferator-activated receptor-gamma but FASN and ACACA were not altered. An action of testosterone on hepatic lipid deposition which is independent of the classic AR is implicated. Testosterone may act in part via an effect on the key regulatory lipogenic enzymes to protect against hepatic steatosis. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

A preliminary investigation into the potential role of waist hip ratio (WHR) preference within the assortative mating hypothesis of autistic spectrum disorders.

PubMed

Brosnan, Mark; Walker, Ian

2009-01-01

Of particular interest to studying the etiology of Autistic Spectrum Disorders (ASDs) is the potential for multiple risk factors to combine through non-random mechanisms-assortative mating. Both genetic influences and a high-testosterone prenatal environment have been implicated in the etiology of ASDs, and given that waist-hip ratio (WHR) is indicative of a woman's circulating testosterone level, a man attracted to higher-than-average WHR women is likely to have a higher-than-average prenatal testosterone exposure for their offspring. We show that whereas fathers of children without ASD show a statistically reliable preference for WHRs at the low end of the normal range, indicative of women with low testosterone levels, fathers of children diagnosed with ASD do not consistently show this preference.

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

PubMed

Hay, Cathy J; Brady, Brian M; Zitzmann, Michael; Osmanagaoglu, Kaan; Pollanen, Pasi; Apter, Dan; Wu, Frederick C W; Anderson, Richard A; Nieschlag, Eberhard; Devroey, Paul; Huhtaniemi, Ilpo; Kersemaekers, Wendy M

2005-04-01

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive.

PubMed

Brady, B M; Amory, J K; Perheentupa, A; Zitzmann, M; Hay, C J; Apter, D; Anderson, R A; Bremner, W J; Pollanen, P; Nieschlag, E; Wu, F C W; Kersemaekers, W M

2006-01-01

The combination of etonogestrel implants with injectable testosterone decanoate was investigated as a potential male contraceptive. One hundred and thirty subjects were randomly assigned to three treatment groups, all receiving two etonogestrel rods (204 mg etonogestrel) and 400 mg testosterone decanoate either every 4 weeks (group I, n = 42), or every 6 weeks (group II, n = 51) or 600 mg testosterone decanoate every 6 weeks (group III, n = 37) for a treatment period of 48 weeks. One hundred and ten men completed 48 weeks of treatment. Sperm concentrations of <1 x 10(6)/ml were achieved in 90% (group I), 82% (group II) and 89% (group III) of subjects by week 24. Suppression was slower in group II, which also demonstrated more frequent escape from gonadotrophin suppression than groups I and III. Peak testosterone concentrations remained in the normal range throughout in all groups. Mean trough testosterone concentrations were initially subphysiological but increased into the normal range during treatment. Mean haemoglobin levels increased in group I, and a non-significant increase in weight and decline in high-density lipoprotein cholesterol was observed in all groups. Fourteen subjects discontinued treatment due to adverse events. Subcutaneous etonogestrel implants in combination with injectable testosterone decanoate resulted in profound suppression of spermatogenesis that could be maintained for up to 1 year. Efficacy of suppression was less in group II, probably due to inadequate testosterone dosage. This combination has potential as a long-acting male hormonal contraceptive.

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.

[Hormonal and metabolic effects of drinking mineral water and phytoaeronisation in experimental prostatitis].

PubMed

Polushina, N D; Agaev, A A; Shchelkunov, A V; Eseneev, S M

2004-01-01

Prostatitis modelled in 53 Wistar male rats (300-350 body mass) 7 days after its induction was treated with mineral water "Essentuki N 17" (MW) which was taken in a dose 1.5-2 ml per 100 g body mass for 23-24 days. In addition, some animals received phytoaeroionisation (PAI) with solution of essential oils of mint, sage and lavender. Prostatitis is associated with disorders in prostatic tissue, levels of sex hormones (testosterone, prolactin, FSH, LH), a rise in total cholesterol, glucose. Watering of animals with MW and PAI raised blood insulin, hydrocortisone and testosterone, normalized blood glucose and cholesterol. There was a correlation between blood levels of hydrocortisone and testosterone.

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

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

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

[Number of teeth and hormonal profile of postmenopausal women with osteoporosis, osteopenia and normal bone mineral density--a preliminary study].

PubMed

Stagraczyński, Maciej; Kulczyk, Tomasz; Leszczyński, Piotr; Męczekalski, Błażej

2015-10-01

Profound hypoestrogenism causes increased risk of osteoporosis and bone fracture in menopause. This period of women life is also characterized by decrease number of teeth and deterioration of oral cavity health. The aim of the study was to assess the number of teeth, hormonal profile (Follicle-stimualting hormone (FSH), estradiol (E2), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) and the bone mineral density (BMD) of the lumbar part of the spine in postmenopausal women with osteoporosis, osteopenia and normal BMD. The next step of the study was to determine whether there was a correlation between vertebral mineral bone density, the hormonal profile and the number of teeth. A total number of 47 women was involved in the study. Based on the results of densitometry tests (DEXA) of vertebral column the subjects were divided into 3 groups: 10 with osteoporosis, 20 with osteopenia and 17 with normal BMD. All the subjects had undergone a hormonal assessment which included blood serum estimation for FSH, E2, DHEA-S and T levels. Also the total number of teeth present was recorded. Serum estradiol and testosterone levels in postmenopausal women were found to be positively correlated with the number of teeth present. A negative correlation was found between age and the number of maxillary teeth in postmenopausal women with osteopenia. There was no influence of serum FSH, estradiol, testosterone and DHEA-S levels on vertebral BMD loss in postmenopausal women. There was no correlation between teeth number and BMD of vertebral column. Serum levels of estradiol and testosterone in postmenopausal women positively correlate with teeth numbers. Age is the main risk factor for teeth loss in postmenopausal women. © 2015 MEDPRESS.

Enhanced Androgen Signaling with Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality, and Bone Architecture

DTIC Science & Technology

2005-12-01

the BMD of female-to-male transsexuals treated with ‘male’ levels of testosterone increased to normal male levels at cortical sites [35]. Finally, men...Testosterone increases bone mineral density in female-to- male transsexuals : a case series of 15 subjects.Clin Endocrinol (Oxf) 2004, 61:560-566. 35...Ruetsche A, Kneubuehl R, Birkhaeuser M, Lippuner K: Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment

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.

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.

Leuprolide acetate-stimulated androgen response during female puberty.

PubMed

Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty. © 2014 John Wiley & Sons Ltd.

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

Testicular function during puberty and young adulthood in patients with Klinefelter's syndrome with and without spermatozoa in seminal fluid.

PubMed

Rohayem, J; Nieschlag, E; Zitzmann, M; Kliesch, S

2016-11-01

Patients with Klinefelter's syndrome experience progressive testicular degeneration resulting in impaired endocrine function and azoospermia. What proportion of adolescents develop testosterone deficiency during puberty and how many have spermatozoa in their semen is unclear to date. We aimed to investigate testicular function during puberty and young adulthood in patients with Klinefelter's syndrome and to assess testosterone effects in target tissues. The clinical data of 281 patients with non-mosaic Klinefelter's syndrome aged 10-25 years without previous testosterone replacement were reviewed. In late pubertal adolescents, semen analyses were evaluated, and testicular volumes, hormone and haemoglobin (Hb) levels, the number of CAG repeats and final height data were compared to those of 233 age-matched controls with pubertal gynaecomastia. Spontaneous pubertal virilisation to Tanner stages IV-V occurred. Serum T levels ≥10 nmol/L were reached in 62% of patients with Klinefelter's syndrome and in 85% of controls at ages 15-25 (T KFS : 12.2 ± 5.4 vs. T C : 16.6 ± 7.2 nmol/L). LH KFS levels were elevated >10 U/L in 84%, and normal in all controls (LH KFS : 18.6 ± 12.2 vs. LH C : 3.5 ± 1.6 U/L). In nine of 130 (7%) adolescents with Klinefelter's syndrome, spermatozoa (oligozoospermia) were found in semen; all had T levels >7 nmol/L and eight of nine had LH levels ≤18 U/L, while their hormone levels, number of CAG repeats and testicular volumes were not different from those of adolescents with azoospermia. Controls had normal sperm concentrations in 73% (46/63). Semen volumes KFS were normal in 55% vs. 78% in controls; Hb KFS was normal in 89% (Hb C : 97%). Mean final height KFS was 185 ± 8 cm vs. 181 ± 7 cm in controls. Hypergonadotropic hypogonadism develops during early puberty in adolescents with Klinefelter's syndrome and remains compensated in over 60% during ages 15-25, with sufficient testosterone secretion for spontaneous accomplishment of pubertal development. Spermatozoa in semen are rare and associated with T levels >7 nmol/L. Parameters reflecting androgen deficiency in target tissues may help to optimise timing of testosterone substitution, which should preferably not be initiated before fertility status has been clarified. © 2016 American Society of Andrology and European Academy of Andrology.

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

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.

Comparative morphophysiological evaluation of the testis of adult Wistar rats fed low protein-energy diet and dosed with aqueous extracts of Cuscuta australis.

PubMed

Ozegbe, P C; Omirinde, J O

2012-12-18

Cuscuta australis (C. australis) seed and stem are historically used by the local population as dietary supplement for the management of infertility. This study, therefore, evaluated the effect of orally administered aqueous extracts of C. australis seed and stem, 300 mg/kg body weight/day for seven days, on the testis of the adult Wistar rat fed either low or normal protein-energy diets. The control group received water. The relative weight of the testis was non-significantly increased (p>0.05) in the Low Protein-energy diet-Water-treated (LPWA), Low Protein-energy diet-Seed-treated (LPSE) and Normal Protein-energy diet-Seed-treated (NPSE) groups relative to the Normal Protein-energy diet-Water-treated (NPWA). The weight of the testis was also non-significantly increased (p˃0.05) in the Low Protein-energy diet-Stem-treated (LPST), but decreased in the Normal Protein-energy diet-Stem-treated (NPST), relative to LPWA and NPWA. Heights of germinal epithelium were significantly decreased (p<0.05) in the LPWA, LPSE and LPST relative to the NPWA, NPSE and NPST. Diet significantly influenced (p<0.001) the effect of stem extract on the height of germinal epithelium. The NPSE, LPSE, NPST, LPST and LPWA showed significantly decreased (p<0.001) plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) relative to NPWA. The LPWA, LPSE and NPST also showed significantly decreased (p<0.001) levels of testosterone relative to NPWA and LPST. Diet significantly influenced (p<0.001) the effect of seed on the level of LH. Seed-diet interactions significantly affected the levels of FSH (p<0.001) and LH (p<0.05), but not testosterone. Diet significantly influenced (p<0.001) the effects of stem extract on the levels of FSH, LH and testosterone. Stem-diet interactions significantly affected (p<0.001) the levels of FSH, LH and testosterone. Our data suggest that the aqueous extract of C. australis stem is more potent than the seed extract and that dietary protein-energy intake may influence the efficacy of orally administered aqueous extracts of C. australis.

Hyperandrogenism due to a testosterone-secreting Sertoli-Leydig cell tumor associated with a dehydroepiandrosterone sulfate-secreting adrenal adenoma in a postmenopausal woman: case presentation and review of literature.

PubMed

Herrera, Jorge D; Davidson, Jaime A; Mestman, Jorge H

2009-03-01

To report a case of hyperandrogenism attributable to the presence of an adrenal adenoma secreting dehydroepiandrosterone sulfate (DHEA-S) and an ovarian Sertoli-Leydig cell tumor secreting testosterone in a postmenopausal woman. The laboratory, radiologic, and pathologic findings in our case are described. In addition, the pertinent literature is reviewed. A 56-year-old woman presented with a history of gradual increase in facial and body hair, scalp hair loss, male pattern baldness, and deepening of her voice, beginning a few years after spontaneous menopause at age 49 years. She had hypertension, obesity, and type 2 diabetes mellitus. Laboratory tests showed elevated levels of total testosterone (348 ng/dL) and DHEA-S (2,058 microg/dL), and a left adrenal tumor (3 by 4 cm) was detected on abdominal computed tomographic scan. Laparoscopic left adrenalectomy was performed, and the pathologic diagnosis was adrenal adenoma. The DHEA-S returned to normal levels, but the serum testosterone concentration remained elevated. Transvaginal ultrasonography disclosed an ovarian tumor. Bilateral oophorectomy was performed, and an ovarian Sertoli-Leydig cell tumor was diagnosed. The hormonal and clinical picture normalized after this surgical intervention. After extensive review of the literature, we believe that this is the first reported case of a coincidental DHEA-S-secreting adrenal adenoma and a testosterone- secreting ovarian Leydig cell tumor causing signs of virilization.

Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

PubMed Central

Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2011-01-01

Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

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 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.

Sex-specific association of sex hormones and gonadotropins, with brain amyloid and hippocampal neurodegeneration.

PubMed

Lee, Jun Ho; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Choi, Hyo Jung; Baek, Hyewon; Sohn, Bo Kyung; Lee, Jun-Young; Kim, Hyun Jung; Kim, Jee Wook; Lee, Younghwa; Kim, Yu Kyeong; Sohn, Chul-Ho; Woo, Jong Inn; Lee, Dong Young

2017-10-01

This study aimed to examine the sex-specific association between serum sex hormones and gonadotropins and the cerebral beta-amyloid (Aβ) burden and hippocampal neurodegeneration in subjects with normal cognition and impaired cognition. Two hundred sixty-five older subjects received clinical assessments, serum measurements of sex hormones, gonadotropins, 11 C-Pittsburgh compound B-positron emission tomography, and magnetic resonance imaging. In females, higher free testosterone and gonadotropin levels were associated with lower cerebral Aβ positivity. In males, free testosterone was positively related to hippocampal volume with significant interaction with cognitive status. Further subgroup analyses showed that the association was significant only in impaired cognition but not in normal cognition. Free estradiol was not associated with Aβ burden or hippocampal neurodegeneration in either sex. These results suggest that testosterone might inhibit the early pathological accumulation of Aβ in females and delay neurodegeneration in males. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function.

PubMed

Okon, M A; Laird, S M; Tuckerman, E M; Li, T C

1998-04-01

To compare plasma androgen concentrations in women who have recurrent miscarriages and in fertile women, and to correlate the results with concentrations of the endometrial protein PP14 in uterine flushings and plasma from women who have recurrent miscarriages. Retrospective study. Hospital research unit. Women attending a recurrent miscarriage clinic and normal fertile volunteers. Ten of the women with recurrent miscarriages had polycystic ovary disease (PCOD) as assessed by ultrasonography or increased follicular LH levels. Plasma samples were obtained from the women on days LH-7, LH-4, LH+0, and LH+7 or LH+10 of a cycle. An endometrial flushing sample and a biopsy specimen were taken from women with recurrent miscarriages on day LH+7 or LH+10. Androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured in the plasma samples. The endometrial protein PP14 was measured in the uterine flushings and in the LH+7 or LH+10 plasma samples from the women with recurrent miscarriages. Testosterone concentrations were higher in the women with recurrent miscarriages both with and without PCOD on days LH-7 and LH-4 of the cycle. Concentrations of androstenedione also were higher in the women with recurrent miscarriages, but without PCOD on day LH-7. Testosterone SHBG ratios were higher in the women with recurrent miscarriages, without PCOD compared with the controls on days LH-7, LH+0, and LH+7. Mean follicular testosterone concentrations were correlated negatively with both uterine (r = -0.47) and plasma (r = -0.49) PP14 levels on day LH+10. Mean luteal phase testosterone SHBG ratios were correlated negatively with uterine PP14 concentrations on day LH+7 of the cycle (r = -0.674). Androgen levels are higher in women who have recurrent miscarriages than in normal fertile controls. These high levels of androgens may have a detrimental effect on endometrial function.

Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism.

PubMed

Skjöldebrand Sparre, L; Kollind, M; Carlström, K

2002-01-01

To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO. Copyright 2002 S. Karger AG, Basel

Amino-terminal propeptide of C-type natriuretic peptide and linear growth in children: effects of puberty, testosterone, and growth hormone.

PubMed

Olney, Robert C; Prickett, Timothy C R; Yandle, Timothy G; Espiner, Eric A; Han, Joan C; Mauras, Nelly

2007-11-01

C-type natriuretic peptide (CNP), a paracrine factor of the growth plate, plays a key role in stimulating bone growth. The amino-terminal propeptide of CNP (NTproCNP) is produced in equimolar amounts with CNP and is measurable in plasma, providing a potential biomarker for growth plate activity and, hence, linear growth. We explored the effects of puberty, testosterone, and GH treatment on NTproCNP levels in normal and short-statured children. This was a retrospective analysis of samples obtained during previous studies. The study was conducted at a pediatric clinical research center. Children with short stature due to GH deficiency, idiopathic short stature (ISS), or constitutional delay of growth and maturation (CDGM) were studied (n = 37). A cohort of normal-statured adolescent boys was also studied (n = 23). Children with GH deficiency and ISS were studied before and during testosterone and/or GH treatment. Boys with CDGM and healthy controls were studied once. The main outcomes were NTproCNP levels before and during growth-promoting therapy and during pubertal growth. Children with short stature due to GH deficiency, ISS, or CDGM had comparable baseline levels of NTproCNP, and levels increased markedly in response to GH or testosterone treatment. In boys with CDGM, levels were comparable with height-matched controls but were less than those from age-matched controls. In healthy boys, NTproCNP appears to peak with the pubertal growth spurt. NTproCNP levels increase during growth-promoting therapy and are increased during puberty in boys. This novel biomarker of growth may have clinical utility in the evaluation of children with short stature and for monitoring growth-promoting therapy.

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.

Long-term side-effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study.

PubMed

Malone, Shawn; Perry, Gad; Segal, Roanne; Dahrouge, Simone; Crook, Juanita

2005-09-01

To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer. Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate-specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan-Meier method. In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%). IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.

Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 9 Days in Normal Men With Experimental Hypogonadism

PubMed Central

Lee, Ada; Rubinow, Katya; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Zhi, Hui; Roth, Mara Y; Page, Stephanie T.; Bremner, William J.; Amory, John K.

2014-01-01

Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 µg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone–binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P > .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency. PMID:21868746

The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors

PubMed Central

Juntti, Scott A; Tollkuhn, Jessica; Wu, Melody V; Fraser, Eleanor J; Soderborg, Taylor; Tan, Stella; Honda, Shin-Ichiro; Harada, Nobuhiro; Shah, Nirao M

2010-01-01

SUMMARY Testosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior remains to be established. Circulating testosterone activates the androgen receptor (AR) and also serves as the source of estrogen in the brain. We have used a genetic strategy to delete AR specifically in the mouse nervous system. This approach permits us to determine the function of AR in sexually dimorphic behaviors in males while maintaining circulating testosterone levels within the normal range. We find that AR mutant males exhibit masculine sexual and territorial displays, but they have striking deficits in specific components of these behaviors. Taken together with the surprisingly limited expression of AR in the developing brain, our findings indicate that testosterone acts as a precursor to estrogen to masculinize the brain and behavior, and signals via AR to control the levels of male behavioral displays. PMID:20435002

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.

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.

C-reactive protein and lipoprotein-a as markers of coronary heart disease in polycystic ovary syndrome.

PubMed

Güdücü, Nilgün; Işçi, Herman; Yiğiter, Alin Başgül; Dünder, Ilkkan

2012-01-01

The aim of this study was to investigate the risk factors of coronary heart disease, CRP and Lipoprotein-a in polycystic ovary syndrome patients. Prospectively collected data of polycystic ovary syndrome patients (n=62) and control group (n=40) were compared. PCOS patients had higher HOMA-IR, CRP, DHEAS, free testosterone, FAI, LH and prolactin levels when compared to the control group. Lipoprotein-a levels did not differ between the groups. The obese PCOS group had statistically significantly higher fasting blood glucose, total cholesterol, triglyceride, free testosterone, insulin, CRP and HOMA-IR and statistically significantly lower HDL and SHBG when compared to normal weight PCOS persons. Fasting blood glucose, total cholesterol, LDL, SHBG, CRP, Lipoprotein-a, FSH, LH, TSH, DHEAS and prolactin levels did not differ between the normal weight and obese control groups. CRP levels increase in polycystic ovary syndrome patients and can be used as a marker of coronary heart disease. Future studies can be directed at treatments to decrease CRP levels, including antiinflammatory treatments.

Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

PubMed

Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

2012-04-01

Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with testosterone replacement therapy. Replacement therapy is often simple, using an injectable testosterone ester as first line treatment. Fertility can be restored rather quickly, provided there is no independent primary testicular damage and the partner is fertile. Copyright © 2012. Published by Elsevier Masson SAS.

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.

Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men

PubMed Central

Allen, N E; Appleby, P N; Davey, G K; Key, T J

2000-01-01

Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone. © 2000 Cancer Research Campaign PMID:10883675

Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event

PubMed Central

2011-01-01

Background Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST). It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. Methods Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. Results In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl), which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml). Three patients had higher levels (43.79~71.21 pg/ml) and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05) Conclusions Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate. PMID:22047550

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

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.

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

From prenatal life into senescence, testosterone is essential requirement for manhood.

PubMed

Pradidarcheep, Wisuit; Showpittapornchai, Udomsri

2009-04-01

Prenatally, organisms have the bipotentiality to differentiate along either male or female lines, a process with different stages, each with a narrow window of time, during which testosterone plays a pivotal role in the case of male sexual differentiation. During puberty, the body directs the masculinization process with growth of the genitalia and prostate. Body contours become male, with an average height of 10-15 centimeters greater than that of females, a greater bone and muscle mass, a male hair pattern and a male-type fat distribution. These pubertal developments, largely reversible in case of severe androgen deficiency, require adult levels of testosterone throughout life. A new area of interest is in exploring how far age-related body changes (loss of bone and muscle mass, a shift into a higher ratio of body fat/lean body mass) are part of an age-related decline of testicular testosterone production. Therefore, throughout life, testosterone is essential for a normal male life.

Serum leptin levels, hormone levels, and hot flashes in midlife women.

PubMed

Alexander, Carolyn; Cochran, Chrissy J; Gallicchio, Lisa; Miller, Susan R; Flaws, Jodi A; Zacur, Howard

2010-08-01

To examine the associations between serum leptin levels, sex steroid hormone levels, and hot flashes in normal weight and obese midlife women. Cross-sectional study. University clinic. 201 Caucasian, nonsmoking women aged 45 to 54 years with a body mass index of <25 kg/m2 or >or=30 kg/m2. Questionnaire, fasting blood samples. Serum leptin and sex steroid hormone levels. Correlation and regression models were performed to examine associations between leptin levels, hormone levels, and hot flashes. Leptin levels were associated with BMI, with "ever experiencing hot flashes" (questionnaire), with hot flashes within the last 30 days, and with duration of hot flashes (>1 year, P=.03). Leptin was positively correlated with testosterone, free testosterone index, and free estrogen index and inversely associated with levels of sex hormone-binding globulin. In women with a body mass index>or=30 kg/m2, leptin levels no longer correlated with testosterone levels. Serum leptin levels are associated with the occurrence and duration of hot flashes in midlife women; however, no correlation was found between leptin and serum estradiol. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction.

PubMed

Podlasek, Carol A; Mulhall, John; Davies, Kelvin; Wingard, Christopher J; Hannan, Johanna L; Bivalacqua, Trinity J; Musicki, Biljana; Khera, Mohit; González-Cadavid, Nestor F; Burnett, Arthur L

2016-08-01

The biological importance of testosterone is generally accepted by the medical community; however, controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. To provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Testosterone plays an important role in sexual function through multiple processes: physiologic (stimulates activity of nitric oxide synthase), developmental (establishes and maintains the structural and functional integrity of the penis), neural (development, maintenance, function, and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes, and prostatectomy), and phosphodiesterase type 5 inhibition (testosterone supplement to counteract phosphodiesterase type 5 inhibitor resistance). Despite controversies concerning testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction. Published by Elsevier Inc.

Prenatal testosterone and gender-related behaviour.

PubMed

Hines, Melissa

2006-11-01

Testosterone plays an important role in mammalian brain development. In neural regions with appropriate receptors testosterone, or its metabolites, influences patterns of cell death and survival, neural connectivity and neurochemical characterization. Consequently, testosterone exposure during critical periods of early development produces permanent behavioural changes. In humans, affected behaviours include childhood play behaviour, sexual orientation, core gender identity and other characteristics that show sex differences (i.e. differ on average between males and females). These influences have been demonstrated primarily in individuals who experienced marked prenatal hormone abnormalities and associated ambiguities of genital development (e.g. congenital adrenal hyperplasia). However, there is also evidence that testosterone works within the normal range to make some individuals within each sex more sex-typical than others. The size of testosterone-related influences, and perhaps even their existence, varies from one sex-typed characteristic to another. For instance: prenatal exposure to high levels of testosterone has a substantial influence on sex-typical play behaviour, including sex-typed toy preferences, whereas influences on core gender identify and sexual orientation are less dramatic. In addition: there appears to be little or no influence of prenatal testosterone on mental rotations ability, although mental rotations ability shows a marked sex difference. These findings have implications for basic understanding of the role of testosterone in normative gender development, as well as for the clinical management of individuals with disorders of sex development (formerly called intersex syndromes).

Testosterone and mortality.

PubMed

Muraleedharan, Vakkat; Jones, T Hugh

2014-10-01

Epidemiological studies have found that men with low or low normal endogenous testosterone are at an increased risk of mortality than those with higher levels. Cardiovascular disease accounts for the greater proportion of deaths in those with low testosterone. Cancer and respiratory deaths in some of the studies are also significantly more prevalent. Disease-specific studies have identified that there are higher mortality rates in men with cardiovascular, respiratory and renal diseases, type 2 diabetes and cancer with low testosterone. Obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease and inflammatory disorders are all associated with an increased prevalence of testosterone deficiency. Two major questions that arise from these findings are (1) is testosterone deficiency directly involved in the pathogenesis of these conditions and/or a contributory factor impairing the body's natural defences or is it merely a biomarker of ill health and the severity of underlying disease process? (2) Does testosterone replacement therapy retard disease progression and ultimately enhance the clinical prognosis and survival? This review will discuss the current state of knowledge and discuss whether or not there are any answers to either of these questions. There is convincing evidence that low testosterone is a biomarker for disease severity and mortality. Testosterone deficiency is associated with adverse effects on certain cardiovascular risk factors that when combined could potentially promote atherosclerosis. The issue of whether or not testosterone replacement therapy improves outcomes is controversial. Two retrospective studies in men with diagnosed hypogonadism with or without type 2 diabetes have reported significantly improved survival. © 2014 John Wiley & Sons Ltd.

