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Sample records for oral testosterone undecanoate

  1. [Oral Testosterone Undecanoate Capsules combined with Qilin Pills for late-onset hypogonadism in males].

    PubMed

    Mao, Jun-Biao; Chen, Xiao-Gang; Gui, Ding-Wen; Peng, Wei; Zheng, Jie

    2017-05-01

    To investigate the clinical effects of oral Testosterone Undecanoate Capsules (TUC) combined with Qilin Pills (QLP) on late-onset hypogonadism (LOH) in men. Sixty-three LOH patients meeting the inclusion criteria were randomly divided into a control group (aged [48.4 ± 6.2] yr, n = 32) and an experimental group (aged [47.2 ± 5.6] yr, n = 31) to be treated with oral TUC (80 mg, qd) and TUC + QLP (6g, tid), respectively, both for 3 months. Comparisons were made between the two groups of patients in the IIEF-5 scores, total testosterone (TT) levels, and scores in the Aging Males' Symptoms (AMS) scale before and after treatment. After treatment, the patients of the experimental group, as compared with the controls, showed a significantly increased IIEF-5 score (21.7 ± 5.8 vs 15.9 ± 4.7, P <0.05) and TT level ([16.7 ± 2.2] vs [13.1 ± 2.8] nmol/L, P <0.05), but a decreased AMS score (20.7 ± 5.7 vs 31.3±6.5, P <0.05). TUC combined with Qilin Pills has a better effect and a lower rate of adverse reactions than TUC used alone in the treatment of late-onset hypogonadism in males.

  2. 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

  3. An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations.

    PubMed

    Kamischke, Axel; Heuermann, Tanja; Krüger, Kathrin; von Eckardstein, Sigrid; Schellschmidt, Ilka; Rübig, Alexander; Nieschlag, Eberhard

    2002-02-01

    Suppression of spermatogenesis to azoospermia is the goal of hormonal male contraception based on T combined with gestagens. The combination of the long-acting T, ester testosterone undecanoate (TU), with norethisterone (NET) enanthate (E) showed high efficacy. In the present study, we tested the validity of this approach by varying the NET dose and mode of application. The aim of the study was to achieve high rates of suppression of spermatogenesis as reflected by sperm counts, monitor gonadotropins as well as other hormones, and evaluate any possible side effects. In a phase II clinical trial, groups of normal volunteers received: 1000 mg TU im at wk 2, 6, 12, and 18 combined with 200 mg NETE im at wk 0, 6, 12, and 18 (group I); 1000 mg TU im and 400 mg NETE im at wk 0, 6, 12, and 18 (group II); and 1000 mg TU im at wk 0, 6, 12, and 18 with daily oral NET acetate (NETA) from wk 0 to 24 (group III). In all groups marked suppression of gonadotropins resulted in a significant decrease of spermatogenesis and azoospermia in 13/14, 11/12, and 12/14 men in groups I to III, respectively. The remaining men all had less than 1 million sperm/ml. Reversible side effects included increase in body weight, erythrocytes, hemoglobin, and hematocrit and decrease in high-density lipoprotein cholesterol and alkaline phosphatase in all groups and increase in liver enzymes in the oral NETA group. This study documents the high efficacy of TU in combination with NET and confirms that this dose and mode of application (1000 mg TU im every 6 wk plus 400 mg NETE im every 6 wk or plus 10 mg daily oral NETA) is as effective as the previously reported regimen containing 1000 mg TU + 200 mg NETE im every 6 wk. The contraceptive efficacy of this combination of TU and NETE should be evaluated in further clinical trials.

  4. Proteomic analysis of testis biopsies in men treated with injectable testosterone undecanoate alone or in combination with oral levonorgestrel as potential male contraceptive.

    PubMed

    Cui, Yugui; Zhu, Hui; Zhu, Yefei; Guo, Xuejiang; Huo, Ran; Wang, Xinghai; Tong, Jiansun; Qian, Lixin; Zhou, Zuomin; Jia, Yue; Lue, Yan-He; Hikim, Amiya Sinha; Wang, Christina; Swerdloff, Ronald S; Sha, Jiahao

    2008-09-01

    Treatment with injectable testosterone undecanoate (TU) alone or in combination with oral levonorgestrel (LNG) resulted in marked decreases in sperm concentrations. In this study, we used proteomic analyses to examine the cellular/molecular events occurring in the human testis after TU or TU + LNG treatment. We conducted a global proteomic analysis of the human testicular biopsies before and at 2 weeks after TU alone or TU + LNG treatment. Proteins showing significant changes in expression were identified and analyzed. As a result, 17 and 46 protein spots were found with significant differential expression after the treatment with TU alone and TU + LNG, respectively. TU treatment changed the expression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), proteasome inhibitor PI31 subunit (PSMF1), and superoxide dismutase [Mn] mitochondrial precursor (SOD2). These proteins inhibit "assembly", induce cell death, and promote compensatory "cell survival" in the testis. After TU + LNG treatment, "proliferation/cell survival" and "apoptosis/death" were the predominant responses in the testis. TU + LNG treatment inhibited the expression of Prolyl 4-hydroxylase beta subunit (P4HB) and Annexin A2 (Annexin II). These proteins are involved in apoptosis and cell proliferation, respectively. TU + LNG treatment also enhanced the expression of SOD2 and Parvalbumin alpha (Pvalb). These two proteins may protect testicular cells against apoptosis/death and promote cell survival. In conclusion, TU and TU + LNG treatments suppress spermatogenesis through different pathways by changing the expression of different proteins. hnRNP K, PSMF1, SOD2, P4HB, Annexin II, and Pvalb, are key proteins that may be early molecular targets responsible for spermatogenesis suppression induced by hormone treatment.

  5. 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.

  6. 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.

  7. Acceptability of an injectable male contraceptive regimen of norethisterone enanthate and testosterone undecanoate for men.

    PubMed

    Meriggiola, M Cristina; Cerpolini, S; Bremner, W J; Mbizvo, M T; Vogelsong, K M; Martorana, G; Pelusi, G

    2006-08-01

    We assessed attitudes towards and acceptability of male hormonal contraception among volunteers participating in a clinical trial of a prototype regimen, consisting of progestin and testosterone injections. After completing screening, eligible men were randomly assigned to the no-treatment group (n = 40) or to receive injections of norethisterone enanthate and testosterone undecanoate or placebo at different intervals (n = 50) according to a blocked randomization list. They underwent self-administered questionnaires. The average age of the participants was approximately 28 years; most were involved in a stable relationship and had no children. Ninety-two percentage of the respondents thought that men and women should share responsibility for contraception and 75% said they would try a hormonal contraceptive if available. At the end of the treatment phase, 66% of the participants said that they would use such a method, and most rated its acceptability very highly; none reported it to be unacceptable. The injections themselves were indicated as the biggest disadvantage. No significant changes in sexual function or mood states were detected among the men who underwent hormone injections. The contraceptive tested in this study was well accepted by the participants over the course of 1 year.

  8. Effectiveness and tolerability of parenteral testosterone undecanoate: a post-marketing surveillance study.

    PubMed

    Wolf, Jan; Keipert, Dieter; Motazedi, Heiko; Ernst, Michael; Nettleship, Joanne; Gooren, Louis

    2017-12-01

    This observational post-marketing study of parenteral testosterone undecanoate (TU) in a non-selected population aimed to: examine the effectiveness of TU as treatment of hypogonadism; record adverse drug reactions (ADR) quantitatively particularly regarding polycythemia, prostate safety and cardiovascular-related metabolic risk factors; and verify whether recommended injection intervals apply to routine clinical practice. Eight hundred and seventy subjects from 259 outpatient units scheduled to visit the clinic six times were included. Effectiveness and tolerability of TU administration were assessed on a 4-point scale. Body weight, waist girth, blood pressure, hemoglobin levels, hematocrit, prostate-specific antigen (PSA), and digital rectal prostate examination were assessed. Over 90% of subjects completed the observational duration of 52.8 ± 9.7 weeks (mean ± SD) and 56% judged effectiveness as very good, 30.8% as good. 63.1% judged tolerability as very good, and 24.4% as good. No adverse effects on indicators of cardiovascular risk were observed. Polycythemia occurred in one subject and a supranormal hematocrit in one subject. Four subjects developed supranormal PSA levels. Prostate carcinoma was found in one subject, one subject had recurrence of a previously surgically treated prostate carcinoma, and the other two showed no indication of malignancy. Parenteral TU is safe, effective, and well-tolerated in clinical practice proving a good therapeutic option for hypogonadism.

  9. Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features.

    PubMed

    Yu, Mingcan; Cao, Xiaomei; Xu, Jinju; Wang, Xiaolei; Yang, Jing; Wang, Xinghai; Ben, Kunlong

    2003-11-01

    Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.

  10. 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.

  11. Retrospective investigation of testosterone undecanoate depot for the long-term treatment of male hypogonadism in clinical practice.

    PubMed

    Conaglen, Helen M; Paul, Ryan G; Yarndley, Tania; Kamp, Jozef; Elston, Marianne S; Conaglen, John V

    2014-02-01

    Testosterone undecanoate depot (TUD) administered intramuscularly is an effective form of testosterone replacement therapy (TRT) for male hypogonadism. Because of the ease of administration, TUD therapy may be preferable to subcutaneously implanted extended release T pellet implants (TI). The primary objective was to retrospectively assess the efficacy and safety of long-term (≥ 2 years therapy) TUD therapy in the clinical setting. The secondary objective was to retrospectively compare TUD with TI therapy. Retrospective data were collected from the Waikato Hospital Endocrine Database for 179 hypogonadal men treated with TUD for ≥ 2 years from 1998-2011, with 124 of these men receiving previous TI therapy. The main outcome measure for efficacy was serum trough total testosterone (TT), and for safety an increase in hemoglobin (Hb) and/or hematocrit (Hct), rise in prostate-specific antigen (PSA) and/or prostatic biopsy and alteration in body mass index and lipid profile. Additional outcome measures were changes in the dosing and/or interval regimens for TUD therapy. Overall, 72% of trough TT levels were in the normal range for TUD therapy compared with 53% of trough TT levels during TI therapy. TUD therapy was well tolerated with 162 men (90.5%) completing 2 years of treatment, and only seven men (3.9%) stopping TUD because of adverse effects. A rise in Hb and/or Hct occurred in 25 men (14%), and a significant rise in PSA in 20 men (13%) at some stage during TUD therapy. At 2 years, 91% of men received the standard 1,000 mg TUD dose with 66% at the standard dosing interval of 10-14 weekly. TUD is an efficacious, safe, and well tolerated form of TRT, and individual optimisation of the dose and/or interval is only required in the minority of men. Particularly given the ease of administration, TUD was the preferred TRT for both patients and clinicians. © 2013 International Society for Sexual Medicine.

  12. Safety aspects of 36 months of administration of long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals.

    PubMed

    Jacobeit, J W; Gooren, L J; Schulte, H M

    2009-11-01

    Testosterone treatment is essential for the induction and maintenance of virilization of female-to-male (FTM) transsexuals. Aim To test the safety of a novel testosterone preparation for this purpose. Parenteral long-acting testosterone undecanoate (TU) was administered to 17 FTM transsexuals over 36 months. Observations were made while subjects received treatment. Serum testosterone rose from 0.50+/-0.25 to 6.2+/-1.3 ng/ml at 6 months and remained stable thereafter. The testosterone profiles were largely identical with those in hypogonadal receiving TU. There were no side effects. Over the 36 months of the study, there was a small but significant decrease in plasma cholesterol (from 218+/-47 to 188+/-42 mg/dl) and low-density lipoprotein-cholesterol (from 139+/-48 to 139+/-48 mg/dl), while plasma levels of high-density lipoprotein-cholesterol and triglycerides did not change significantly. Liver enzymes did not change during treatment. There was an increase of both levels in hemoglobin (from 13.6+/-1.2 to 16.0+/-1.5 g/dl) and hematocrit (from 41+/-4 to 46+/-4) upon administration but they remained almost without exception within the physiological range. No special measures were needed. Breast and gonads/internal genitalia did not show pathological changes over the observation period. This study reports that TU is suited for induction of virilization in FTM transsexuals without significant side effects over a longer term.

  13. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes.

    PubMed

    Hackett, Geoffrey; Cole, Nigel; Bhartia, Mithun; Kennedy, David; Raju, Jessie; Wilkinson, Peter

    2013-06-01

    Sexual dysfunction, particularly erectile dysfunction (ED), is common in men with type 2 diabetes, occurring in up to 75% of cases. The prevalence of hypogonadism is also high in men with diabetes and low testosterone is associated with both sexual dysfunction and a reduced response to oral therapy for ED. This study aimed to determine the effect of testosterone replacement with long-acting Testosterone Undecanoate (TU) on sexual function, mood and quality of life vs. placebo over a treatment period of 30 weeks followed by 52 weeks of open-label medication. The study was conducted in a primary care population of men with type 2 diabetes attending their primary care physician for routine visits. The male diabetic populations of seven general practices were screened at routine diabetes visits to detect symptomatic men with total testosterone levels of 12 nmol/L or less or with free testosterones of 250 pmol/L or less. Two hundred eleven men were screened. A double-blind placebo-controlled study was conducted in 199 men with type 2 diabetes and hypogonadism treated for 30 weeks with either 1,000 mg of TU or matching placebo followed by 52-week open-label follow on. The primary outcome measure, International Index of Erectile Function (IIEF), was used to evaluate sexual dysfunction, and the Ageing Male Symptom (AMS), Hospital Anxiety and Depression Scale, and Global Efficacy Question were used as secondary outcome measures to assess mood and self-reported quality of life. Testosterone replacement therapy with long-acting TU improved all domains of sexual function at 30 weeks (erectile function [EF], P = 0.005; intercourse satisfaction, P = 0.015; sexual desire, P = 0.001; overall satisfaction, P = 0.05; and orgasm, P = 0.04), with benefit as early as 6 weeks. Improvements in AMS score were significant in men without depression (P = 0.02) and the presence of depression at baseline was associated with marked reduction in response to both sexual function and psychological

  14. Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

    PubMed

    Ayoub, R; Page, S T; Swerdloff, R S; Liu, P Y; Amory, J K; Leung, A; Hull, L; Blithe, D; Christy, A; Chao, J H; Bremner, W J; Wang, C

    2017-03-01

    Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be

  15. Trials for development of once-a-month injectable, hormonal male contraceptive using dienogest plus testosterone undecanoate: dose standardization, efficacy and reversibility studies in rats.

    PubMed

    Misro, Man M; Chaki, Shankar P; Kaushik, Mahesh C; Nandan, Deoki

    2009-06-01

    The study was conducted to test the potential of using dienogest (DNG) plus testosterone undecanoate (TU) in rats for development of a once-a-month injectable male hormonal contraceptive. Dose selection studies were initiated with administration of DNG in three different doses of 20, 30 and 40 mg/kg body weight (bw) per week plus TU 25 mg/kg bw once in every 6 weeks. Status of spermatogenesis and sperm count in epididymis was evaluated. The frequency of DNG intervention was later extended to every 2- and 4-week intervals. Mating studies, toxicity and reversibility of spermatogenesis following stoppage of treatment were carried out with DNG 40 mg/kg bw at 4-week intervals. Complete arrest of spermatogenesis was observed after 60 days of treatment at all doses of DNG (20, 30 and 40 mg/kg bw per week)+TU. However, weights of testis and accessory sex organs (epididymis, prostate and seminal vesicle) declined significantly 60 days post treatment compared to vehicle-treated controls. Epididymis in the treated animals was completely devoid of sperm. When the frequency of DNG injection (20 mg/kg bw) was extended to once every 15 days, a few immotile and decapitated sperm were observed in the epididymis. With TU treatment unchanged, animals receiving DNG (40 mg/kg bw) once either every 2- or 4-week intervals demonstrated good and uniform arrest of spermatogenesis. DNG 40 mg/kg per 4 weeks+TU also demonstrated a significant rise in germ cell apoptosis in the seminiferous epithelium. There was no significant increase in the serum high-density lipoprotein and low-density lipoprotein levels at the end of 120 days of treatment. Following withdrawal of treatment after 60 or 120 days, qualitative restoration of spermatogenesis was rapid in the former compared to the latter. Dienogest plus TU has the potential for development as a monthly injectable showing reversible hormonal male contraception with good efficacy.

  16. 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

  17. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

    PubMed

    Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

    2014-04-01

    Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body

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

    PubMed

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

    2016-08-01

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

  19. 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) ...

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

    PubMed

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

    2009-01-01

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

  1. 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

  2. Testosterone deficiency: a historical perspective

    PubMed Central

    Nieschlag, Eberhard; Nieschlag, Susan

    2014-01-01

    Castillo and Pasqualini. In the 1950s longer-acting injectable testosterone enanthate became the preferred therapeutic modality. In the 1950s and 1960s, research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. Although anabolic steroids have largely disappeared from clinical medicine, they continue to live an illegal life for doping in athletics. In the 1970s the orally effective testosterone undecanoate was added to the spectrum of preparations. Recent transdermal gels and long-acting injectable preparations provide options for physiological testosterone substitution therapy. PMID:24435052

  3. Recent trends in the treatment of testosterone deficiency syndrome.

    PubMed

    Hong, Bum Sik; Ahn, Tai Young

    2007-11-01

    Testosterone deficiency syndrome (TDS) is defined as a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels. TDS is a result of the interaction of hypothalamo-pituitary and testicular factors. Now, treatment of TDS with testosterone is still controversial due to a lack of large, controlled clinical trials on efficacy. The risks of treatment with testosterone appear to be minimal, although long-term studies on the safety of testosterone therapy are lacking. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Newer testosterone patches seem not to cause severe skin irritation. Testosterone gels minimize the skin irritation while providing flexibility in dosing and a low discontinuation rate. Oral testosterone undecanoate (TU) is free of liver toxicity. Recent formulation of oral TU markedly increased shelf-live, a major drawback in the older preparation. Producing swings in testosterone levels rising rapidly to the supraphysiological range is not the case with the new injectable long-acting preparation of TU. To be able to rapidly react and stop treatment in cases where side-effects and contraindications are detected, the short-acting transdermal and oral delivery modes have certain advantages. However, there is no evidence that the use of an injectable long-acting TU in men with TDS has limitations in clinical application for this reason. The use of dehydroepiandrosterone is still controversial because of a lack of well designed long-term trials, although some recent studies suggest positive effects on various body systems. Only a few studies have been carried out to investigate the effect of hCG (human

  4. 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

  5. Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis.

    PubMed

    Macció, Daniela R; Calfa, Gastón; Roth, German A

    2005-01-01

    Considering that sex steroids can influence the immune system, we studied the development of experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of the central nervous system, and the concomitant cell-mediated immunity in gonadally intact and gonadectomized male Wistar rats given testosterone supplementation. Sham-operated rats and surgically castrated animals were orally self-administered with vehicle or testosterone added in the water bottle for 20 days before EAE induction. The androgenic effect of oral testosterone self-administration was evidenced by changes in body weight, and in the weights of androgen-dependent testes and seminal vesicles. Testosterone administration reduced the incidence of clinical signs of EAE in sham-operated animals and reversed the clinical symptoms of the disease associated with castrated EAE animals. The clinical signs observed in the different groups correlated with changes in delayed-type hypersensitivity and mononuclear cell-proliferative responses to the encephalitogenic myelin basic protein. Moreover, testosterone but not cholesterol supplementation in vitro suppressed the proliferative response of mononuclear cells to myelin basic protein suggesting that testosterone may affect specific immune functions through direct actions on immune cells. Finally, self-administration of testosterone induced also elevated corticosterone levels that in sham-operated rats correlated with the low incidence of the disease and in gonadectomized animals could be involved in the remission of clinical symptoms of EAE. These results suggest that orally self-administered testosterone can modulate specific cellular immune responses and serum corticosterone levels leading to changes in the development of EAE. Copyright 2005 S. Karger AG, Basel.

  6. 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

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

    PubMed

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

    2016-02-01

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

  8. Profiling of steroid metabolites after transdermal and oral administration of testosterone by ultra-high pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

    PubMed

    Badoud, F; Boccard, J; Schweizer, C; Pralong, F; Saugy, M; Baume, N

    2013-11-01

    The screening of testosterone (T) misuse for doping control is based on the urinary steroid profile, including T, its precursors and metabolites. Modifications of individual levels and ratio between those metabolites are indicators of T misuse. In the context of screening analysis, the most discriminant criterion known to date is based on the T glucuronide (TG) to epitestosterone glucuronide (EG) ratio (TG/EG). Following the World Anti-Doping Agency (WADA) recommendations, there is suspicion of T misuse when the ratio reaches 4 or beyond. While this marker remains very sensitive and specific, it suffers from large inter-individual variability, with important influence of enzyme polymorphisms. Moreover, use of low dose or topical administration forms makes the screening of endogenous steroids difficult while the detection window no longer suits the doping habit. As reference limits are estimated on the basis of population studies, which encompass inter-individual and inter-ethnic variability, new strategies including individual threshold monitoring and alternative biomarkers were proposed to detect T misuse. The purpose of this study was to evaluate the potential of ultra-high pressure liquid chromatography (UHPLC) coupled with a new generation high resolution quadrupole time-of-flight mass spectrometer (QTOF-MS) to investigate the steroid metabolism after transdermal and oral T administration. An approach was developed to quantify 12 targeted urinary steroids as direct glucuro- and sulfo-conjugated metabolites, allowing the conservation of the phase II metabolism information, reflecting genetic and environmental influences. The UHPLC-QTOF-MS(E) platform was applied to clinical study samples from 19 healthy male volunteers, having different genotypes for the UGT2B17 enzyme responsible for the glucuroconjugation of T. Based on reference population ranges, none of the traditional markers of T misuse could detect doping after topical administration of T, while the

  9. 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

  10. Novel double-layer Silastic testicular prosthesis with controlled release of testosterone in vitro, and its effects on castrated rats

    PubMed Central

    Chen, Hui-Xing; Yang, Shi; Ning, Ye; Shao, Hai-Hao; Ma, Meng; Tian, Ru-Hui; Liu, Yu-Fei; Gao, Wei-Qiang; Li, Zheng; Xia, Wei-Liang

    2017-01-01

    Testicular prostheses have been used to deal with anorchia for nearly 80 years. Here, we evaluated a novel testicular prosthesis that can controllably release hormones to maintain physiological levels of testosterone in vivo for a long time. Silastic testicular prostheses with controlled release of testosterone (STPT) with different dosages of testosterone undecanoate (TU) were prepared and implanted into castrated Sprague-Dawley rats. TU oil was applied by oral administration to a separate group of castrated rats. Castrated untreated and sham-operated groups were used as controls. Serum samples from every group were collected to measure the levels of testosterone (T), follicle-stimulating hormone and luteinizing hormone (LH). Maximum intracavernous penile pressure (ICPmax) was recorded. The prostates and seminal vesicles were weighed and subjected to histology, and a terminal dexynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) assay was used to evaluate apoptosis. Our results revealed that the weights of these tissues and the levels of T and LH showed significant statistical differences in the oral administration and TU replacement groups compared with the castrated group (P < 0.05). Compared with the sham-operated group, the ICPmax, histology and TUNEL staining for apoptosis, showed no significant differences in the hormone replacement groups implanted with medium and high doses of STPT. Our results suggested that this new STPT could release TU stably through its double semi-permeable membranes with excellent biocompatibility. The study provides a new approach for testosterone replacement therapy. PMID:27174160

  11. Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism.

    PubMed

    Wu, F C; Balasubramanian, R; Mulders, T M; Coelingh-Bennink, H J

    1999-01-01

    The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 microg DSG/100 mg T enanthate group, but was not different from that in the 150 microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 microg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference

  12. 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.

  13. Effects of menstrual cycle, oral contraception, and training on exercise-induced changes in circulating DHEA-sulphate and testosterone in young women.

    PubMed

    Enea, C; Boisseau, N; Ottavy, M; Mulliez, J; Millet, C; Ingrand, I; Diaz, V; Dugué, B

    2009-06-01

    The objective of this study was to ascertain the effects of menstrual cycle, oral contraception, and training status on the exercise-induced changes in circulating DHEA-sulphate and testosterone in young women. Twenty-eight healthy women were assigned to an untrained group (n = 16) or a trained group (n = 12) depending on their training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-). The trained group was composed of OC+ subjects only. All the OC+ subjects were taking the same low-dose oral contraception. Three laboratory sessions were organised in a randomised order: a prolonged exercise test until exhaustion, a short-term exhaustive exercise test, and a control session. Blood specimens were collected before, during and after the exercise tests and at the same time of the day during the control session. Basal circulating testosterone was significantly lower in trained as compared to untrained subjects. In all subjects, the prolonged exhaustive exercise induced a significant increase in circulating DHEA-s and testosterone. The short-term exercise induced a significant increase in circulating DHEA-s in untrained eumenorrheic and in trained OC users only. Menstrual phases in OC- did not influence the responses. It was found that exhaustive physical exercise induced an increase in circulating DHEA-s and testosterone in young women. Oral contraception may limit short-term exercise-induced changes.

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

    PubMed

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

    2013-12-01

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

  15. 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.

  16. Single dose sublingual testosterone and oral sildenafil vs. a dual route/dual release fixed dose combination tablet: a pharmacokinetic comparison

    PubMed Central

    van Rooij, Kim; de Leede, Leo; Frijlink, Henderik W.; Koppeschaar, Hans P. F.; Olivier, Berend; Tuiten, Adriaan

    2016-01-01

    Aim The aim was to compare the pharmacokinetic profiles of two formulations of a combination drug product containing 0.5 mg testosterone and 50 mg sildenafil for female sexual interest/arousal disorder. The prototype (formulation 1) consists of a testosterone solution for sublingual administration and a sildenafil tablet that is administered 2.5 h later. The dual route/dual release fixed dose combination tablet (formulation 2) employs a sublingual and an oral route for systemic uptake. This tablet has an inner core of sildenafil with a polymeric time delay coating and an outer polymeric coating containing testosterone. It was designed to increase dosing practicality and decrease potential temporal non‐adherence through circumventing the relatively complex temporal dosing scheme. Methods Twelve healthy premenopausal subjects received both formulations randomly on separate days. Blood was sampled frequently to determine the pharmacokinetics of free testosterone, total testosterone, dihydrotestosterone, sildenafil and N‐desmethyl‐sildenafil. Results Formulation 2 had a higher maximum concentration (C max) for testosterone, 8.06 ng ml–1 (95% confidence interval [CI] 6.84, 9.28) and higher area under the plasma concentration–time curve (AUC), 7.69 ng ml–1 h (95% CI 6.22, 9.16) than formulation 1, 5.66 ng ml–1 (95% CI 4.63, 6.69) and 5.12 ng ml–1 h (95% CI 4.51, 5.73), respectively. Formulation 2 had a lower C max for sildenafil, 173 ng ml–1 (95% CI 126, 220) and a lower AUC, 476 ng ml–1 h (95% CI 401, 551) than formulation 1, 268 ng ml–1 (95% CI 188, 348) and 577 ng ml–1 h (95% CI 462, 692), respectively. Formulation 2 released sildenafil after 2.75 h (95% CI 2.40, 3.10). Conclusions The dual route/dual release fixed dose combination tablet fulfilled its design criteria and is considered suitable for further clinical testing. What is Already Known about this Subject Female sexual interest/arousal disorder (FSIAD) is a

  17. Effects of testosterone treatment on bone mineral density in men with testosterone deficiency syndrome.

    PubMed

    Rodriguez-Tolrà, J; Torremadé, J; di Gregorio, S; Del Rio, L; Franco, E

    2013-07-01

    The decline in testosterone levels found in men with testosterone deficiency syndrome (TDS) is associated with a decrease in bone mineral density (BMD). To study the safety profile and efficacy of testosterone treatment on BMD in patients with TDS. In this 2-year prospective open-label study, patients were administered 50 mg of testosterone gel daily (adjustable after 3 months up to 75-100 mg or down to 25 mg) for 12 months, followed by treatment with 1000 mg of testosterone undecanoate every 2-3 months from months 12-24. Outcome measures were as follows: (i) Changes in clinical chemistry safety parameters and total testosterone, sex hormone binding globulin and calculated free testosterone (cFT) levels; (ii) Changes in Aging Males' Symptoms Scale (AMS) and International Prostate Symptom Score scores; and (iii) Changes in lumbar spine and hip BMD. A total of 50 men aged 50-65 years with TDS (AMS >26 and cFT <0.250 nmol/mL) took part in the study. There was no significant impact of testosterone on safety. Prostate-specific antigen and haematopoietic parameters increased significantly, although the changes were not clinically significant. Total and cFT increased significantly after 3 months (p < 0.001) and there were significant improvements after 3 months in AMS scores (p < 0.001). BMD improved significantly in L2-L4 (2.90 and 4.5%), total femur (0.74 and 3%) and trochanter (1.09 and 3.2%) at 12 and 24 months respectively. Testosterone treatment in men with TDS has a good safety profile, leads to significant improvement in lumbar spine and hip BMD, and improves symptoms, as assessed by the AMS questionnaire. © 2013 American Society of Andrology and European Academy of Andrology.

  18. Testosterone Topical

    MedlinePlus

    ... in single use tubes, packets, and a multiple-use pump. The pump releases a specific amount of testosterone each time the top is ... have been reports of serious side effects in people who use testosterone at higher doses, along with other male ...

  19. Testosterone metabolism revisited: discovery of new metabolites.

    PubMed

    Pozo, Oscar J; Marcos, Josep; Ventura, Rosa; Fabregat, Andreu; Segura, Jordi

    2010-10-01

    The metabolism of testosterone is revisited. Four previously unreported metabolites were detected in urine after hydrolysis with KOH using a liquid chromatography-tandem mass spectrometry method and precursor ion scan mode. The metabolites were characterized by a product ion scan obtained with accurate mass measurements. Androsta-4,6-dien-3,17-dione, androsta-1,4-dien-3,17-dione, 17-hydroxy-androsta-4,6-dien-3-one and 15-androsten-3,17-dione were proposed as feasible structures for these metabolites on the basis of the mass spectrometry data. The proposed structures were confirmed by analysis of synthetic reference compounds. Only 15-androsten-3,17-dione could not be confirmed, owing to the lack of a commercially available standard. That all four compounds are testosterone metabolites was confirmed by the qualitative analysis of several urine samples collected before and after administration of testosterone undecanoate. The metabolite androsta-1,4-dien-3,17-dione has a structure analogous to that of the exogenous anabolic steroid boldenone. Specific transitions for boldenone and its metabolite 17β-hydroxy-5β-androst-1-en-3-one were also monitored. Both compounds were also detected after KOH treatment, suggesting that this metabolic pathway is involved in the endogenous detection of boldenone previously reported by several authors.

  20. 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.

  1. Testosterone Buccal

    MedlinePlus

    ... left and right of the two front teeth). Alternate sides at every dose so that you never ... thoughts or beliefs that have no basis in reality). People who use higher doses of testosterone than ...

  2. Testosterone Injection

    MedlinePlus

    ... symptoms of low testosterone in men who have hypogonadism (a condition in which the body does not ... hypothalamus (a part of the brain) that cause hypogonadism. Your doctor will order certain lab tests to ...

  3. Integrity of the blood-testis barrier in healthy men after suppression of spermatogenesis with testosterone and levonorgestrel.

    PubMed

    Ilani, Niloufar; Armanious, Nancy; Lue, Yan-He; Swerdloff, Ronald S; Baravarian, Sima; Adler, Alex; Tsang, Christina; Jia, Yue; Cui, Yu-Gui; Wang, Xing-Hai; Zhou, Zuo-Min; Sha, Jia-Hao; Wang, Christina

    2012-12-01

    Do exogenous male hormonal contraceptives that suppress intratesticular testosterone and spermatogenesis interfere with the blood-testis barrier integrity in men? When spermatogenesis was suppressed by testosterone alone or combined with levonorgestrel (LNG) treatment in men, the structural appearance of Sertoli cell tight junctions remained intact in the human testis. Testosterone promotes the integrity of the blood-testis barrier. Intratesticular androgen deprivation induced by exogenous testosterone plus a progestin to suppress spermatogenesis in a contraceptive regimen may disturb the structural and functional integrity of the blood-testis barrier. Testicular biopsies were obtained from a sub-study of a randomized clinical trial of 36 healthy Chinese men who were treated for 18 weeks and followed for at least a 12-week recovery period. Healthy Chinese male volunteers (27-48 years) were randomized to two treatment groups (n = 18/group) for 18 weeks: (1) testosterone undecanoate (TU) 1000 mg i.m. injection followed by a 500 mg injection every 6 weeks and (2) TU + LNG 250 μg orally daily. Blood samples were obtained from all participants before and during treatment and at the end of the recovery phase. Open testicular biopsies for this study were obtained from four men before treatment and from four men in each of the TU and TU + LNG groups at 2 and 9 weeks of treatment. The presence of antisperm antibodies was checked in the archived serum samples of the subjects at baseline, during treatment and at the end of the recovery period. Stored testicular biopsy samples from cynomolgus monkeys treated with either sub-cutaneous testosterone or placebo for 12 weeks were used for additional protein expression studies. Expression of blood-testis barrier associated proteins quantified by immunohistochemistry (claudin 3, claudin 11, junctional adhesion molecule-A, zonula occludens-1) remained unchanged despite a significant decrease in the numbers of pachytene spermatocytes

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

    SciTech Connect

    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

  5. Sex, age, pubertal development and use of oral contraceptives in relation to serum concentrations of DHEA, DHEAS, 17α-hydroxyprogesterone, Δ4-androstenedione, testosterone and their ratios in children, adolescents and young adults.