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.

Interleukin-18 and testosterone levels in men with metabolic syndrome.

PubMed

Angelova, Petya; Kamenov, Zdravko; Tsakova, Adelina; El-Darawish, Yosif; Okamura, Haruki

2018-06-01

Interleukin 18 (IL-18) is an adipokine associated with obesity. Data about the relationship of IL-18 to the metabolic syndrome (MS) are still scarce. Low testosterone (T) levels are common in men with MS, but we did not find data about the levels of IL-18 in men with low T. The aim of this study was to determine the levels of IL-18 in men with MS with or without low T. A total of 251 men were included in the study. Of them 218 had MS (IDF 2005) and they were divided according to their morning total testosterone (TT) level (cutoff 10.4 nmol/l) into two groups: MS-low T (N = 84) and MS-normal T (N = 134). The control group consisted of 33 men without MS and low T. IL-18 was determined in serum using enzyme-linked immunosorbent assay. A small group of eight men with MS and low T levels received testosterone therapy for three months and physical and laboratory parameters were monitored at the end of that period. MS men were at mean age (±SD) = 53.77 ± 9.59 years; body mass index (BMI) = 34.0 ± 6.3 kg/m 2 ; and TT = 12.59 ± 5.66 nmol/l. The control group was at age = 52.12 ± 5.2 years (NS); BMI = 25.6 ± 2.4 kg/m 2 (p < .001); and TT = 17.8 ± 5.68 nmol/l (p < .001), respectively. The levels of IL-18 were higher in the MS group - 345 pg/ml compared to the control one - 264 pg/ml (p < .01). There was no significant difference between MS-low T (330.6 pg/ml) and MS-normal T (350.2 pg/ml) subgroups. The MS-normal T differed more significantly from the control group (p < .001). Significant correlation of testosterone with IL-18 levels was not found. IL-18 correlated with parameters of obesity, lipids, fasting blood sugar (p < .05) and the number of criteria for MS (p < .001). Three months on T treatment showed improvement in obesity parameters and only in one patient IL-18 had clear reduction while the rest showed no change. In this study, higher IL-18 levels were found in the presence of MS compared to healthy men, but they did not differ between men having MS with or without LOH.

Hypogonadism and erectile dysfunction associated with soy product consumption.

PubMed

Siepmann, Timo; Roofeh, Joseph; Kiefer, Florian W; Edelson, David G

2011-01-01

Previous research has focused on the beneficial effects of soy and its active ingredients, isoflavones. For instance, soy consumption has been associated with lower cardiovascular and breast cancer risks. However, the number of reports demonstrating adverse effects of isoflavones due to their estrogenlike properties has increased. We present the case of a 19-y-old type 1 diabetic but otherwise healthy man with sudden onset of loss of libido and erectile dysfunction after the ingestion of large quantities of soy-based products in a vegan-style diet. Blood levels of free and total testosterone and dehydroepiandrosterone (DHEA) were taken at the initial presentation for examination and continuously monitored up to 2 y after discontinuation of the vegan diet. Blood concentrations of free and total testosterone were initially decreased, whereas DHEA was increased. These parameters normalized within 1 y after cessation of the vegan diet. Normalization of testosterone and DHEA levels was paralleled by a constant improvement of symptoms; full sexual function was regained 1 y after cessation of the vegan diet. This case indicates that soy product consumption is related to hypogonadism and erectile dysfunction. To the best of our knowledge, this is the first report of a combination of decreased free testosterone and increased DHEA blood concentrations after consuming a soy-rich diet. Hence, this case emphasizes the impact of isoflavones in the regulation of sex hormones and associated physical alterations. Copyright © 2011 Elsevier Inc. All rights reserved.

Decrease in water-soluble 17beta-Estradiol and testosterone in composted poultry manure with time.

PubMed

Hakk, Heldur; Millner, Patricia; Larsen, Gerald

2005-01-01

Little attention has been paid to the environmental fate of the hormones 17beta-estradiol and testosterone excreted in animal waste. Land application of manure has a considerable potential to affect the environment with these endocrine disrupting compounds (EDCs). Composting is known to decompose organic matter to a stable, humus-like material. The goal of the present study was to quantitatively assess levels of water-soluble 17beta-estradiol and testosterone in composting chicken manure with time. Chicken layer manure was mixed with hay, straw, decomposed leaves, and starter compost, adjusted to approximately 60% moisture, and placed into a windrow. A clay-amended windrow was also prepared. Windrows were turned weekly, and temperature, oxygen, and CO(2) in the composting mass were monitored for either 133 or 139 d. Commercial enzyme immunoassay kits were used to quantitate the levels of 17beta-estradiol and testosterone in aqueous sample extracts. Water-soluble quantities of both hormones diminished during composting. The decrease in 17beta-estradiol followed first-order kinetics, with a rate constant k = -0.010/d. Testosterone levels declined at a slightly higher rate than 17beta-estradiol (i.e., k = -0.015/d). Both hormones could still be measured in aqueous extracts of compost sampled at the conclusion of composting. The decline in water-soluble 17beta-estradiol and testosterone in extracts of clay-amended compost was not statistically different from normal compost. These data suggest that composting may be an environmentally friendly technology suitable for reducing, but not eliminating, the concentrations of these endocrine disrupting hormones at concentrated animal operation facilities.

Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

PubMed

Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

2011-07-01

Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older, hypogonadal men with symptomatic benign prostatic hyperplasia. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer.

PubMed

Planas, Jacques; Celma, Ana; Placer, José; Cuadras, Mercè; Regis, Lucas; Gasanz, Carlos; Trilla, Enrique; Salvador, Carlos; Lorente, David; Morote, Juan

2016-12-01

The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients. Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation. After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (< 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone >50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029). Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.

Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

NASA Technical Reports Server (NTRS)

Yeagle, S. P.; Mayer, R. F.; Max, S. R.

1983-01-01

The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

Developmental effects of androgens in the human brain.

PubMed

Nguyen, T-V

2018-02-01

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions. © 2017 British Society for Neuroendocrinology.

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.

Spurious testosterone laboratory results in a patient taking synthetic alkaline phosphatase (asfotase alfa).

PubMed

Sofronescu, Alina G; Ross, Meredith; Rush, Eric; Goldner, Whitney

2018-04-27

We report a case of discordant total and free testosterone values in a patient with hypogonadism and juvenile hypophosphatasia after he initiated treatment with asfotase alfa, recombinant tissue non-specific alkaline phosphatase. Total testosterone was evaluated using immunoassay pre and post initiation of therapy with asfotase alfa, and free testosterone was evaluated using radioimmunoassay and LC-MS/MS while on asfotase alfa therapy. Total testosterone measured by immunoassay was normal prior to therapy with asfotase alfa, and was low post initiation of therapy. During the same time frame, free testosterone measured using RAI and total testosterone measured using LC-MS/MS were normal on asfotase alfa therapy. This suggests assay interference with the total testosterone immunoassay. When laboratory results are discordant or do not match the clinical impression, the possibility of assay interference should be considered. Alternative laboratory methods free of the interference should be selected to evaluate these patients. ALPL gene, Approved name: Alkaline phosphatase, liver/bone/kidney, Synonym: Tissue non-specific alkaline phosphatase (TNSAP). Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Testosterone and reproductive effort in male primates

PubMed Central

Muller, Martin N.

2016-01-01

Considerable evidence suggests that the steroid hormone testosterone mediates major life-history trade-offs in vertebrates, promoting mating effort at the expense of parenting effort or survival. Observations from a range of wild primates support the “Challenge Hypothesis,” which posits that variation in male testosterone is more closely associated with aggressive mating competition than with reproductive physiology. In both seasonally and non-seasonally breeding species, males increase testosterone production primarily when competing for fecund females. In species where males compete to maintain long-term access to females, testosterone increases when males are threatened with losing access to females, rather than during mating periods. And when male status is linked to mating success, and dependent on aggression, high-ranking males normally maintain higher testosterone levels than subordinates, particularly when dominance hierarchies are unstable. Trade-offs between parenting effort and mating effort appear to be weak in most primates, because direct investment in the form of infant transport and provisioning is rare. Instead, infant protection is the primary form of paternal investment in the order. Testosterone does not inhibit this form of investment, which relies on male aggression. Testosterone has a wide range of effects in primates that plausibly function to support male competitive behavior. These include psychological effects related to dominance striving, analgesic effects, and effects on the development and maintenance of the armaments and adornments that males employ in mating competition. PMID:27616559

Testosterone and reproductive effort in male primates.

PubMed

Muller, Martin N

2017-05-01

Considerable evidence suggests that the steroid hormone testosterone mediates major life-history trade-offs in vertebrates, promoting mating effort at the expense of parenting effort or survival. Observations from a range of wild primates support the "Challenge Hypothesis," which posits that variation in male testosterone is more closely associated with aggressive mating competition than with reproductive physiology. In both seasonally and non-seasonally breeding species, males increase testosterone production primarily when competing for fecund females. In species where males compete to maintain long-term access to females, testosterone increases when males are threatened with losing access to females, rather than during mating periods. And when male status is linked to mating success, and dependent on aggression, high-ranking males normally maintain higher testosterone levels than subordinates, particularly when dominance hierarchies are unstable. Trade-offs between parenting effort and mating effort appear to be weak in most primates, because direct investment in the form of infant transport and provisioning is rare. Instead, infant protection is the primary form of paternal investment in the order. Testosterone does not inhibit this form of investment, which relies on male aggression. Testosterone has a wide range of effects in primates that plausibly function to support male competitive behavior. These include psychological effects related to dominance striving, analgesic effects, and effects on the development and maintenance of the armaments and adornments that males employ in mating competition. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

PubMed Central

Crosnoe-Shipley, Lindsey E; Elkelany, Osama O; Rahnema, Cyrus D; Kim, Edward D

2015-01-01

The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the efficacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin (hCG) therapy or selective estrogen receptor modulators (SERMs), but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment. PMID:25949938

Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder.

PubMed

Markianos, Manolis; Tripodianakis, John; Sarantidis, Democritos; Hatzimanolis, John

2007-08-01

Depressive symptomatology has been connected with an activation of the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

PubMed

Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan

2015-08-01

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis.

PubMed

Corona, Giovanni; Rastrelli, Giulia; Monami, Matteo; Saad, Farid; Luconi, Michaela; Lucchese, Marcello; Facchiano, Enrico; Sforza, Alessandra; Forti, Gianni; Mannucci, Edoardo; Maggi, Mario

2013-06-01

Few randomized clinical studies have evaluated the impact of diet and physical activity on testosterone levels in obese men with conflicting results. Conversely, studies on bariatric surgery in men generally have shown an increase in testosterone levels. The aim of this study is to perform a systematic review and meta-analysis of available trials on the effect of body weight loss on sex hormones levels. Meta-analysis. An extensive Medline search was performed including the following words: 'testosterone', 'diet', 'weight loss', 'bariatric surgery', and 'males'. The search was restricted to data from January 1, 1969 up to August 31, 2012. Out of 266 retrieved articles, 24 were included in the study. Of the latter, 22 evaluated the effect of diet or bariatric surgery, whereas two compared diet and bariatric surgery. Overall, both a low-calorie diet and bariatric surgery are associated with a significant (P<0.0001) increase in plasma sex hormone-binding globulin-bound and -unbound testosterone levels (total testosterone (TT)), with bariatric surgery being more effective in comparison with the low-calorie diet (TT increase: 8.73 (6.51-10.95) vs 2.87 (1.68-4.07) for bariatric surgery and the low-calorie diet, respectively; both P<0.0001 vs baseline). Androgen rise is greater in those patients who lose more weight as well as in younger, non-diabetic subjects with a greater degree of obesity. Body weight loss is also associated with a decrease in estradiol and an increase in gonadotropins levels. Multiple regression analysis shows that the degree of body weight loss is the best determinant of TT rise (B=2.50±0.98, P=0.029). These data show that weight loss is associated with an increase in both bound and unbound testosterone levels. The normalization of sex hormones induced by body weight loss is a possible mechanism contributing to the beneficial effects of surgery in morbid obesity.

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

A higher score on the Aging Males' Symptoms scale is associated with insulin resistance in middle-aged men.

PubMed

Hamanoue, Nobuya; Tanabe, Makito; Tanaka, Tomoko; Akehi, Yuko; Murakami, Junji; Nomiyama, Takashi; Yanase, Toshihiko

2017-05-30

An age-associated androgen decrease and its pathological conditions are defined as late-onset hypogonadism (LOH). Among the various symptoms associated with LOH, a visceral fat increase is strongly associated with relatively low levels of testosterone. However, few studies have investigated the relationship between the Aging Males' Symptoms (AMS) scores and metabolic abnormalities. Thus, we aimed to clarify this relationship by investigating the relationship between AMS scores and various markers in blood. During routine health examinations in 241 middle-aged males (52.7±7.5 years of age, mean±SD), 150 males (62.2%) displayed higher AMS values than normal. No statistical association was observed between total AMS scores and any testosterone value. All mental, physical and sexual AMS subscales were significantly positively correlated with insulin levels and HOMA-IR. Only sexual subscale scores were significantly inversely associated with free or bioavailable testosterone level. Males with insulin resistance (HOMA-IR≥2.5) demonstrated significantly higher AMS scores than those with normal insulin sensitivity (HOMA-IR<2.5). AMS values were positively correlated with fasting blood glucose, insulin and HOMA-IR values. Interestingly, univariate and multivariate analyses revealed that HOMA-IR≥2.5 was a significant predictor for detection of moderately severe AMS values (AMS≥37), whereas AMS≥37 was not a predictor of metabolic syndrome by International Diabetes Federation (IDF) criterion. In conclusion, almost 60% of healthy male subjects displayed abnormal AMS scores. AMS values were not associated with testosterone values but rather were related to insulin resistance, particularly in subjects with moderately severe AMS values. Insulin resistance-related general unwellness might be reflected by AMS values.

Effect of altered reproductive function and lowered testosterone levels on bone density in male endurance athletes.

PubMed

Bennell, K L; Brukner, P D; Malcolm, S A

1996-09-01

It is apparent that bone density in male athletes can be reduced without a concomitant decrease in testosterone, suggesting that bone density and testosterone concentrations in the normal range are not closely related in male athletes. Further research is necessary to monitor concurrent changes in bone density and testosterone over a period of time in exercising males. In any case, the effect of exercise on the male reproductive system does not appear as extreme as that which can occur in female athletes, and any impact on bone density is not nearly as evident. These results imply that factors apart from testosterone concentrations must be responsible for the observed osteopenia in some male athletes. Many factors have the potential to adversely affect bone density, independently of alterations in reproductive function. These include low calcium intake, energy deficit, weight loss, psychological stress, and low body fat, all of which may be associated with intense endurance training. Future research investigating skeletal health in male athletes should include a thorough assessment of reproductive function in addition to these other factors.

Honest sexual signalling mediated by parasite and testosterone effects on oxidative balance.

PubMed

Mougeot, Francois; Martínez-Padilla, Jesús; Webster, Lucy M I; Blount, Jonathan D; Pérez-Rodríguez, Lorenzo; Piertney, Stuart B

2009-03-22

Extravagant ornaments evolved to advertise their bearers' quality, the honesty of the signal being ensured by the cost paid to produce or maintain it. The oxidation handicap hypothesis (OHH) proposes that a main cost of testosterone-dependent ornamentation is oxidative stress, a condition whereby the production of reactive oxygen and nitrogen species (ROS/RNS) overwhelms the capacity of antioxidant defences. ROS/RNS are unstable, very reactive by-products of normal metabolic processes that can cause extensive damage to key biomolecules (cellular proteins, lipids and DNA). Oxidative stress has been implicated in the aetiology of many diseases and could link ornamentation and genetic variation in fitness-related traits. We tested the OHH in a free-living bird, the red grouse. We show that elevated testosterone enhanced ornamentation and increased circulating antioxidant levels, but caused oxidative damage. Males with smaller ornaments suffered more oxidative damage than those with larger ornaments when forced to increase testosterone levels, consistent with a handicap mechanism. Parasites depleted antioxidant defences, caused oxidative damage and reduced ornament expression. Oxidative damage extent and the ability of males to increase antioxidant defences also explained the impacts of testosterone and parasites on ornamentation within treatment groups. Because oxidative stress is intimately linked to immune function, parasite resistance and fitness, it provides a reliable currency in the trade-off between individual health and ornamentation. The costs induced by oxidative stress can apply to a wide range of signals, which are testosterone-dependent or coloured by pigments with antioxidant properties.

Honest sexual signalling mediated by parasite and testosterone effects on oxidative balance

PubMed Central

Mougeot, Francois; Martínez-Padilla, Jesu´s; Webster, Lucy M.I.; Blount, Jonathan D.; Pérez-Rodríguez, Lorenzo; Piertney, Stuart B.

2008-01-01

Extravagant ornaments evolved to advertise their bearers' quality, the honesty of the signal being ensured by the cost paid to produce or maintain it. The oxidation handicap hypothesis (OHH) proposes that a main cost of testosterone-dependent ornamentation is oxidative stress, a condition whereby the production of reactive oxygen and nitrogen species (ROS/RNS) overwhelms the capacity of antioxidant defences. ROS/RNS are unstable, very reactive by-products of normal metabolic processes that can cause extensive damage to key biomolecules (cellular proteins, lipids and DNA). Oxidative stress has been implicated in the aetiology of many diseases and could link ornamentation and genetic variation in fitness-related traits. We tested the OHH in a free-living bird, the red grouse. We show that elevated testosterone enhanced ornamentation and increased circulating antioxidant levels, but caused oxidative damage. Males with smaller ornaments suffered more oxidative damage than those with larger ornaments when forced to increase testosterone levels, consistent with a handicap mechanism. Parasites depleted antioxidant defences, caused oxidative damage and reduced ornament expression. Oxidative damage extent and the ability of males to increase antioxidant defences also explained the impacts of testosterone and parasites on ornamentation within treatment groups. Because oxidative stress is intimately linked to immune function, parasite resistance and fitness, it provides a reliable currency in the trade-off between individual health and ornamentation. The costs induced by oxidative stress can apply to a wide range of signals, which are testosterone-dependent or coloured by pigments with antioxidant properties. PMID:19129122

The interactive effect of dietary protein and vitamin levels on the depression of gonadal development in growing male rats kept under disturbed daily rhythm.

PubMed

Hanai, Miho; Esashi, Takatoshi

2007-04-01

The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. The present study examined protein and vitamins, and their interactions. This study was based on three-way ANOVA; the three factors were lighting conditions, dietary protein and dietary vitamins, respectively. The levels of dietary protein were low or normal: 9% casein or 20% casein. The levels of dietary vitamins were low, normal or high: 1/3.3 of normal (AIN-93G diet) content, normal content, or three times the normal content, respectively. Other compositions were the same as those of the AIN-93G diet, and six kinds of experimental diet were prepared. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum testosterone content were evaluated. In the constant darkness groups (D-groups), the low-protein diet induced reduction of gonadal organ weights and serum testosterone concentrations. This reduction of gonadal organ weights was exacerbated by progressively higher levels of dietary vitamins. In the case of a normal-protein diet, the depression of gonadal development was not accelerated by high-vitamin intake. In the normal lighting groups (N-groups), the low-protein and high-vitamin diet slightly depressed gonadal development. These results suggest that the metabolism of protein and vitamins is different in rats being kept under constant darkness, and that excess dietary vitamins have an adverse effect on gonadal development in rats fed a low-protein diet.

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.

An Update on Plant Derived Anti-Androgens

PubMed Central

Grant, Paul; Ramasamy, Shamin

2012-01-01

Anti-androgens are an assorted group of drugs and compounds that reduce the levels or activity of androgen hormones within the human body. Disease states in which this is relevant include polycystic ovarian syndrome, hirsutism, acne, benign prostatic hyperplasia, and endocrine related cancers such as carcinoma of the prostate. We provide an overview and discussion of the use of anti-androgen medications in clinical practice and explore the increasing recognition of the benefits of plant-derived anti-androgens, for example, spearmint tea in the management of PCOS, for which some evidence about efficacy is beginning to emerge. Other agents covered include red reishi, which has been shown to reduce levels 5-alpha reductase, the enzyme that facilitates conversion of testosterone to dihydrotestosterone (DHT); licorice, which has phytoestrogen effects and reduces testosterone levels; Chinese peony, which promotes the aromatization of testosterone into estrogen; green tea, which contains epigallocatechins and also inhibits 5-alpha reductase, thereby reducing the conversion of normal testosterone into the more potent DHT; black cohosh, which has been shown to kill both androgenresponsive and non-responsive human prostate cancer cells; chaste tree, which has a reduces prolactin from the anterior pituitary; and saw palmetto extract, which is used as an anti-androgen although it shown no difference in comparison to placebo in clinical trials. PMID:23843810

Woman with virilizing congenital adrenal hyperplasia and Leydig cell tumor of the ovary.

PubMed

Fernández-García Salazar, Rosario; Muñoz-Darias, Carmen; Haro-Mora, Juan Jesús; Almaraz, M Cruz; Audí, Laura; Martínez-Tudela, Juana; Yahyaoui, Raquel; Esteva, Isabel

2014-08-01

We report the case of a 36-year-old woman with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, and corticosteroid replacement therapy since birth. She manifested persistent virilization and high testosterone levels that were attributed to nonadherence to medical treatment. The patient was referred to our gender unit for genitoplastic surgery. We recommended the patient for left oophorectomy after detecting an ovarian mass. Pathologic findings confirmed an ovarian hilus cell tumor. Testosterone levels fell back to normal and masculinization disappeared but ACTH remained elevated. This case represents a very rare type of primary ovarian tumor that must be considered in persistent virilizing symptoms in women with CAH.

[Solid phase radioimmunoassay for plasma testosterone using plastic microtiter tray (author's transl)].

PubMed

Hosogi, H

1975-03-20

In order to simply radioimmunoassay for plasma testosterone and to measure many samples at the same time, a method of solid phase radioimmunoassay utilizing a plastic disposable microtiter tray (DMT) by which chromatography can be omitted was investigated. The antiserum was obtained by immunizing rabbits with testosterone-3 BSA which had been synthesized according to the Erlarnger's method. Plasma samples (male: 0.05ml, female: 0.2 ml) were extracted with 1.0 ml of ether. After freezing the plasma layer in an acetone-dryice bath, the ether phase was transfered to a glass tube and evaporated to dryness. These samples and the dried standard testosterone were dissolved with borate buffer containing 3H-testosterone and transfered to plastic DMT which had been precoated with the diluted antiserum, and incubated for 24 hrs. After removal of the incubated solution, the cups of DMT were cut off and were dissolved with toluene scintillator in counting vials. The radioactivity was counted with a liquid scintillation counter. Other steroids except for 5alpha-dihydrotestosterone (5alpha-DHT) had a low degree of cross reactivity with the antiserum. Five alpha-DHT which could be measured together with testosterone in this assay was not a problem clinically because of its strong androgenic activity. The best standard curve was obtained when the antiserum was diluted to 1:1000. The sensitivity of this assay was 10 pg/tube. The maximal adsorption of antibody to plastic DMT was observed when the pH of antiserum was within the range of 6.5-9.5 and the precoating time was 24 hr at room termperature. The best pH of incubation buffer was 8.0, and the antigen-antibody reaction became a plateau when the incubation exceeded 6 hrs. Water blank in this assay was 4.6 +/- 2.1 pg/tube. The recovery of testosterone (50, 100, 200 pg) added to 0.1 ml female plasma was 99 +/- 6.8%. Coefficients of variation within assay and between assay were below 11.2% and 20.0%, respectively. Correlation between this method and the dextran-coated charcoal method was fairly good (r=0.938). Plasma testosterone levels in 10 normal males and 12 normal females were 616 +/- 202 (mean +/- SD) ng/dl and 66 +/- 29 (mean +/- SD) ng/dl, respectively. The levels were low in patients with hypopituitarism, hypogonadism and acromegaly. They were normal in patients with Cushing's syndrome due to adrenal hyperplasia and adenoma, but they were high in a patient with adrenal carcinoma. In a patient with testicular feminization, the level was 632 ng/dl. This increased after the administration of HCG, and decreased to 127.5 ng/dl after castration. This solid phase radioimmunoassay (using plastic DMT) is economically feasible as well as simple because it is possible to separate the bound hormone from the free hormone of all samples at the same time and there is little restriction in time and temperature. According to the above results, this method is suitable for routine clinical use.

Mothers of autistic children: lower plasma levels of oxytocin and Arg-vasopressin and a higher level of testosterone.

PubMed

Xu, Xin-Jie; Shou, Xiao-Jing; Li, Jin; Jia, Mei-Xiang; Zhang, Ji-Shui; Guo, Yan; Wei, Qing-Yun; Zhang, Xiu-Ting; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

2013-01-01

Autism is a pervasive neurodevelopmental disorder,thought to be caused by a combination of genetic heritability and environmental risk factors. Some autistic-like traits have been reported in mothers of autistic children. We hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex hormones, found in autistic children, may also exist in their mothers. We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal children by enzyme immunoassay and radioimmunoassay, respectively and investigated their relationships with the children's autistic behavior scores (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)). Significantly lower plasma concentrations of OXT (p<0.001) and AVP (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found in mothers of autistic children vs. those of control. The children's autistic behavior scores were negatively associated with maternal plasma levels of OXT and AVP. These results suggest that dysregulation of OXT, AVP and/or testosterone systems exist in mothers of autistic children, which may impact children's susceptibility to autism.

Low incidence of new biochemical hypogonadism after intensity modulated radiation therapy for prostate cancer.