    PubMed

    Søeborg, Tue; Frederiksen, Hanne; Mouritsen, Annette; Johannsen, Trine Holm; Main, Katharina Maria; Jørgensen, Niels; Petersen, Jørgen Holm; Andersson, Anna-Maria; Juul, Anders

    2014-11-01

    The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analyzed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analyzed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 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.

  7. 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 ...

  8. Sexual Health: Testosterone Therapy

    MedlinePlus

    ... or if it is due to a disease (hypogonadism). Hypogonadism is a disease in which the body is ... Testosterone therapy can help reverse the effects of hypogonadism, but it's unclear whether testosterone therapy would have ...

  9. 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…

  10. Low Testosterone and Men's Health

    MedlinePlus

    ... Cancer Featured Resource Find an Endocrinologist Search Low Testosterone Download PDFs English Espanol Editors Glenn R. Cunningham, ... Association Mayo Clinic What is the role of testosterone in men’s health? Testosterone is the most important ...

  11. [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.

  12. Testosterone and Social Behavior

    ERIC Educational Resources Information Center

    Booth, Alan; Granger, Douglas A.; Mazur, Allan; Kivlighan, Katie T.

    2006-01-01

    Popular perceptions of the effect of testosterone on "manly" behavior are inaccurate. We need to move away from such simplistic notions by treating testosterone as one component along with other physiological, psychological and sociological variables in interactive and reciprocal models of behavior. Several hormones can now be measured in saliva,…

  13. 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.…

  14. 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.

  15. Testosterone and the Prostate.

    PubMed

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

    2014-10-01

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

  16. A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men.

    PubMed

    Hair, W M; Kitteridge, K; O'Connor, D B; Wu, F C

    2001-11-01

    This study investigated the effect of transdermal T and oral desogestrel on the reproductive axis of healthy men. Twenty-three men were randomized to 1 of 3 treatment groups and received a daily transdermal T patch plus oral desogestrel at a dose of 75, 150, or 300 microg/d for 24 wk. Baseline blood and semen samples were obtained and then every 4 wk thereafter for 32 wk. The outcome measures were sperm density and plasma levels of FSH, LH, total and free T. The results show a dose-dependent suppression of spermatogenesis and gonadotropins. Seven of the 17 subjects became azoospermic. Desogestrel (300 microg daily) in combination with 5 mg daily transdermal T was the most effective (57% azoospermic), whereas a dose of 75 microg was ineffective (0% azoospermic). Total and free plasma T were reduced by approximately 30%. High density lipoprotein cholesterol was significantly reduced. No serious side-effects were encountered. We conclude that daily self-administered desogestrel with transdermal T is capable of suppressing the male reproductive axis, although the efficacy was less marked and less consistent than injectable regimens. The lower efficacy is likely to be due to failure of the transdermal T system to maintain circulating T levels consistently in the required range.

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

    PubMed

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

    2015-04-01

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

  18. Testosterone and Cardiovascular Disease

    PubMed Central

    Tambo, Amos; Roshan, Mohsin H.K.; Pace, Nikolai P.

    2016-01-01

    Cardiovascular disease [CVD] is a leading cause of mortality accounting for a global incidence of over 31%. Atherosclerosis is the primary pathophysiology underpinning most types of CVD. Historically, modifiable and non-modifiable risk factors were suggested to precipitate CVD. Recently, epidemiological studies have identified emerging risk factors including hypotestosteronaemia, which have been associated with CVD. Previously considered in the realms of reproductive biology, testosterone is now believed to play a critical role in the cardiovascular system in health and disease. The actions of testosterone as they relate to the cardiac vasculature and its implication in cardiovascular pathology is reviewed. PMID:27014372

  19. Testosterone and Men's Marriages.

    ERIC Educational Resources Information Center

    Booth, Alan; Dabbs, James M., Jr.

    1993-01-01

    Among 4,462 former servicemen surveyed, testosterone levels were positively related to not marrying and marital instability, and negatively related to every aspect of marital quality examined. Findings are analyzed in relation to three sociological theories of marital success based on socioeconomic status (educational attainment, income, and…

  20. 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.

  1. 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.

  2. 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

  3. Prenatal testosterone and stuttering.

    PubMed

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Accuracy of testosterone concentrations in compounded testosterone products.

    PubMed

    Grober, Ethan D; Garbens, Alaina; Božović, Andrea; Kulasingam, Vathany; Fanipour, Majid; Diamandis, Eleftherios P

    2015-06-01

    This study aims to evaluate the accuracy of the testosterone concentrations within testosterone gels and creams manufactured by compounding pharmacies. Ten compounding pharmacies within Toronto area were included. Pharmacies were blinded as to the nature of the study. A standardized prescription for 50 mg of compounded testosterone gel/cream applied once daily was presented to each pharmacy. Two independently compounded batches were analyzed from each pharmacy 1 month apart. Testosterone concentrations in a 5-g sachet of Androgel® 1% (Abbott) and 5-g tube of Testim®1% (Auxilium) were evaluated as controls. Samples were analyzed independently and in a blinded fashion by the Laboratory Medicine Program at the University Health Network. Measurement of testosterone concentration was performed using a modified liquid chromatography tandem mass spectrometry validated for serum testosterone. Compounded formulations included seven gels and three creams with a volume/daily dose ranging from 0.2 mL to 1.25 mL. Product cost ranged from $57.32 to $160.71 for a 30-day supply. There was significant variability both within and between pharmacies with respect to the measured concentration of testosterone in the compounded products. In contrast, the concentration of testosterone within Androgel and Testim was consistent and accurate. Collectively, only 50% (batch 1) and 30% (batch 2) of the compounding pharmacies provided a product with a testosterone concentration within ± 20% of the prescribed dose. Two pharmacies compounded products with >20% of the prescribed dose. One pharmacy compounded a product with essentially no testosterone. Testosterone concentrations in compounded testosterone products can be variable and potentially compromise the efficacy and safety of treatment. © 2015 International Society for Sexual Medicine.

  5. [The method of tonifying kidneys and activating blood circulation increases testosterone secretion index in late-onset hypogonadism males with kidney deficiency].

    PubMed

    Zhou, Shao-Hu; Weng, Zhi-Wei; Li, Tang-Lin

    2013-07-01

    To investigate the effect of the method of tonifying the kidney and activating blood circulation on the testosterone secretion index (TSI) in late-onset hypogonadism (LOH) male patients with kidney deficiency and its possible mechanisms. We screened 60 LOH male patients with kidney deficiency based on the scores on Partial Androgen Deficiency in Aging Males (PADAM), the levels of serum total testosterone (TT) and luteinizing hormone (LH), and TSI (TT/LH). We randomly divided the patients into a Nan Geng Ning (NGN) group (n = 40, aged 55.02 +/- 11.37 years) and a control group (n = 20, aged 54.56 +/- 12.12 years) to be treated orally with NGN decoction and testosterone undecanoate capsules, respectively, both for 12 consecutive weeks. We obtained the scores on psychological status, physical status and sexual function and observed the changes in serum TT, LH and TSI after 4, 8 and 12 weeks of treatment. Compared with the baseline, both the NGN and control groups showed a significant reduction after 12 weeks of medication in the LH level ([5.32 +/- 2.08] vs [4.89 +/- 1.46] IU/L and [5.36 +/- 2.07] vs [4.81 +/- 1.75] IU/L, P < 0.05), psychological status score (5.2 +/- 1.3 vs 2.7 +/- 1.4 and 4.8 +/- 2.2 vs 2.9 +/- 1.2, P < 0.05), physical status score (6.9 +/- 2.5 vs 2.9 +/- 1.6 and 7.1 +/- 2.7 vs 3.1 +/- 1.5, P < 0.05) and sexual function score (10.2 +/- 3.3 vs 4.5 +/- 2.9 and 9.8 +/- 3.1 vs 4.8 +/- 3.0, P < 0.05), but a remarkable increase in the TT level ([11.13 +/- 0.69] vs [14.55 +/- 0.75] nmol/L and [10.99 +/- 0.74] vs [14.74 +/- 0.83] nmol/L, P < 0.05) and TSI ([2.14 +/- 0.65] vs [2.99 +/- 0.72] nmol/IU and ([2.05 +/- 0.73] vs [3.11 +/- 0.65] nmol/IU, P < 0.05). However, no significant differences were found between the NGN and control groups at 12 weeks in LH ([4.89 +/- 1.46] vs [4.81 +/- 1.75] IU/L, P > 0.05), TT ([14.55 +/- 0.75] vs [14.74 +/- 0.83] nmol/L, P > 0.05), TSI ([2.99 +/- 0.72] vs [3.11 +/- 0.65] nmol/IU, P > 0.05), psychological status score (2

  6. Who Gets Testosterone? Patient Characteristics Associated with Testosterone Prescribing in the Veteran Affairs System: a Cross-Sectional Study.

    PubMed

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

    2017-03-01

    There has been concern about the growing off-label use of testosterone. Understanding the context within which testosterone is prescribed may contribute to interventions to improve prescribing. To evaluate patient characteristics associated with receipt of testosterone. Cross-sectional. A national cohort of male patients, who had received at least one outpatient prescription within the Veterans Affairs (VA) system during Fiscal Year 2008- Fiscal Year 2012. The study sample consisted of 682,915 non-HIV male patients, of whom 132,764 had received testosterone and a random 10% sample, 550,151, had not. Conditions and medications associated with testosterone prescription. Only 6.3% of men who received testosterone from the VA during the study period had a disorder of the testis, pituitary or hypothalamus associated with male hypogonadism. Among patients without a diagnosed disorder of hypogonadism, the use of opioids and obesity were the strongest predictors of testosterone prescription. Patients receiving >100 mg/equivalents of oral morphine daily (adjusted odds ratio = 5.75, p < 0.001) and those with body mass index (BMI) >40 kg/m 2 (adjusted odds ratio = 3.01, p < 0.001) were more likely to receive testosterone than non-opioid users and men with BMI <25 kg/m 2 . Certain demographics (age 40-54, White race), comorbid conditions (sleep apnea, depression, and diabetes), and medications (antidepressants, systemic corticosteroids) also predicted a higher likelihood of testosterone receipt, all with an adjusted odds ratio less than 2 (p < 0.001). In the VA, 93.7% of men receiving testosterone did not have a diagnosed condition of the testes, pituitary, or hypothalamus. The strongest predictors of testosterone receipt (e.g., obesity, receipt of opioids), which though are associated with unapproved, off-label use, may be valid reasons for therapy. Interventions should aim to increase the proportion of testosterone recipients who have a valid

  7. Influence of androgen receptor CAG polymorphism on sexual function recovery after testosterone therapy in late-onset hypogonadism.

    PubMed

    Tirabassi, Giacomo; Corona, Giovanni; Biagioli, Andrea; Buldreghini, Eddi; delli Muti, Nicola; Maggi, Mario; Balercia, Giancarlo

    2015-02-01

    Androgen receptor (AR) CAG polymorphism has been found to influence sexual function. However, no study has evaluated its potential to condition sexual function recovery after testosterone replacement therapy (TRT) in a large cohort of hypogonadic subjects. To evaluate the role of this polymorphism in sexual function improvement after TRT in late-onset hypogonadism (LOH). Seventy-three men affected by LOH were retrospectively considered. Evaluations were performed before TRT started (time 0) and before the sixth undecanoate testosterone injection. International Index of Erectile Function (IIEF) questionnaire (erectile function [EF], orgasmic function [OF], sexual desire [SD], intercourse satisfaction [IS], overall satisfaction [OS], and total IIEF-15 score); total and free testosterone and estradiol; AR gene CAG repeat number. TRT induced a significant increase in total and free testosterone and estradiol. All IIEF domains significantly improved after TRT. AR CAG repeats negatively and significantly correlated with all the variations (Δ-) of sexual function domains, except for Δ-OS. Conversely, Δ-total testosterone was found to be positively and significantly correlated with sexual function domain variations, except for Δ-IS and Δ-OS. Δ-estradiol did not correlate significantly with any of the variations of sexual function domains. After inclusion in generalized linear models, the number of AR gene CAG triplets was found to be independently and negatively associated with Δ-EF, Δ-SD, Δ-IS, and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated with Δ-EF, Δ-OF, Δ-SD, and Δ-Total IIEF-15 score. However, after including time 0 total testosterone in the model, AR gene CAG triplets remained independently and negatively associated only with Δ-EF and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated only with Δ-EF. Longer length of AR gene CAG repeat tract seems to

  8. 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).

  9. 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.

  10. Testosterone and the Heart.

    PubMed

    Goodale, Travis; Sadhu, Archana; Petak, Steven; Robbins, Richard

    2017-01-01

    Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

  11. Testosterone and the Heart

    PubMed Central

    Goodale, Travis; Sadhu, Archana; Petak, Steven; Robbins, Richard

    2017-01-01

    Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men. PMID:28740585

  12. 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.

  13. 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

  14. Preparation, crystallization and preliminary X-ray diffraction analysis of two intestinal fatty-acid binding proteins in the presence of 11-(dansylamino)undecanoic acid

    PubMed Central

    Laguerre, Aisha; Wielens, Jerome; Parker, Michael W.; Porter, Christopher J. H.; Scanlon, Martin J.

    2011-01-01

    Fatty-acid binding proteins (FABPs) are abundantly expressed proteins that bind a range of lipophilic molecules. They have been implicated in the import and intracellular distribution of their ligands and have been linked with metabolic and inflammatory responses in the cells in which they are expressed. Despite their high sequence identity, human intestinal FABP (hIFABP) and rat intestinal FABP (rIFABP) bind some ligands with different affinities. In order to address the structural basis of this differential binding, diffraction-quality crystals have been obtained of hIFABP and rIFABP in complex with the fluorescent fatty-acid analogue 11-(dansylamino)undecanoic acid. PMID:21301109

  15. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  16. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  17. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  18. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  19. 21 CFR 556.710 - Testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Testosterone propionate. 556.710 Section 556.710... Tolerances for Residues of New Animal Drugs § 556.710 Testosterone propionate. No residues of testosterone, resulting from the use of testosterone propionate, are permitted in excess of the following increments above...

  20. Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats.

    PubMed

    Halmenschlager, Graziele; Rhoden, Ernani Luis; Motta, Gabriela Almeida; Sagrillo Fagundes, Lucas; Medeiros, Jorge Luiz; Meurer, Rosalva; Rhoden, Cláudia Ramos

    2017-10-01

    To evaluate the effects of testosterone (T) on the maintenance of corpus cavernosum (CC) structure and apoptosis. Animals were divided into three groups: sham operation group ( n  = 8) underwent sham operation; Orchiectomized (Orchiec)+ oily vehicle group ( n  = 8) underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection (i.m.) 30 days after orchiectomy; and Orchiec + T group ( n  = 8) underwent bilateral orchiectomy and received a single dose of T undecanoate 100 mg/kg i.m. 30 days after the surgery. Animals were euthanized 60 days after the beginning of the experiment with an anesthetic overdose of ketamine and xylazine. Blood samples and penile tissue were collected on euthanasia. Azan's trichrome staining was used to evaluate smooth muscle, Weigert's Fucsin-Resorcin staining was used to evaluate elastic fibers and Picrosirius red staining was used to evaluate collagen. Apoptosis was evaluated using TUNEL technique. T levels decreased in Orchiec + oily vehicle when compared to sham operation and Orchiec + T groups ( p  < 0.001). T deprivation reduced trabecular smooth muscle content and penile diameter and T replacement maintained both parameters ( p  = 0.005 and p  = 0.001, respectively). No difference was observed in the content of sinusoidal space ( p  = 0.207), elastic fibers ( p  = 0.849), collagen ( p  = 0.216) and in apoptosis ( p  = 0.095). Normal testosterone levels maintain CC smooth muscle content and do not influence elastic fibers, collagen content and apoptotic index. Further studies should be performed in order to investigate the mechanisms by which androgen mediates its effects on CC structure.

  1. 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.

  2. Testosterone and benign prostatic hyperplasia

    PubMed Central

    Jarvis, Thomas R; Chughtai, Bilal; Kaplan, Steven A

    2015-01-01

    The use of testosterone to treat the symptoms of late-onset hypogonadal men has increased recently due to patient and physician awareness. However, concerns regarding the effect of testosterone on the prostate, in particular any possible effect on the risk of prostate cancer have prompted further research in this regard. Surprisingly, numerous retrospective or small, randomized trials have pointed to a possible improvement in male lower urinary tract symptoms (LUTS) in patients treated with testosterone. The exact mechanism of this improvement is still debated but may have a close relationship to metabolic syndrome. For the clinician, the results of these studies are promising but do not constitute high levels of evidence. A thorough clinical examination (including history, examination and laboratory testing of testosterone) should be undertaken before considering the diagnosis of late-onset hypogonadism or instigating treatment for it. Warnings still remain on the testosterone supplement product labels regarding the risk of urinary retention and worsening LUTS, and these should be explained to patients. PMID:25337845

  3. 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

  4. 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.

  5. Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone.