PubMed

Markovina, Stephanie; Weschenfelder, Débora Cristina; Gay, Hiram; McCandless, Audrey; Carey, Bethany; DeWees, Todd; Knutson, Nels; Michalski, Jeff

2014-01-01

To evaluate serum testosterone and the incidence of biochemical hypogonadism in men treated with intensity modulated radiation therapy (IMRT) for prostate cancer. Serum testosterone was evaluated prospectively in 51 men at pretreatment and at 6-month time points for 2 years posttreatment with IMRT for prostate cancer. Forty-one patients (80%) were treated with definitive intent and 10 patients with postprostatectomy radiation to median total doses of 7380 cGy and 6480 cGy, respectively. No patients received hormone therapy within 12 months of any serum testosterone value. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Incidental testicular dose was calculated using planning software when computed tomography information was available (n = 21) and using a published method of estimation when not available (n = 24), and was available for 45 patients. A statistically significant decrease in testosterone, though small in magnitude, was seen at 6 months after completion of therapy, with no significant difference by 1 year after completion of therapy. There was no increase in biochemical hypogonadism after IMRT. Below-normal pretreatment testosterone was not associated with a transient decrease. Estimated cumulative testicular dose, including dose from daily imaging, was not associated with a change in testosterone, nor was radiation therapy prescription dose or treatment intent (postoperative vs definitive). The mild transient decrease in serum testosterone following IMRT monotherapy for prostate cancer is not associated with new biochemical hypogonadism.

Effects of simvastatin and pravastatin on gonadal function in male hypercholesterolemic patients.

PubMed

Dobs, A S; Miller, S; Neri, G; Weiss, S; Tate, A C; Shapiro, D R; Musliner, T A

2000-01-01

Inhibition of cholesterol biosynthesis by hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors could, in theory, adversely affect male gonadal function because cholesterol is a precursor of steroid hormones. The objective of this randomized double-blind trial was to compare the effects of simvastatin, pravastatin, and placebo on gonadal testosterone production and spermatogenesis. After a 6-week placebo and lipid-lowering diet run-in period, 159 male patients aged 21 to 55 years with type IIa or IIb hypercholesterolemia, low-density lipoprotein (LDL) cholesterol between 145 and 240 mg/dL, and normal basal levels of testosterone were randomly assigned to treatment with simvastatin 20 mg (n = 40), simvastatin 40 mg (n = 41), pravastatin 40 mg (n = 39), or placebo (n = 39) once daily. After 24 weeks of treatment, mean total cholesterol levels were decreased 24% to 27% and mean LDL cholesterol was decreased 30% to 34% in the 3 active-treatment groups (P < .001 for all comparisons to placebo). At 24 weeks, there were no statistically significant differences between the placebo group and any of the active-treatment groups for the change from baseline in testosterone, human chorionic gonadotropin (hCG)stimulated testosterone, free testosterone index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), or sex hormone-binding globulin (SHBG). Moreover, there were no statistically significant differences at week 12 or week 24 for the change from baseline in sperm concentration, ejaculate volume, or sperm motility for any active treatment relative to placebo. Both simvastatin and pravastatin were well tolerated. In summary, we found no evidence for clinically meaningful effects of simvastatin or pravastatin on gonadal testosterone production, testosterone reserve, or multiple parameters of semen quality.

Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis.

PubMed

Cangiano, B; Cacciatore, C; Persani, L; Bonomi, M

2017-01-01

We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.

Heart rate variability in normal-weight patients with polycystic ovary syndrome.

PubMed

Kilit, Celal; Paşalı Kilit, Türkan

2017-05-01

Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors of cardiovascular disease. Obese women with PCOS show altered autonomic modulation. The results of studies investigating cardiac autonomic functions of normal-weight women with PCOS are conflicting. The aim of the study was to assess the reactivity of cardiac sympathovagal balance in normal-weight women with PCOS by heart rate variability analysis. We examined the heart rate variability in 60 normal-weight women with PCOS and compared them with that in 60 age-matched healthy women having a similar metabolic profile. Time and frequency domain parameters of heart rate variability were analyzed based on 5-min-long continuous electrocardiography recordings for the following 3 periods: (1) during rest in supine position, (2) during controlled breathing, and (3) during isometric handgrip exercise. Time and frequency domain parameters of heart rate variability for the 3 periods assessed were similar in the two groups. Although modified Ferriman-Gallwey score and serum testosterone and luteinizing hormone levels were significantly higher in women with PCOS, homeostatic model assessment-insulin resistance (HOMA-IR) was not different the between the PCOS and control groups. There were no significant correlations between serum testosterone levels and heart rate variability parameters among the study population. The findings of this study suggest that the reactivity of cardiac sympathovagal balance is not altered in normal-weight women with PCOS having a normal HOMA-IR.

Protective Effect of Selenium on Aflatoxin B1-Induced Testicular Toxicity in Mice.

PubMed

Cao, Zheng; Shao, Bing; Xu, Feibo; Liu, Yunfeng; Li, Yanfei; Zhu, Yanzhu

2017-12-01

Aflatoxins have been considered as one of the major risk factors of male infertility, and aflatoxin B1 (AFB1) is the most highly toxic and prevalent member of the aflatoxins family. Selenium (Se), an essential nutritional trace mineral for normal testicular development and male fertility, has received extensive intensive on protective effects of male reproductive system due to its potential antioxidant and activating testosterone synthesis. To investigate the protective effect of Se on AFB1-induced testicular toxicity, the mice were orally administered with AFB1 (0.75 mg/kg) and Se (0.2 mg/kg or 0.4 mg/kg) for 45 days. We found that that Se elevated testes index, sperm functional parameters (concentration, malformation, and motility), and the level of serum testosterone in AFB1-exposed mice. Moreover, our results showed that Se attenuated the AFB1-induced oxidative stress and the reduction of testicular testosterone synthesis enzyme protein expression such as steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), and 17β-hydroxysteroid dehydrogenase (17β-HSD) in AFB1-exposed mice. These results demonstrated that Se conferred protection against AFB1-induced testicular toxicity and can be attributed to its antioxidant and increased testosterone level by stimulating protein expression of StAR and testosterone synthetic enzymes.

Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: a meta-analysis of randomized controlled trials.

PubMed

Nian, Y; Ding, M; Hu, S; He, H; Cheng, S; Yi, L; Li, Y; Wang, Y

2017-05-01

Although testosterone replacement therapy can restore serum testosterone concentrations to normal level in late-onset hypogonadism patients, whether it can improve patients' quality of life remains uncertain. Therefore, we perform a meta-analysis of randomized controlled trials on this issue. Five randomized controlled trials total 1,212 patients were included. Fixed-effect model was used to calculate the weighted mean difference of score of Aging Males' Symptom rating scale. Our result reveals that testosterone replacement therapy improves patients' health-related quality of life in terms of the decrease in the AMS total score [WMD = -2.96 (-4.21, -1.71), p < .00001] and the psychological [WMD = -0.89 (-1.41, -0.37), p = .0008], somatic [WMD = -0.89 (-1.41, -0.37), p = .0008] and sexual [WMD = -1.29 (-1.75, -0.83), p < .00001] subscale score. © 2016 Blackwell Verlag GmbH.

High dose androgen therapy in male pseudohermaphroditism due to 5 alpha-reductase deficiency and disorders of the androgen receptor.

PubMed

Price, P; Wass, J A; Griffin, J E; Leshin, M; Savage, M O; Large, D M; Bu'Lock, D E; Anderson, D C; Wilson, J D; Besser, G M

1984-10-01

We describe the clinical and biochemical features of six men with male pseudohermaphroditism due to androgen resistance. Each of the subjects had male-gender behavior but incomplete virilization. The underlying defects in androgen metabolism were defined by studies of the 5 alpha-reductase enzyme and the androgen receptor in fibroblasts cultured from biopsies of genital skin. Four of the six have 5 alpha-reductase deficiency, and two have defects of the androgen receptor (the Reifenstein syndrome). The responses of these men to androgen treatment were assessed by monitoring nitrogen balance, plasma luteinizing hormone (LH) values, and clinical parameters of virilization including penile growth, potency and ejaculatory volume, muscle bulk, and growth of body and facial hair. In all of the subjects with 5 alpha-reductase deficiency and one man with the Reifenstein syndrome significant response occurred, as evidence by nitrogen retention, lowered plasma LH levels, and improved virilization, with doses of parenteral testosterone esters that raised plasma testosterone levels above the normal male range and brought plasma dihydrotestosterone levels into the normal male range. The subject who did not respond with clinical virilization nevertheless showed nitrogen retention in response to acute testosterone administration. This patient had a profound deficiency of the androgen receptor, whereas the man with a receptor defect who did respond clinically to therapy had normal amounts of a qualitatively abnormal receptor. We conclude that high dose androgen therapy may be of benefit in improving virilization, self-image, and sexual performance in subjects with 5 alpha-reductase deficiency who have male-gender behavior and in some subjects with defects of the androgen receptor.

Effects of long-term fasting on female hormone levels: Ramadan model.

PubMed

Cağlayan, E K; Göçmen, A Y; Delibas, N

2014-01-01

Ramadan fasting is a special model of hunger and particularly affects metabolic processes, including carbohydrate and lipid levels. Endocrine changes induced by Ramadan fasting are not well known. The aim of this article was to evaluate the changes in hormone levels in women before and after the special Muslim fasting period of Ramadan. This study was performed in 30 healthy women in Obstetrics and Gynecology department during the Ramadan month of2011. Patients during and after the first menstrual period had menstrual cycles fasting blood samples taken on the same days. Luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, and prolactin (PRL) levels were determined. Before and during fasting LH, FSH, E2, testosterone and PRL levels were not statistically different. Despite the limited available studies on these subjects in women, effect of Ramadan fasting on hormone levels were found to be within the normal limits.

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43

PubMed Central

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-01-01

Aim: Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Methods: Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg−1·d−1, po) or testosterone replacement (0.5 mg·kg−1·d−1, sc) for 5 days, and STZ-injected rats were treated with argirein (40–120 mg·kg−1·d−1, po) or aminoguanidine (100 mg·kg−1·d−1, po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). Results: ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3–3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Conclusion: Two types of hypogonadism of male rats exhibit increased expression of ETA and depressed expression of Cx43 in testes, despite different patterns of serum FSH and LH. Argirein alleviates the two types of male hypogonadism via normalizing ETA and Cx43 in testes. PMID:26775665

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

PubMed

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-02-01

Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of hypogonadism of male rats exhibit increased expression of ETA and depressed expression of Cx43 in testes, despite different patterns of serum FSH and LH. Argirein alleviates the two types of male hypogonadism via normalizing ETA and Cx43 in testes.

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

Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours.

PubMed

Masugi-Tokita, M; Yoshida, T; Kageyama, S; Kawata, M; Kawauchi, A

2018-03-01

Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours such as intermale aggression and fear response. © 2018 British Society for Neuroendocrinology.

Protective effect of ethyl pyruvate on mice sperm parameters in phenylhydrazine induced hemolytic anemia.

PubMed

Mozafari, Ali Akbar; Shahrooz, Rasoul; Ahmadi, Abbas; Malekinjad, Hassan; Mardani, Karim

2016-01-01

The aim of the present study was to assess the protective effect of ethyl pyruvate (EP) on sperm quality parameters, testosterone level and malondialdehyde (MDA) in phenylhydrazine (PHZ) treated mice. For this purpose, 32 NMRI mice with the age range of 8 to 10 weeks, weight average 26.0 ± 2.0 g, were randomly divided into four equal groups. The control group (1) received normal saline (0. 1 mL per day) by intraperitoneal injection (IP). Group 2 (PHZ group) was treated with initial dose of PHZ (8 mg 100 g(-1), IP) followed by 6 mg 100 g(-1) , IP every 48 hr. Group 3, (Group PHZ+EP) received PHZ (according to the previous prescription) with EP (40 mg kg(-1), daily, IP). Ethyl pyruvate group (4) received only EP (40 mg kg(-1), daily, IP). Treatment period was 35 days. After euthanasia, sperms from caudal region of epididymis were collected and the total mean sperm count, sperm viability, motility and morphology were determined. Testis tissue MDA and serum testosterone levels of all experimental groups were also evaluated. A considerable reduction in mean percentage of number, natural morphology of sperm, sperm motility and viability and serum testosterone concentration besides DNA injury increment among mice treating with PHZ in comparison with control group were observed. However, in PHZ+EP group the above mentioned parameters were improved. This study showed that PHZ caused induction of toxicity on sperm parameters and reduction of testosterone as well as the increment of MDA level and EP as an antioxidant could reduce destructive effects of PHZ on sperm parameters, testosterone level and lipid peroxidation.

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.

Testosterone Therapy and Glucose Homeostasis in Men with Testosterone Deficiency (Hypogonadism).

PubMed

Saad, Farid

2017-01-01

Since the early 1990s, it has been recognized that testosterone (T) levels are lower in men with type 2 diabetes mellitus (T2DM) compared with nondiabetic men (controls). Hypogonadism has been reported in approximately 50% of men with T2DM with robust correlations with measures of obesity, such as waist circumference and body mass index (BMI). In longitudinal studies, hypogonadism has been identified as a predictor of incident T2DM. Experimental withdrawal of T led to acute decreased insulin sensitivity, which can be reversed by normalization of T concentrations. Androgen deprivation therapy, commonly used in men with advanced prostate cancer, increases the risk of incident T2DM significantly.While short-term studies of T therapy in hypogonadal men with T2DM show only minor effects, long-term administration of T leads to meaningful and sustained improvements of glycemic control with parallel reductions in body weight and waist circumference. The more insulin-resistant and obese a patient is at the time of initiation of T therapy, the more improvements are noted. The observed effects are likely mediated by the increase in lean body mass invariably achieved by T therapy, as well as the improvement in energy and motivation, referred to as the psychotropic effects of T. As recommended by various guidelines, measuring T levels and, if indicated, restoring men's T levels into the normal physiological range can have a substantial impact on ameliorating T2DM in hypogonadal men.

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.

Hypothalamic-pituitary dysfunction following traumatic brain injury affects functional improvement during acute inpatient rehabilitation.

PubMed

Rosario, Emily R; Aqeel, Rubina; Brown, Meghan A; Sanchez, Gabriel; Moore, Colleen; Patterson, David

2013-01-01

To evaluate the occurrence of hypothalamic-pituitary dysfunction following a traumatic brain injury (TBI) and to determine its effect on functional improvement in acute inpatient rehabilitation. A retrospective chart review identified male patients with a primary diagnosis of TBI with or without a skull fracture, an onset date within 6 months prior to admission, and were 16 years of age or older. The percentage of individuals in this population with abnormal hormone levels was determined on the basis of the established normal reference range for each hormone assay. The functional independence measure, which assesses functional outcomes in acute inpatient rehabilitation, was used to examine the relationship between hormone levels and functional improvement. Hypothalamic-pituitary dysfunction was identified in nearly 70% of men following TBI. Hypogonadism, or low testosterone levels, was observed in 66% of the patients, followed by low levels of free T4 in 46% and low levels of insulin growth factor-1 in 26% of patients. Hypopituitarism associated with impaired functional recovery. Specifically, the functional independence measure change per day was significantly lower in patients with low levels of testosterone and insulin growth factor-1. These findings suggest the importance of testosterone and insulin growth factor-1 activity in the early stages of physical and cognitive rehabilitation.

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

PubMed Central

Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

2016-01-01

Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

"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

Mothers of Autistic Children: Lower Plasma Levels of Oxytocin and Arg-Vasopressin and a Higher Level of Testosterone

PubMed Central

Xu, Xin-Jie; Shou, Xiao-Jing; Li, Jin; Jia, Mei-Xiang; Zhang, Ji-Shui; Guo, Yan; Wei, Qing-Yun; Zhang, Xiu-Ting; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

2013-01-01

Background Autism is a pervasive neurodevelopmental disorder,thought to be caused by a combination of genetic heritability and environmental risk factors. Some autistic-like traits have been reported in mothers of autistic children. We hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex hormones, found in autistic children, may also exist in their mothers. Methods We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal children by enzyme immunoassay and radioimmunoassay, respectively and investigated their relationships with the children’s autistic behavior scores (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)). Results Significantly lower plasma concentrations of OXT (p<0.001) and AVP (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found in mothers of autistic children vs. those of control. The children’s autistic behavior scores were negatively associated with maternal plasma levels of OXT and AVP. Conclusions These results suggest that dysregulation of OXT, AVP and/or testosterone systems exist in mothers of autistic children, which may impact children’s susceptibility to autism. PMID:24086383

Maternal thyroid hormones enhance hatching success but decrease nestling body mass in the rock pigeon (Columba livia).

PubMed

Hsu, Bin-Yan; Dijkstra, Cor; Darras, Veerle M; de Vries, Bonnie; Groothuis, Ton G G

2017-01-01

Thyroid hormones (THs) - triiodothyronine (T3) and thyroxine (T4) - are essential for embryonic development in vertebrates. All vertebrate embryos are exposed to THs from maternal origin. As maternal TH levels are known to be essential to embryonic development, the natural variation of maternal THs probably represents a pathway of maternal effects that can modify offspring phenotype. However, potential fitness consequences of variation of maternal TH exposure within the normal physiological range and without confounding effects of the mother have never been experimentally investigated. We experimentally manipulated the levels of yolk T3 and T4 within the physiological range in a species in which the embryo develops outside the mother's body, the Rock Pigeon (Columba livia) eggs. Making use of the natural difference of yolk testosterone between the two eggs of pigeon clutches, we were also able to investigate the potential interaction between THs and testosterone. Elevated yolk TH levels enhanced embryonic development and hatching success, and reduced body mass but not tarsus length between day 14 and fledging. The yolk hormones increased plasma T4 concentrations in females but reduced it in males, in line with the effect on metabolic rate at hatching. Plasma concentrations of T3 and testosterone were not significantly affected. The effects of treatment did not differ between eggs with high or low testosterone levels. Our data indicate that natural variation in maternal yolk TH levels affects offspring phenotype and embryonic survival, potentially influencing maternal and chick fitness. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

PubMed Central

Chin, Kok-Yong; Soelaiman, Ima-Nirwana; Mohamed, Isa Naina; Ahmad, Fairus; Ramli, Elvy Suhana Mohd; Aminuddin, Amilia; Ngah, Wan Zurinah Wan

2013-01-01

OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia. PMID:23525310

Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

PubMed

Chin, Kok-Yong; Soelaiman, Ima-Nirwana; Mohamed, Isa Naina; Ahmad, Fairus; Ramli, Elvy Suhana Mohd; Aminuddin, Amilia; Ngah, Wan Zurinah Wan

2013-01-01

Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

The mechanism underlying dibutyl phthalate induced shortened anogenital distance and hypospadias in rats.

PubMed

Li, Ning; Chen, Xuyong; Zhou, Xuefeng; Zhang, Wen; Yuan, Jiyan; Feng, Jiexiong

2015-12-01

The purpose of this study was to investigate the mechanism of dibutyl phthalate (DBP) induced hypospadias and shortened anogenital distance (AGD). AGD, hypospadias, and cryptorchidism incidence was observed in male offspring of DBP treated pregnant Wistar rats. Testicular development and testosterone levels of normal and DBP-treated rat embryos were compared. Male offspring of 300mg and 900mg DBP-treated pregnant Wistar rats exhibited shortened average AGD compared with the control group. A 22.7% hypospadias incidence was observed in the 300mg group, but no offspring with cryptorchidism were identified. In the 900mg group, hypospadias and cryptorchidism incidence reached 43.5% and 17.4%, respectively. Between E15.5 and E17.5, the 300mg group exhibited delayed testicular development and testosterone secretion. However, testicular development and testosterone secretion subsequently recovered. The 300mg treated and control groups had similar measures after E19.5. Contrastingly, testicular development and testosterone secretion were significantly diminished throughout development in the 900mg group. Exogenous testosterone partially counteracted DBP-induced changes in the reproductive organs of male offspring of DBP-treated rats. High-dose DBP exposure may induce testicular dysgenesis in rat embryos. Additionally, low-dose DBP may delay testicular development and testosterone secretion during urethral development. This disruption may result in hypospadias. Copyright © 2015 Elsevier Inc. All rights reserved.

Conversion of blood androgens to estrogens in normal adult men and women

PubMed Central

Longcope, Christopher; Kato, Tatsuo; Horton, Richard

1969-01-01

Continuous infusions of Δ4-androstenedione-7-3H and testosterone-7-3H have been used to demonstrate that these androgens are converted to estrone and 17β-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [χ-PRO] and free precursor steroid [χ-PRE], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [ρ]BBAE1, for androstenedione conversion to estrone ([ρ]BBAE1 = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [ρ]BBTE2, for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [ρ]BB value are greater in males than females. For the androgen interconversions, [ρ]BBAT is 4.5% in males and 2.2% in females; [ρ]BBTA is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03. PMID:5355335

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.

Detection of endogenous boldenone in the entire male horses.

PubMed

Ho, Emmie N M; Yiu, Kenneth C H; Tang, Francis P W; Dehennin, Louis; Plou, Philippe; Bonnaire, Yves; Wan, Terence S M

2004-09-05

Boldenone (1,2-dehydrotestosterone) is a common veterinary anabolic agent. Its structure is very similar to testosterone. Testosterone is endogenous in the horse, whereas there has been no report concerning the detection of endogenous boldenone. This paper reports the direct observation of sulphate conjugate of boldenone in equine urine from entires. The detection procedures involved solid-phase extraction, immunoaffinity column (IAC) purification, and then LC-MS-MS analysis on a Q-ToF instrument. The identification of boldenone sulphate has provided direct evidence for the endogenous nature of boldenone in entire male horses. Quantification data for the normal level of boldenone in Hong Kong racehorses will also be discussed.

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Restoration and maintenance of spermatogenesis by HCG therapy in patients with hypothalamo-hypophyseal damage.

PubMed

Levalle, O; Bokser, L; Pacenza, N; Aszenmil, G; Fiszlejder, L; Chervin, A; Guitelman, A

1984-01-01

Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients.

Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males

PubMed Central

Shi, Hongliang; Faessel, Hélène M.; Saad, Fred

2015-01-01

Context: TAK-385 is a highly selective, oral, nonpeptide GnRH antagonist being investigated as a possible prostate cancer treatment. Objective: The objectives were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-385 on LH and testosterone. Design, Setting, and Participants: This was a three-part, randomized, double-blind, placebo-controlled, phase 1 dose-escalation study in 176 healthy male UK volunteers. Interventions: Part 1, single doses of TAK-385 (0 [placebo], 80, 120, 180, or 360 mg). Part 2, 14-day TAK-385 (0, 20, 40, 80, or 180 mg) daily. Part 3, 28-day TAK-385 (40 [with loading dose], 60, 80, or 160 mg) or placebo daily. Parts 2 and 3 included men aged 40–75 years. Main Outcome Measures: Main outcome measures included plasma concentrations of TAK-385, LH, and testosterone. Results: Oral TAK-385 was readily absorbed, and steady state was reached in ≤14 days. Food reduced TAK-385 systemic exposure by 47–52%. Mean serum testosterone levels declined ≤6 hours after TAK-385 administration. Loading doses up to 360 mg on day 1 or 360 mg on day 1 followed by 240 mg on day 2 reduced the time to achieve castrate testosterone levels from ≥7 to <3 days. TAK-385 doses ≥80 mg/d achieved sustained medical castration and trough TAK-385 concentrations >4 ng/mL. After discontinuation of TAK-385 on day 28, testosterone levels normalized in most subjects in ≤ 28 days. Common adverse events included bradycardia, headache, and hot flush (all grade ≤2). Conclusions: Oral TAK-385 (40–180 mg/d) was well tolerated and effectively lowered testosterone in healthy men. Planned phase 2 doses in men with hormone-sensitive prostate cancer are 80 and 120 mg/d. PMID:26502357

Gestational Protein Restriction Reduces Expression of Hsd17b2 in Rat Placental Labyrinth1

PubMed Central

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2012-01-01

ABSTRACT Accumulating evidence strongly supports the premise that testosterone may be a key player in fetal programming on hypertension. Studies have shown that gestational protein restriction doubles the plasma testosterone levels in pregnant rats. In this study, we hypothesized that elevated testosterone levels in response to gestational protein restriction were caused by enhanced expression of steroidogenic enzymes or impaired expression of Hsd17b2, a known testosterone inactivator that converts testosterone to androstenedione in placenta. Pregnant Sprague-Dawley rats were fed normal (20% protein, control; n = 10) or a low-protein diet (6% protein, PR; n = 10) from Day 1 of pregnancy until killed at Days 14, 18, or 21. Junctional (JZ) and labyrinth (LZ) zones of placenta were collected for expression assay on steroidogenic genes (Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b2, and Srd5a1) by real-time PCR. The main findings include the following: 1) expressions of Cyp11a1, Hsd3b1, and Cyp17a1 in JZ were not affected by diet but were affected by day of pregnancy; 2) expression of Hsd17b2 in both female and male JZs was remarkably increased by PR at Days 18 and 21 of pregnancy; 3) expressions of Hsd17b2 were reduced by PR in both female and male LZ at Day 18 of pregnancy and in female LZ at Day 21 of pregnancy; and 4) expression of Srd5a1in LZ was not affected by day of pregnancy, gender, or diet. These results indicate that in response to gestational protein restriction, Hsd17b2 may be a key regulator of testosterone levels and associated activities in placental zones, apparently in a paradoxical manner. PMID:22837477

Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients

PubMed Central

Hohl, Alexandre; Zanela, Fernando Areas; Ghisi, Gabriela; Ronsoni, Marcelo Fernando; Diaz, Alexandre Paim; Schwarzbold, Marcelo Liborio; Dafre, Alcir Luiz; Reddi, Benjamin; Lin, Kátia; Pizzol, Felipe Dal; Walz, Roger

2018-01-01

Traumatic brain injury (TBI) is a worldwide core public health problem affecting mostly young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults as well as a tremendous resource burden on the health and welfare sector. Hormone dysfunction is highly prevalent during the acute phase of severe TBI. In particular, investigation of the luteinizing hormone (LH) and testosterone levels during the acute phase of severe TBI in male has identified a high incidence of low testosterone levels in male patients (36.5–100%) but the prognostic significance of which remains controversial. Two independent studies showed that normal or elevated levels of LH levels earlier during hospitalization are significantly associated with higher mortality/morbidity. The association between LH levels and prognosis was independent of other predictive variables such as neuroimaging, admission Glasgow coma scale, and pupillary reaction. The possible mechanisms underlying this association and further research directions in this field are discussed. Overall, current data suggest that LH levels during the acute phase of TBI might contribute to accurate prognostication and further prospective multicentric studies are required to develop more sophisticated predictive models incorporating biomarkers such as LH in the quest for accurate outcome prediction following TBI. Moreover, the potential therapeutic benefits of modulating LH during the acute phase of TBI warrant investigation. PMID:29487565

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.

Experiment K-6-16. Morphological examination of rat testes. The effect of Cosmos 1887 flight on spermatogonial population and testosterone level in rat testes

NASA Technical Reports Server (NTRS)

Philpott, D. E.; Kato, K.; Stevenson, J.; Vasques, M.; Sapp, W.; Williams, C.; Popova, I. A.; Serova, L. V.

1990-01-01

Testes from rats flown on Cosmos 1887 for twelve and a half days were compared to basal control, synchronous control and vivarium maintained rats. When the mean weights of flight testes, normalized for weight/100 gms, were compared to the vivarium controls they were 6.7 percent lighter. Although the flight testes were lighter than the synchronous, the difference is not significant. Counts of spermatogonial cells from 5 animals in each group revealed a 4 percent decrease in flight compared to vivarium controls. In both cases the t-Test significance was less than 0.02. The serum testosterone levels of all animals (flight, synchronous and vivarium) were significantly below the basal controls.

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.

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.

Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study.

PubMed

Morgentaler, Abraham; Dobs, Adrian S; Kaufman, Joel M; Miner, Martin M; Shabsigh, Ridwan; Swerdloff, Ronald S; Wang, Christina

2008-12-01

We determined the pharmacokinetics and safety of 750 mg long acting testosterone undecanoate given intramuscularly at 0, 4 and 14 weeks to men with hypogonadism. A 24-week, single arm, open label, multicenter trial in 130 hypogonadal men 18 years or older who were screened for serum total testosterone less than 300 ng/dl was performed at 31 research sites in the United States between March and November 2007. Testosterone undecanoate (750 mg) was administered at baseline, and at weeks 4 and 14. Serum testosterone samples were collected on days 4, 7, 11, 14, 21, 28, 42, 56 and 70 following injection 3. Safety was assessed, eg biochemical markers and adverse events, secondary to testosterone undecanoate treatment. Of the 130 patients 116 with a mean +/- SE age of 54.2 +/- 0.90 years completed the 24-week trial. Following the week 14 injection mean +/- SD average serum testosterone was 494.9 +/- 141.46 ng/dl during the 70-day dosing interval and mean +/- SD maximum serum testosterone was 890.6 +/- 345.11 ng/dl with a mean concentration within the young healthy adult male range (300 to 1,000 ng/dl) in 94% of patients and a mean maximum concentration of below 1,500 ng/dl in 92%. Mean +/- SE hematocrit and hemoglobin increased from baseline to week 24 (43.3% +/- 0.32% to 45.7% +/- 0.35% and 14.6 +/- 0.11 to 15.5 +/- 0.13 gm/dl, respectively). Mean +/- SE prostate specific antigen increased from baseline to 24 weeks (1.0 +/- 0.08 to 1.3 +/- 0.10 ng/ml). No prostate cancer or gynecomastia was observed during this 24-week study. This 24-week clinical study demonstrated that 750 mg testosterone undecanoate depot injection administered intramuscularly at 0, 4 and 14 weeks achieves serum testosterone levels in the normal range during a 10-week dosing interval.

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.

Association between hypogonadism, symptom burden, and survival in male patients with advanced cancer.

PubMed

Dev, Rony; Hui, David; Del Fabbro, Egidio; Delgado-Guay, Marvin O; Sobti, Nikhil; Dalal, Shalini; Bruera, Eduardo

2014-05-15

A high frequency of hypogonadism has been reported in male patients with advanced cancer. The current study was performed to evaluate the association between low testosterone levels, symptom burden, and survival in male patients with cancer. Of 131 consecutive male patients with cancer, 119 (91%) had an endocrine evaluation of total (TT), free (FT), and bioavailable testosterone (BT); high-sensitivity C-reactive protein (CRP); vitamin B12; thyroid-stimulating hormone; 25-hydroxy vitamin D; and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. The authors examined the correlation using the Spearman test and survival with the log-rank test and Cox regression analysis. The median age of the patients was 64 years; the majority of patients were white (85 patients; 71%). The median TT level was 209 ng/dL (normal: ≥ 200 ng/dL), the median FT was 4.4 ng/dL (normal: ≥ 9 ng/dL), and the median BT was 22.0 ng/dL (normal: ≥ 61 ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (P ≤ .04), poor Eastern Cooperative Oncology Group performance status (P ≤ .05), weight loss (P ≤ .01), and opioid use (P ≤ .005). Low TT and FT were associated with increased anxiety (P ≤ .04), a decreased feeling of well-being (P ≤ .04), and increased dyspnea (P ≤ .05), whereas low BT was only found to be associated with anorexia (P = .05). Decreased TT, FT, and BT values were all found to be significantly associated with elevated CRP and low albumin and hemoglobin. On multivariate analysis, decreased survival was associated with low TT (hazards ratio [HR], 1.66; P = .034), declining Eastern Cooperative Oncology Group performance status (HR, 1.55; P = .004), high CRP (HR, 3.28; P < .001), and decreased albumin (HR, 2.52; P < .001). In male patients with cancer, low testosterone levels were associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival. A high frequency of hypogonadism has been reported in male patients with advanced cancer. In the current study, an increased symptom burden, systemic inflammation, weight loss, opioid use, and poor survival were found to be associated with decreased testosterone levels in male patients with cancer. Cancer 2014;120:1586-1593. © 2014 American Cancer Society. © 2014 American Cancer Society.

Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia.

PubMed

Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm; Main, Katharina M; Duno, Morten; Juul, Anders

2012-05-01

To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome. Tertiary paediatric endocrine centre. Retrospective evaluation of 14 male patients with partial androgen insensitivity syndrome (PAIS) with verified androgen receptor (AR) mutations. The authors recorded phenotypic characteristics at birth and external masculinisation score (EMS), registered longitudinal growth, circulating levels of testosterone, estradiol, luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin-B and sex hormone binding globulin (SHBG), in addition to phenotype at postpubertal follow up. The EMS ranged from 5 to 12 in PAIS at birth. Six patients were born with hypospadias and all patients developed gynaecomastia in puberty. Eight of the patients received testosterone treatment. At follow-up penile size was impaired irrespective of EMS at birth, but responded to pubertal androgen therapy in some of the patients. Serum levels of testosterone, estradiol, SHBG and LH, but not FSH and inhibin B, were markedly elevated in puberty. Final height was 181.3 cm (165.7-190.5 cm) corresponding to an SD score of 0.7 (-2.1 to +2.1 SD, n=10). Gynaecomastia and impaired phallic growth are frequently observed in adults with PAIS, but may be ameliorated by androgen therapy. The authors suggest that male patients presenting with gynaecomastia in puberty, and elevated circulating levels of testosterone, estradiol and LH in puberty, but normal FSH, should be suspected of having PAIS and undergo genetic testing for AR mutations.

Pubertal Onset in Apparently Healthy Indian Boys and Impact of Obesity.

PubMed

Surana, Vineet; Dabas, Aashima; Khadgawat, Rajesh; Marwaha, Raman Kumar; Sreenivas, V; Ganie, M Ashraf; Gupta, Nandita; Mehan, Neena

2017-01-01

Primary - to determine the age of pubertal onset in Indian boys. Secondary - (a) to assess the impact of obesity on pubertal timing, (b) to assess the relationship between gonadotropins and puberty. Cross-sectional. General community-seven schools across New Delhi. Random sample of 1306 school boys, aged 6-17 years. Anthropometric measurement for weight and height and pubertal staging was performed for all subjects. Body mass index (BMI) was calculated to define overweight/obesity. Serum luteinizing hormone (LH), follicle stimulating hormone, and serum testosterone were measured in every sixth subject. Age at pubertal onset-testicular volume ≥4 mL (gonadarche) and pubic hair Stage II. Median age of attaining gonadarche and pubarche was 10.41 years (95% confidence interval [CI]: 10.2-10.6 years) and 13.60 (95% CI: 13.3-14.0 years), respectively. No significant difference in the age of attainment of gonadarche was observed in boys with normal or raised BMI, though pubarche occurred 8 months earlier in the latter group. Serum gonadotropins and testosterone increased with increasing stages of puberty but were unaffected by BMI. Serum LH level of 1.02 mIU/mL and testosterone level of >0.14 ng/mL showed the best prediction for pubertal onset. The study establishes a secular trend of the age of onset of puberty in Indian boys. Pubarche occurred earlier in overweight/obese boys. The cutoff levels of serum LH and testosterone for prediction of pubertal onset have been established.

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

PubMed

Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

2016-01-01

When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

The sensitivity of male rat reproductive organs to monosodium glutamate.

PubMed

Iamsaard, Sitthichai; Sukhorum, Wannisa; Samrid, Rarinthorn; Yimdee, Jindaporn; Kanla, Pipatphong; Chaisiwamongkol, Kowit; Hipkaeo, Wiphawi; Fongmoon, Duriya; Kondo, Hisatake

2014-01-01

This study aimed to investigate the sensitivity of the testis, epididymis, seminal vesicle, and sperm acrosome reaction (AR) to monosodium L- glutamate (MSG) in rats. Rats were divided into four groups and fed with non-acidic MSG at 0.25, 3 or 6 g/kg body weight for 30 days or without MSG. The morphological changes in the reproductive organs were studied. The plasma testosterone level, epididymal sperm concentration, and sperm AR status were assayed. Compared to the control, no significant changes were discerned in the morphology and weight of the testes, or the histological structures of epididymis, vas deferens and seminal vesicle. In contrast, significant decreases were detected in the weight of the epididymis, testosterone levels, and sperm concentration of rats treated with 6 g/kg body weight of MSG. The weight loss was evident in the seminal vesicle in MSG-administered rats. Moreover, rats treated with MSG 3 and 6 g/kg exhibited partial testicular damage, characterized by sloughing of spermatogenic cells into the seminiferous tubular lumen, and their plasma testosterone levels were significantly decreased. In the 6 g/kg MSG group, the sperm concentration was significantly decreased compared with the control or two lower dose MSG groups. In AR assays, there was no statistically significant difference between MSG-rats and normal rats. Testicular morphological changes, testosterone level, and sperm concentration were sensitive to high doses of MSG while the rate of AR was not affected. Therefore, the consumption of high dose MSG must be avoided because it may cause partial infertility in male. Copyright © 2014 by Academy of Sciences and Arts of Bosnia and Herzegovina.

[Severe postmenopausal hyperandrogenism due to an ovarian lipoid cell tumor: a case report].

PubMed

Bernasconi, D; Del Monte, P; Marinaro, E; Marugo, A; Marugo, M

2004-03-01

The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

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.

A comparison of a novel testosterone bioadhesive buccal system, striant, with a testosterone adhesive patch in hypogonadal males.

PubMed

Korbonits, Márta; Slawik, Marc; Cullen, Derek; Ross, Richard J; Stalla, Günter; Schneider, Harald; Reincke, Martin; Bouloux, Pierre M; Grossman, Ashley B

2004-05-01

A novel delivery system has been developed for testosterone replacement. This formulation, COL-1621 (Striant), a testosterone-containing buccal mucoadhesive system, has been shown in preliminary studies to replace testosterone at physiological levels when used twice daily. Therefore, the current study compared the steady-state pharmacokinetics and tolerability of the buccal system with a testosterone-containing skin patch (Andropatch or Androderm) in an international multicenter study of a group of hypogonadal men. Sixty-six patients were randomized into two groups; one applied the buccal system twice daily, whereas the other applied the transdermal patch daily, in each case for 7 d. Serum total testosterone and dihydrotestosterone concentrations were measured at d 1, 3 or 4, and 6, and serially over the last 24 h of the study. Pharmacokinetic parameters for each formulation were calculated, and the two groups were compared. The tolerability of both formulations was also evaluated. Thirty-three patients were treated with the buccal preparation, and 34 were treated with the transdermal patch. The average serum testosterone concentration over 24 h showed a mean of 18.74 nmol/liter (SD =; 5.90) in the buccal system group and 12.15 nmol/liter (SD =; 5.55) in the transdermal patch group (P < 0.01). Of the patients treated with the buccal system, 97% had average steady-state testosterone concentrations within the physiological range (10.41-36.44 nmol/liter), whereas only 56% of the transdermal patch patients achieved physiological total testosterone concentrations (P < 0.001 between groups). Testosterone concentrations were within the physiological range in the buccal system group for a significantly greater portion of the 24-h treatment period than in the transdermal patch group (mean, 84.9% vs. 54.9%; P < 0.001). Testosterone/dihydrotestosterone ratios were physiological and similar in both groups. Few patients experienced major adverse effects from either treatment. No significant local tolerability problems were noted with the buccal system, other than a single patient withdrawal. We conclude that this buccal system is superior to the transdermal patch in achieving testosterone concentrations within the normal range. It may, therefore, be a valuable addition to the range of choices for testosterone replacement therapy.

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

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.

Relationship Between Gonadal Function and Cardiometabolic Risk in Young Men With Chronic Spinal Cord Injury.

PubMed

Sullivan, Shannon D; Nash, Mark S; Tefara, Eshetu; Tinsley, Emily; Groah, Suzanne

2018-04-01

We reported previously that young men with chronic spinal cord injury (SCI) have a greater prevalence of testosterone deficiency compared with an age-matched, healthy control population. Young men with SCI also are at increased risk for developing cardiometabolic dysfunction after injury. It is unclear whether testosterone deficiency is associated with heightened cardiometabolic risk in men with SCI. To investigate associations among levels of testosterone in young men with chronic SCI and surrogate markers of cardiometabolic risk. Secondary cross-sectional analysis. Rehabilitation research centers in Washington, DC, and Miami, Florida. Men (n = 58) aged 18-45 years with chronic (≥1 year), motor complete SCI without comorbidities or use of testosterone therapy. Plasma concentrations of testosterone, lipids, inflammatory markers (C-reactive protein and interleukin-6), percent hemoglobin A1c, glucose, and insulin were measured in a fasting state using standard assays. A 2-hour oral glucose tolerance test and Framingham Risk Score were assessed for each subject. Body composition was assessed by dual X-ray absorptiometry scan. Surrogate markers of cardiometabolic risk among men based on the level of total testosterone (TT; ≤300, 301-500, or >500 ng/dL) and free testosterone (fT; ≤9 or >9 ng/dL). Comparisons were made between men with normal and low TT or fT. Framingham Risk Score was significantly greater in men with low fT (P < .05). Percent body fat (P < .05) and waist-to-hip ratio (P < .05) but not body mass index (P > .08), were greater in men with low TT or low fT. Men with low TT or low fT had lower high-density lipoprotein cholesterol levels (P < .05) without differences in fasting triglycerides (P > .1) or low-density lipoprotein cholesterol (P > .07). Men with low TT had greater levels of inflammatory markers C-reactive protein (P < .05) and interleukin-6 (P < .05). Men with low TT or low fT had greater fasting glucose (P < .05) and greater insulin resistance (P < .04), without differences in percent hemoglobin A1c (P > .8). In young men with chronic SCI who undergo an accelerated aging process postinjury, hypogonadism is associated with an unfavorable cardiometabolic risk profile. Further research is needed to determine whether a causal relationship exists between hypogonadism and heightened cardiometabolic risk in men with SCI and whether routine screening for testosterone deficiency is warranted in this population. IV. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

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

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.

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

PubMed

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

Kinetics of removal of intravenous testosterone pulses in normal men.

PubMed

Veldhuis, Johannes D; Keenan, Daniel M; Liu, Peter Y; Takahashi, Paul Y

2010-04-01

Testosterone is secreted into the bloodstream episodically, putatively distributing into total, bioavailable (bio) nonsex hormone-binding globulin (nonSHBG-bound), and free testosterone moieties. The kinetics of total, bio, and free testosterone pulses are unknown. Design Adrenal and gonadal steroidogenesis was blocked pharmacologically, glucocorticoid was replaced, and testosterone was infused in pulses in four distinct doses in 14 healthy men under two different paradigms (a total of 220 testosterone pulses). Testosterone kinetics were assessed by deconvolution analysis of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone concentration-time profiles. Independently of testosterone dose or paradigm, rapid-phase half-lives (min) of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone were comparable at 1.4+/-0.22 min (grand mean+/-S.E.M. of geometric means). Slow-phase testosterone half-lives were highest for SHBG-bound testosterone (32 min) and total testosterone (27 min) with the former exceeding that of free testosterone (18 min), bioavailable testosterone (14 min), and albumin-bound testosterone (18 min; P<0.001). Collective outcomes indicate that i) the rapid phase of testosterone disappearance from point sampling in the circulation is not explained by testosterone dose; ii) SHBG-bound testosterone and total testosterone kinetics are prolonged; and iii) the half-lives of bioavailable, albumin-bound, and free testosterone are short. A frequent-sampling strategy comprising an experimental hormone clamp, estimation of hormone concentrations as bound and free moieties, mimicry of physiological pulses, and deconvolution analysis may have utility in estimating the in vivo kinetics of other hormones, substrates, and metabolites.

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.

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.

Echocardiographic evaluation of left ventricular mass index in children with hypospadias after hormonal stimulation with topical testosterone: A randomized controlled trial.

PubMed

de Andrade, Elisabeth Campos; de Castro Paiva, Kelly Christina; da Silva Guedes, Sarah; Souza, Mariana Lima C; Pereira, Marina Novellino; Miana, Laura Pimenta; de Figueiredo, André Avarese; de Bessa, José; Netto, José Murillo B

2017-08-01

Testosterone is often used in the preoperative period of hypospadias surgery. Previous studies have demonstrated the presence of androgen receptors in cardiac myocytes that can modulate the phenotype. The use of supraphysiological doses of androgens can lead to toxicity on the heart muscle and, in some cases, to left ventricular hypertrophy. This randomized double blind controlled clinical trial aims to evaluate the effect of topical testosterone on left ventricular mass index in boys with hypospadias. Boys with hypospadias aged 6 months to 9 years were included. Children were divided into two groups: G1 - boys who received testosterone propionate 1% ointment twice a day for 30 days, and G2 - boys receiving placebo ointment in the same regimen. All children were submitted to bi-dimensional echocardiographic evaluation to compare the left ventricular mass index, blood pressure, and body mass index before and after treatment (30 and 90 days). Levels of serum testosterone, LH, and FSH were measured. Thirty-five children were analyzed: 17 in G1 and 18 in G2. No differences were found in left ventricular mass index (left ventricular mass indexed by body surface area) prior to treatment. Left ventricular mass index was 59.21 ± 11.91 g/m 2 in G1 and 55.12 ± 8.29 g/m 2 in G2 (p = 0.244) after 30 days of treatment, and 61.13 ± 11.69 g/m 2 in G1 and 62.84 ± 35.99 g/m 2 in G2 (p = 0.852) after 90 days. Serum testosterone levels were 12 (7-80) ng/dL in G1 and 5 (5-7) ng/dL in G2 (p = 0.018) after 30 days of treatment, and 10 (5-11) ng/dL in G1 and 5 (4-5) ng/dL in G2 (p = 0.155), after 90 days (Figure). There was a small increase in systolic blood pressure (SBP) after 30 days (83.82 ± 7.18 mmHg) in the group who receive testosterone (G1) compared with controls (77.5 ± 6.69 mmHg) (p = 0.010). After 90 days, SBP levels returned to basal levels in G1 (82.35 ± 5.62 mmHg) and in G2 (81.38 ± 4.79 mmHg) (p = 0.588). Topical testosterone can be considered safe in the preoperative period of children with hypospadias with no risk of left ventricular hypertrophy. An increase in systolic blood pressure occurs while using testosterone but it is transitory, returning to normal levels after 90 days. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

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.

Developmental reprogramming of reproductive and metabolic dysfunction in sheep: native steroids vs. environmental steroid receptor modulators

PubMed Central

Padmanabhan, Vasantha; Sarma, Hiren N.; Savabieasfahani, Mozhgan; Steckler, Teresa L.; Veiga-Lopez, Almudena

2014-01-01

The inappropriate programming of developing organ systems by exposure to excess native or environmental steroids, particularly the contamination of our environment and our food sources with synthetic endocrine disrupting chemicals that can interact with steroid receptors, is a major concern. Studies with native steroids have found that in utero exposure of sheep to excess testosterone, an estrogen precursor, results in low birth weight offspring and leads to an array of adult reproductive / metabolic deficits manifested as cycle defects, functional hyperandrogenism, neuroendocrine / ovarian defects, insulin resistance, and hypertension. Furthermore, the severity of reproductive dysfunction is amplified by excess postnatal weight gain. The constellation of adult reproductive and metabolic dysfunction in prenatal testosterone-treated sheep is similar to features seen in women with polycystic ovary syndrome. Prenatal dihydrotestosterone treatment failed to result in similar phenotype suggesting that many effects of prenatal testosterone excess are likely facilitated via aromatization to estradiol. Similarly, exposure to environmental steroid imposters such as bisphenol A (BPA) and methoxychlor (MXC) from days 30-90 of gestation had long-term but differential effects. Exposure of sheep to BPA, which resulted in maternal levels of 30-50 ng/ml BPA, culminated in low birth-weight offspring. These female offspring were hypergonadotropic during early postnatal life and characterized by severely dampened preovulatory LH surges. Prenatal MXC-treated females had normal birth weight and manifested delayed but normal amplitude LH surges. Importantly, the effects of BPA were evident at levels, which approximated twice the highest levels found in human maternal circulation of industrialized nations. These findings provide evidence in support of developmental origin of adult reproductive and metabolic diseases and highlight the risk posed by exposure to environmental endocrine disrupting chemicals. PMID:20070410

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

Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones.

PubMed

Sainsbury, A; Herzog, H

2001-03-01

Neuropeptide Y (NPY) in the hypothalamus exerts multiple physiological functions including stimulation of adipogenic pathways such as feeding and insulin secretion as well as inhibition of the somatotropic and gonadotropic axes. Since hypothalamic NPY-ergic activity is increased by negative energy balance, NPY enables coordinated regulation of growth and reproduction in parallel with energy availability. Chronic pathological increases in central NPY-ergic activity contribute to obesity. Many of the adipogenic effects of NPY are specifically dependent on adrenal glucocorticoids. However, in the current study we show that central NPY does not require adrenal hormones to inhibit the somatotropic and gonadotropic axes in rats. Male adrenalectomized and sham-operated normal rats were intracerebroventricularly (ICV) infused with NPY (15 microg/day) or saline for 5-7 days, and plasma leptin, insulin-like growth factor (IGF-1) and testosterone were assayed, and epididymal white adipose tissue (WATe) was weighed. In normal intact rats, WATe weight and leptinemia were significantly increased by NPY, and these effects were prevented by adrenalectomy. In normal rats, NPY markedly reduced plasma IGF-1 levels (470 +/- 40 versus 1260 +/- 90 ng/ml) and testosterone (0.53 +/- 0.28 versus 5.4 +/- 0.80 nmol/l in saline-infused controls, p < 0.0001). Adrenalectomy decreased plasma IGF-1 concentrations to 290 +/- 30 (p < 0.0001 versus normal rats), which were significantly reduced further by NPY. However, adrenalectomy had no significant effect on basal nor on NPY-induced plasma testosterone concentrations. In conclusion unlike the stimulatory effects of NPY on fat mass and leptinemia, NPY-induced inhibition of the somatotropic and gonadotropic axes in male rats do not require adrenal hormones.

Angiotensin II type 2 receptor stimulation improves fatty acid ovarian uptake and hyperandrogenemia in an obese rat model of polycystic ovary syndrome.

PubMed

Leblanc, Samuel; Battista, Marie-Claude; Noll, Christophe; Hallberg, Anders; Gallo-Payet, Nicole; Carpentier, André C; Vine, Donna F; Baillargeon, Jean-Patrice

2014-09-01

Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenism but is also characterized by insulin resistance (IR). Studies showed that overexposure of nonadipose tissues to nonesterified fatty acids (NEFA) may explain both IR and hyperandrogenism. Recent studies indicate that treatment with an angiotensin II type 2 receptor (AT2R)-selective agonist improves diet-induced IR. We thus hypothesized that PCOS hyperandrogenism is triggered by ovarian NEFA overexposure and is improved after treatment with an AT2R agonist. Experiments were conducted in 12-week-old female JCR:LA-cp/cp rats, which are characterized by visceral obesity, IR, hyperandrogenism, and polycystic ovaries. Control JCR:LA +/? rats have a normal phenotype. Rats were treated for 8 days with saline or the selective AT2R agonist C21/M24 and then assessed for: 1) fasting testosterone, NEFA, and insulin levels; and 2) an iv 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid test to determine NEFA ovarian tissue uptake (Km). Compared with controls, saline-treated PCOS/cp rats displayed higher insulin (100 vs 5.6 μU/mL), testosterone (0.12 vs 0.04 nmol/L), NEFA (0.98 vs 0.48 mmol/L), and Km (20.7 vs 12.9 nmol/g·min) (all P < .0001). In PCOS/cp rats, C21/M24 did not significantly improve insulin or NEFA but normalized testosterone (P = .004) and Km (P = .009), which were strongly correlated together in all PCOS/cp rats (ρ = 0.74, P = .009). In conclusion, in an obese PCOS rat model, ovarian NEFA uptake and testosterone levels are strongly associated and are both significantly reduced after short-term C21/M24 therapy. These findings provide new information on the role of NEFA in PCOS hyperandrogenemia and suggest a potential role for AT2R agonists in the treatment of PCOS.

Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats.

PubMed

Pomjunya, Atchariya; Ratthanophart, Jasada; Fungfuang, Wirasak

2017-03-23

The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats.

Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats

PubMed Central

POMJUNYA, Atchariya; RATTHANOPHART, Jasada; FUNGFUANG, Wirasak

2017-01-01

The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats. PMID:28190818

Dihydrotestosterone in prostatic hypertrophy

PubMed Central

Siiteri, Pentti K.; Wilson, Jean D.