    PubMed

    Dias, Jenny Pena; Veldhuis, Johannes D; Carlson, Olga; Shardell, Michelle; Chia, Chee W; Melvin, Denise; Egan, Josephine M; Basaria, Shehzad

    2017-04-01

    Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone. Thirty-seven men, ≥65years with total testosterone <350ng/dL were randomized to 5g transdermal testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months. At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059). In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Testosterone and weight loss: the evidence

    PubMed Central

    Traish, Abdulmaged M.

    2014-01-01

    Purpose of review The purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency. Recent findings Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome. The aforementioned improvements are attributed to improved mitochondrial function, increased energy utilization, increased motivation and vigor resulting in improved cardio-metabolic function and enhanced physical activity. Summary The implication of testosterone therapy in management of obesity in men with testosterone deficiency is of paramount clinical significance, as it produces sustained weight loss without recidivism. On the contrary, alternative therapeutic approaches other than bariatric surgery failed to produce significant and sustained outcome and exhibit a high rate of recidivism. These findings represent strong foundations for testosterone therapy in obese men with testosterone deficiency and should spur clinical research for better understanding of usefulness of testosterone therapy in treatment of underlying pathophysiological conditions of obesity. PMID:25105998

  7. Gender-Typed Play and Amniotic Testosterone

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  8. Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

    PubMed

    Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

    2014-01-01

    Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering

  9. 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.

  10. 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

  11. 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.

  12. Encapsulation of testosterone by chitosan nanoparticles.

    PubMed

    Chanphai, P; Tajmir-Riahi, H A

    2017-05-01

    The loading of testosterone by chitosan nanoparticles was investigated, using multiple spectroscopic methods, thermodynamic analysis, TEM images and modeling. Thermodynamic parameters showed testosterone-chitosan bindings occur mainly via H-bonding and van der Waals contacts. As polymer size increased more stable steroid-chitosan conjugates formed and hydrophobic contact was also observed. The loading efficacy of testosterone-nanocarrier was 40-55% and increased as chitosan size increased. Testosterone encapsulation markedly alters chitosan morphology. Chitosan nanoparticles are capable of transporting testosterone in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Alternatives to Testosterone Therapy: A Review.

    PubMed

    Lo, Eric M; Rodriguez, Katherine M; Pastuszak, Alexander W; Khera, Mohit

    2018-01-01

    Although testosterone therapy (TTh) is an effective treatment for hypogonadism, recent concerns regarding its safety have been raised. In 2015, the US Food and Drug Administration issued a warning about potential cardiovascular risks resulting from TTh. Fertility preservation is another reason to search for viable alternative therapies to conventional TTh, and in this review we evaluate the literature examining these alternatives. To review the role and limitations of non-testosterone treatments for hypogonadism. A literature search was conducted using PubMed to identify relevant studies examining medical and non-medical alternatives to TTh. Search terms included hypogonadism, testosterone replacement therapy, testosterone therapy, testosterone replacement alternatives, diet and exercise and testosterone, varicocele repair and testosterone, stress reduction and testosterone, and sleep apnea and testosterone. Review of peer-reviewed literature. Medical therapies examined include human chorionic gonadotropins, aromatase inhibitors, and selective estrogen receptor modulators. Non-drug therapies that are reviewed include lifestyle modifications including diet and exercise, improvements in sleep, decreasing stress, and varicocele repair. The high prevalence of obesity and metabolic syndrome in the United States suggests that disease modification could represent a viable treatment approach for affected men with hypogonadism. These alternatives to TTh can increase testosterone levels and should be considered before TTh. Lo EM, Rodriguez KM, Pastuszak AW, Khera M. Alternatives to Testosterone Therapy: A Review. Sex Med Rev 2018;6:106-113. Copyright © 2017. Published by Elsevier Inc.

  14. Testosterone in women--the clinical significance.

    PubMed

    Davis, Susan R; Wahlin-Jacobsen, Sarah

    2015-12-01

    Testosterone is an essential hormone for women, with physiological actions mediated directly or via aromatisation to oestradiol throughout the body. Despite the crucial role of testosterone and the high circulating concentrations of this hormone relative to oestradiol in women, studies of its action and the effects of testosterone deficiency and replacement in women are scarce. The primary indication for the prescription of testosterone for women is loss of sexual desire, which causes affected women substantial concern. That no formulation has been approved for this purpose has not impeded the widespread use of testosterone by women--either off-label or as compounded therapy. Observational studies indicate that testosterone has favourable cardiovascular effects measured by surrogate outcomes; however, associations between endogenous testosterone and the risk of cardiovascular disease and total mortality, particularly in older women, are yet to be established. Adverse cardiovascular effects have not been seen in studies of transdermal testosterone therapy in women. Clinical trials suggest that exogenous testosterone enhances cognitive performance and improves musculoskeletal health in postmenopausal women. Unmet needs include the availability of approved testosterone formulations for women and studies to elucidate the contribution of testosterone to cardiovascular, cognitive, and musculoskeletal health and the risk of cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial.

    PubMed

    Hoyos, Camilla M; Yee, Brendon J; Phillips, Craig L; Machan, Elizabeth A; Grunstein, Ronald R; Liu, Peter Y

    2012-10-01

    The combination of male gender, obstructive sleep apnoea (OSA) and obesity magnifies cardiometabolic risk. There has been no systematic study evaluating whether testosterone therapy can improve cardiometabolic health in obese men with OSA by improving body composition, visceral abdominal fat and insulin sensitivity. To assess body compositional and cardiometabolic effects of testosterone treatment in obese men with severe OSA. An 18-week randomised, double-blind, placebo-controlled and parallel group trial in 67 men. Participants (age=49 ± 12 years, apnoea hypopnoea index=39.9 ± 17.7 events/h, BMI=31.3 ± 5.2 kg/m(2)) were placed on a hypocaloric diet and received i.m. injections of either 1000 mg testosterone undecanoate (n=33) or placebo (n=34) for 18 weeks. Outcomes were the changes in body composition (total muscle mass, total and abdominal fat, total body dual-energy X-ray absorptiometry and computerised tomography (CT)), weight, insulin sensitivity (homeostasis model assessment), abdominal liver fat (CT), arterial stiffness (pulse wave analysis), resting metabolic rate and respiratory quotient (indirect calorimetry) and blood lipids and metabolic syndrome from baseline to week 18. After 18 weeks, testosterone treatment increased insulin sensitivity (-1.14 units, 95% confidence interval (95% CI) -2.27 to -0.01, P<0.05), reduced liver fat (0.09 Hounsfield attenuation ratio, 95% CI 0.009 to 0.17, P=0.03) and increased muscle mass (1.6 kg, 95% CI 0.69 to 2.5, P=0.0009) to a greater extent than placebo. Other measures of body composition and regional adiposity as well as the number of participants with metabolic syndrome did not change. Testosterone also decreased arterial stiffness (augmentation index) by 3.2% (95% CI -6.01 to -0.46%, P=0.02) and decreased the respiratory quotient (95% CI -0.04, -0.08 to -0.001, P=0.04) after 18 weeks compared with placebo. Eighteen weeks of testosterone therapy in obese men with OSA improved several important cardiometabolic

  17. 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

  18. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  19. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  20. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Testosterone test system. 862.1680 Section 862....1680 Testosterone test system. (a) Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are...

  1. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    PubMed Central

    Anderson, Richard A.; Johnston, Zoe C.; Chetty, Tarini; Smith, Lee B.; Mckinnell, Chris; Dean, Afshan; Homer, Natalie Z.; Jorgensen, Anne; Camacho-Moll, Maria-Elena; Sharpe, Richard M.; Mitchell, Rod T.

    2016-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; p=0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; p=0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect. PMID:25995226

  2. Testosterone regulates bone response to inflammation.

    PubMed

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

    2014-03-01

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

  3. Testosterone Therapy in Men With Prostate Cancer

    PubMed Central

    Kaplan, Alan L.; Hu, Jim C.; Morgentaler, Abraham; Mulhall, John P.; Schulman, Claude C.; Montorsi, Francesco

    2016-01-01

    Context The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer. Objective To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer. Evidence acquisition We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer. Evidence synthesis The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events. Conclusions An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life—and the ability of testosterone therapy to mitigate these effects—has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone

  4. 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.

  5. 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.

  6. 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.

  7. Testosterone, Marital Quality, and Role Overload

    ERIC Educational Resources Information Center

    Booth, Alan; Johnson, David R.; Granger, Douglas A.

    2005-01-01

    In a sample of established working- and middle-class families with school-aged children (N= 307 wives and 307 husbands), neither husbands nor wives testosterone showed a direct connection with marital quality. In contrast, the association between husbands' testosterone and positive and negative marital quality (as evaluated by both spouses) was…

  8. 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).

  9. Testosterone Replacement Therapy and the Cardiovascular System.

    PubMed

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  10. Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

    PubMed

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

    2017-01-01

    The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial.

    PubMed

    Ng Tang Fui, Mark; Prendergast, Luke A; Dupuis, Philippe; Raval, Manjri; Strauss, Boyd J; Zajac, Jeffrey D; Grossmann, Mathis

    2016-10-07

    Whether testosterone treatment has benefits on body composition over and above caloric restriction in men is unknown. We hypothesised that testosterone treatment augments diet-induced loss of fat mass and prevents loss of muscle mass. We conducted a randomised double-blind, parallel, placebo controlled trial at a tertiary referral centre. A total of 100 obese men (body mass index ≥ 30 kg/m 2 ) with a total testosterone level of or below 12 nmol/L and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). The main outcome measures were the between-group difference in fat and lean mass by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography). A total of 82 men completed the study. At study end, compared to controls, cases had greater reductions in fat mass, with a mean adjusted between-group difference (MAD) of -2.9 kg (-5.7 to -0.2; P = 0.04), and in visceral fat (MAD -2678 mm 2 ; -5180 to -176; P = 0.04). Although both groups lost the same lean mass following VLED (cases -3.9 kg (-5.3 to -2.6); controls -4.8 kg (-6.2 to -3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P < 0.001) during weight maintenance, in contrast to controls (0.8 kg (-0.7 to 2.3), P = 0.29) so that, at study end, cases had an attenuated reduction in lean mass compared to controls (MAD 3.4 kg (1.3 to 5.5), P = 0.002). While dieting men receiving placebo lost both fat and lean mass, the weight loss with testosterone treatment was almost exclusively due to loss of body fat. clinicaltrials.gov, identifier NCT01616732 , registration date: June 8, 2012.

  12. 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

  13. 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

  14. 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.

  15. Testosterone and aggressive behavior in man.

    PubMed

    Batrinos, Menelaos L

    2012-01-01

    Atavistic residues of aggressive behavior prevailing in animal life, determined by testosterone, remain attenuated in man and suppressed through familial and social inhibitions. However, it still manifests itself in various intensities and forms from; thoughts, anger, verbal aggressiveness, competition, dominance behavior, to physical violence. Testosterone plays a significant role in the arousal of these behavioral manifestations in the brain centers involved in aggression and on the development of the muscular system that enables their realization. There is evidence that testosterone levels are higher in individuals with aggressive behavior, such as prisoners who have committed violent crimes. Several field studies have also shown that testosterone levels increase during the aggressive phases of sports games. In more sensitive laboratory paradigms, it has been observed that participant's testosterone rises in the winners of; competitions, dominance trials or in confrontations with factitious opponents. Aggressive behavior arises in the brain through interplay between subcortical structures in the amygdala and the hypothalamus in which emotions are born and the prefrontal cognitive centers where emotions are perceived and controlled. The action of testosterone on the brain begins in the embryonic stage. Earlier in development at the DNA level, the number of CAG repeats in the androgen receptor gene seems to play a role in the expression of aggressive behavior. Neuroimaging techniques in adult males have shown that testosterone activates the amygdala enhancing its emotional activity and its resistance to prefrontal restraining control. This effect is opposed by the action of cortisol which facilitates prefrontal area cognitive control on impulsive tendencies aroused in the subcortical structures. The degree of impulsivity is regulated by serotonin inhibiting receptors, and with the intervention of this neurotransmitter the major agents of the neuroendocrine

  16. Testosterone replacement therapy and voiding dysfunction

    PubMed Central

    Baas, Wesley

    2016-01-01

    Testosterone replacement therapy (TRT) represents an increasing popular treatment option for men with late-onset hypogonadism (LOH). Because of unsubstantiated beliefs of testosterone’s effect on the prostate, the FDA has recently placed a warning on testosterone products, stating that TRT may worsen benign prostatic hyperplasia (BPH). Within this review article we have demonstrated the current understanding of the physiology of testosterone and its relationship with prostatic and lower urinary tract physiology. The current evidence suggests that not only does TRT not worsen lower urinary tract symptoms (LUTS), but that hypogonadism itself is an important risk factor for LUTS/BPH. PMID:28078221

  17. 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.

  18. 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

  19. Early testosterone replacement attenuates intracellular calcium dyshomeostasis in the heart of testosterone-deprived male rats.

    PubMed

    Weerateerangkul, Punate; Shinlapawittayatorn, Krekwit; Palee, Siripong; Apaijai, Nattayaporn; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2017-11-01

    Testosterone deficiency in elderly men increases the risk of cardiovascular disease. In bilateral orchiectomized (ORX) animals, impaired cardiac Ca 2+ regulation was observed, and this impairment could be improved by testosterone replacement, indicating the important role of testosterone in cardiac Ca 2+ regulation. However, the temporal changes of Ca 2+ dyshomeostasis in testosterone-deprived conditions are unclear. Moreover, the effects of early vs. late testosterone replacement are unknown. We hypothesized that the longer the deprivation of testosterone, the greater the impairment of cardiac Ca 2+ homeostasis, and that early testosterone replacement can effectively reduce this adverse effect. Male Wistar rats were randomly divided into twelve groups, four sets of three. The first set were ORX for 2, 4 and 8 weeks, the second set were sham-operated groups of the same periods, the third set were ORX for 8 weeks coupled with a subcutaneous injection of vehicle (control), testosterone during weeks 1-8 (early replacement) or testosterone during weeks 5-8 (late replacement), and finally the 12-week sham-operated, ORX and ORX treated with testosterone groups. Cardiac Ca 2+ transients (n=4-5/group), L-type calcium current (I Ca-L ) (n=4/group), Ca 2+ regulatory proteins (n=6/group) and cardiac function (n=5/group) were determined. In the ORX rats, impaired cardiac Ca 2+ transients and reduced I Ca-L were observed initially 4 weeks after ORX as shown by decreased Ca 2+ transient amplitude, rising rate and maximum and average decay rates. No alteration of Ca 2+ regulatory proteins such as the L-type Ca 2+ channels, ryanodine receptor type 2, Na + -Ca 2+ exchangers and SERCA2a were observed. Early testosterone replacement markedly improved cardiac Ca 2+ transients, whereas late testosterone replacement did not. The cardiac contractility was also improved after early testosterone replacement. Impaired cardiac Ca 2+ homeostasis is time-dependent after testosterone

  20. 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.

  1. Serum Testosterone Levels in Sex Offenders.

    ERIC Educational Resources Information Center

    Gurnani, Prem D.; Dwyer, Margretta

    1986-01-01

    Reports that with the increase in diagnosis of offenders across the nation, physicians and psychiatric personnel need to be aware of low testosterone as a possible indicator of hypo-sexuality and possible concurrent offending behavior. (Author/ABB)

  2. Diagnosis and management of testosterone deficiency.

    PubMed

    McBride, James A; Carson, Culley C; Coward, Robert M

    2015-01-01

    Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.

  3. Diagnosis and management of testosterone deficiency

    PubMed Central

    McBride, James A; Carson, Culley C; Coward, Robert M

    2015-01-01

    Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD. PMID:25532575

  4. Testosterone and breast cancer prevention.

    PubMed

    Glaser, R; Dimitrakakis, C

    2015-11-01

    Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis. Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

    PubMed

    Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

    2016-11-01

    Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled

  6. Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males.

    PubMed

    Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

    2018-01-01

    Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status-seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants' choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se . In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone.

  7. Exogenous Testosterone Enhances the Reactivity to Social Provocation in Males

    PubMed Central

    Wagels, Lisa; Votinov, Mikhail; Kellermann, Thilo; Eisert, Albrecht; Beyer, Cordian; Habel, Ute

    2018-01-01

    Testosterone affects human social behavior in various ways. While testosterone effects are generally associated with muscular strength and aggressiveness, human studies also point towards enhanced status–seeking motives after testosterone administration. The current study tested the causal influence of exogenous testosterone on male behavior during a competitive provocation paradigm. In this double blind, randomized, placebo (PL)-controlled study, 103 males were assigned to a PL or testosterone group receiving a colorless PL or testosterone gel. To induce provocation, males played a rigged reaction time game against an ostensible opponent. When participants lost, the opponent subtracted money from the participant who in return could subtract money from the ostensible opponent. Participants subjectively indicated anger and self-estimated treatment affiliation (testosterone or PL administration). A trial-by-trial analysis demonstrated that provocation and success during the repeated games had a stronger influence on participants’ choice to reduce money from the opponent if they had received testosterone. Participants who believed to be in the testosterone group were angrier after the experiment and increased monetary reductions during the task course. In line with theories about mechanisms of testosterone in humans, provocation is shown to be necessary for the agency of exogenous testosterone. Thus, testosterone reinforces the conditional adjustment of aggressive behavior but not aggressive behavior per se. In contrast undirected frustration is not increased by testosterone but probably interferes with cognitive appraisals about biological mechanisms of testosterone. PMID:29551966

  8. 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.

  9. Stable isotope ratio profiling of testosterone preparations.

    PubMed

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

    2010-01-01

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

  10. 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.

  11. Testosterone Administration Reduces Lying in Men

    PubMed Central

    Wibral, Matthias; Dohmen, Thomas; Klingmüller, Dietrich; Weber, Bernd; Falk, Armin

    2012-01-01

    Lying is a pervasive phenomenon with important social and economic implications. However, despite substantial interest in the prevalence and determinants of lying, little is known about its biological foundations. Here we study a potential hormonal influence, focusing on the steroid hormone testosterone, which has been shown to play an important role in social behavior. In a double-blind placebo-controlled study, 91 healthy men (24.32±2.73 years) received a transdermal administration of 50 mg of testosterone (n = 46) or a placebo (n = 45). Subsequently, subjects participated in a simple task, in which their payoff depended on the self-reported outcome of a die-roll. Subjects could increase their payoff by lying without fear of being caught. Our results show that testosterone administration substantially decreases lying in men. Self-serving lying occurred in both groups, however, reported payoffs were significantly lower in the testosterone group (p<0.01). Our results contribute to the recent debate on the effect of testosterone on prosocial behavior and its underlying channels. PMID:23071635

  12. Testosterone facilitates the sense of agency.

    PubMed

    van der Westhuizen, Donné; Moore, James; Solms, Mark; van Honk, Jack

    2017-11-01

    Sense of agency (SoA) refers to feelings of being in control of one's actions. Evidence suggests that SoA might contribute towards higher-order feelings of personal control - a key attribute of powerful individuals. Whether testosterone, a steroid hormone linked to power in dominance hierarchies, also influences the SoA is not yet established. In a repeated-measures design, 26 females participated in a double-blind, placebo-controlled trial to test the effects of 0.5 mg testosterone on SoA, using an implicit measure based upon perceived shifts in time between a voluntary action and its outcome. Illusions of control, as operationalized by optimism in affective forecasting, were also assessed. Testosterone increased action binding but there was no significant effect on tone binding. Affective forecasting was found to be significantly more positive on testosterone. SoA and optimistic expectations are basic manifestations of power which may contribute to feelings of infallibility often associated with dominance and testosterone. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an associationmore » between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA

  14. Fathers' decline in testosterone and synchrony with partner testosterone during pregnancy predicts greater postpartum relationship investment.

    PubMed

    Saxbe, Darby E; Edelstein, Robin S; Lyden, Hannah M; Wardecker, Britney M; Chopik, William J; Moors, Amy C

    2017-04-01

    The transition to parenthood has been associated with declines in testosterone among partnered fathers, which may reflect males' motivation to invest in the family. Moreover, preliminary evidence has found that couples show correlations in hormone levels across pregnancy that may also be linked to fathers' preparation for parenthood. The current study used repeated-measures sampling of testosterone across pregnancy to explore whether fathers' change in T, and correlations with mothers' T, were associated with fathers' and mothers' postpartum investment. In a sample of 27 couples (54 individuals) expecting their first child, both parents' salivary testosterone was measured multiple times across pregnancy. At approximately 3.5months postpartum, participants rated their investment, commitment, and satisfaction with their partner. A multilevel model was used to measure change in testosterone over time and associations between mother and father testosterone. Fathers who showed stronger declines in T across pregnancy, and stronger correlations with mothers' testosterone, reported higher postpartum investment, commitment, and satisfaction. Mothers reported more postpartum investment and satisfaction if fathers showed greater prenatal declines in T. These results held even after controlling for paternal investment, commitment, and satisfaction measured prenatally at study entry. Our results suggest that changes in paternal testosterone across pregnancy, and hormonal linkage with the pregnant partner, may underlie fathers' dedication to the partner relationship across the transition to parenthood. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Annatto tocotrienol improves indices of bone static histomorphometry in osteoporosis due to testosterone deficiency in rats.

    PubMed

    Chin, Kok-Yong; Abdul-Majeed, Saif; Fozi, Nur Farhana Mohd; Ima-Nirwana, Soelaiman

    2014-11-10

    This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.

  16. Annatto Tocotrienol Improves Indices of Bone Static Histomorphometry in Osteoporosis Due to Testosterone Deficiency in Rats

    PubMed Central

    Chin, Kok-Yong; Abdul-Majeed, Saif; Mohd. Fozi, Nur Farhana; Ima-Nirwana, Soelaiman

    2014-01-01

    This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent. PMID:25389899

  17. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including...

  18. 21 CFR 862.1680 - Testosterone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including...

  19. Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism.

    PubMed

    Giagulli, V A; Carbone, M D; Ramunni, M I; Licchelli, B; De Pergola, G; Sabbà, C; Guastamacchia, E; Triggiani, V

    2015-11-01

    The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol

  20. Precocious puberty secondary to topical testosterone exposure.

    PubMed

    Franklin, Sherry Lynn; Geffner, Mitchell E

    2003-01-01

    We report a case of pronounced virilization, including marked penile and pubic hair growth, accelerated height velocity and skeletal maturation, and increased muscle mass in a 2.67 year-old boy resulting from presumed inadvertent, long-term exposure to a topical testosterone cream being used by his father.

  1. Testosterone abolishes implicit subordination in social anxiety.

    PubMed

    Terburg, David; Syal, Supriya; Rosenberger, Lisa A; Heany, Sarah J; Stein, Dan J; Honk, Jack van

    2016-10-01

    Neuro-evolutionary theories describe social anxiety as habitual subordinate tendencies acquired through a recursive cycle of social defeat and submissive reactions. If so, the steroid hormone testosterone might be of therapeutic value, as testosterone is a main force behind implicit dominance drive in many species including humans. We combined these two theories to investigate whether the tendency to submit to the dominance of others is an implicit mechanism in social anxiety (Study-1), and whether this can be relieved through testosterone administration (Study-2). Using interactive eye-tracking we demonstrate that socially anxious humans more rapidly avert gaze from subliminal angry eye contact (Study-1). We replicate this effect of implicit subordination in social anxiety in an independent sample, which is subsequently completely abolished after a single placebo-controlled sublingual testosterone administration (Study-2). These findings provide crucial evidence for hormonal and behavioral treatment strategies that specifically target mechanisms of dominance and subordination in social anxiety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The marketing of testosterone treatments for age-related low testosterone or 'Low T'.

    PubMed

    Mintzes, Barbara

    2018-06-01

    To summarize the research evidence on promotion of testosterone for 'Low T', or age-related hypogonadism. Marketing of testosterone for 'Low T' has relied on strategies that are inadequately regulated to prevent off-label promotion, such as unbranded 'disease-awareness' advertising campaigns targeting the general public, sponsored continuing medical education (CME) and ghostwriting. A recent US analysis of television advertising exposure levels versus insurance claims found that both unbranded 'disease-awareness' advertising and branded ads were associated with increased rates of testosterone testing, treatment initiation, and treatment without prior testing. Exposés of sponsored CME and ghostwriting indicate misrepresentation of the research evidence on the sequelae of untreated low testosterone and on treatment efficacy. In the United States, advertising to the general public ceased in 2014 after the Food and Drug Administration changed product labeling to clarify that testosterone is only indicated for pathological hypogonadism. Unbranded 'disease-awareness' advertising to the general public and 'Low T' messages for health professionals have continued elsewhere. The review of the experience of promotion of testosterone for 'Low T' and research evidence on effects of advertising targeting the public highlights the need for improved regulation of unbranded 'disease awareness' advertising to ensure adequate protection of public.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Hormonal Treatment of Transgender Women with Oral Estradiol.

    PubMed

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

    2018-01-01

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

  8. 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.

  9. The impact of testosterone imbalance on depression and women's health.

    PubMed

    Rohr, Uwe D

    2002-04-15

    Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone (T) levels are related to depression and well-being in women, T plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6 ng/ml plasma free T a minimum of depression is detected. Lower levels are related to depression, osteoporosis, declining libido, dyspareunia and an increase in total body fat mass. Androgen levels in women decrease continuously to about 50% before menopause compared to a 20-year-old women. Androgen levels even decline 70% within 24 h when women undergo surgical removal of the ovaries. Conventional oral contraception or HRT cause a decline in androgens because of higher levels of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary syndrome. Social research suggests high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression. Higher androgen values are more pronounced at young ages and before and after delivery of a baby and might be responsible for the "baby blues". It was found that depression in pubertal girls correlated best with an increase in T levels in contrast to the common belief that "environmental factors" during the time of growing up might be responsible for emotional "up and downs". T replacement therapy might be useful in perimenopausal women suffering from hip obesity, also named gynoid obesity. Abdominal obesity in men and women is linked to type 2 diabetes and coronary heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal women might not only protect against obesity but also reduce the risk of developing these diseases. Antiandrogenic progestins might be useful for women suffering from hyperandrogenic state in peri- and postmenopause. Individual dosing schemes balancing side effects and beneficial effects are absolutely necessary. Substantial

  10. Plasma testosterone levels in Alzheimer and Parkinson diseases.

    PubMed

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

    2004-02-10

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

  11. Testosterone and androstanediol glucuronide among men in NHANES III.

    PubMed

    Duan, Chuan Wei; Xu, Lin

    2018-03-09

    Most of the androgen replacement therapies were based on serum testosterone and without measurements of total androgen activities. Whether those with low testosterone also have low levels of androgen activity is largely unknown. We hence examined the association between testosterone and androstanediol glucuronide (AG), a reliable measure of androgen activity, in a nationally representative sample of US men. Cross-sectional analysis was based on 1493 men from the Third National Health and Nutrition examination Survey (NHANES III) conducted from 1988 to 1991. Serum testosterone and AG were measured by immunoassay. Kernel density was used to estimate the average density of serum AG concentrations by quartiles of testosterone. Testosterone was weakly and positively correlated with AG (correlation coefficient = 0.18). The kernel density estimates show that the distributions are quite similar between the quartiles of testosterone. After adjustment for age, the distributions of AG in quartiles of testosterone did not change. The correlation between testosterone and AG was stronger in men with younger age, lower body mass index, non-smoking and good self-rated health and health status. Serum testosterone is weakly correlated with total androgen activities, and the correlation is even weaker for those with poor self-rated health. Our results suggest that measurement of total androgen activity in addition to testosterone is necessary in clinical practice, especially before administration of androgen replacement therapy.

  12. 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.

  13. 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.

  14. The effect of pomegranate fruit extract on testosterone-induced BPH in rats.

    PubMed

    Ammar, Amr E; Esmat, Ahmed; Hassona, Mohammed D H; Tadros, Mariane G; Abdel-Naim, Ashraf B; Guns, Emma S Tomlinson

    2015-05-01

    Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties. © 2015 Wiley Periodicals, Inc.

  15. The TRPM8 Protein Is a Testosterone Receptor

    PubMed Central

    Asuthkar, Swapna; Demirkhanyan, Lusine; Sun, Xiaohui; Elustondo, Pia A.; Krishnan, Vivek; Baskaran, Padmamalini; Velpula, Kiran Kumar; Thyagarajan, Baskaran; Pavlov, Evgeny V.; Zakharian, Eleonora

    2015-01-01

    Testosterone is a key steroid hormone in the development of male reproductive tissues and the regulation of the central nervous system. The rapid signaling mechanism induced by testosterone affects numerous behavioral traits, including sexual drive, aggressiveness, and fear conditioning. However, the currently identified testosterone receptor(s) is not believed to underlie the fast signaling, suggesting an orphan pathway. Here we report that an ion channel from the transient receptor potential family, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-induced rapid actions. Using cultured and primary cell lines along with the purified TRPM8 protein, we demonstrate that testosterone directly activates TRPM8 channel at low picomolar range. Specifically, testosterone induced TRPM8 responses in primary human prostate cells, PC3 prostate cancer cells, dorsal root ganglion neurons, and hippocampal neurons. Picomolar concentrations of testosterone resulted in full openings of the purified TRPM8 channel in planar lipid bilayers. Furthermore, acute applications of testosterone on human skin elicited a cooling sensation. Our data conclusively demonstrate that testosterone is an endogenous and highly potent agonist of TRPM8, suggesting a role of TRPM8 channels well beyond their well established function in somatosensory neurons. This discovery may further imply TRPM8 channel function in testosterone-dependent behavioral traits. PMID:25480785

  16. 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.

  17. The renal effects of prenatal testosterone in rats.

    PubMed

    Bábíčková, Janka; Borbélyová, Veronika; Tóthová, L'ubomíra; Kubišová, Katarína; Janega, Pavol; Hodosy, Július; Celec, Peter

    2015-05-01

    Previous studies have shown that prenatal testosterone affects the development of not only reproductive organs but also the brain and even glucose metabolism. Whether prenatal testosterone influences the kidney development is largely unknown. We analyzed whether testosterone modulation during prenatal development would affect renal function and the number of nephrons in adult offspring. Pregnant rats were treated with olive oil, testosterone (2 mg/kg), the androgen receptor blocker flutamide (5 mg/kg) or testosterone plus flutamide via daily intramuscular injections from gestation day 14 until delivery. Renal histology and functional parameters were assessed in male and female adult offspring. Macerated kidneys were used for nephron counting. Prenatal testosterone administration increased proteinuria in male rats by 256%. A similar 134% effect in female rats was not statistically significant. This effect was prevented when flutamide was co-administered. In male rats prenatal testosterone increased blood urea nitrogen. In female rats flutamide increased creatinine clearance. In male rats prenatal testosterone and flutamide led to higher and lower, respectively, interstitial collagen deposition in adulthood. Prenatal testosterone induces proteinuria in adulthood. This effect is mediated via androgen receptor. Additional effects seem to be sex specific. Further studies should focus on the timing and dosing of testosterone as well as the applicability to human development. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  18. [Testosterone replacement therapy and cardiovascular risk].

    PubMed

    Corona, Giovanni; Dicuio, Mauro; Rastrelli, Giulia; Sforza, Alessandra; Maggi, Mario

    2017-11-01

    Late onset hypogonadism (LOH) is the most commonly used term to indicate the age-dependent reduction of testosterone. Sexual dysfunction represents the most important determinant for medical consultation and the most specific symptoms associated with LOH. In particular, data from the European Male Ageing Study (EMAS), a population-based survey on more than 3400 subjects, recognized that a triad of sexual symptoms (low libido and reduced spontaneous and sex-related erections) is the only syndromic association with decreased testosterone levels. Accordingly, a meta-analysis of the available randomized controlled trials documented that testosterone therapy (TTh) is able to improve all aspects of sexual function when compared to placebo. Despite this evidence, however, the relative clinical significance and the potential benefit of TTh in LOH are still the subject of strong criticisms in the scientific community. The debate is further complicated by the recent position statement of the US Food and Drug Administration (FDA) emphasizing a possible increased cardiovascular risk of TTh. However, this position was not endorsed by the European Medicines Association (EMA), which reached an opposite position after a specific review of the available data. In this review, all the conflicting data supporting the different positions of the FDA and EMA will be discussed. In particular, data derived from either population-based studies or interventional trials will be analyzed in detail. Although some evidence suggests an increase in TTh-related cardiovascular risk, the data derived from controlled trials do not support this position especially when the incidence of major adverse cardiovascular events are considered. Symptomatic men with documented reduced testosterone levels can be safely treated with TTh.

  19. Effects of gendered behavior on testosterone in women and men.

    PubMed

    van Anders, Sari M; Steiger, Jeffrey; Goldey, Katherine L

    2015-11-10

    Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to "sex differences" in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology.

  20. Effects of gendered behavior on testosterone in women and men

    PubMed Central

    van Anders, Sari M.; Steiger, Jeffrey; Goldey, Katherine L.

    2015-01-01

    Testosterone is typically understood to contribute to maleness and masculinity, although it also responds to behaviors such as competition. Competition is crucial to evolution and may increase testosterone but also is selectively discouraged for women and encouraged for men via gender norms. We conducted an experiment to test how gender norms might modulate testosterone as mediated by two possible gender→testosterone pathways. Using a novel experimental design, participants (trained actors) performed a specific type of competition (wielding power) in stereotypically masculine vs. feminine ways. We hypothesized in H1 (stereotyped behavior) that wielding power increases testosterone regardless of how it is performed, vs. H2 (stereotyped performance), that wielding power performed in masculine but not feminine ways increases testosterone. We found that wielding power increased testosterone in women compared with a control, regardless of whether it was performed in gender-stereotyped masculine or feminine ways. Results supported H1 over H2: stereotyped behavior but not performance modulated testosterone. These results also supported theory that competition modulates testosterone over masculinity. Our findings thus support a gender→testosterone pathway mediated by competitive behavior. Accordingly, cultural pushes for men to wield power and women to avoid doing so may partially explain, in addition to heritable factors, why testosterone levels tend to be higher in men than in women: A lifetime of gender socialization could contribute to “sex differences” in testosterone. Our experiment opens up new questions of gender→testosterone pathways, highlighting the potential of examining nature/nurture interactions and effects of socialization on human biology. PMID:26504229

  1. Transdermal testosterone replacement therapy in men

    PubMed Central

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  2. The TRPM8 protein is a testosterone receptor: II. Functional evidence for an ionotropic effect of testosterone on TRPM8.