1970-01-01

To explore the relation between androgens and prostatic hypertrophy in man, the concentrations of testosterone, dihydrotestosterone, and androstenedione and the rate of conversion of testosterone to dihydrotestosterone have been measured in normal and hypertrophic prostate tissue. First, a double isotope derivative technique was adapted for the measurement of tissue androgen content in 15 normal and 10 hypertrophic prostates. Although there was no significant difference in the content of androstenedione and testosterone between the two types of tissue, the content of dihydrotestosterone was significantly greater in the hypertrophic tissue (0.60 ±0.10 μg/100 g) than in the normal glands (0.13 ±0.05 μg/100 g). Second, a regional study was performed in three normal prostates and four glands with early hypertrophy, and it was demonstrated that the dihydrotestosterone content was two and three fold greater in the periurethral area where prostatic hypertrophy usually commences than in the outer regions of the gland. Finally, the rate of conversion of testosterone to dihydrotestosterone has been measured under standardized conditions in tissue slices from 4 normal and 20 hypertrophic prostates. There was no significant difference in the rate of dihydrotestosterone formation between the two types of gland (6.0 ±0.8 and 7.8 ±0.5 μμmoles/15 mg of tissue per hr). While the mechanism by which dihydrotestosterone accumulation occurs remains unexplained, it is possible that the local accumulation of dihydrotestosterone may be involved in the pathogenesis of prostatic hypertrophy in man. Images PMID:4194768

Effects of fenoterol on the skeletal system depend on the androgen level.

PubMed

Śliwiński, Leszek; Cegieła, Urszula; Pytlik, Maria; Folwarczna, Joanna; Janas, Aleksandra; Zbrojkiewicz, Małgorzata

2017-04-01

The role of sympathetic nervous system in the osseous tissue remodeling is not clear enough. The effects of fenoterol, a selective β 2 -adrenomimetic drug, on the skeletal system of normal and androgen deficient (orchidectomized) rats were studied in vivo. Osteoclastogenesis and mRNA expression in osteoblasts were investigated in vitro in mouse cell cultures. Fenoterol administered to animals with physiological androgen level unfavorably affected the skeletal system, damaging the bone microarchitecture. Androgen deficiency induced osteoporotic changes, and fenoterol protected the osseous tissue from consequences of androgen deficiency. The results of in vitro studies correlated with the in vivo observations. A significantly increased number of osteoclasts in bone marrow cell cultures to which testosterone and fenoterol were added simultaneously was demonstrated. In cultures without the addition of testosterone, fenoterol significantly inhibited osteoclastogenesis in comparison with control cultures. The results indicate the favorable action of fenoterol in conditions of testosterone deficiency, and its destructive influence upon the skeleton in the presence of androgens. The results confirm the key role of sympathetic nervous system in the regulation of bone remodeling. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Severe oligozoospermia in a patient with myxedema coma.

PubMed

Komiya, Akira; Watanabe, Akihiko; Kawauchi, Yoko; Takano, Atsuko; Fuse, Hideki

2012-10-01

A case of severe oligozoospermia with myxedema coma is herein presented. The patient was referred to a male infertility clinic with a 5-year history of primary infertility. Decreased serum testosterone and elevated serum prolactin without abnormal MRI findings in the hypothalamus, and decreased semen volume and sperm motility were noted. A GnRH test revealed a decreased luteinizing hormone response, whereas the HCG test showed a normal testosterone increase. Because a urinalysis after ejaculation indicated retrograde ejaculation, imipramine administration was started. However, the semen quality deteriorated, so the patient was referred to an ART clinic. Twenty-one months from the initial visit, the patient developed a loss of consciousness and edema due to myxedema coma, a life-threatening state of hypothyroidism. The patient recovered after 1 month of thyroid hormone replacement therapy (HRT) with corticosteroids. Three months after the myxedema coma, a semen analysis showed a decreased semen volume (0.2 mL) and severe oligozoospermia (two spermatozoa/ejaculate). Elevated prolactin and decreased testosterone levels were still present. These parameters gradually improved after restoration of euthyroidism by HRT. In conclusion, physicians should confirm the thyroid function in the management of male infertility, especially in patients with elevated prolactin levels.

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.

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.

Endocrine antecedents of polycystic ovary syndrome (PCOS) in fetal and infant prenatally androgenized female rhesus monkeys

PubMed Central

Abbott, David H; Barnett, Deborah K; Levine, Jon E; Padmanabhan, Vasantha; Dumesic, Daniel A; Jacoris, Steve; Tarantal, Alice F

2008-01-01

Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits in adult female rhesus monkeys. Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily subcutaneous injections of 15 mg testosterone propionate (TP) and six received injections of oil vehicle (controls) from 40 through 80 days of gestation (term 165 [range: ±10] days), and all fetuses were delivered by Cesarean-section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels mostly normalized, while serum androstenedione levels in PA infants were elevated. TP injections did not increase estrogen levels in the dams, PA fetuses and infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally-induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants, and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood. PMID:18385445

Oxytocin, testosterone, and human social cognition.

PubMed

Crespi, Bernard J

2016-05-01

I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint effects partially mediate risks and phenotypes of autism and psychotic-affective conditions. These considerations have direct implications for the development of therapies for alleviating disorders of social cognition, and for understanding how such disorders are associated with the evolution of human cognitive-affective architecture. © 2015 Cambridge Philosophical Society.

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis

PubMed Central

Felix-Patrício, Bruno; Miranda, Alexandre F.; Medeiros, Jorge L.; Gallo, Carla B. M.; Gregório, Bianca M.; de Souza, Diogo B.; Costa, Waldemar S.; Sampaio, Francisco J. B.

2017-01-01

ABSTRACT Purpose: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. Materials and Methods: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Results: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Conclusion: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations. PMID:28379662

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis.

PubMed

Felix-Patrício, Bruno; Miranda, Alexandre F; Medeiros, Jorge L; Gallo, Carla B M; Gregório, Bianca M; Souza, Diogo B; Costa, Waldemar S; Sampaio, Francisco J B

2017-01-01

To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations. Copyright® by the International Brazilian Journal of Urology.

Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI.

PubMed

Wagner, Amy K; Brett, Christopher A; McCullough, Emily H; Niyonkuru, Christian; Loucks, Tammy L; Dixon, C Edward; Ricker, Joseph; Arenth, Patricia; Berga, Sarah L

2012-01-01

Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1-52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6-12 months post-TBI. AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.

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.

Late-onset 3 beta-hydroxysteroid dehydrogenase deficiency with virilization induced by a large ovarian cyst.

PubMed

Heinrich, U; Eberlein-Gonska, M; Benz, G; Haack, D; Otto, H F

1993-01-01

A midpubertal girl presented with secondary amenorrhea and a rapidly progressive deepening of her voice as the only signs of virilization. Diagnostic work-up yielded an extremely elevated plasma testosterone (289 ng/dl), low estradiol (29 pg/ml) levels and a large solitary cyst of the right ovary, which was totally removed. Pathohistology was in keeping with a granulosa cyst with mild luteinization. Normalization of testosterone (to 27.3 ng/dl) and estradiol (to 62 pg/ml) and resumption of regular menses after 2 months clearly indicated an autonomous function of the cyst. A malignant tumor was unequivocally excluded. Basal and ACTH stimulated levels of adrenal androgens pointed to a late-onset 3 beta-hydroxysteroid dehydrogenase deficiency, which per se is known to induce polycystic ovarian changes, but to date has never been described to be accompanied with a large and autonomous follicular cyst.

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

Obesity-related hypogonadism: a reversible condition.

PubMed

Zouras, Stamatios; Stephens, Jeffrey W; Price, David

2017-06-23

Obesity is associated with hypogonadism. While this association is widely accepted, the underlying mechanisms remain unclear. Furthermore, obesity is a risk factor for hypogonadism and conversely hypogonadism may be a risk factor for obesity. We present the case of a morbidly obese man aged 30 years with hypogonadotrophic hypogonadism that underwent a Roux-en-Y gastric bypass operation. Following the surgical treatment of his obesity, the testosterone level returned to normal with improvements in hypogonadal symptoms, which allowed discontinuation of exogenous testosterone therapy. This case report demonstrates reversal of hypogonadism following weight loss with restoration of gonadal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins

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

Sayed, Rabab H., E-mail: rabab.sayed@pharma.cu.edu

Serotonin level plays a role in suppressing the pathological findings of benign prostatic hyperplasia (BPH). Thus a new selective serotonin reuptake inhibitor, dapoxetine was used to test its ability to ameliorate the pathological changes in the rat prostate. A dose response curve was constructed between the dose of dapoxetine and prostate weight as well as relative prostate weight, then a 5 mg/kg dose was used as a representative dose for dapoxetine administration. Rats were divided into four groups; the control group that received the vehicle; the BPH-induced group received daily s.c injection of 3 mg/kg testosterone propionate dissolved in olivemore » oil for four weeks; BPH-induced group treated with finasteride 5 mg/kg/day p.o and BPH-induced group treated with dapoxetine 5 mg/kg/day p.o. Injection of testosterone increased prostate weight and relative prostate weight which were both returned back to the normal value after treatment with dapoxetine as well as finasteride. Testosterone also upregulated androgen receptor (AR) and proliferating cell nuclear antigen gene expression. Furthermore, testosterone injection elevated cyclooxygenase-II (COX II), inducible nitric oxide synthase (iNOS), B-cell lymphoma-2 (Bcl2) expression and tumor necrosis factor alpha content and reduced caspase-3 activity, Bcl-2-associated X protein (Bax) expression and Bax/Bcl2 ratio. Dapoxetine and finasteride administration reverted most of the changes made by testosterone injection. In conclusion, the current study provides an evidence for the protective effects of dapoxetine against testosterone-induced BPH in rats. This can be attributed, at least in part, to decreasing AR expression, and the anti-proliferative, anti-inflammatory and pro-apoptotic activities of dapoxetine in BPH. - Highlights: • Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats. • Dapoxetine decreased androgen receptor gene expression in rat prostate. • Dapoxetine possess anti-proliferative, anti-inflammatory and pro-apoptotic activities.« less

Testosterone inhibits the growth of prostate cancer xenografts in nude mice.

PubMed

Song, Weitao; Soni, Vikram; Soni, Samit; Khera, Mohit

2017-09-07

Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested. The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001). These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.

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.

Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner.

PubMed

Landry, David; Paré, Aurélie; Jean, Stéphanie; Martin, Luc J

2015-04-01

Obesity in men is associated with lower testosterone levels, related to reduced sperm concentration and the development of various diseases with aging. Hormones produced by the adipose tissue may have influences on both metabolism and reproductive function. Among them, the production and secretion of adiponectin is inversely correlated to total body fat. Adiponectin receptors (AdipoR1 and AdipoR2) have been found to be expressed in testicular Leydig cells (producing testosterone). Since StAR and Cyp11a1 are essential for testosterone synthesis and adiponectin has been shown to regulate StAR mRNA in swine granulosa cells, we hypothesized that adiponectin might also regulate these genes in Leydig cells. Our objective was to determine whether adiponectin regulates StAR and Cyp11a1 genes in Leydig cells and to better define its mechanisms of action. Methods used in the current study are qPCR for the mRNA levels, transfections for promoter activities, and enzyme-linked immunosorbent assay for the progesterone concentration. We have found that adiponectin cooperates with cAMP-dependent stimulation to activate StAR and Cyp11a1 mRNA expressions in a dose-dependent manner in MA-10 Leydig cells as demonstrated by transfection of a luciferase reporter plasmid. These results led to a significant increase in progesterone production from MA-10 cells. Thus, our data suggest that high doses of adiponectin typical of normal body weight may promote testosterone production from Leydig cells.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome.

PubMed

Iglesias, P; Prado, F; Macías, M C; Guerrero, M T; Muñoz, A; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2014-02-01

Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. 150 patients, aged ≥65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Two organizational effects of pubertal testosterone in male rats: transient social memory and a shift away from long-term potentiation following a tetanus in hippocampal CA1.

PubMed

Hebbard, Pamela C; King, Rebecca R; Malsbury, Charles W; Harley, Carolyn W

2003-08-01

The organizational role of pubertal androgen receptor (AR) activation in synaptic plasticity in hippocampal CA1 and in social memory was assessed. Earlier data suggest pubertal testosterone reduces adult hippocampal synaptic plasticity. Four groups were created following gonadectomy at the onset of puberty: rats given testosterone; rats given testosterone but with the AR antagonist flutamide, present during puberty; rats given testosterone at the end of puberty; and rats given cholesterol at the end of puberty. A tetanus normally inducing long-term potentiation (LTP) was used to stimulate CA1 in the urethane-anesthetized adults during the dark phase of their cycle. Social memory was assessed prior to electrophysiology. Social memory for a juvenile rat at 120 min was seen only in rats not exposed to AR activation during puberty. Pubertal AR activation may induce the reduced social memory of male rats. Early CA1 LTP occurred following tetanus in rats with no pubertal testosterone. Short-term potentiation occurred in rats exposed to pubertal testosterone. Unexpectedly, rats with pubertal AR activation developed long-term depression (LTD). The same pattern was seen in normal male rats. Lack of LTP during the dark phase is consistent with other data on circadian modulation of CA1 LTP. No correlations were seen among social memory scores and CA1 plasticity measures. These data argue for two organizational effects of pubertal testosterone: (1) CA1 synaptic plasticity shifts away from potentiation toward depression; (2) social memory is reduced. Enduring effects of pubertal androgen on limbic circuits may contribute to reorganized behaviors in the postpubertal period.

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.

Polycystic Ovary Syndrome

PubMed Central

McCartney, Christopher R.; Marshall, John C.

2017-01-01

A 22-year-old woman reports having hirsutism and irregular menses. She describes unpredictable and infrequent menses (five or six per year) since menarche at 11 years of age. Dark, coarse facial hair began to develop at 13 years of age. The symptoms worsened after she gained weight in college. The physical examination includes a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 29, blood pressure of 135/85 mm Hg, and moderate hirsutism without virilization. Laboratory tests reveal a total testosterone level of 65 ng per deciliter (2.3 nmol per liter) (assay reference range, 14 to 53 ng per deciliter [0.5 to 1.8 nmol per liter]), calculated free testosterone level of 15.3 pg per milliliter (53.1 pmol per liter) (assay reference range, 0.6 to 6.8 pg per milliliter [2.1 to 23.6 pmol per liter]), and glycated hemoglobin level of 5.7% (normal value, ≤5.6%). How should this case be evaluated and managed? PMID:27406348

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) ...

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.

Age-related changes in urinary testosterone levels suggest differences in puberty onset and divergent life history strategies in bonobos and chimpanzees.

PubMed

Behringer, V; Deschner, T; Deimel, C; Stevens, J M G; Hohmann, G

2014-08-01

Research on age-related changes in morphology, social behavior, and cognition suggests that the development of bonobos (Pan paniscus) is delayed in comparison to chimpanzees (Pan troglodytes). However, there is also evidence for earlier reproductive maturation in bonobos. Since developmental changes such as reproductive maturation are induced by a number of endocrine processes, changes in hormone levels are indicators of different developmental stages. Age-related changes in testosterone excretion are an indirect marker for the onset of puberty in human and non-human primates. In this study we investigated patterns of urinary testosterone levels in male and female bonobos and chimpanzees to determine the onset of puberty. In contrast to other studies, we found that both species experience age-related changes in urinary testosterone levels. Older individuals of both sexes had significantly higher urinary testosterone levels than younger individuals, indicating that bonobos and chimpanzees experience juvenile pause. The males of both species showed a similar pattern of age-related changes in urinary testosterone levels, with a sharp increase in levels around the age of eight years. This suggests that species-differences in aggression and male mate competition evolved independently of developmental changes in testosterone levels. Females showed a similar pattern of age-related urinary testosterone increase. However, in female bonobos the onset was about three years earlier than in female chimpanzees. The earlier rise of urinary testosterone levels in female bonobos is in line with reports of their younger age of dispersal, and suggests that female bonobos experience puberty at a younger age than female chimpanzees. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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.

ALTERATIONS IN SEXUALLY DIMORPHIC BIOTRANSFORMATION OF TESTOSTERONE IN JUVENILE AMERICAN ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS) FROM CONTAMINATED LAKES

EPA Science Inventory

The goal of this study was to determine whether hepatic biotransformation of testosterone is normally sexually dimorphic in juvenile alligators and whether living in a contaminated environment affects hepatic dimorphism. Lake Woodruff served as our reference site. Moonshine Bay, ...

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

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.

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

Brizzi, E.; Giannardi, G.

Eight-month-old rats were irradiated with 1000 r in the suprapubic region and injected intramuscularly 1 hr later with 10 mg testosterone propionate. Histologic changes in seminal vesicle were studied 7 and 15 days later. At 7 days the vesicles of irradiated uninjected rats showed very little cellular modification, except for a few pyknotic nuclei in epithelial and stromal cells. After 15 days the changes were more severe and included separation of epithelial cells from their underlying basement membrane and desquamation and degeneration of these cells. Other cells were relatively normal. In rats treated with testosterone, causing epithelial hyperplasia, the radiation-inducedmore » injury to epithelial cells was more severe 7 days after irradiation, but after 15 days, testosterone appeared to have stimulated recovery of the epithelium and a more normal vesicular structure was evident. (H.H.D.)« less

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.

Associations between maternal phenolic exposure and cord sex hormones in male newborns.

PubMed

Liu, Chunhua; Xu, Xijin; Zhang, Yuling; Li, Weiqiu; Huo, Xia

2016-03-01

Are maternal urinary phenol concentrations associated with cord steroid hormone levels and anogenital distance (AGD) in male newborns? High maternal urinary Bisphenol A (BPA) levels are associated with decreases in cord testosterone levels and the ratio of testosterone to estradiol in male newborns, but there was no significant association with AGD. Early life exposure to phenolic endocrine disrupting compounds (EDCs) is known to disrupt hormonal activities and affect reproductive development in males. However, studies on the health effects of prenatal human exposure are scarce. This was a cross-sectional study to investigate the association between maternal phenolic exposure and cord sex steroid hormones and AGD in male newborns. We recruited 100 mother-infant pairs from each of two hospitals, one in a polluted town (Guiyu) and the other in a cleaner town (Haojiang), from September 2010 to September 2011. One hundred and seventy eight maternal urine samples and 137 cord blood samples were available for quantification, thus 137 complete records entered into the final analysis. Of them, 77 pairs were from Guiyu, and 60 were from Haojiang. The chemical concentrations were determined by solid phase extraction and gas chromatography-mass spectrometry (SPE-GC-MS), and cord sex hormones were detected by radioimmunoassay (RIA). Neonatal anthropometric parameters including AGD were measured. Log2-transformed maternal urinary BPA concentration was negatively correlated with testosterone level and the ratio of testosterone to estradiol (T/E2) in male fetal cord blood after adjustment for potential confounders in linear regression models (βadjusted = -31.09 (95% CI, -53.07 to -9.11) and βadjusted = -0.08 (95% CI, -0.13 to -0.01), respectively). Moreover, compared with the lowest quartile group of BPA level, the highest group showed a significant decrease in testosterone level and T/E2 (βadjusted = -179.84 (95% CI, -333.45 to -26.24) and βadjusted = -0.37 (95% CI, -0.81 to 0.07), respectively). No significant associations between AGD or anogenital index (AGI, [AGI = AGD/birthweight (mm/kg)]) and phenolic EDCs or cord hormone levels were found. Results in the present study should be interpreted with caution because of its cross-sectional nature, small sample size and sampling time. Testosterone plays an important role in sex differentiation and normal development of the fetus and newborn, and the balance between testosterone and estradiol is thought an important mediator of prostate disease. Therefore, our findings may have important implications for human reproductive health. This work was supported by the National Natural Science Foundation of China (21377077) and Guangdong University Project for International Cooperation and Innovation Platform (2013gjhz0007). The authors declare they have no actual or potential competing financial interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid, and Strontium Levels in Adult Men According to the US 2011–2012 National Health and Nutrition Examination Survey

PubMed Central

Liu, Hui; Héroux, Paul; Zhang, Qunwei; Jiang, Zhao-Yan; Gu, Aihua

2015-01-01

Background Little is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011–2012). Methods Urinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio. Results Adjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone. Conclusions The National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men. PMID:25996772

Spermatogenetic inhibition in men taking a combination of oral medroxyprogesterone acetate and percutaneous testosterone as a male contraceptive method.

PubMed

Soufir, J-C; Meduri, G; Ziyyat, A

2011-07-01

We previously demonstrated in a small pilot study that oral medroxyprogesterone acetate and percutaneous testosterone (OMP/PT) induce reversible spermatogenesis suppression. The aims of this study were to determine the rate of spermatogenetic inhibition and recovery and to obtain preliminary data on efficacy for a larger population under OMP/PT. A total of 35 healthy men with normal spermiograms requesting male hormonal contraception were treated with OMP (20 mg/day) and PT (50-125 mg/day) for periods up to 18 months. Couples were included in a contraceptive efficacy phase after a value of ≤1 million/ml spermatozoa was reached between 1 and 3 months of treatment. Sperm counts decreased by 47% at 1 month, reaching 90% at 2 months and 98-100% between 4 and 8 months. At 3 months, 80% of men had ≤1 million/ml spermatozoa. Follicle-stimulating hormone and luteinizing hormone decreased to 35% of pretreatment levels after 1 month of treatment and to 75-80% at 2 and 6 months, respectively. Plasma testosterone and estradiol levels were in the eugonadal range at 3, 6, 9 and 12 months of treatment. Dihydrotestosterone concentrations were 2-4 times higher than pretreatment values. The rate of spermatogenetic recovery was rapid (73 ± 29.5 days). During the efficacy phase (211 months for 25 couples), one pregnancy attributable to poor compliance of the male partner was observed. OMP/PT efficiently inhibits spermatogenesis in 80% of men, maintains testosterone at physiological levels and avoids the need for parenteral administration, which is poorly accepted by French men. These results justify larger studies to define a more adequate dosage of OMP/PT and to confirm its efficacy and safety.

Sexual differentiation of pheromone processing: Links to male-typical mating behavior and partner preference

PubMed Central

Baum, Michael J.

2009-01-01

Phoenix et al. (Phoenix et al., 1959) were the first to propose an essential role of fetal testosterone exposure in the sexual differentiation of the capacity of mammals to display male-typical mating behavior. In one experiment control male and female guinea pigs as well as females given fetal testosterone actually showed equivalent levels of mounting behavior when gonadectomized and given ovarian steroids prior to adult tests with a stimulus female. This finding is discussed in the context of a recent, high-profile paper by Kimchi and co-workers (Kimchi et al., 2007) arguing that female rodents possess the circuits that control the expression of male-typical mating behavior and that their function is normally suppressed in this sex by pheromonal inputs that are processed via the vomeronasal organ (VNO)—accessory olfactory nervous system. In another Phoenix et al. experiment, significantly more mounting behavior was observed in male guinea pigs and in females given fetal testosterone than in control females following adult gonadectomy and treatment with testosterone. Literature is reviewed that attempts to link sex differences in the anatomy and function of the accessory versus the main olfactory projections to the amygdala and hypothalamus to parallel sex differences in courtship behaviors, including sex partner preference, as well as the capacity to display mounting behavior. PMID:19446074

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

PubMed

Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

2012-01-01

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

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.

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.

Direct radioimmunoassay (RIA) of salivary testosterone: correlation with free and total serium testosterone

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

Vittek, J.; L'Hommedieu, D.G.; Gordon, G.G.

Simple and sensitive direct RIA for determination of salivary testosterone was developed by using RSL NOSOLVEX TM (125 1) kit produced by Radioassay System Laboratories (Carcon, California). In addition, a relationship between salivary and serum free and total testosterone concentrations was studied in randomly selected 45 healthy subjects, 5 females on oral contraceptive pills and 28 hypertensive patients on various treatment regimens. The lowest weight of testosterone detectable by the modified method was equivalent to 1 pg/ml of saliva, taking into account analytical variability. Intra- and interassay coefficients of variation were 5.09 +/- 2.7% and 8.2 +/- 5.9% respectively. Statisticallymore » significant correlations were found between salivary and serum free testosterone (r = 0.97) and salivary and serum total testosterone concentrations (r = 0.70 - 0.87). The exception to this was a group of hypertensive females in which no correlation (r = 0.14) between salivary and total serum testosterone was found. It is also of interest that, while salivary testosterone was significantly increased in subjects taking oral contraceptives and most of the hypertensive patients, the total serum testosterone concentration was in normal range. These findings suggest that the determination of salivary testosterone is a reliable method to detect changes in the concentration of available biologically active hormone in the circulation. 21 references, 4 figures, 1 table.« less

Steady-state pharmacokinetics of oral testosterone undecanoate with concomitant inhibition of 5α-reductase by finasteride

PubMed Central

Roth, M. Y.; Dudley, R. E.; Hull, L.; Leung, A.; Christenson, P.; Wang, C.; Swerdloff, R.; Amory, J. K.

2014-01-01

Summary Oral testosterone undecanoate (TU) is used to treat testosterone deficiency; however, oral TU treatment elevates dihydrotestosterone (DHT), which may be associated with an increased risk of acne, male pattern baldness and prostate hyperplasia. Co-administration of 5α-reductase inhibitors with other formulations of oral testosterone suppresses DHT production and increases serum testosterone. We hypothesized that finasteride would increase serum testosterone and lower DHT during treatment with oral TU. Therefore, we studied the steady-state pharmacokinetics of oral TU, 200 mg equivalents of testosterone twice daily for 7 days, alone and with finasteride 0.5 and 1.0 mg po twice daily in an open-label, three-way crossover study in 11 young men with experimentally induced hypogonadism. On the seventh day of each dosing period, serum testosterone, DHT and oestradiol were measured at baseline and 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 h after the morning dose. Serum testosterone and DHT were significantly increased into and above their normal ranges similarly by all three treatments. Co-administration of finasteride at 0.5 and 1.0 mg po twice daily had no significant effect on either serum testosterone or DHT. Oral TU differs from other formulations of oral testosterone in its response to concomitant inhibition of 5α-reductase, perhaps because of its unique lymphatic route of absorption. PMID:20969601

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.

Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity

PubMed Central

Rosenfield, Robert L; Bordini, Brian

2010-01-01

Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty. PMID:20816944

Persistent organic contaminants and steroid hormones levels in Morelet's crocodiles from the Southern Gulf of Mexico.

PubMed

Gonzalez-Jauregui, Mauricio; Valdespino, Carolina; Salame-Méndez, Arturo; Aguirre-León, Gustavo; Rendón-Vonosten, Jaime

2012-04-01

Effects of endocrine disruptors on reproductive variables of top predators, such as alligators and crocodiles, have long been cited. Due to their long life span, these predators provide us with historic contaminant annals. In this study we tried to test whether lifestyle (free-ranging vs. farm animals) and reproductive age of Morelet's crocodiles in Campeche, Mexico, affect the bioaccumulation of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). Subsequently, we tested to see whether their concentration was related to steroid hormones (testosterone and estradiol-17β) levels once normal cyclic hormone variation and reproductive age had been taken into account. From the group of contaminants considered (analyzed as families), only frequency of hexachlorocyclohexanes (∑HCH) and ∑PCB permitted analyses. Whereas there was a greater concentration of ∑HCH bioaccumulated by free-ranging crocodiles, ∑PCB was found in equal quantities in free-ranging and farm animals. No difference was observed in relation to reproductive age for any of the contaminants. However, ∑PCB concentrations were related to testosterone levels among female crocodiles. This androgenic effect of ∑PCB has not been reported previously. Because testosterone promotes aggressive behavior in vertebrates, excessive aggression during the estrous season, or when female crocodiles should be caring for their young, could result in reproductive failure in Morelet's crocodiles and potential long-term decline of the population.

Crocin Improves Damage Induced by Nicotine on A Number of Reproductive Parameters in Male Mice

PubMed Central

Salahshoor, Mohammad Reza; Khazaei, Mozafar; Jalili, Cyrus; Keivan, Mona

2016-01-01

Background Crocin, a carotenoid isolated from Crocus sativus L. (saffron), is a pharmacologically active component of saffron. Nicotine consumption can decrease fertility in males through induction of oxidative stress and DNA damage. The aim of this study is to determine the effects of crocin on reproductive parameter damages in male mice exposed to nicotine. Materials and Methods In this experimental study, we divided 48 mice into 8 groups (n=6 per group): control (normal saline), nicotine (2.5 mg/kg), crocin (12.5, 25 and 50 mg/kg) and crocin (12.5, 25 and 50 mg/kg)+nicotine (2.5 mg/kg). Mice received once daily intraperitoneal injections of crocin, nicotine and crocin+nicotine for 4 weeks. Sperm parameters (count, motility, and viability), testis weight, seminiferous tube diameters, testosterone, and serum nitric oxide levels were analyzed and compared. Results Nicotine administration significantly decreased testosterone level; sperm count, viability, and motility; testis weight and seminiferous tubule diameters compared to the control group (P<0.05). However, increasing the dose of crocin in the crocin and crocin+nicotine groups significantly boosted sperm motility and viability; seminiferous tubule diameters; testis weight; and testosterone levels in all groups compared to the nicotine group (P<0.05). Conclusion Crocin improves nicotine-induced adverse effects on reproductive parameters in male mice. PMID:27123203

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.

Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis.

PubMed

Li, Li; Feng, Qiong; Ye, Ming; He, Yaojuan; Yao, Aling; Shi, Kun

2017-11-01

This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents require further investigation.

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.

[Effects of smoking and alcohol consumptionon reproductive and metabolic indicators in young men in western siberia].

PubMed

Osadchuk, L V; Popova, A V; Erkovich, A A; Voroshilova, N A; Osadchuk, A V

2017-09-01

Smoking and alcohol consumption remain widespread throughout the world, including Russia. Recently, due to the increase in male infertility and subfertility, special attention has been paid to the effects of smoking and alcohol on the reproductive health of young men. The aim of this study was to assess the effects of smoking and moderate alcohol consumption on spermatogenesis, reproductive hormone levels and metabolic status in young men living in Western Siberia (Novosibirsk). One hundred thirty-three volunteers (mean age 21.1+/-0.3 years) were tested for the sperm concentration, the proportion of mobile and morphologically normal spermatozoa in the ejaculate, blood serum levels of follicle-stimulating and luteinizing hormones, prolactin, testosterone, estradiol, inhibin B, triglycerides, total cholesterol, high and low density lipoprotein cholesterol, glucose and uric acid. and conclusions The studied lifestyle factors were found to have no effects on spermatogenesis. Smoking more than 10 cigarettes per day and a moderate frequency of alcohol consumption (up to 1 time per week) was associated with higher blood serum testosterone levels and engaging in more frequent sexual contacts compared to non-smoking and non-drinking men. Drinking alcohol more than once a week and smoking more than 8 cigarettes per day was associated, along with the increase in testosterone levels and the frequency of sexual contacts, with lower levels of follicle-stimulating hormone and higher serum triglyceride levels. Thus, in young men, frequent drinking and smoking can alter the hormonal and metabolic balance, which, as the duration of the exposure and the strength of the factors increase, will increase the risk of reproductive disorders.

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.

Pituitary-adrenal hormones and testosterone across the menstrual cycle in women with premenstrual syndrome and controls.

PubMed

Bloch, M; Schmidt, P J; Su, T P; Tobin, M B; Rubinow, D R

1998-06-15

Premenstrual syndrome (PMS) is a cyclic mood disorder, widely believed, yet not conclusively shown, to be of endocrine etiology. This study examines basal levels of several hormones reported, albeit inconsistently, to differ in women with PMS compared with controls. Subjects (10 PMS patients and 10 controls) had their blood drawn for one full menstrual cycle. Subjects' mood and behavioral symptoms were assessed by daily self-ratings and objective ratings. Plasma was assayed for total and free testosterone (T), beta-endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and cortisol. No differences were observed between the PMS and control groups for beta-EP, ACTH, or cortisol. PMS subjects had significantly lower total and free T plasma levels with a blunting of the normal periovulatory peak, a finding that may be epiphenomenal to age. This study does not confirm previous reports of abnormalities in plasma levels of either ACTH or beta-EP in women with PMS; it also fails to replicate a previous observation of high free T levels in women with PMS. These results are not supportive of a primary endocrine abnormality in PMS patients.

Physiological and psychological effects of testosterone during severe energy deficit and recovery: A study protocol for a randomized, placebo-controlled trial for Optimizing Performance for Soldiers (OPS).

PubMed

Pasiakos, Stefan M; Berryman, Claire E; Karl, J Philip; Lieberman, Harris R; Orr, Jeb S; Margolis, Lee M; Caldwell, John A; Young, Andrew J; Montano, Monty A; Evans, William J; Vartanian, Oshin; Carmichael, Owen T; Gadde, Kishore M; Harris, Melissa; Rood, Jennifer C

2017-07-01

The physiological consequences of severe energy deficit include hypogonadism and the loss of fat-free mass. Prolonged energy deficit also impacts physical performance, mood, attentiveness, and decision-making capabilities. This study will determine whether maintaining a eugonadal state during severe, sustained energy deficit attenuates physiological decrements and maintains mental performance. This study will also assess the effects of normalizing testosterone levels during severe energy deficit and recovery on gut health and appetite regulation. Fifty physically active men will participate in a 3-phase, randomized, placebo-controlled study. After completing a 14-d, energy-adequate, diet acclimation phase (protein: 1.6g∙kg -1 ∙d -1 ; fat: 30% total energy intake), participants will be randomized to undergo a 28-d, 55% energy deficit phase with (DEF+TEST: 200mg testosterone enanthate per week) or without (DEF) exogenous testosterone. Diet and physical activity will be rigorously controlled. Recovery from the energy deficit (ad libitum diet, no testosterone) will be assessed until body mass has been recovered within ±2.5% of initial body mass. Body composition, stable isotope methodologies, proteomics, muscle biopsies, whole-room calorimetry, molecular biology, activity/sleep monitoring, personality and cognitive function assessments, functional MRI, and comprehensive biochemistries will be used to assess physiological and psychological responses to energy restriction and recovery feeding while volunteers are in an expected hypogonadal versus eugonadal state. The Optimizing Performance for Soldiers (OPS) study aims to determine whether preventing hypogonadism will mitigate declines in physical and mental function that typically occur during prolonged energy deficit, and the efficacy of testosterone replacement on recovery from severe underfeeding. NCT02734238. Copyright © 2017. Published by Elsevier Inc.

On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

PubMed

Etelälahti, T J; Eriksson, C J P

2013-11-01

Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction. © 2013.

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.

Ovarian hilus-cell hyperplasia and high serum testosterone in a patient with postmenopausal virilization.

PubMed

Delibasi, Tuncay; Erdogan, Murat F; Serinsöz, Ebru; Kaygusuz, Gulsah; Erdogan, Gurbuz; Sertçelik, Ayse

2007-09-01

To describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia. We present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature. A 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient's plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum. In the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered.

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 ...

Sex steroids and personality traits in the middle luteal phase of healthy normally menstruating young professional women.

PubMed

Avgoustinaki, Pavlina D; Mitsopoulou, Effrosyni; Chlouverakis, Gregorios; Triantafillou, Theoni; Venihaki, Maria; Koukouli, Sofia; Margioris, Andrew N

2012-01-01

Sex steroids affect human behavior. The aim of the present study was to determine the associations, if any, between the circulating levels of gonadal and adrenal sex steroids in the mid luteal phase (21st day of a normal menstrual cycle, MC) of young professional women and psychometric parameters as assessed by the Minnesota Multiphasic Personality Inventory (MMPI). Our results are as follows: (a) The metabolic product of activated adrenal and gonadal androgens, 3alpha-diolG, was modestly but significantly associated with the social introversion scale (10-SI) (r=0.36, p<0.05), independently accounting for 13% of its variation across participants (R²=0.13, F(1,45)=6.58, p=0.014). (b) Total testosterone was significantly associated with the paranoia scale (6-Pa) (r=0.27, p<0.05). Multiple regression analyses indicated that 10% of the variability in paranoia scores could be independently explained by total testosterone levels (R²=0.10, F(1,57)=6.23, p=0.016). We were unable to find any association between the circulating androgens and scores on the masculinity-femininity scale (Mf). We were also unable to document any association between the weak adrenal androgens DHEA and DHEA-S and depression in contrast to several published reports. (c) Our data suggest a marginally significant association between progesterone and scores on the 7-Pt (obsessive/compulsive/psychasthenia) scale (r=0.27, p<0.05). However, only 7% of the 7-Pt variance was explained by progesterone (R²=0.071, F(1,50)=3.81, p=0.057). We have found that total testosterone was associated with the paranoia score, the metabolic product of activated androgens, 3alpha-diolG, to social introversion and, finally, progesterone to obsessive-compulsive behavior.

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.

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

Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

PubMed

Somali, Maria; Mpatakoias, Vassilios; Avramides, Avraam; Sakellari, Ioanna; Kaloyannidis, Panayotis; Smias, Christos; Anagnostopoulos, Achilleas; Kourtis, Anargyros; Rousso, David; Panidis, Dimitrios; Vagenakis, Apostolos

2005-07-01

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

Chorionic morphine, naltrexone and pentoxifylline effect on hypophyso-gonadal hormones of male rats.

PubMed

Moradi, M; Mahmoodi, M; Raoofi, A; Ghanbari, A

2015-01-01

Knowledge about harmful effects of morphine on hormone secretion seems to be necessary. The aim of the present study was to evaluate the effect of pentoxifylline on side effects derived by morphine on hypophyso-gonadal hormones of male rats. 32 male rats were divided into the 4 groups of OSS: control (received 40 g Sucrose/l drinking water and intraperitoneal injection of 1 l/kg normal saline), OMS: morphine group (received 0.4 mg/l + 40 g Sucrose/l in drinking water and intraperitoneal injection of 1 l/kg normal saline), NMS: morphine+naltrexane group (received 0.4 mg/l + 40 g Sucrose/l in drinking water and IP injection dose of 10 mg/kg/ml/day Naltrexane) and PMS: morphine + pentoxifylline group (received 0.4 mg/dl + 40 g Sucrose/l in drinking water and IP injection dose of 12 mg/kg/ml/day Pentoxifylline) for 56 days, respectively. Serum levels of testosterone, LH, FSH hormones were measured. Pentoxifylline increased serum levels of testosterone, LH, FSH hormones compared to control, morphine and morphine-naltrexane groups. Pentoxifylline has a significant efficacy for increasing serum levels of sexual hormones. Considering that Pentoxifylline is safe and cheap, with easy application, we suggest for the usage of this drug for improving semen parameter's quality before performing ART for the treatment of morphine addicts (Fig. 1, Ref. 31).

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

Testosterone supplementation, glucocorticoid milieu and bone homeostasis in the ageing male.

PubMed

Ajdžanović, Vladimir Z; Filipović, Branko R; Šošić Jurjević, Branka T; Milošević, Verica Lj

2017-08-01

Male ageing is entwined with a continuous fall in free testosterone levels, which contributes to the pathogenesis of bone loss. Glucocorticoid excess, either dependent on the ageing process or iatrogenically induced, was found to additionally impair the bone structure and metabolism. Cautious testosterone supplementation in this respect may positively affect the glucocorticoid milieu and bone homeostasis, while testosterone-induced changes in the glucocorticoid output could serve as a determinant of bone-related therapeutic outcome. Namely, bone mineral content/density, the parameters of trabecular bone structure as well as bone strength are enhanced, serum calcitonin levels tend to increase, while serum osteocalcin, serum parathyroid hormone and urinary calcium decrease, all upon testosterone administration to the ageing male. In parallel, testosterone application decreases glucocorticoid secretion in the animal models of male ageing, while clinical data in this field are still inconsistent. Importantly, a physiological link exists between testosterone-induced changes in glucocorticoid levels and the tendency of bone status improvement in the ageing male. We believe that the assessment of circulating adrenocorticotropic hormone concentrations together with glucocorticoid levels, reflecting the hypothalamic-pituitary-adrenal axis feedback loop operativeness during testosterone supplementation, represents a well-balanced bone-related therapeutic update. © 2017 Société Française de Pharmacologie et de Thérapeutique.

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.

TESTOSTERONE AND SPORT: CURRENT PERSPECTIVES

PubMed Central

Wood, Ruth I.; Stanton, Steven J.

2011-01-01

Testosterone and other anabolic-androgenic steroids enhance athletic performance in men and women. As a result, exogenous androgen is banned from most competitive sports. However, due to variability in endogenous secretion, and similarities with exogenous testosterone, it has been challenging to establish allowable limits for testosterone in competition. Endogenous androgen production is dynamically regulated by both exercise and winning in competition. Furthermore, testosterone may promote athletic performance, not only through its long-term anabolic actions, but also through rapid effects on behavior. In women, excess production of endogenous testosterone due to inborn disorders of sexual development (DSD) may convey a competitive advantage. For many years, female competitors have been subject to tests of sexual genotype and phenotype known as gender verification. Although gender verification has not identified any normal man competing as a woman, this process has identified women athletes with DSD. As understanding of DSD has expanded in recent years, women with DSD are increasingly able to continue athletic competition. PMID:21983229

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.

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.

Growth, sexual and bone development in a boy with bilateral anorchia under testosterone treatment guided by the development of his monozygotic twin.

PubMed

Vandewalle, Sara; Van Caenegem, Eva; Craen, Margarita; Taes, Youri; Kaufman, Jean-Marc; T'Sjoen, Guy

2018-03-28

Sex steroids are essential for sexual maturation, linear growth and bone development. However, there is no consensus on the optimal timing, dosage and dosage interval of testosterone therapy to induce pubertal development and achieve a normal adult height and bone mass in children with hypogonadism. A monozygotic monochorial male twin pair, of which one boy was diagnosed with anorchia at birth due to testicular regression syndrome was followed from the age of 3 until the age of 18 years. Low dose testosterone substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected twin based on the start of pubertal development in the healthy twin and then gradually increased accordingly. Both boys were followed until age 18 and were compared as regards to linear growth, sexual maturation, bone maturation and bone development. Before puberty induction both boys had a similar weight and height. During puberty, a slightly faster weight and height gain was observed in the affected twin. Both boys ended up however, with a similar and normal (near) adult height and weight and experienced a normal development of secondary sex characteristics. At the age of 17 and 18 years, bone mineral density, body composition and volumetric bone parameters at the forearm and calf were evaluated in both boys. The affected boy had a higher lean mass and muscle cross-sectional area. The bone mineral density at the lumbar spine and whole body was similar. Trabecular and cortical volumetric bone parameters were comparable. At one cortical site (proximal radius), however, the affected twin had a smaller periosteal and endosteal circumference with a thicker cortex. In conclusion, a low dose testosterone substitution in bilateral anorchia led to a normal onset of pubertal development and (near) adult height. Furthermore, there was no difference in bone mineral density at the age of 17 and 18 years.

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

Quality of life, self-esteem, fatigue, and sexual function in young men after cancer: a controlled cross-sectional study.

PubMed

Greenfield, Diana M; Walters, Stephen J; Coleman, Robert E; Hancock, Barry W; Snowden, John A; Shalet, Stephen M; DeRogatis, Leonard R; Ross, Richard J M

2010-03-15

Androgen deficiency is increasingly recognized in young male cancer survivors; however, its impact on quality of life (QOL) is not established. The authors investigated the relationship between androgen levels, QOL, self-esteem, fatigue, and sexual function in young male cancer survivors compared with control subjects. A cross-sectional, observational study of 176 male cancer survivors and 213 male controls aged 25 to 45 years was performed. Subjects completed 3 QOL scales (Medical Outcomes Study 36-Item Short-Form Health Survey version 2, the 12-item General Health Questionnaire [GHQ-12], and Aging Male Scale), and measures of self-esteem (Rosenberg Self-Esteem Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and sexual function (Derogatis Interview for Sexual Functioning-II Self-Report-Male). Cancer survivors had lower scores for all components of the Short-Form Health Survey, Aging Male Scale, and Functional Assessment of Chronic Illness Therapy-Fatigue, and for 4 of 5 subsections of the Derogatis Interview for Sexual Functioning than controls. The majority of these differences remained after adjusting by linear regression analysis. Levels of psychiatric disorder or self-esteem did not differ between the 2 groups. In cancer survivors, those with androgen deficiency (serum testosterone < or = 10 nmol/L) had lower scores than those without for all components of the Short-Form Health Survey, the General Health Questionnaire, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Derogatis Interview for Sexual Functioning. Serum testosterone only weakly correlated with health measures. Young male cancer survivors self-report a marked impairment in QOL, energy levels, and quality of sexual functioning, and this was exacerbated in those with androgen deficiency. However, psychological distress was not elevated, self-esteem was normal, and sexual relationships were not impaired. The relationship with testosterone is complex, and appears dependent on a threshold level rather than direct correlation. Interventional trials are needed to determine whether testosterone replacement would improve QOL in young male cancer survivors.

The effect of Eurycoma longifolia on sperm quality of male rats.

PubMed

Chan, Kit-Lam; Low, Bin-Seng; Teh, Chin-Hoe; Das, Prashanta K

2009-10-01

The present study investigated the effects of a standardized methanol extract of E. longifolia Jack containing the major quassinoid constituents of 13alpha(21)-epoxyeurycomanone (1), eurycomanone (2), 13alpha,21-dihydroeurycomanone (3) and eurycomanol (4) on the epididymal spermatozoa profile of normal and Andrographis paniculata induced infertile rats. The standardized MeOH extract at doses of 50, 100 and 200 mg/kg, the EtOAc fraction (70 mg/kg), and standardized MeOH extract at 200 mg/kg co-administered with the EtOAc fraction of A. paniculata at 70 mg/kg were each given orally to male Sprague-Dawley albino rats for 48 consecutive days. The spermatozoa count, morphology, motility, plasma testosterone level and Leydig cell count of the animals were statistically analyzed by ANOVA with a post-hoc Tukey HSD test. The results showed that the sperm count of rats given the standardized MeOH extract alone at doses of 50, 100 and 200 mg/kg were increased by 78.9, 94.3 and 99.2%, respectively when compared with that of control (p < 0.01). The low count, poor motility and abnormal morphology of the spermatozoa induced by the A. paniculata fraction were significantly reversed by the standardized MeOH extract of E. longifolia (p < 0.001). The plasma testosterone level of the rats treated with the standardized MeOH extract at 200 mg/kg was significantly increased (p < 0.01) when compared with that of the control and infertile animals. The spermatocytes in the seminiferous tubules and the Leydig cells appeared normal. Testosterone level was significantly higher in the testes (p < 0.01) than in the plasma after 30 days of oral treatment with the standardized MeOH extract. Interestingly, eurycomanone (2) alone was detected in the rat testis homogenates by HPLC-UV and confirmed by LC/MS, and may have contributed towards the improvement of sperm quality. Thus, the plant may potentially be suitable for the management of male infertility.

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.

Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer.

PubMed

Weickhardt, Andrew J; Rothman, Micol S; Salian-Mehta, Smita; Kiseljak-Vassiliades, Katja; Oton, Ana B; Doebele, Robert C; Wierman, Margaret E; Camidge, D Ross

2012-11-01

The objective of this study was to document the differences in testosterone (T) levels between crizotinib-treated and noncrizotinib-treated patients with metastatic nonsmall cell lung cancer (NSCLC). Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib. Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate. Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment. Total T levels were low (<241 ng/dL) in 19 of 19 (100%) crizotinib-treated men and in 6 of 19 men (32%) with metastatic NSCLC who did not receive crizotinib (mean T levels, 131 ng/dL and 311 ng/dL, respectively; P = .0002). Only 1 in 5 patients who had anaplastic lymphoma kinase (ALK) gene rearrangements and had not yet received crizotinib had low T. The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21 days. Discontinuation of crizotinib led to increases back to normal T levels. Crizotinib therapy caused rapid suppression of T levels in men. The current results indicated that the site of action must include a central (hypothalamic or pituitary) effect, but additional direct testicular effects could not be excluded. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity. Copyright © 2012 American Cancer Society.

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

Potashnik, G.; Yanai-Inbar, I.

The current study summarizes an 8-year reassessment of testicular function and reproductive performance in 15 workers with dibromochloropropane (DBCP)-induced azoospermia and oligozoospermia. Recovery of spermatogenesis was observed in four oligozoospermic and three azoospermic men whose plasma follicle-stimulating hormone (FSH) concentration was normal during the whole period. A marked increase in FSH and luteinizing hormone concentrations above the upper limit of normal was found in the azoospermic workers who did not recover. No significant changes in FSH concentrations were detected in both recovered and nonrecovered oligozoospermic men. Testosterone levels of all patients were normal at all times. Paternal exposure to DBCPmore » was not associated with increased risk of fetal malformations or spontaneous abortion.« less

Endothelin and sex hormones modulate the fibronectin synthesis by cultured human skin scleroderma fibroblasts

PubMed Central

Soldano, S; Montagna, P; Villaggio, B; Parodi, A; Gianotti, G; Sulli, A; Seriolo, B; Secchi, M E; Cutolo, M

2009-01-01

Objective: To evaluate the influence of endothelin-1 (ET-1) and sex hormones on cell proliferation and extracellular matrix (ECM) synthesis (ie, fibronectin, laminin) by cultured normal and scleroderma (SSc) human skin fibroblasts (FBs). Methods: Primary cultures of FBs were treated with ET-1 and sex hormones (17β-oestradiol or testosterone) for 24 h. Cell growth was analysed by methiltetrazolium salt test, ECM synthesis was evaluated by immunocytochemistry and western blot, both at 24 h. Results: In normal FBs, ET-1 and 17β-oestradiol, as well as their combination, increased cell growth (p<0.001, p<0.001, p<0.01 vs untreated cells (control), respectively) and fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). By contrast, testosterone either alone or in combination with ET-1 did not influence cell proliferation, but decreased fibronectin synthesis (p<0.05, testosterone vs control). In SSc FBs, ET-1 and 17β-oestradiol alone or their combination induced an increased fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). Unexpectedly, testosterone induced an increase of fibronectin synthesis (p<0.05 vs control). Conclusions: ET-1 and 17β-oestradiol seem to exert a profibrotic effect in normal and SSc culture FBs and might suggest their synergistic effect in the pathogenesis of the fibrotic process in SSc. PMID:18952637

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.

Correlation between benzene and testosterone in workers exposed to urban pollution.

PubMed

Rosati, M V; Sancini, A; Tomei, F; Sacco, C; Traversini, V; De Vita, A; De Cesare, D P; Giammichele, G; De Marco, F; Pagliara, F; Massoni, F; Ricci, L; Tomei, G; Ricci, S

2017-01-01

Many studies have examined the effects of benzene on testosterone. The purpose of this study was to evaluate the possible correlation between the blood levels of benzene and the levels of testosterone. The study involved a group of 148 subjects. For every worker have been made out a blood sample for the evaluation of benzene and testosterone levels and an urine analysis for the evaluation of the levels of trans, trans-muconic acid and S-phenylmercapturic acid. We estimated the Pearson correlation coefficient between the variables in the sample and the urinary metabolites, age, length of service, gender, BMI. For the analysis of the major confounding factors it was performed a multiple linear regression. The Pearson correlation coefficiet showed: 1. a significant inverse correlation between the S-phenyl mercapturic acid and free testosterone; 2. a significant direct correlation between trans-trans muconic acid and BMI. After dividing the sample according to the median of blood benzene (161.0 ng / L), Pearson correlation coefficient showed a significant inverse correlation between the S-phenyl mercapturic acid and free testosterone in the group with values below this median. Our results, to be considered preliminary, suggest that occupational exposure to low levels of benzene, present in urban pollution, affect the blood levels of testosterone. These results need to be confirmed in future studies, with the eventual possibility of including more specific fertility tests.

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.

Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice.

PubMed

Jalili, Cyrus; Salahshoor, Mohammad Reza; Naseri, Ali

2014-06-01

Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. In this study, hydro-alcoholic extract of U.dioica was prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56 male mice for 28 consequent days. These mice were randomly assigned to 8 groups (n=7) and sperm parameters (sperm cells viability, count, motility, and morphology), testis and prostate weight, testis histology and testosterone hormone were analyzed and compared. The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperm cells, and testis weight compared to control group (p=0.00). However, increasing the dose of U.dioica significantly boosted motility, count, normal morphology of sperm cells, seminiferous tubules diameter, and testosterone in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg doses in comparison with control group (p=0.00). It seems that U.dioica hydro-alcoholic extract administration could increase the quality of spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters.