    PubMed

    Asuthkar, Swapna; Demirkhanyan, Lusine; Sun, Xiaohui; Elustondo, Pia A; Krishnan, Vivek; Baskaran, Padmamalini; Velpula, Kiran Kumar; Thyagarajan, Baskaran; Pavlov, Evgeny V; Zakharian, Eleonora

    2015-01-30

    Testosterone is a key steroid hormone in the development of male reproductive tissues and the regulation of the central nervous system. The rapid signaling mechanism induced by testosterone affects numerous behavioral traits, including sexual drive, aggressiveness, and fear conditioning. However, the currently identified testosterone receptor(s) is not believed to underlie the fast signaling, suggesting an orphan pathway. Here we report that an ion channel from the transient receptor potential family, TRPM8, commonly known as the cold and menthol receptor is the major component of testosterone-induced rapid actions. Using cultured and primary cell lines along with the purified TRPM8 protein, we demonstrate that testosterone directly activates TRPM8 channel at low picomolar range. Specifically, testosterone induced TRPM8 responses in primary human prostate cells, PC3 prostate cancer cells, dorsal root ganglion neurons, and hippocampal neurons. Picomolar concentrations of testosterone resulted in full openings of the purified TRPM8 channel in planar lipid bilayers. Furthermore, acute applications of testosterone on human skin elicited a cooling sensation. Our data conclusively demonstrate that testosterone is an endogenous and highly potent agonist of TRPM8, suggesting a role of TRPM8 channels well beyond their well established function in somatosensory neurons. This discovery may further imply TRPM8 channel function in testosterone-dependent behavioral traits. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. 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

  4. Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

    PubMed

    Melehan, K L; Hoyos, C M; Yee, B J; Wong, K K; Buchanan, P R; Grunstein, R R; Liu, P Y

    2016-01-01

    Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing. © 2015 American Society of Andrology and European

  5. Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism

    PubMed Central

    Haider, Ahmad; Haider, Karim Sultan; Doros, Gheorghe; Saad, Farid

    2017-01-01

    Objectives: In the absence of large, prospective, placebo-controlled studies of longer duration, substantial evidence regarding the safety and risk of testosterone (T) therapy (TTh) with regard to cardiovascular (CV) outcomes can only be gleaned from observational studies. To date, there are limited studies comparing the effects of long-term TTh in men with hypogonadism who were treated or remained untreated with T, for obvious reasons. We have established a registry to assess the long-term effectiveness and safety of T in men in a urological setting. Here, we sought to compare the effects of T on a host of parameters considered to contribute to CV risk in treated and untreated men with hypogonadism (control group). Patients and Methods: Observational, prospective, cumulative registry study in 656 men (age: 60.7 ± 7.2 years) with total T levels ≤12.1 nmol/L and symptoms of hypogonadism. In the treatment group, men (n = 360) received parenteral T undecanoate (TU) 1000 mg/12 weeks following an initial 6-week interval for up to 10 years. Men (n = 296) who had opted against TTh served as controls. Median follow-up in both groups was 7 years. Measurements were taken at least twice a year, and 8-year data were analyzed. Mean changes over time between the 2 groups were compared by means of a mixed-effects model for repeated measures, with a random effect for intercept and fixed effects for time, group, and their interaction. To account for baseline differences between the 2 groups, changes were adjusted for age, weight, waist circumference, fasting glucose, blood pressure, and lipids. Results: There were 2 deaths in the T-treated group, none was related to CV events. There were 21 deaths in the untreated (control) group, 19 of which were related to CV events. The incidence of death in 10 patient-years was 0.1145 in the control group (95% confidence interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95% CI: 0.0023-0.0368; P < .000); the estimated

  6. Pharmacokinetics of testosterone cream applied to scrotal skin.

    PubMed

    Iyer, R; Mok, S F; Savkovic, S; Turner, L; Fraser, G; Desai, R; Jayadev, V; Conway, A J; Handelsman, D J

    2017-07-01

    Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nm) at 4.9 h which was delayed by 2 h after peak serum testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route. © 2017 American Society of Andrology and European Academy of Andrology.

  7. 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

  8. THE TESTOSTERONE TRIALS: THE DESIGN OF SEVEN COORDINATED TRIALS TO DETERMINE IF TESTOSTERONE TREATMENT BENEFITS ELDERLY MEN

    PubMed Central

    Snyder, Peter J; Ellenberg, Susan S; Cunningham, Glenn R; Matsumoto, Alvin M; Bhasin, Shalender; Barrett-Connor, Elizabeth; Gill, Thomas M; Farrar, John T; Cella, David; Rosen, Raymond C; Resnick, Susan M; Swerdloff, Ronald S; Cauley, Jane A; Cifelli, Denise; Fluharty, Laura; Pahor, Marco; Ensrud, Kristine E; Lewis, Cora E; Molitch, Mark E; Crandall, Jill P; Wang, Christina; Budoff, Matthew J; Wenger, Nanette K; Mohler, Emile R; Bild, Diane E; Cook, Nakela L; Keaveny, Tony M; Kopperdahl, David L; Lee, David; Schwartz, Ann V; Storer, Thomas W; Ershler, William B; Roy, Cindy N; Raffel, Leslie J; Romashkan, Sergei; Hadley, Evan

    2014-01-01

    Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and determine definitively if testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this trial. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and also symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, treatment and monitoring and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data safety monitoring board (DSMB), the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in subject selection was setting the eligibility criterion

  9. Benzo[a]pyrene Reduces Testosterone Production in Rat Leydig Cells via a Direct Disturbance of Testicular Steroidogenic Machinery

    PubMed Central

    Chung, Jin-Yong; Lee, Seung Gee; Park, Ji-Eun; Yoon, Yong-Dal; Yoo, Ki Soo; Yoo, Young Hyun

    2011-01-01

    Background: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells. Objective: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins. Results: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[a]P can negatively target 3β-HSD, which is required for testosterone production. Conclusions: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs. PMID:21737371

  10. Testosterone therapy in microphallic hypospadias: topical or parenteral?

    PubMed

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

    2003-02-01

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

  11. 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.

  12. "Mitochondrial Eve", "Y Chromosome Adam", testosterone, and human evolution.

    PubMed

    Howard, James Michael

    2002-01-01

    I suggest primate evolution began as a consequence of increased testosterone in males which increased aggression and sexuality, therefore, reproduction and success. With time, negative effects of excessive testosterone reduced spermatogenesis and started a decline of the group. Approximately 30-40 million years ago, the gene DAZ (Deleted in AZoospermia) appeared on the Y chromosome, increased spermatogenesis, and rescued the early primates from extinction. (Note: DAZ is considered by some to specifically, positively affect spermatogenesis; others suggest it has no effect on spermatogenesis.) Hominid evolution continued with increasing testosterone. The advent of increased testosterone in females of Homo erectus (or Homo ergaster) increased the female-to-male body size ratio, and eventually produced another era of excessive testosterone. Excessive testosterone caused a reduction in population size (bottleneck) that produced the "Mitochondrial Eve" (ME) mechanism. (Only certain females continued during the bottleneck to transmit their mitochondrial DNA.) That is, the ME mechanism culminated, again, in excessive testosterone and reduced spermatogenesis in the hominid line. Approximately 50,000 to 200,000 years ago, a "doubling" of the DAZ gene occurred on the Y chromosome in hominid males which rescued the hominid line with increased spermatogenesis in certain males. This produced the "Y Chromosome Adam" event. The doubling of DAZ allowed further increases in testosterone in hominids that resulted in the increased size and development of the brain. Modern humans periodically fluctuate between the positive and negative consequences of increased levels of testosterone, currently identifiable as the secular trend, increased infections, and reduced spermatogenesis.

  13. 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

  14. 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

  15. Switching between forest and trees: Opposite relationship of progesterone and testosterone to global–local processing

    PubMed Central

    Pletzer, Belinda; Petasis, Ourania; Cahill, Larry

    2014-01-01

    Sex differences in attentional selection of global and local components of stimuli have been hypothesized to underlie sex differences in cognitive strategy choice. A Navon figure paradigm was employed in 32 men, 41 naturally cycling women (22 follicular, 19 luteal) and 19 users of oral contraceptives (OCs) containing first to third generation progestins in their active pill phase. Participants were first asked to detect targets at any level (divided attention) and then at either the global or the local level only (focused attention). In the focused attention condition, luteal women showed reduced global advantage (i.e. faster responses to global vs. local targets) compared to men, follicular women and OC users. Accordingly, global advantage during the focused attention condition related significantly positively to testosterone levels and significantly negatively to progesterone, but not estradiol levels in a multiple regression model including all naturally cycling women and men. Interference (i.e. delayed rejection of stimuli displaying targets at the non-attended level) was significantly enhanced in OC users as compared to naturally cycling women and related positively to testosterone levels in all naturally cycling women and men. Remarkably, when analyzed separately for each group, the relationship of testosterone to global advantage and interference was reversed in women during their luteal phase as opposed to men and women during their follicular phase. As global processing is lateralized to the right and local processing to the left hemisphere, we speculate that these effects stem from a testosterone-mediated enhancement of right-hemisphere functioning as well as progesterone-mediated inter-hemispheric decoupling. PMID:24874173

  16. Amount of Testosterone on Laundered Clothing After Use of Testosterone Topical 2% Solution by Healthy Male Volunteers.

    PubMed

    Satonin, Darlene K; Ni, Xiao; Mitchell, Malcolm I; Joly, Hellen; Muram, David; Small, David S

    2016-02-01

    Testosterone 2% solution (Axiron) applied to armpit(s) is used for replacement therapy in men with a deficiency of endogenous testosterone. To determine the amount of testosterone on subjects' T-shirts 12 hours after applying testosterone solution, the residual testosterone on subjects' T-shirts after laundering, and the testosterone transferred to unworn textile items during laundering with worn T-shirts. Healthy males ≥18 years old applied 2 × 1.5 mL of testosterone 2% solution to both axillae (total testosterone dose: 120 mg) and dressed in cotton long-sleeved T-shirts after a ≥3-minute waiting period. T-shirts were worn 12 hours before being removed and cut into halves, after which a 10 × 10 cm sample of each armpit area was excised for testosterone quantification before or after laundering with samples of unworn textiles. Testosterone on worn T-shirts before and after laundering, and on unworn textiles laundered with the worn T-shirts. Twelve subjects enrolled and completed, with only minor adverse events. Mean testosterone in unwashed worn T-shirts was 7603 μg, with high between-subject variability (3359 μg to 13,069 μg), representing 13% of the dose to 1 armpit. Mean testosterone in worn, laundered T-shirts was 260 μg (7.55 μg to 1343 μg), representing 3% of the dose to 1 armpit. Mean transferred testosterone to other textiles during laundering ranged from 69 μg on texturized Dacron 56T Double to 10,402 μg on 87/13 nylon/Lycra knit, representing 0.0382% to 5.78% of the dose to 1 armpit. Thirteen percent of the testosterone applied to axillae was transferred to T-shirts during wear. Ninety-seven percent of the transferred testosterone was removed from the T-shirts during washing, some of which was then absorbed to various degrees by other textiles. Clinical implications of these findings and biological activity of the remaining/transferred testosterone are unknown. Copyright © 2016 International Society for Sexual Medicine. Published by

  17. 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.

  18. Retrospective Analysis of Dose Titration and Serum Testosterone Level Assessments in Patients Treated With Topical Testosterone.

    PubMed

    Muram, David; Kaltenboeck, Anna; Boytsov, Natalie; Hayes-Larson, Eleanor; Ivanova, Jasmina; Birnbaum, Howard G; Swindle, Ralph

    2015-11-01

    Patterns of care following topical testosterone agent (TTA) initiation are poorly understood. This study aimed to characterize care following TTA initiation and compare results between patients with and without a serum testosterone (T) assay within 30 days before and including TTA initiation. Adult men (N=4,146) initiating TTAs from January 1, 2011, to March 31, 2012, were identified from a commercially insured database. Patients were included if they initiated at recommended starting dose (RSD) and had ≥12 and ≥6 months of continuous eligibility preinitiation (baseline) and postinitiation (study period), respectively. Patients were stratified by preinitiation T assay. Maintenance dose attainment month was determined using unadjusted generalized estimating equations regression to compare dose relative to RSD month by month. Outcomes included maintenance dose attainment month, time to stopping of index TTA refills or a claim for nonindex testosterone replacement therapy (TRT), and proportion of patients with study period T assay or diagnosis of hypogonadism (HG) or another low testosterone condition, and were compared using chi-square and Wilcoxon rank-sum tests for categorical and continuous variables, respectively. Maintenance dose was attained in Month 4 postinitiation, at 115.2% of RSD. Approximately 46% of patients had a preinitiation T assay; these men were more likely to receive a diagnosis of HG or another low testosterone condition, to have a follow-up T assay, to continue treatment by filling a nonindex TRT, and less likely to stop refilling treatment with their index TTA. Differences in care following TTA initiation suggest that preinitiation T assays (i.e., guideline-based care) may be helpful in ensuring treatment benefits. © The Author(s) 2014.

  19. Change in cytokine levels after administration of saikokaryuukotsuboreito or testosterone in patients with symptoms of late-onset hypogonadism.

    PubMed

    Tsujimura, Akira; Miyagawa, Yasushi; Okuda, Hidenobu; Yamamoto, Keisuke; Fukuhara, Shinichiro; Nakayama, Jiro; Takao, Tetsuya; Nonomura, Norio; Okuyama, Akihiko

    2011-03-01

    The purpose of this study was to evaluate plasma cytokine levels after treatment with saikokaryukotsuboreito (SKRBT), which is a herbal medicine, or androgen replacement treatment (ART), for patients with late-onset hypogonadism (LOH)-related symptoms. Thirty-one patients over 40 years of age with LOH-related symptoms were included in this study. SKRBT was given orally three times daily to a total of 7.5 g/day for 15 eugonadal patients and ART was give to 16 hypogonadal patients by intramuscular injection of testosterone enanthate at 125 mg each time every 2 weeks. Plasma levels of testosterone and 18 cytokines, as well as LOH-related symptoms scored according to the Aging Males' Symptoms (AMS) scale, were compared before and more than 2 months after treatment. In the ART group, the total AMS score was decreased and testosterone was increased significantly after treatment. No cytokine variables were altered significantly after the treatment. In the SKRBT group, although the total AMS score was significantly decreased, testosterone did not change. From the evaluation of cytokines, a significant increase was found in interleukin (IL)- 8, IL-13, interferon-gamma and tumour necrosis factor-alpha. We conclude that SKRBT might improve LOH-related symptoms in eugonadal patients through the beneficial effect of cytokines, a mechanism that is quite different from ART.

  20. A Mendelian randomization study of testosterone and cognition in men

    PubMed Central

    Zhao, Jie V.; Lam, Tai Hing; Jiang, Chaoqiang; Cherny, Stacey S.; Liu, Bin; Cheng, Kar Keung; Zhang, Weisen; Leung, Gabriel M.; Schooling, C Mary

    2016-01-01

    Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (−0.02 per nmol/L testosterone, 95% confidence interval (CI) −0.06–0.02) or MMSE score (0.06, 95% CI −0.002–0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men. PMID:26864717

  1. Fetal Testosterone, Socio-Emotional Engagement and Language Development

    ERIC Educational Resources Information Center

    Farrant, Brad M.; Mattes, Eugen; Keelan, Jeff A.; Hickey, Martha; Whitehouse, Andrew J. O.

    2013-01-01

    The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly…

  2. Functional significance of men's testosterone reactivity to social stimuli.

    PubMed

    Zilioli, Samuele; Bird, Brian M

    2017-10-01

    Rapid testosterone fluctuations in response to social stimuli are observed across a wide range of species, and the highly conserved nature of these fluctuations suggests an adaptive function. This paper reviews the current literature on testosterone reactivity, primarily in human males, and illustrates how life-history theory provides an adequate theoretical framework to interpret findings. The review is structured around supporting evidence suggesting that situations implicated in mating effort either directly (e.g., interactions with a mate) or indirectly (e.g., intrasexual competition) are generally associated with a brief elevation of testosterone, while situations implicated in parenting effort (e.g., nurturant interactions with offspring) are generally associated with a decline in testosterone. Further, we discuss how these fluctuations in testosterone have been linked to future behaviors, and how situational, motivational, and physiological variables moderate the interplay between social stimuli, testosterone reactivity, and behavior. Supporting the notion that testosterone can play a causal role in modulating behavior in response to social stimuli, we also summarize recent single administration studies examining the effects of testosterone on physiology, neurobiology, and behavior. A conceptual model provides links between supported findings, and hypothesized pathways requiring future testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Single-Dose Testosterone Administration Impairs Cognitive Reflection in Men.