Protective effect of Urtica dioica L against nicotine-induced damage on sperm parameters, testosterone and testis tissue in mice

PubMed Central

Jalili, Cyrus; Salahshoor, Mohammad Reza; Naseri, Ali

2014-01-01

Background: Nicotine consumption can decrease fertility drive in males by inducing oxidative stress and DNA damage. Urtica dioica L (U.dioica) is a multipurpose herb in traditional medicine for which some anti-oxidative and anti-inflammatory properties have been identified. Objective: The main goal is to investigate whether the U.dioica could inhibit nicotine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone. Materials and Methods: In this study, hydro-alcoholic extract of U.dioica was prepared and various doses of U.dioica (0, 10, 20, and 50 mg/kg) and U.dioica plus nicotine (0, 10, 20, and 50 mg/kg) were administered intraperitoneally to 56 male mice for 28 consequent days. These mice were randomly assigned to 8 groups (n=7) and sperm parameters (sperm cells viability, count, motility, and morphology), testis and prostate weight, testis histology and testosterone hormone were analyzed and compared. Results: The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperm cells, and testis weight compared to control group (p=0.00). However, increasing the dose of U.dioica significantly boosted motility, count, normal morphology of sperm cells, seminiferous tubules diameter, and testosterone in all groups compared to control (p=0.00) and testis weight in 20 and 50 mg/kg doses in comparison with control group (p=0.00). Conclusion: It seems that U.dioica hydro-alcoholic extract administration could increase the quality of spermatozoa and inhibits nicotine-induced adverse effects on sperm parameters. PMID:25071848

Longitudinal changes in bone-testis axis and their associations with insulin resistance in 11- to 12-year-old boys.

PubMed

Jürimäe, Jaak; Lätt, Evelin; Remmel, Liina; Purge, Priit; Tillmann, Vallo

2018-03-01

Associations between osteocalcin (OCN), an osteoblast-specific hormone, and different markers of energy metabolism and insulin resistance have been reported in adults, but few studies have investigated this in children. The aim of the current study was to investigate serum OCN levels during pubertal development in normal weight (NW) and overweight (OW) boys, and to evaluate possible associations of OCN with body composition, testosterone, insulin resistance and adipocytokine values during puberty. Ninety 11- to 12-year-old boys were investigated at 12-month intervals over the next 2years. Boys were divided by their BMI into NW (n=60) and OW (n=30) groups. Serum OCN, testosterone, leptin, adiponectin, insulin, HOMA-IR score, and body composition were measured. Pubertal development over the 2-year period was similar in both groups. Serum OCN was not different at the beginning of the study and increased similarly in both groups. However, at the end of the study, NW had higher OCN than OW (142.9±5.2 vs. 124.0±7.4ng/ml; p<0.05). OW had higher leptin, insulin and HOMA-IR compared to NW, and these differences remained significant through the 2-year period. Testosterone, insulin and HOMA-IR increased through the study period in both groups. In multiple regression analyses increment in OCN was associated with the increase in testosterone in NW (p<0.001) and OW (p=0.049) boys. Increment in OCN was also associated with the increase in insulin (p=0.019) and HOMA-IR (p=0.012) over the 2-year period in NW boys. Serum OCN concentration increases in puberty and the increment is positively associated with the rise in testosterone level in both NW and OW boys. The positive association between the rise in OCN and insulin in NW boys would suggest that OCN may have a role in the development of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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

Androstenedione and testosterone biosynthesis by the adrenal cortex of the horse

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

Silberzahn, P.; Rashed, F.; Zwain, I.

1984-02-01

An homogenate from cortical tissue of mare adrenals was incubated in the presence of tritiated pregnenolone. The (/sup 3/H) androstenedione and the (/sup 3/H) testosterone synthesized during the incubation were extracted, purified, and co-crystallized to constant specific activity in the presence of unlabeled carriers. The rate of conversion of pregnenolone to androstenedione and testosterone was of the order of 5 and 0.15 per cent respectively. The high ratio of (/sup 3/H) androstenedione to (/sup 3/H) testosterone observed in this study suggests that androstenedione is the main androgen produced by mare adrenals. It is concluded that adrenals could contribute to themore » production of blood androgens in normal as well as hyperandrogenic mares.« less

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

Testosterone during pregnancy and gender role behavior of preschool children: a longitudinal, population study.

PubMed

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

2002-01-01

Levels of testosterone (T) and sex hormone-binding globulin (SHBG) were measured in blood samples from pregnant women and related to gender role behavior in 342 male and 337 female offspring at the age of 3.5 years. Gender role behavior was assessed using the Pre-School Activities Inventory, a standardized measure on which a parent indicates the child's involvement with sex-typical toys, games, and activities. Levels of T, but not SHBG, related linearly to gender role behavior in preschool girls. Neither hormone related to gender role behavior in boys. Other factors, including the presence of older brothers or sisters in the home, parental adherence to traditional sex roles, the presence of a male partner in the home, and maternal education, did not relate to gender role behavior in this sample and did not account for the relation observed between T and behavior. Although other, unmeasured factors may explain the relation, the results suggest that normal variability in T levels prenatally may contribute to the development of individual differences in the gender role behavior of preschool girls.

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.

Nestin in the epididymis is expressed in vascular wall cells and is regulated during postnatal development and in case of testosterone deficiency.

PubMed

Reckmann, Ansgar N; Tomczyk, Claudia U M; Davidoff, Michail S; Michurina, Tatyana V; Arnhold, Stefan; Müller, Dieter; Mietens, Andrea; Middendorff, Ralf

2018-01-01

Vascular smooth muscle cells (SMCs), distinguished by the expression of the neuronal stem cell marker nestin, may represent stem cell-like progenitor cells in various organs including the testis. We investigated epididymal tissues of adult nestin-GFP mice, rats after Leydig cell depletion via ethane dimethane sulfonate (EDS), rats and mice during postnatal development and human tissues. By use of Clarity, a histochemical method to illustrate a three-dimensional picture, we could demonstrate nestin-GFP positive cells within the vascular network. We localized nestin in the epididymis in proliferating vascular SMCs by colocalization with both smooth muscle actin and PCNA, and it was distinct from CD31-positive endothelial cells. The same nestin localization was found in the human epididymis. However, nestin was not found in SMCs of the epididymal duct. Nestin expression is high during postnatal development of mouse and rat and down-regulated towards adulthood when testosterone levels increase. Nestin increases dramatically in rats after Leydig cell ablation with EDS and subsequently low testosterone levels. Interestingly, during this period, the expression of androgen receptor in the epididymis is low and increases until nestin reaches normal levels of adulthood. Here we show that nestin, a common marker for neuronal stem cells, is also expressed in the vasculature of the epididymis. Our results give new insights into the yet underestimated role of proliferating nestin-expressing vascular SMCs during postnatal development and repair of the epididymis.

Anti-Müllerian hormone: correlation with testosterone and oligo- or amenorrhoea in female adolescence in a population-based cohort study

PubMed Central

Pinola, P.; Morin-Papunen, L.C.; Bloigu, A.; Puukka, K.; Ruokonen, A.; Järvelin, M.-R.; Franks, S.; Tapanainen, J.S.; Lashen, H.

2014-01-01

STUDY QUESTIONS Can serum anti-Müllerian hormone (AMH) levels measured in female adolescents predict polycystic ovary syndrome (PCOS)-associated features in adolescence and early adulthood? SUMMARY ANSWER AMH levels associated well with PCOS-associated features (such as testosterone levels and oligoamenorrhoea) in adolescence, but was not an ideal marker to predict PCOS-associated features in early adulthood. WHAT IS KNOWN ALREADY Several studies have reported that there is a strong correlation between antral follicle count and serum AMH levels and that women with PCOS/PCO have significantly higher serum AMH levels than women with normal ovaries. Other studies have reported an association between AMH serum levels and hyperandrogenism in adolescence, but none has prospectively assessed AMH as a risk predictor for developing features of PCOS during adulthood. STUDY DESIGN, SIZE, DURATION A subset of 400 girls was selected from the prospective population-based Northern Finland Birth Cohort 1986 (n = 4567 at age 16 and n = 4503 at age 26). The population has been followed from 1986 to the present. PARTICIPANTS/MATERIAL, SETTING, METHODS At age 16, 400 girls (100 from each testosterone quartile: 50 with oligo- or amenorrhoea and 50 with a normal menstrual cycle) were selected at random from the cohort for AMH measurement. Metabolic parameters were also assessed at age 16 in all participants. Postal questionnaires enquired about oligo- or amenorrhoea, hirsutism, contraceptive use and reproductive health at ages 16 and 26. MAIN RESULTS AND ROLE OF CHANCE There was a significant correlation between AMH and testosterone at age 16 (r = 0.36, P < 0.001). AMH levels at age 16 were significantly higher among girls with oligo- or amenorrhoea compared with girls with normal menstrual cycles (35.9 pmol/l [95% CI: 33.2;38.6] versus 27.7 pmol/l [95% CI: 25.0;30.4], P < 0.001). AMH at age 16 was higher in girls who developed hirsutism at age 26 compared with the non-hirsute group (31.4 pmol/l [95% CI 27.1;36.5] versus 25.8 pmol/l [95% CI 23.3;28.6], P = 0.036). AMH at age 16 was also higher in women with PCOS at age 26 compared with the non-PCOS subjects (38.1 pmol/l [95% CI 29.1;48.4] versus 30.2 pmol/l [95% CI 27.9;32.4], P = 0.044). The sensitivity and specificity of the AMH (cut-off 22.5 pmol/l) for predicting PCOS at age 26 was 85.7 and 37.5%, respectively. The addition of testosterone did not significantly improve the accuracy of the test. There was no significant correlation between AMH levels and metabolic indices at age 16. IMPLICATIONS, REASONS FOR CAUTION AMH is related to oligo- or amenorrhoea in adolescence, but it is not a good marker for metabolic factors. The relatively low rate of participation in the questionnaire at age 26 may also have affected the results. AMH was measured in a subset of the whole cohort. AMH measurement is lacking international standardization and therefore the concentrations and cut-off points are method dependent. WIDER IMPLICATIONS FOR THE FINDINGS Using a high enough cut-off value of AMH to predict which adolescents are likely to develop PCOS in adulthood could help to manage the condition from an early age due to a good sensitivity. However, because of its low specificity, it is not an ideal diagnostic marker, and its routine use in clinical practice cannot, at present, be recommended. STUDY FUNDINGS AND COMPETING INTERESTS The study was funded by a grant from Wellcome Trust (089549/Z/09/Z) to H.L., S.F. and M.-R.J. Study funding was also received from Oulu University Hospital Research Funds, Sigrid Juselius Foundation and the Academy of Finland. None of the authors have any competing interest to declare. PMID:25056088

Fulfilling Desire: Evidence for negative feedback between men’s testosterone, sociosexual psychology, and sexual partner number

PubMed Central

Puts, David A.; Pope, Lauramarie E.; Hill, Alexander K.; Cárdenas, Rodrigo A.; Welling, Lisa L. M.; Wheatley, John R.; Breedlove, S. Marc

2015-01-01

Across human societies and many nonhuman animals, males have greater interest in uncommitted sex (more unrestricted sociosexuality) than do females. Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology (attitudes and desires) is mediated by testosterone, whether any relationships between testosterone and sociosexuality differ between men and women, and what the nature of these possible relationships might be. In studies to resolve these questions, we examined relationships between salivary testosterone concentrations and sociosexual psychology and behavior in men and women. We measured testosterone in all men in our sample, but only in those women taking oral contraception (OC-using women) in order to reduce the influence of ovulatory cycle variation in ovarian hormone production. We found that OC-using women did not differ from normally-ovulating women in sociosexual psychology or behavior, but that circulating testosterone mediated the sex difference in human sociosexuality and predicted sociosexual psychology in men but not OC-using women. Moreover, when sociosexual psychology was controlled, men’s sociosexual behavior (number of sexual partners) was negatively related to testosterone, suggesting that testosterone drives sociosexual psychology in men and is inhibited when those desires are fulfilled. This more complex relationship between androgen and male sexuality may reconcile some conflicting prior reports. PMID:25644313

Fulfilling desire: evidence for negative feedback between men's testosterone, sociosexual psychology, and sexual partner number.

PubMed

Puts, David A; Pope, Lauramarie E; Hill, Alexander K; Cárdenas, Rodrigo A; Welling, Lisa L M; Wheatley, John R; Marc Breedlove, S

2015-04-01

Across human societies and many nonhuman animals, males have greater interest in uncommitted sex (more unrestricted sociosexuality) than do females. Testosterone shows positive associations with male-typical sociosexual behavior in nonhuman animals. Yet, it remains unclear whether the human sex difference in sociosexual psychology (attitudes and desires) is mediated by testosterone, whether any relationships between testosterone and sociosexuality differ between men and women, and what the nature of these possible relationships might be. In studies to resolve these questions, we examined relationships between salivary testosterone concentrations and sociosexual psychology and behavior in men and women. We measured testosterone in all men in our sample, but only in those women taking oral contraception (OC-using women) in order to reduce the influence of ovulatory cycle variation in ovarian hormone production. We found that OC-using women did not differ from normally-ovulating women in sociosexual psychology or behavior, but that circulating testosterone mediated the sex difference in human sociosexuality and predicted sociosexual psychology in men but not OC-using women. Moreover, when sociosexual psychology was controlled, men's sociosexual behavior (number of sexual partners) was negatively related to testosterone, suggesting that testosterone drives sociosexual psychology in men and is inhibited when those desires are fulfilled. This more complex relationship between androgens and male sexuality may reconcile some conflicting prior reports. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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.

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.

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

Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

DTIC Science & Technology

2007-06-01

When you eat fried or baked pork or beef , you normally prefer that: Entire surface is brown with a slight burnt flavor 1...Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) is involved in catalyzing estrogen, the hormone that plays a central role in the etiology of...relationship of UGT1A1 genotypes with plasma levels of estrone, estrone sulfate, estradiol, testosterone, and sex hormone binding globulins (SHBG

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

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.

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.

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

Menstrual cycle-related changes in circulating androgens in healthy women with self-reported normal sexual function.

PubMed

Salonia, Andrea; Pontillo, Marina; Nappi, Rossella E; Zanni, Giuseppe; Fabbri, Fabio; Scavini, Marina; Daverio, Rita; Gallina, Andrea; Rigatti, Patrizio; Bosi, Emanuele; Bonini, Pier Angelo; Montorsi, Francesco

2008-04-01

There is currently neither a clinically useful, reliable and inexpensive assay to measure circulating levels of free testosterone (T) in the range observed in women, nor is there agreement on the serum free T threshold defining hypoandrogenism that is associated with female-impaired sexual function. Following the Clinical and Laboratory Standards Institute guidelines, we generated clinically applicable ranges for circulating androgens during specific phases of the menstrual cycle in a convenience sample of 120 reproductive-aged, regularly cycling healthy European Caucasian women with self-reported normal sexual function. All participants were asked to complete a semistructured interview and fill out a set of validated questionnaires, including the Female Sexual Function Index, the Female Sexual Distress Scale, and the 21-item Beck's Inventory for Depression. Between 8 am and 10 am, a venous blood sample was drawn from each participant during the midfollicular (day 5 to 8), the ovulatory (day 13 to 15), and the midluteal phase (day 19 to 22) of the same menstrual cycle. Serum levels of total and free testosterone, Delta(4)-androstenedione, dehydroepiandrosterone sulphate and sex hormone-binding globulin during the midfollicular, ovulatory and midluteal phase of the same menstrual cycle. Total and free T levels showed significant fluctuations, peaking during the ovulatory phase. No significant variation during the menstrual cycle were observed for Delta(4)-androstenedione and dehydroepiandrosterone sulphate. Despite the careful selection of participants that yielded an homogeneous group of women without sexual disorders, we observed a wide range of distribution for each of the circulating androgens measured in this study. This report provides clinically applicable ranges for androgens throughout the menstrual cycle in reproductive-aged, regularly cycling, young healthy Caucasian European women with self-reported normal sexual function.

Hormonal profile impact on female sexual function in young women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Craina, Marius; Pater, Liana; Pater, Flavius

2014-12-01

Female sexual function is dependent, in physiological milieu upon hormonal impulses: estradiol, testosterone, cortisol, progesterone, prolactin and TSH. Out study tries to appreciate the impact of testosterone, estradiol and prolactin, the major hormones involved in the sexual response, on the normal sexual function. This parameter is approximated by the value of the total FSFI score, a validated international structured interview.

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

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.

Prolonged hypogonadism in males following withdrawal from anabolic-androgenic steroids: an under-recognized problem.

PubMed

Kanayama, Gen; Hudson, James I; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G

2015-05-01

To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Cross-sectional, naturalistic. Out-patient facility. Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiological testosterone replacement, leaving 19 untreated users for the numerical comparisons below. The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations and the International Index of Erectile Function (IIEF). Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes [estimated difference, 95% confidence interval (CI) = 2.3 (0.1, 4.5) ml; P = 0.042] and lower serum testosterone levels [estimated difference: 95% CI = 131 (25, 227) dl; P = 0.009], with five users showing testosterone levels below 200 ng/dl despite abstinence from AAS for 3-26 months. Untreated former users also displayed significantly lower scores on the IIEF sexual desire subscale [estimated difference: 95% CI = 2.4 (1.3, 3.4) points on a 10-point scale; P < 0.001]. In the overall group of 24 treated plus untreated former users, seven (29%) had experienced major depressive episodes during AAS withdrawal; four of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged and associated with substantial morbidity. © 2015 Society for the Study of Addiction.

Prolonged Hypogonadism in Males Following Withdrawal from Anabolic-Androgenic Steroids: an Underrecognized Problem

PubMed Central

Kanayama, Gen; Hudson, James I.; DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory; Bhasin, Shalender; Pope, Harrison G.

2015-01-01

Aims To assess the frequency and severity of hypogonadal symptoms in male long-term anabolic-androgenic steroid (AAS) misusers who have discontinued AAS use. Design Cross-sectional, naturalistic. Setting Outpatient facility. Participants Twenty-four male former long-term AAS users and 36 non-AAS-using weightlifters, recruited by advertisement in Massachusetts, USA. Five of the former users were currently receiving treatment with physiologic testosterone replacement, leaving 19 untreated users for the numerical comparisons below. Measurements The Structured Clinical Interview for DSM-IV, questions regarding history of AAS use, physical examination, serum hormone determinations, and the International Index of Erectile Function (IIEF). Findings Compared with the 36 non-AAS-using weightlifters, the 19 untreated former AAS users displayed significantly smaller testicular volumes (estimated difference [95% confidence interval (CI)]: 2.3 [0.1, 4.5] ml; p = 0.042) and lower serum testosterone levels (estimated difference: 131 [25, 227] dL; p = 0.009), with five users showing testosterone levels below 200 ng/dL despite abstinence from AAS for 3–26 months. Untreated former users also displayed significantly lower scores on the IIEF Sexual Desire subscale (estimated difference: 2.4 [1.3, 3.5] points on a 10-point scale; p < 0.001). In the overall group of 24 treated plus untreated former users, 7 (29%) had experienced major depressive episodes during AAS withdrawal; 4 of these had not experienced major depressive episodes at any other time. Two men (8%) had failed to regain normal libidinal or erectile function despite adequate replacement testosterone treatment. Conclusions Among long-term anabolic-androgenic steroid misusers, anabolic-androgenic steroid-withdrawal hypogonadism appears to be common, frequently prolonged, and associated with substantial morbidity. PMID:25598171

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism

PubMed Central

Nord, Christoffer; Ahlgren, Ulf; Eriksson, Maria; Vernersson-Lindahl, Emma; Helland, Åslaug; Alexeyev, Oleg A.; Hallberg, Bengt; Palmer, Ruth H.

2015-01-01

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis. PMID:25955180

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.

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.

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

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 enables growth and hypertrophy in fusion impaired myoblasts that display myotube atrophy: deciphering the role of androgen and IGF-I receptors.

PubMed

Hughes, David C; Stewart, Claire E; Sculthorpe, Nicholas; Dugdale, Hannah F; Yousefian, Farzad; Lewis, Mark P; Sharples, Adam P

2016-06-01

We have previously highlighted the ability of testosterone (T) to improve differentiation and myotube hypertrophy in fusion impaired myoblasts that display reduced myotube hypertrophy via multiple population doublings (PD) versus their parental controls (CON); an observation which is abrogated via PI3K/Akt inhibition (Deane et al. 2013). However, whether the most predominant molecular mechanism responsible for T induced hypertrophy occurs directly via androgen receptor or indirectly via IGF-IR/PI3K/Akt pathway is currently debated. PD and CON C2C12 muscle cells were exposed to low serum conditions in the presence or absence of T (100 nM) ± inhibitors of AR (flutamide/F, 40 μm) and IGF-IR (picropodophyllin/PPP, 150 nM) for 72 h and 7 days (early/late muscle differentiation respectively). T increased AR and Akt abundance, myogenin gene expression, and myotube hypertrophy, but not ERK1/2 activity in both CON and PD cell types. Akt activity was not increased significantly in either cell type with T. Testosterone was also unable to promote early differentiation in the presence of IGF-IR inhibitor (PPP) yet still able to promote appropriate later increases in myotube hypertrophy and AR abundance despite IGF-IR inhibition. The addition of the AR inhibitor powerfully attenuated all T induced increases in differentiation and myotube hypertrophy with corresponding reductions in AR abundance, phosphorylated Akt, ERK1/2 and gene expression of IGF-IR, myoD and myogenin with increases in myostatin mRNA in both cell types. Interestingly, despite basally reduced differentiation and myotube hypertrophy, PD cells showed larger T induced increases in AR abundance vs. CON cells, a response abrogated in the presence of AR but not IGF-IR inhibitors. Furthermore, T induced increases in Akt abundance were sustained despite the presence of IGF-IR inhibition in PD cells only. Importantly, flutamide alone reduced IGF-IR mRNA in both cell types across time points, with an observed reduction in activity of ERK and Akt, suggesting that IGF-IR was transcriptionally regulated by AR. However, where testosterone increased AR protein content there was no increases observed in IGF-IR gene expression. This suggested that sufficient AR was important to enable normal IGF-IR expression and downstream signalling, yet elevated levels of AR due to testosterone had no further effect on IGF-IR mRNA, despite testosterone increasing Akt abundance in the presence of IGF-IR inhibitor. In conclusion, testosterones ability to improve differentiation and myotube hypertrophy occurred predominately via increases in AR and Akt abundance in both CON and PD cells, with fusion impaired cells (PD) showing an increased responsiveness to T induced AR levels. Finally, T induced increases in myotube hypertrophy (but not early differentiation) occurred independently of upstream IGF-IR input, however it was apparent  that normal AR function in basal conditions was required for adequate IGF-IR gene expression and downstream ERK/Akt activity.

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…

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.

Does endothelial dysfunction correlate with endocrinal abnormalities in patients with polycystic ovary syndrome?

PubMed Central

Dube, Rajani

2016-01-01

To study and critically analyze the published evidence on correlation of hormonal abnormalities and endothelial dysfunction (ED) in polycystic ovary syndrome (PCOS) through a systematic review. The databases including MEDLINE, PubMed, Up-To-Date, and Science Direct were searched using Medical subject handling terms and free text term keywords such as endocrine abnormalities in PCOS, ED assessment in PCOS, ED in combination with insulin resistance (IR), hyperandrogenism (HA), increased free testosterone, free androgen index (FAI), gonadotrophin levels, luteinizing hormone (LH), prolactin, estrogen, adipocytokines to search trials, and observational studies published from January 1987 to September 2015. Authors of original studies were contacted for additional data when necessary. PCOS increases the risk of cardiovascular disease in women. ED, which is a reliable indicator of cardiovascular risk in general population, is seen in most (but not all) women with PCOS. IR, seen in 70% patients with PCOS, is associated with ED in these women, but patients can have normal endothelial function even in the presence of IR. Free testosterone and FAI are consistently associated with ED, but endothelial function can be normal despite HA. Estradiol (not estrone) appears to be protective against ED though estrone is the predominant estrogen produced in PCOS. Increased levels of adipocytokines (visfatin) are promising in predicting ED and cardiovascular risk. However, more studies are required focusing on direct correlation of levels of prolactin, LH, estrone, and visfatin with ED in PCOS. PMID:27843797

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.

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.

Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease.

PubMed

Laatikainen, T; Tulenheimo, A; Andersson, B; Kärkkäinen, J

1983-04-01

Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.

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.

Neural activation-based sexual orientation and its correlation with free testosterone level in postoperative female-to-male transsexuals: preliminary study with 3.0-T fMRI.

PubMed

Kim, Gwang-Won; Kim, Seok-Kwun; Jeong, Gwang-Woo

2016-03-01

The purpose of this study was to evaluate the brain activation pattern associated with sexual orientation and its correlation with the level of the free testosterone (free T) in postoperative female-to-male (FtM) transsexuals using a 3.0-Tesla functional magnetic resonance imaging (fMRI). Eleven postoperative FtM transsexuals with sex reassignment surgery underwent fMRI on a 3.0-T MR scanner. Brain activity was measured while viewing erotic male and female nude pictures. The average level of free T in the FtM transsexuals was in the normal range of heterosexual men. The brain areas with predominant activities during viewing female nude pictures in contrast to male pictures included the hippocampus, parahippocampal gyrus, anterior cingulate gyrus, putamen, amygdala, hypothalamus, and insula (p < 0.005). The free T levels were positively correlated with the BOLD signal changes in the parahippocampal gyrus (Spearman's rho = 0.91, p < 0.001), hippocampus (rho = 0.90, p < 0.001), insula (rho = 0.68, p < 0.05), putamen (rho = 0.66, p < 0.05), and amygdala (rho = 0.64, p < 0.05). Compared to FtM transsexuals with deficient level of free T, the FtM transsexuals with normal range of free T showed significantly higher activities in the parahippocampal gyrus, hippocampus, insula, putamen, and amygdala during viewing female nude pictures (p < 0.005). This study revealed the specific brain activation pattern associated with sexual orientation and its correlation with free T in the postoperative FtM transsexuals. These findings are applicable in understanding the neural mechanism on sexual arousal in FtM transsexuals and their sexual orientation in connection with the free T levels.