    PubMed

    Nave, Gideon; Nadler, Amos; Zava, David; Camerer, Colin

    2017-10-01

    In nonhumans, the sex steroid testosterone regulates reproductive behaviors such as fighting between males and mating. In humans, correlational studies have linked testosterone with aggression and disorders associated with poor impulse control, but the neuropsychological processes at work are poorly understood. Building on a dual-process framework, we propose a mechanism underlying testosterone's behavioral effects in humans: reduction in cognitive reflection. In the largest study of behavioral effects of testosterone administration to date, 243 men received either testosterone or placebo and took the Cognitive Reflection Test (CRT), which estimates the capacity to override incorrect intuitive judgments with deliberate correct responses. Testosterone administration reduced CRT scores. The effect remained after we controlled for age, mood, math skills, whether participants believed they had received the placebo or testosterone, and the effects of 14 additional hormones, and it held for each of the CRT questions in isolation. Our findings suggest a mechanism underlying testosterone's diverse effects on humans' judgments and decision making and provide novel, clear, and testable predictions.

  4. 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

  5. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.

    PubMed

    Ide, Hisamitsu; Lu, Yan; Noguchi, Takahiro; Muto, Satoru; Okada, Hiroshi; Kawato, Suguru; Horie, Shigeo

    2018-04-01

    Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1-month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose-dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1-month oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  6. 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.

  7. 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.

  8. Antispermatogenic Mechanism of Trona is Associated with Lipid Peroxidation but Not Testosterone Suppression.

    PubMed

    Ajayi, Ayodeji F; Akhigbe, Roland E

    2017-01-01

    About half of the cases of infertility in couples have been attributed to male factor. Despite the claim in folklore medicine that trona (a sesquicarbonate or hydrated carbonate of sodium) causes fetal loss, its effect on male reproductive function has not been investigated. This study sought to provide scientific evidence on the effect of trona on sperm characteristics, male reproductive hormones and organs, and lipid peroxidation. Forty male Wistar rats of comparable weights were used for the study. Rats were randomized into four different groups. The control received 1 mL of distilled water orally, whereas those in groups 1, 2, and 3 (test groups) received orally, same volume of trona preparation corresponding to 100, 200, and 400 mg/kg body weight, respectively, for 28 days. Body weight was monitored throughout the study period, and at the end of the experiment, testicular morphometry, sperm characteristic, reproductive hormones, and malondialdehyde (MDA), an index of lipid peroxidation, were determined. Sperm count, motility, progressibility, and percentage of normal sperm were significantly decreased in the trona-treated rats ( P < 0.05). The percentage of abnormal sperm, luteinizing hormone, follicle stimulating hormone, and MDA were significantly increased in the treated rats ( P < 0.05). Body weight, testicular morphometry, and testosterone level were comparable across all groups ( P > 0.05). The study showed that trona has a dose-dependent deleterious effect on sperm characteristic. The antispermatogenic effect of trona was associated with lipid peroxidation but not testosterone.

  9. 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

  10. Body mass reduction markedly improves muscle performance and body composition in obese females aged 61-75 years: comparison between the effects exerted by energy-restricted diet plus moderate aerobic-strength training alone or associated with rGH or nandrolone undecanoate.

    PubMed

    Sartorio, Alessandro; Maffiuletti, Nicola A; Agosti, Fiorenza; Marinone, Pier Giulio; Ottolini, Saverio; Lafortuna, Claudio L

    2004-04-01

    To investigate the effectiveness of a body mass reduction programme entailing diet caloric restriction and moderate physical activity with or without supplementary treatment with recombinant (r) GH or steroids to improve body composition and muscle performance in severely obese women aged 61-75 years. Twenty women were randomly assigned to one of three groups: body mass reduction alone; body mass reduction plus rGH; body mass reduction plus nandrolone undecanoate. Body composition, isotonic muscle strength and anaerobic power output during jumping were determined before and after the 3-week period. Whatever the experimental group considered, body mass (P<0.01), body mass index (P<0.05) and fat mass (P<0.05) decreased significantly, whereas muscle strength and power increased significantly (P<0.05) after the intervention. Small body mass reductions after 3 weeks of energy-restricted diet combined with moderate aerobic and strength exercise are associated with significant improvements in upper and lower limb muscle strength and power and reduction of fat mass in severely obese women aged 61-75 years. Although the association of rGH or nandrolone undecanoate does not appear to exert additional effects on body composition and muscle performance attained by body mass reduction alone, further additional studies with larger study groups, different dosages and more prolonged periods are required for definitive conclusions to be drawn.

  11. Quantum Tunneling in Testosterone 6β-Hydroxylation by Cytochrome P450: Reaction Dynamics Calculations Employing Multiconfiguration Molecular-Mechanical Potential Energy Surfaces

    NASA Astrophysics Data System (ADS)

    Zhang, Yan; Lin, Hai

    2009-05-01

    Testosterone hydroxylation is a prototypical reaction of human cytochrome P450 3A4, which metabolizes about 50% of oral drugs on the market. Reaction dynamics calculations were carried out for the testosterone 6β-hydrogen abstraction and the 6β-d1-testosterone 6β-duterium abstraction employing a model that consists of the substrate and the active oxidant compound I. The calculations were performed at the level of canonical variational transition state theory with multidimensional tunneling and were based on a semiglobal full-dimensional potential energy surface generated by the multiconfiguration molecular mechanics technique. The tunneling coefficients were found to be around 3, indicating substantial contributions by quantum tunneling. However, the tunneling made only modest contributions to the kinetic isotope effects. The kinetic isotope effects were computed to be about 2 in the doublet spin state and about 5 in the quartet spin state.

  12. Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation.

    PubMed

    Sharma, Rishi; Oni, Olurinde A; Gupta, Kamal; Sharma, Mukut; Sharma, Ram; Singh, Vikas; Parashara, Deepak; Kamalakar, Surineni; Dawn, Buddhadeb; Chen, Guoqing; Ambrose, John A; Barua, Rajat S

    2017-05-09

    Atrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone. Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score-weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post-TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81-0.99, P =0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70-0.89, P =0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78- 1.0009, P =0.0675) in incidence of AF. These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  13. Plasmatic testosterone values in 105 Klinefelters.

    PubMed

    Raboch, J; Neuwirth, J; Starka, L

    1975-01-01

    Clinical, spermiologic and karyologic examinations and determinations of plasmatic testosterone were performed in a group of 105 chromatin-positive patients aged 16 to 45 years. A comparison with a control group of 108 somatosexually well developed and fertile men at the age of 21 to 55 years has established that in the Klinefelter's syndrome the male sex hormone level in the blood was highly significantly lower. Whereas in the control group the male sex hormone values in the blood were dependent on age, it was not possible to prove any dynamic changes in the process of ageing between 21 and 45 years in chromatin-positive patients. A comparison of some phenotypical and laboratory findings in the various chromosomal variants of Klinefelter's syndrome shows that comparatively the least changes were found in patients with a mosaic of 46,XY/47,XXY.

  14. Testosterone, Cortisol and Financial Risk-Taking

    PubMed Central

    Herbert, Joe

    2018-01-01

    Both testosterone and cortisol have major actions on financial decision-making closely related to their primary biological functions, reproductive success and response to stress, respectively. Financial risk-taking represents a particular example of strategic decisions made in the context of choice under conditions of uncertainty. Such decisions have multiple components, and this article considers how much we know of how either hormone affects risk-appetite, reward value, information processing and estimation of the costs and benefits of potential success or failure, both personal and social. It also considers how far we can map these actions on neural mechanisms underlying risk appetite and decision-making, with particular reference to areas of the brain concerned in either cognitive or emotional functions. PMID:29867399

  15. Testosterone and muscle hypertrophy in female rats

    NASA Technical Reports Server (NTRS)

    Kuhn, F. E.; Max, S. R.

    1985-01-01

    The effects of chronic treatment with testosterone propionate (TP) on compensatory muscle hypertropy in female rats are examined. The 48 female rats were placed in one of four test groups: (1) no overload (synergist removal), no TP, (2) overload, no TP, (3) no overload + TP, and (4) overload + TP. The technique used to administer the TP is described. The preparation of the plantaris muscle, the analysis of pyruvate oxidation and the determination of malate and lactate dehydrogenases and the noncollogen protein are explained. The results which reveal the effect of overload and TP on body weight, noncollogen protein concentration, lactate and malate dehydrogenase activities, and pyruvate oxidation are presented and discussed. It is concluded that in terms of body weight, protein content, pyruvate, glycolysis, and oxidative metabolisms chronic TP treatments do not change compensatory muscle hypertropy.

  16. Associations of cortisol/testosterone and cortisol/sex hormone-binding globulin ratios with atherosclerosis in middle-age women.

    PubMed

    Lee, Ju-Mi; Colangelo, Laura A; Schwartz, Joseph E; Yano, Yuichiro; Siscovick, David S; Seeman, Teresa; Schreiner, Pamela J; Liu, Kiang J; Lloyd-Jones, Donald M; Greenland, Philip

    2016-05-01

    The cortisol/testosterone (C/T) ratio has been hypothesized to be a better predictor of atherosclerosis than cortisol alone. No study has assessed whether the C/T and C/sex hormone-binding globulin (SHBG) ratios are associated with atherosclerosis in a U.S. population sample. This substudy included 367 women who had both cortisol from year 15 and testosterone and SHBG at year 16 of the Coronary Artery Risk Development in Young Adults study, an ongoing observational cohort in the United States. Of these, intima-media thickness (IMT) was available at follow-up year 20 in 339 (n = 332 with measurement at carotid bulb), and 303 were free of prevalent coronary artery calcium (CAC) at year 15. Area under the curve (AUC) of salivary cortisol was available in 302 individuals. Ratios of AUCs of cortisol to total testosterone, free testosterone, and SHBG were categorized into tertiles. Associations with CAC and IMT were assessed by regression models adjusted for age, race, body mass index, systolic blood pressure, menopause, oral contraceptive use, diabetes, alcohol, and smoking. Only the highest tertile of the AUC/free testosterone ratio was positively associated with carotid bulb IMT (β = 0.088, P = 0.006). This tertile was also positively associated with new onset CAC between year 15 and 25 (OR 3.45, 95% CI 1.18-10.06). Tertiles of cortisol or testosterone alone were not associated with new onset CAC. AUC/Free testosterone ratio may be more associated with atherosclerosis in women than either indicator alone. The ratio may serve as a suitable biomarker of cortisol-linked stress. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. Recruitment and Screening for the Testosterone Trials.

    PubMed

    Cauley, Jane A; Fluharty, Laura; Ellenberg, Susan S; Gill, Thomas M; Ensrud, Kristine E; Barrett-Connor, Elizabeth; Cifelli, Denise; Cunningham, Glenn R; Matsumoto, Alvin M; Bhasin, Shalender; Pahor, Marco; Farrar, John T; Cella, David; Rosen, Raymond C; Resnick, Susan M; Swerdloff, Ronald S; Lewis, Cora E; Molitch, Mark E; Crandall, Jill P; Stephens-Shields, Alisa J; Strorer, Thomas W; Wang, Christina; Anton, Stephen; Basaria, Shehzad; Diem, Susan; Tabatabaie, Vafa; Dougar, Darlene; Hou, Xiaoling; Snyder, Peter J

    2015-09-01

    We describe the recruitment of men for The Testosterone (T) Trials, which were designed to determine the efficacy of T treatment. Men were eligible if they were ≥65 years, had an average of two morning total T values <275 ng/dL with neither value >300 ng/mL, and had symptoms and objective evidence of mobility limitation, sexual dysfunction, and/or low vitality. Men had to be eligible for and enroll in at least one of these three main trials (physical function, sexual function, vitality). Men were recruited primarily through mass mailings in 12 U.S. communities: 82% of men who contacted the sites did so in response to mailings. Men who responded were screened by telephone to ascertain eligibility. Of 51,085 telephone screens, 53.5% were eligible for further screening. Of 23,889 initial screening visits (SV1), 2,781 (11.6%) men were eligible for the second screening visit (SV2), which 2,261 (81.3%) completed. At SV2, 931 (41.2%) men met the criteria for one or more trials, the T level criterion and had no other exclusions. Of these, 790 (84.6%) were randomized; 99 (12.5%) in all three trials and 348 (44%) in two trials. Their mean age was 72 years and mean body mass index (BMI) was 31.0 kg/m(2). Mean (standard deviation) total T (ng/dL) was 212.0 (40.0). Despite the telephone screening to enrollment ratio of 65 to 1, we met the recruitment goals for each trial. Recruitment of symptomatic older men with low testosterone levels is difficult but feasible. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Reactive oxygen species: players in the cardiovascular effects of testosterone

    PubMed Central

    Carneiro, Fernando S.; Carvalho, Maria Helena C.; Reckelhoff, Jane F.

    2015-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

  19. 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

  20. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  1. Testosterone Replacement Therapy and Polycythemia in HIV-infected Patients

    PubMed Central

    Vorkas, Charles Kyriakos; Vaamonde, Carlos M.; Glesby, Marshall J.

    2013-01-01

    We conducted a case-control study to assess testosterone use as a primary risk factor for polycythemia in 21 HIV-infected men. Any testosterone use within two months of first elevated hemoglobin was associated with polycythemia (matched odds ratio 6.55; 95% CI 1.83-23.4; P=0.004) and intramuscular administration demonstrated a stronger association than topical use. No adverse cardiovascular or thrombotic events were observed. HIV-infected patients taking testosterone should undergo routine hematologic monitoring with adjustment of therapy when appropriate. PMID:22008652

  2. The endocrine pharmacology of testosterone therapy in men

    NASA Astrophysics Data System (ADS)

    Oettel, Michael

    The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.

  3. 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.

  4. 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

  5. Protective effect of royal jelly on the sperm parameters and testosterone level and lipid peroxidation in adult mice treated with oxymetholone.

    PubMed

    Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid; Heidari, Reza

    2014-01-01

    Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production in mice. Thirty-two adult male NMRI mice weighing 30±2 g were used. All the animals were divided into 4 groups. received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally. Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for 30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of 100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm motility, viability, maturity, and DNA integrity were analyzed. Furthermore, serum testosterone and MDA concentrations were determined. In Oxymetholone group, sperm count, motility as well as testosterone concentration reduced significantly (p<0.05), while significant (p<0.05) increases in immature sperm, sperm with DNA damaged, and MDA concentration were announced in Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone group. RJ caused partially amelioration in all of the above- mentioned parameters in Royal Jelly+Oxymetholone group. In conclusion, RJ may be used in combination with OX to improve OX-induced oxidative stress and male infertility.

  6. Protective effect of royal jelly on the sperm parameters and testosterone level and lipid peroxidation in adult mice treated with oxymetholone

    PubMed Central

    Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid; Heidari, Reza

    2014-01-01

    Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production in mice. Materials and Methods: Thirty-two adult male NMRI mice weighing 30±2 g were used. All the animals were divided into 4 groups. Control group: received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally. Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for 30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of 100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm motility, viability, maturity, and DNA integrity were analyzed. Furthermore, serum testosterone and MDA concentrations were determined. Results: In Oxymetholone group, sperm count, motility as well as testosterone concentration reduced significantly (p<0.05), while significant (p<0.05) increases in immature sperm, sperm with DNA damaged, and MDA concentration were announced in Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone group. RJ caused partially amelioration in all of the above- mentioned parameters in Royal Jelly+Oxymetholone group. Conclusion: In conclusion, RJ may be used in combination with OX to improve OX-induced oxidative stress and male infertility. PMID:25050300

  7. 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

  8. 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.

  9. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer - oral; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  10. Oral Cancer

    MedlinePlus

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  11. Herpes - oral

    MedlinePlus

    ... items such as towels and linens in boiling hot water after each use. Do not share utensils, straws, glasses, or other items if someone has oral herpes. Do not have oral sex if you have oral herpes, especially if you ...

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Stress-induced suppression of testosterone secretion in male alligators.

    PubMed

    Lance, V A; Elsey, R M

    1986-08-01

    In order to test the effect of acute stress on gonadal hormone secretion in reptiles, six mature male alligators were captured, and a blood sample was taken within 5 min of capture. Additional blood samples were taken at timed intervals for up to 41 hr, and plasma testosterone and corticosterone were measured by radioimmunoassay. Plasma testosterone declined to 50% of the initial value by 4 hr and dropped to less than 10% of initial by 24 hr. Plasma corticosterone increased during the first 12 hr, declined at 24 hr, and rose again at 40 hr. Blood samples from male alligators collected in North and South Carolina, south Florida, and in south Louisiana in two consecutive breeding seasons were also assayed for testosterone and corticosterone. In these populations there were significant differences in mean plasma testosterone and corticosterone levels. Elevated corticosterone levels were consistently seen in alligators caught in traps and from which a blood sample was taken several hours later. Plasma testosterone, although consistently lower in trapped alligators, did not show a negative correlation with plasma corticosterone. Farm-reared alligators bled once, released, and bled again at 24 hr also showed a highly significant suppression of testosterone secretion. These results demonstrate that stress has a rapid and dramatic effect on testicular steroid secretion in both farm-reared and wild alligators.