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.

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

PubMed

Taylor, Frederick; Levine, Laurence

2010-01-01

The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1-2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim 1% (5 gm daily) is $270, Androgel 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

Long-term follow-up of the genital organs and eye lenses in three cases of acute radiation sickness from a 60Co radiation accident in China.

PubMed

Xing, Zhi Wei; Jiang, En Hai; Du, Jian Ying; Zhao, Feng Ling; Fu, Bao Hua; Jiang, Li Ping; Wang, Xiao Guang; Zhao, Xin Ran; Liu, Qiang; Jiang, Bo

2015-01-01

A follow-up study aimed primarily at investigating late radiation effects on the genital organs and eye lenses was performed between 1999 and 2010 on three individuals who suffered from acute radiation sickness in China. The examination included a medical history, a physical examination, ultrasonography, laboratory analysis, and an ophthalmologic examination. In Case 1, amenorrhea occurred after exposure to a Co source. The uterus and ovaries were significantly narrowed in the second year following exposure. The estradiol level decreased significantly during the first 3 y; progesterone was lowest in the second year; and levels of follicle-stimulating hormone and luteinizing hormone increased, especially in the first year. The lenses in both eyes appeared opaque 6 mo after the exposure, resulting in a gradual deterioration in visual acuity. In Case 2 (8 y old), the levels of testosterone and estradiol were normal. In Case 3, the levels of testosterone and estradiol were also normal, but the sperm count was 0 from 6 mo to 1 y, and the proportion of abnormal sperm was increased from 3-5 y after the accident. The lenses in Case 3 also began to turn opaque in the ninth year after the accident. In Case 1, the ovarian function was reduced, leading to amenorrhea and early menopause. In Case 3, the sperm count was reduced and the number of abnormal sperm was increased due to testicular damage by radiation. Radiation-induced cataracts occurred in both Case 1 and Case 3.

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.

Late onset hypogonadism of men is not equivalent to the menopause.

PubMed

Saad, Farid; Gooren, Louis J

2014-09-01

Some men between the ages 45 and 60 years develop complaints and symptoms reminiscent of menopausal complaints in women. So, parallels were sought between the changes in female and male endocrinology during that period of life. Indeed, men do show a decline of serum testosterone from age 40 to 50 years onwards but it is a slow decline of 1-2% per year and over time it may amount to hypogonadism. The mechanism of a decline in serum testosterone in men does not resemble the menopause; it is partially an aging neuroendocrine system with a less efficient testosterone production but equally or more important, the result of inhibition of testosterone production by metabolic factors in relation to visceral obesity. These effects are in part reversible with weight loss. A hypogonadal state in aging men has deleterious effects. Mortality of all causes is highest in men with low testosterone impacting on their metabolic state leading to diabetes mellitus, cardiovascular disease, osteoporosis, and sexual dysfunction. Normalization of testosterone in aging hypogonadal men has a beneficial effect on the above pathologies. The fear that testosterone treatment of elderly men would lead to prostate disease has not been substantiated in studies. So, while men do not have a 'menopause', testosterone deficiency in old age deserves serious attention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

New male contraceptive entering clinical trials worldwide.

PubMed

1989-10-01

250 men are participating in a clinical trial of a reversible male testosterone contraceptive at the University of Washington in Seattle and at 9 other centers in Europe, Asia, and Australia. Clinicians inject the WHO-developed testosterone enanthate (200 mg) into these men once a week. The testosterone contraceptive instructs the pituitary gland to deactivate 2 hormones which normally maintain the testes' function resulting in a temporary stop of spermatogenesis just like the female oral contraceptive instructs the pituitary gland to suppress ovulation. Tests of 5 ejaculates in preliminary trials have indicated that 50-60% of the men experience azoospermia. Investigators are concerned with the possibility that ejaculates during normal intercourse may contain enough sperm to impregnate the partner. An investigator at the University of Washington believes this clinical trial of 250 men will determine whether this is indeed the case. The concern about contraceptive failure is the main problem with contraceptive testosterone. The minor side effects include weight gain which may be due to increased muscle mass and some sodium retention, acne, and possible reduction of libido but that has not yet occurred in the 250 men in the clinical trial. This contraceptive testosterone does not remain active for long periods of time if administered orally. Researchers are now developing a newer form of the contraceptive which will increase the intervals between administrations from 1 week to 3 months. An investigator from Seattle guesses that this male contraceptive will not be available for marketing in the US until at least 1994.

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.

Sexual dichotomy of gonadal function in Prader-Willi syndrome from early infancy through the fourth decade.

PubMed

Hirsch, H J; Eldar-Geva, T; Bennaroch, F; Pollak, Y; Gross-Tsur, V

2015-11-01

At what age does the type of hypogonadism, namely hypothalamic or primary gonadal defect, become established in men and women with Prader-Willi syndrome (PWS)? The type of hypogonadism becomes established only in late adolescence and early adulthood. The etiology of hypogonadism in PWS is heterogeneous and the clinical expression is variable. Primary testicular failure is common in PWS men, while combinations of ovarian dysfunction and gonadotrophin deficiency are seen in women. This is a prospective study of a cohort of 106 PWS patients followed for a mean duration of 4.5 years. Serial blood samples were obtained and assayed for gonadotrophins, inhibin B, anti-Mullerian hormone (AMH), dehydroepiandrosterone sulfate (DHEAS), testosterone (males), and estradiol (females). Results were compared with normal reference values obtained from the literature. For the purpose of this study, we defined the following age groups: infants <1 year; children 1-10 years; adolescents 11-20 years and adults >20 years. Study participants were 49 males (aged 2 months to 36 years) and 57 females (aged 1 month to 37 years) with genetically confirmed diagnoses of PWS (deletions 60, uniparental disomy 54, imprinting center defect 2) followed in the Israel national multidisciplinary PWS clinic. Serum LH levels were in the normal range (1.0-6.0 mIU/ml) for 7/10 adult men, and high in 3, while FSH (normal range 1.0-6.1 mIU/ml) was elevated (34.4 ± 11.5 mIU/ml) in 6 and normal (3.5 ± 1.6 mIU/ml) in 4 men. Testosterone was low (5.7 ± 3.4 nmol/l) compared with the normal range of 12.0-34.5 nmol/l in the reference population in all men >20 years. AMH showed a normal decrease with age, despite low testosterone levels. Inhibin B was normal (241 ± 105 pg/ml) in infant boys, but low or undetectable in most adult men. Hormonal profiles were more heterogeneous in women than in men. Estradiol was consistently detectable in only 7/13 adult women. Inhibin B was low or undetectable in all PWS females although occasional samples showed levels within the normal range of 15-95 pg/ml. Vaginal bleeding was reported to occur for the first time in eight women at a median age of 20 years (13-34 years), but only one had regular monthly menses. The type of hypogonadism (primary or secondary) in PWS can be determined only after age 20 years. The study cohort was heterogeneous, showing variability in BMI, cognitive disability and medical treatment. Demonstration of the natural history of reproductive hormone development in PWS suggests that androgen replacement may be indicated for most PWS boys in mid-adolescence. Recommendations for hormone replacement in PWS women need to be individually tailored, serial measurements of inhibin B should be performed, and contraception should be considered in those women who may have the potential for fertility. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.

PubMed

Wiehle, Ronald D; Fontenot, Gregory K; Wike, Jenny; Hsu, Kuang; Nydell, Jennifer; Lipshultz, Larry

2014-09-01

To determine the effect of enclomiphene citrate in men with secondary hypogonadism. Phase II clinical trial. Community dwelling men making visits to physician offices. Men with secondary hypogonadism. Oral administration of enclomiphene citrate or 1% topical T gel. Luteinizing hormone, FSH, T, and semen analysis. Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved. Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production. NCT01270841 (ClinicalTrials.gov Identifier NCT01270841). Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

Hypogonadism: Its Prevalence and Diagnosis.

PubMed

Ross, Anna; Bhasin, Shalender

2016-05-01

Hypogonadism is a clinical syndrome, which results from the failure of the testes to produce physiologic levels of testosterone and a normal number of spermatozoa due to defects at one or more levels of the hypothalamic-pituitary-gonadal axis. Primary hypogonadism results from malfunction at the level of the testes due to a genetic cause, injury, inflammation, or infection. Hypothalamic and/or pituitary failure leads to secondary hypogonadism, most often as a result of genetic defects, neoplasm, or infiltrative disorders. The signs and symptoms of hypogonadism depend on the age of onset, severity of androgen deficiency, and underlying cause of androgen deficiency. Copyright © 2016 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.

Early androgen exposure and human gender development.

PubMed

Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

2015-01-01

During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This approach has recently begun to be used, with some promising results relating testosterone during the first few months of postnatal life to later gender-typical play behavior. In replicating and extending these findings, it may be important to assess testosterone when it is maximal (months 1 to 2 postnatal) and to take advantage of the increased reliability afforded by repeated sampling.

Effects of sex steroids on muscarinic sties in the rat brain

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

Al-Dahan, M.I.

1986-03-01

The level of binding sites for (/sup 3/H)scopolamine in the rat hypothalamus and amygdala (but not elsewhere in the brain) is modified by hormonal status. In females, there is an inverse relation between the level of sites and estrogen (E/sub 2/) and progesterone (P) concentration. Binding is high in metoestrous (Met) and in ovariectomized (Ovx) animals but low in proestrous (Pro). Hormone replacement in ovariectomized animals lowers the level of the sites. Castration (Cast) of males reduces the level of sites but subsequent testosterone (T) treatment restores normal levels. The results support a role of hormones in sexual behavior viamore » alteration in levels of muscarinic receptors: male hormone increases and female hormones decrease receptor levels.« less

Effects of microgravity or simulated launch on testicular function in rats

NASA Technical Reports Server (NTRS)

Amann, R. P.; Deaver, D. R.; Zirkin, B. R.; Grills, G. S.; Sapp, W. J.; Veeramachaneni, D. N. R.; Clemens, J. W.; Banerjee, S. D.; Folmer, J.; Gruppi, C. M.

1992-01-01

Reproductive toxicology and cellular and molecular biology approaches were used to evaluate testicular function in rats from Cosmos 2044. It is found that concentrations of testosterone in testicular tissue or peripheral blood plasma were reduced in flight rates to less than 20 percent of values for simulated-launch or vivarium controls. Spermatogenesis was essentially normal in flight rats, but production of testosterone was severely depressed.

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.

Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

PubMed

Pongkan, Wanpitak; Pintana, Hiranya; Jaiwongkam, Thidarat; Kredphoo, Sasiwan; Sivasinprasasn, Sivaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2016-10-01

Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

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.

Endocrinological effects of single daily ketoconazole administration in male beagle dogs.

PubMed

De Coster, R; Beerens, D; Dom, J; Willemsens, G

1984-10-01

Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3-4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-dihydroxyprogesterone increased within 3-10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17 alpha levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17-20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17 beta plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

Evaluation of anabolic steroid induced renal damage with sonography in bodybuilders.

PubMed

Kantarci, Umut H; Punduk, Zekine; Senarslan, Omer; Dirik, Alper

2017-11-17

The aim of this study was to investigate the effect of anabolic steroids on kidneys in bodybuilders. Twenty two bodybuilders were included in the study. Participants were divided into three groups according to the scheme of steroid usage: Group 1 (n=8, intramuscular 500 mg testosterone enanthate, intramuscular 400 mg nandrolone decanoate and oral 40 mg methandrostenolone for 12 weeks), Group 2 (n=7, intramuscular 500 mg testosterone enanthate, intramuscular 300 mg nandrolone decanoate and intramuscular 300 mg boldenone undecylenate for 16 weeks) and Group 3 (n=7, no steroid intake). Blood urea nitrogen (BUN), creatinine (Cr), urine microalbumin and electrolyte levels were measured. Renal volume, cortical thickness and echogenicity were obtained in ultrasonographic scans. Renal volume, cortical thickness, echogenicity and protein intake value were significantly higher in group 2 than group 1 and 3. Plasma levels of BUN and Cr in group 2 were significantly higher than other groups (p ˂ 0.001). Urine microalbumin and electrolyte levels were normal in all groups. The results of this study indicate that high protein intake, steroid usage, particularly the schemes, including boldenone undecylenate increases cortical echogenicity, thickness of renal parenchyma and renal volume in bodybuilders.

Prenatal sex hormones (maternal and amniotic fluid) and gender-related play behavior in 13-month-old Infants.

PubMed

van de Beek, Cornelieke; van Goozen, Stephanie H M; Buitelaar, Jan K; Cohen-Kettenis, Peggy T

2009-02-01

Testosterone, estradiol, and progesterone levels were measured in the second trimester of pregnancy in maternal serum and amniotic fluid, and related to direct observations of gender-related play behavior in 63 male and 63 female offspring at age 13 months. During a structured play session, sex differences in toy preference were found: boys played more with masculine toys than girls (d = .53) and girls played more with feminine toys than boys (d = .35). Normal within-sex variation in prenatal testosterone and estradiol levels was not significantly related to preference for masculine or feminine toys. For progesterone, an unexpected significant positive relationship was found in boys between the level in amniotic fluid and masculine toy preference. The mechanism explaining this relationship is presently not clear, and the finding may be a spurious one. The results of this study may indicate that a hormonal basis for the development of sex-typed toy preferences may manifest itself only after toddlerhood. It may also be that the effect size of this relationship is so small that it should be investigated with more sensitive measures or in larger populations.

Behavioral and biochemical adjustments of the zebrafish Danio rerio exposed to the β-blocker propranolol.

PubMed

Mitchell, Kimberly M; Moon, Thomas W

2016-09-01

Propranolol (PROP) is a β-blocker prescribed mainly to treat human cardiovascular diseases and as a result of its wide usage and persistence, it is reported in aquatic environments. This study examined whether PROP alters developmental patterns and catecholamine (CA)-regulated processes in the zebrafish (Danio rerio) and if exposure during early life alters the stress response and behaviors of adults. The calculated 48h larva LC50 was 21.6mg/L, well above reported environmental levels (0.01-0.59μg/L). Stressed and PROP-exposed adult zebrafish had reduced testosterone and estradiol levels and exhibited behaviors indicating less anxiety than control fish. Furthermore, adults previously PROP-exposed as embryos/larvae had decreased growth in terms of body length and mass. Finally, these adults showed increased cholesterol and a dose-dependent decrease in testosterone levels compared with unexposed zebrafish. Thus PROP-exposure of zebrafish embryos/larvae alters developmental patterns and CA-regulated processes that may affect normal behaviors and responses to stressors, and at least some of these changes persist in the adult zebrafish. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men.

PubMed

Blomberg Jensen, Martin; Gerner Lawaetz, Jacob; Andersson, Anna-Maria; Petersen, Jørgen Holm; Nordkap, Loa; Bang, Anne Kirstine; Ekbom, Pia; Joensen, Ulla Nordström; Prætorius, Lisbeth; Lundstrøm, Peter; Boujida, Vibeke Hartvig; Lanske, Beate; Juul, Anders; Jørgensen, Niels

2016-08-01

Are low vitamin D levels linked with semen quality and sex steroids in infertile men? Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men. This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study. In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses. Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05). All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links between vitamin D, calcium, semen quality and sex steroids in infertile men are causal. The associations between vitamin D deficiency and low calcium with semen quality and sex steroids support the existence of a cross-link between regulators of calcium homeostasis and gonadal function in infertile men. This study was supported by the Danish Agency for Science, Technology and Innovation, Hørslev Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts of interest. NCT01304927. 25 February 2011. 8 March 2011. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

PubMed Central

Gunter, Jennifer H.; Lubik, Amy A.; McKenzie, Ian; Pollak, Michael; Nelson, Colleen C.

2012-01-01

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer. PMID:22548055

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

The Association Among Hypogonadism, Symptom Burden, and Survival in Male Patients with Advanced Cancer

PubMed Central

Dev, R; Hui, D; Del Fabbro, E; Delgado-Guay, MO; Sobti, N; Dalal, S; Bruera, E

2014-01-01

Background A high frequency of hypogonadism has been reported in male patients with advanced cancer. Objectives To evaluate the association among low testosterone, symptom burden and survival in cancer patients. Methods 119/131 (91%) consecutive male cancer patients had an endocrine evaluation of total/free/bioavailable testosterone (TT, FT, BT, respectively), high-sensitivity C-reactive protein (CRP), vitamin B12, thyroid stimulating hormone, 25-hydroxy vitamin D and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. We examined the correlation with Spearman test and survival with log rank test and Cox-regression analysis. Results The median age was 64; majority were white 85 (71%). Median TT was 209ng/dL (normal ≥200 ng/dL), FT was 4.4 ng/dL (normal ≥9 ng/dL), and BT was 22.0 ng/dL (normal ≥61ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (p≤0.04), poor performance status (p≤0.05), weight loss (p≤0.01), and opioid use (p≤0.005). Low TT and FT were associated with increased anxiety (p≤0.04), decreased feeling of well-being (p≤0.04), and increased dyspnea (p≤0.05); while BT was only associated with anorexia (p=0.05). Decreased TT, FT, and BT values were all significantly associated with elevated CRP, low albumin and hemoglobin. In multivariate analysis, decreased survival was associated with low TT (HR 1.66; p=0.034), declining ECOG performance status (HR 1.55; p=0.004), high CRP (HR 3.28; p<0.001), and decreased albumin (HR 2.52; p<0.001). Conclusion In male cancer patients, low testosterone was associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival. PMID:24577665

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations.

PubMed

Wallace, E M; Gow, S M; Wu, F C

1993-07-01

Sex-steroid based male contraceptive regimes induce azoospermia in only 40-70% of Caucasian men. The reason(s) why the remainder maintains a low level of spermatogenesis (oligozoospermia) despite gonadotrophin suppression is unclear. In order to improve our understanding of this phenomenon, we examined the changes in sperm density and plasma LH, FSH, testosterone (T), oestradiol (E2), and inhibin (IN) in 28 normal men who received 200 mg testosterone enanthate (TE) im weekly during a male contraceptive efficacy trial. Gonadotrophins were measured by an ultrasensitive time-resolved immunofluorometric assay (DELFIA) with a sensitivity of 0.04 U/L, to determine the adequacy of suppression. Seventeen of the 28 men achieved azoospermia; the other 11 remained oligozoospermic (sperm density 3.3-4.7 x 10(6)/mL) after 6 months of TE exposure. Azoospermic subjects displayed a more rapid decline in sperm density, a significant difference being apparent by 5 weeks after starting TE. During TE treatment, both LH and FSH were consistently suppressed to below the limits of detection, whereas there was a 2.5-fold rise in T and E2 with a similar decrease in IN. There were no consistent differences in any of these hormone concentrations between the azoospermic and oligozoospermic groups. Recovery of sperm density to baseline levels or above 20 x 10(6)/mL was significantly slower in the azoospermic group. During the recovery phase, the azoospermic men exhibited significantly higher LH and FSH levels compared to baseline and to the oligozoospermic subjects even though no differences in circulating T, E2, or IN were observed. We conclude that incomplete gonadotrophin suppression or differences in sex steroid or inhibin levels are unlikely to be responsible for the maintenance of minor degrees of spermatogenesis in some men during TE administration. The rebound rise in gonadotrophins in azoospermic but not oligozoospermic responders during recovery may reflect a more profound degree of spermatogenic suppression in the former group.

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

Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism.

PubMed

Caronia, Lisa M; Dwyer, Andrew A; Hayden, Douglas; Amati, Francesca; Pitteloud, Nelly; Hayes, Frances J

2013-02-01

This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). Cross-sectional study. 74 men (19-74 years, mean 51·4 ± 1·4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4·2 ± 0·3 nm, P < 0·0001). T levels remained suppressed at 120 min compared with baseline (13·7 ± 0·6 vs 16·5 ± 0·7 nm, P < 0·0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9·7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0·0001). Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state. © 2012 Blackwell Publishing Ltd.

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

Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers.

PubMed

Xu, Yi; Dalrymple, Susan L; Becker, Robyn E; Denmeade, Samuel R; Isaacs, John T

2006-07-01

Prostatic dihydrotestosterone (DHT) concentration is regulated by precursors from systemic circulation and prostatic enzymes of androgen metabolism, particularly 5alpha-reductases (i.e., SRD5A1 and SRD5A2). Therefore, the levels of expression SRD5A1 and SRD5A2 and the antiprostatic cancer growth response to finasteride, a selective SRD5A2 inhibitor, versus the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, were compared. Real-time PCR and enzymatic assays were used to determine the levels of SRD5A1 and SRD5A2 in normal versus malignant rat and human prostatic tissues. Rats bearing the Dunning R-3327H rat prostate cancer and nude mice bearing LNCaP or PC-3 human prostate cancer xenografts were used as model systems. Tissue levels of testosterone and DHT were determined using liquid chromatography-mass spectrometry. Prostate cancer cells express undetectable to low levels of SRD5A2 but elevated levels of SRD5A1 activity compared with nonmalignant prostatic tissue. Daily oral treatment of rats with the SRD5A2 selective inhibitor, finasteride, reduces prostate weight and DHT content but did not inhibit R-3327H rat prostate cancer growth or DHT content in intact (i.e., noncastrated) male rats. In contrast, daily oral treatment with even a low 1 mg/kg/d dose of the dual SRD5A1 and SRD5A2 inhibitor, dutasteride, reduces both normal prostate and H tumor DHT content and weight in intact rats while elevating tissue testosterone. Daily oral treatment with finasteride significantly (P < 0.05) inhibits growth of LNCaP human prostate cancer xenografts in intact male nude mice, but this inhibition is not as great as that by equimolar oral dosing with dutasteride. This anticancer efficacy is not equivalent, however, to that produced by castration. Only combination of dutasteride and castration produces a greater tumor inhibition (P < 0.05) than castration monotherapy against androgen-responsive LNCaP cancers. In contrast, no response was induced by dutasteride in nude mice bearing androgen-independent PC-3 human prostatic cancer xenografts. These results document that testosterone is not as potent as DHT but does stimulate prostate cancer growth, thus combining castration with dutasteride enhances therapeutic efficacy.

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.

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.

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.

Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

PubMed

Crew, Rachael C; Mark, Peter J; Clarke, Michael W; Waddell, Brendan J

2016-09-01

Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids. © 2016 by the Society for the Study of Reproduction, Inc.

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.

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.

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom).

PubMed

Conte, F A; Grumbach, M M; Ito, Y; Fisher, C R; Simpson, E R

1994-06-01

We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. The cardinal features of this syndrome are a consequence of P450arom deficiency: 1) the fetal masculinization in this syndrome can be ascribed to defective placental conversion of C19 steroids to estrogens, leading to exposure of the female fetus to excessive amounts of testosterone; 2) the pubertal failure, mild virilization, multicystic ovaries, and hyperstimulation of the ovaries by FSH and LH are the result of the inability of the ovary to aromatize testosterone and androstenedione to estrogens; and 3) the striking delay in bone age at 14 2/12 yr supports the notion that estrogens, in contrast to androgens, are the major sex steroid driving skeletal maturation during puberty. Familial P450arom deficiency, although rare, may be more common than previously suspected.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Relation of body mass and sex steroid hormone levels to hot flushes in a sample of mid-life women.

PubMed

Schilling, C; Gallicchio, L; Miller, S R; Langenberg, P; Zacur, H; Flaws, J A

2007-02-01

Previous studies indicate that obesity is associated with a higher risk of experiencing hot flushes in mid-life women. The reasons for this association are unknown, although altered hormone levels have been associated with both hot flushes and obesity. Thus, this current study tested the hypothesis that obesity is associated with hot flushes in mid-life women through a mechanism involving levels of total and free androgen, free estrogen, progesterone, and sex hormone binding globulin (SHBG). Women aged 45-54 years were recruited from Baltimore and its surrounding counties. Each participant (n=628) was weighed, measured, completed a questionnaire, and provided a blood sample that was used to measure estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone sulfate, progesterone, and SHBG. Obese mid-life women (body mass index (BMI)>or=30.0 kg/m2) had significantly higher testosterone, and lower estradiol, estrone, progesterone, and SHBG levels than normal-weight mid-life women (BMI

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.

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population.

PubMed

Rosler, Ariel

2006-08-01

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle. Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3 deficiency whereas the three homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia, normal sexual development and revealed no biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is compatible with an autosomal recessive mode of inheritance, sex dependent.

[A case of postmenopausal hyperandrogenism caused by a lipid cell tumor].

PubMed

Witek, Andrzej; Skałba, Piotr; Chełmicki, Zbigniew; Pajak, Jacek

2002-01-01

Steroid-secreting neoplasms of the ovary and adrenal gland comprise a small group of tumors. A 76-year-old woman presented hair loss, facial hirsutism associated with increased serum total testosterone level. The adrenal glands and the ovaries were normal on radiological and ultrasonographic investigation. The patient was submitted to a pelvic exploratory laparotomy. Hysterectomy and salpingo-oophorectomy were performed. A solid and circumscribed ovarian tumor of 2 cm in diameter was found. The pathological diagnosis was lipid cell tumor with stromal hyperplasia. The purpose of this report is to relate how difficult is to establish the diagnosis and the origin of the hyperandrogenism in a patient with normal image studies.

A Case of Unusual Clitoromegaly.

PubMed

Wooi Ch'ng, Tong; Umpaichitra, Vatcharapan

2018-05-03

Mild degree of clitoromegaly can be associated with patient with polycystic ovarian syndrome (PCOS). We describe an unusually significant clitoromegaly in a patient with PCOS. An 18-year old non-obese female referred for clitoromegaly. Her genitalia exam showed significant clitoral enlargement with a well-formed glans, clitoris measured at 35 mm for length and 10 mm for width. Pelvic ultrasound showed left ovarian cyst. Testosterone level ranged from 28.8 to 64.1 ng/dl (normal: 8.4-48.1 ng/dl) with normal sex hormone binding globulin. Other ovarian hormones were in acceptable ranges. This case demonstrates the coexistence of significant clitoromegaly, PCOS, and non-functioning ovarian cyst. Copyright © 2018. Published by Elsevier Inc.

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.…

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