  17. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  18. Pharmacoepidemiology of testosterone: Curbing off-label prescribing.

    PubMed

    Handelsman, David J

    2017-10-01

    To estimate the impact of the first year of new Pharmaceutical Benefits Scheme (PBS) prescribing criteria that dictate eligibility for national health scheme subsidy of testosterone prescribing. Analysis of cumulative PBS data. Retrospective analysis of testosterone prescribing from PBS data. Nil MAIN OUTCOME MEASURES: PBS expenditure analysed by total expenditure, by state, and by product type as well as the age, indication, and prescriber type for new testosterone treatment. Total PBS expenditure continued to exceed $20 million in 2014 before declining from 2015 with changes that were uniform by state and product type. Prior to 2015, over 80% were for men aged over 40 years of age for low circulating testosterone in the absence of reproductive system disorders ("Low T") initiated by GPs. From 2015, these features were markedly reduced without changing the numbers of new prescriptions for pathological reproductive disorders or specialist initiations. The short-term impact of 2015 PBS criteria showed highly effective and well-targeted curbing of off-label testosterone prescribing. The findings indicate that the main driver for the recent upsurge in testosterone prescribing was treatment of middle-aged men for "Low T" initiated by GPs. © 2017 Government of New South Wales. Pharmacoepidemiology & Drug Safety © 2017 John Wiley & Sons Ltd.

  19. 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

  20. Testosterone Attenuates Age-Related Fall in Aerobic Function in Mobility Limited Older Men With Low Testosterone

    PubMed Central

    Bhasin, Shalender; Travison, Thomas G.; Pencina, Karol; Miciek, Renee; McKinnon, Jennifer; Basaria, Shehzad

    2016-01-01

    Context: Testosterone increases skeletal muscle mass and strength, but the effects of testosterone on aerobic performance in mobility-limited older men have not been evaluated. Objective: To determine the effects of testosterone supplementation on aerobic performance, assessed as peak oxygen uptake (V̇O2peak) and gas exchange lactate threshold (V̇O2θ), during symptom-limited incremental cycle ergometer exercise. Design: Subgroup analysis of the Testosterone in Older Men with Mobility Limitations Trial. Setting: Exercise physiology laboratory in an academic medical center. Participants: Sixty-four mobility-limited men 65 years or older with low total (100–350 ng/dL) or free (<50 pg/dL) testosterone. Interventions: Participants were randomized to receive 100-mg testosterone gel or placebo gel daily for 6 months. Main Outcome Measures: V̇O2peak and V̇O2θ from a symptom-limited cycle exercise test. Results: Mean (SD) baseline V̇O2peak was 20.5 (4.3) and 19.9 (4.7) mL/kg/min for testosterone and placebo, respectively. V̇O2peak increased by 0.83 (2.4) mL/kg/min in testosterone but decreased by −0.89 (2.5) mL/kg/min in placebo (P = .035); between group difference in change in V̇O2peak was significant (P = .006). This 6-month reduction in placebo was greater than the expected −0.4-mL/kg/min/y rate of decline in the general population. V̇O2θ did not change significantly in testosterone but decreased by 1.1 (1.8) mL/kg/min in placebo, P = .011 for between-group comparisons. Hemoglobin increased by 1.0 ± 3.5 and 0.1 ± 0.8 g/dL in testosterone and placebo groups, respectively. Conclusion: Testosterone supplementation in mobility-limited older men increased hemoglobin and attenuated the age-related declines in V̇O2peak and V̇O2θ. Long-term intervention studies are needed to determine the durability of this effect. PMID:27050869

  1. Testosterone Attenuates Age-Related Fall in Aerobic Function in Mobility Limited Older Men With Low Testosterone.

    PubMed

    Storer, Thomas W; Bhasin, Shalender; Travison, Thomas G; Pencina, Karol; Miciek, Renee; McKinnon, Jennifer; Basaria, Shehzad

    2016-06-01

    Testosterone increases skeletal muscle mass and strength, but the effects of testosterone on aerobic performance in mobility-limited older men have not been evaluated. To determine the effects of testosterone supplementation on aerobic performance, assessed as peak oxygen uptake (V̇O2peak) and gas exchange lactate threshold (V̇O2θ), during symptom-limited incremental cycle ergometer exercise. Subgroup analysis of the Testosterone in Older Men with Mobility Limitations Trial. Exercise physiology laboratory in an academic medical center. Sixty-four mobility-limited men 65 years or older with low total (100-350 ng/dL) or free (<50 pg/dL) testosterone. Participants were randomized to receive 100-mg testosterone gel or placebo gel daily for 6 months. V̇O2peak and V̇O2θ from a symptom-limited cycle exercise test. Mean (SD) baseline V̇O2peak was 20.5 (4.3) and 19.9 (4.7) mL/kg/min for testosterone and placebo, respectively. V̇O2peak increased by 0.83 (2.4) mL/kg/min in testosterone but decreased by -0.89 (2.5) mL/kg/min in placebo (P = .035); between group difference in change in V̇O2peak was significant (P = .006). This 6-month reduction in placebo was greater than the expected -0.4-mL/kg/min/y rate of decline in the general population. V̇O2θ did not change significantly in testosterone but decreased by 1.1 (1.8) mL/kg/min in placebo, P = .011 for between-group comparisons. Hemoglobin increased by 1.0 ± 3.5 and 0.1 ± 0.8 g/dL in testosterone and placebo groups, respectively. Testosterone supplementation in mobility-limited older men increased hemoglobin and attenuated the age-related declines in V̇O2peak and V̇O2θ. Long-term intervention studies are needed to determine the durability of this effect.

  2. The laboratory diagnosis of testosterone deficiency.

    PubMed

    Paduch, Darius A; Brannigan, Robert E; Fuchs, Eugene F; Kim, Edward D; Marmar, Joel L; Sandlow, Jay I

    2014-05-01

    The evaluation and treatment of hypogonadal men has become an important part of urologic practice. Fatigue, loss of libido, and erectile dysfunction are commonly reported, but nonspecific symptoms and laboratory verification of low testosterone (T) are an important part of evaluation in addition to a detailed history and physical examination. Significant intraindividual fluctuations in serum T levels, biologic variation of T action on end organs, the wide range of T levels in human serum samples, and technical limitations of currently available assays have led to poor reliability of T measurements in the clinical laboratory setting. There is no universally accepted threshold of T concentration that distinguishes eugonadal from hypogonadal men; thus, laboratory results have to be interpreted in the appropriate clinical setting. This review focuses on clinical, biological, and technological challenges that affect serum T measurements to educate clinicians regarding technological advances and limitations of the currently available laboratory methods to diagnose hypogonadism. A collaborative effort led by the American Urological Association between practicing clinicians, patient advocacy groups, government regulatory agencies, industry, and professional societies is underway to provide optimized assay platforms and evidence-based normal assay ranges to guide clinical decision making. Until such standardization is commonplace in clinical laboratories, the decision to treat should be based on the presence of signs and symptoms in addition to serum T measurements. Rigid interpretation of T ranges should not dictate clinical decision making or define coverage of treatment by third party payers. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Testosterone and sexual function in men.

    PubMed

    Rastrelli, Giulia; Corona, Giovanni; Maggi, Mario

    2018-06-01

    Testosterone (T) is deeply involved in every step of the male sexual response. However, the occurrence of sexual disorders cannot be automatically related to a decline in T levels. In fact, this relationship is complicated by organic, relational and psychological factors, which can independently impair sexual function. For example, it is recognized that erectile dysfunction (ED) can result from vascular damage as well as from low levels of T. T therapy (TTh) can improve sexual function but meta-analyses show that it improves erectile function only in men with ED and overt hypogonadism. Similarly, impaired sexual desire can result from a wide range of organic, relational and psychological factors, although it is recognized as one of the most specific symptoms of hypogonadism. Accordingly, low desire is improved by TTh in men with overt hypogonadism. The association between low T levels and delayed ejaculation has not been well studied and needs further confirmation, as does the role of TTh in such cases. Meta-analyses have found that TTh can improve orgasmic function in hypogonadal men. Clinicians should bear in mind that sexual dysfunctions have multifactorial causes and hypogonadism represents only one of these. Only hypogonadal men are likely to improve their sexual symptoms when treated with TTh. The assessment of serum T levels is mandatory before patients are prescribed TTh, as are the assessment and possible treatment of other concomitant conditions. Copyright © 2018. Published by Elsevier B.V.

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

    PubMed

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

    2018-05-01

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

  5. 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.

  6. Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

    PubMed Central

    Khairullah, Ammar; Cousino Klein, Laura; Ingle, Suzanne M.; May, Margaret T.; Whetzel, Courtney A.; Susman, Elizabeth J.; Paus, Tomáš

    2014-01-01

    Purpose Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development. Methods We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant’s testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years. Results The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty. Conclusions The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics. PMID:25268961

  7. Testosterone influences spatial strategy preferences among adult male rats

    PubMed Central

    Spritzer, Mark D.; Fox, Elliott C.; Larsen, Gregory D.; Batson, Christopher G.; Wagner, Benjamin A.; Maher, Jack

    2013-01-01

    Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats’ strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. PMID:23597827

  8. Testosterone influences spatial strategy preferences among adult male rats.

    PubMed

    Spritzer, Mark D; Fox, Elliott C; Larsen, Gregory D; Batson, Christopher G; Wagner, Benjamin A; Maher, Jack

    2013-05-01

    Males outperform females on some spatial tasks, and this may be partially due to the effects of sex steroids on spatial strategy preferences. Previous work with rodents indicates that low estradiol levels bias females toward a striatum-dependent response strategy, whereas high estradiol levels bias them toward a hippocampus-dependent place strategy. We tested whether testosterone influenced the strategy preferences in male rats. All subjects were castrated and assigned to one of three daily injection doses of testosterone (0.125, 0.250, or 0.500 mg/rat) or a control group that received daily injections of the drug vehicle. Three different maze protocols were used to determine rats' strategy preferences. A low dose of testosterone (0.125 mg) biased males toward a motor-response strategy on a T-maze task. In a water maze task in which the platform itself could be used intermittently as a visual cue, a low testosterone dose (0.125 mg) caused a significant increase in the use of a cued-response strategy relative to control males. Results from this second experiment also indicated that males receiving a high dose of testosterone (0.500 mg) were biased toward a place strategy. A third experiment indicated that testosterone dose did not have a strong influence on the ability of rats to use a nearby visual cue (floating ball) in the water maze. For this experiment, all groups seemed to use a combination of place and cued-response strategies. Overall, the results indicate that the effects of testosterone on spatial strategy preference are dose dependent and task dependent. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Recommendations for the Use of Testosterone in Male Transgender.

    PubMed

    Costa, Laura Bregieiro Fernandes; Rosa-E-Silva, Ana Carolina Japur de Sá; Medeiros, Sebastião Freitas de; Nacul, Andrea Prestes; Carvalho, Bruno Ramalho de; Benetti-Pinto, Cristina Laguna; Yela, Daniela Angerame; Maciel, Gustavo Arantes Rosa; Soares Júnior, José Maria; Maranhão, Técia Maria de Oliveira

    2018-05-01

    Gender incongruence is defined as a condition in which an individual self-identifies and desires to have physical characteristics and social roles that connote the opposite biological sex. Gender dysphoria is when an individual displays the anxiety and/or depression disorders that result from the incongruity between the gender identity and the biological sex. The gender affirmation process must be performed by a multidisciplinary team. The main goal of the hormone treatment is to start the development of male physical characteristics by means of testosterone administration that may be offered to transgender men who are 18 years old or over. The use of testosterone is usually well tolerated and improves the quality of life. However, there is still lack of evidence regarding the effects and risks of the long-term use of this hormone. Many different pharmacological formulations have been used in the transsexualization process. The most commonly used formulation is the intramuscular testosterone esters in a short-term release injection, followed by testosterone cypionate or testosterone enanthate. In the majority of testosterone therapy protocols, the male physical characteristics can be seen in almost all users after 6 months of therapy, and the maximum virilization effects are usually achieved after 3 to 5 years of regular use of the hormone. To minimize risks, plasmatic testosterone levels should be kept within male physiological ranges (300 to 1,000 ng/dl) during hormonal treatment. It is recommended that transgender men under androgen therapy be monitored every 3 months during the 1st year of treatment and then, every 6 to 12 months. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

  10. Hypogonadism and metabolic syndrome: implications for testosterone therapy.

    PubMed

    Makhsida, Nawras; Shah, Jay; Yan, Grace; Fisch, Harry; Shabsigh, Ridwan

    2005-09-01

    Metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia and hypertension, is highly prevalent in the United States. When left untreated, it significantly increases the risk of diabetes mellitus and cardiovascular disease. It has been suggested that hypogonadism may be an additional component of metabolic syndrome. This has potential implications for the treatment of metabolic syndrome with testosterone. We reviewed the available literature on metabolic syndrome and hypogonadism with a particular focus on testosterone therapy. A comprehensive MEDLINE review of the world literature from 1988 to 2004 on hypogonadism, testosterone and metabolic syndrome was performed. Observational data suggest that metabolic syndrome is strongly associated with hypogonadism in men. Multiple interventional studies have shown that exogenous testosterone has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure, which are the parameters most often disturbed in metabolic syndrome. Hypogonadism is likely a fundamental component of metabolic syndrome. Testosterone therapy may not only treat hypogonadism, but may also have tremendous potential to slow or halt the progression from metabolic syndrome to overt diabetes or cardiovascular disease via beneficial effects on insulin regulation, lipid profile and blood pressure. Furthermore, the use of testosterone to treat metabolic syndrome may also lead to the prevention of urological complications commonly associated with these chronic disease states, such as neurogenic bladder and erectile dysfunction. Physicians must be mindful to evaluate hypogonadism in all men diagnosed with metabolic syndrome as well as metabolic syndrome in all men diagnosed with hypogonadism. Future research in the form of randomized clinical trials should focus on further defining the role of testosterone for metabolic syndrome.

  11. Testosterone Conversion Blockade Increases Breathing Stability in Healthy Men during NREM Sleep

    PubMed Central

    Chowdhuri, Susmita; Bascom, Amy; Mohan, David; Diamond, Michael P.; Badr, M. Safwan

    2013-01-01

    Study Objectives: Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. Design: Randomization to oral finasteride vs. sham, single-center study. Setting: Sleep research laboratory. Participants: Fourteen healthy young males without sleep apnea Intervention: Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. Measurements and Results: The apnea threshold (AT) was defined as the end-tidal CO2 (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. The apneic threshold and CO2 reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO2 reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. Conclusions: Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations. Citation: Chowdhuri S; Bascom A; Mohan D; Diamond MP; Badr MS. Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep. SLEEP 2013

  12. Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.

    PubMed

    Gasco, M; Villegas, L; Yucra, S; Rubio, J; Gonzales, G F

    2007-08-01

    The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

  13. 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

  14. Effects of prenatal alcohol exposure on testosterone and pubertal development

    PubMed Central

    Carter, R.C.; Jacobson, J.L.; Dodge, N.C.; Granger, D.A.; Jacobson, S.W.

    2014-01-01

    Background Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic-pituitary-gonadal (HPG) axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development. Methods The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over-represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/mL), self-reported Tanner stages for pubertal development, and age at menarche (females). Results Prenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group X testosterone interaction term and potential confounders. Conclusions This study was the first to show a relation between prenatal alcohol exposure and increased testosterone during

  15. Human social neuroendocrinology: Review of the rapid effects of testosterone.

    PubMed

    Geniole, Shawn N; Carré, Justin M

    2018-06-06

    It is well documented that testosterone concentrations change rapidly within reproductively relevant contexts (e.g., competition, mate-seeking). It has been argued that such rapid changes in testosterone may serve to adaptively fine-tune ongoing and/or future social behaviour according to one's social environment. In this paper, we review human correlational and experimental evidence suggesting that testosterone fluctuates rapidly in response to competition and mate-seeking cues, and that such acute changes may serve to modulate ongoing and/or future social behaviours (e.g., risk-taking, competitiveness, mate-seeking, and aggression). Some methodological details, which limit interpretation of some of this human work, are also discussed. We conclude with a new integrative model of testosterone secretion and behaviour, the Fitness Model of Testosterone Dynamics. Although we focus primarily on human aggression in this review, but we also highlight research on risk-taking, competitiveness, and mate-seeking behaviour. Copyright © 2017. Published by Elsevier Inc.

  16. Testosterone and paternal care in East African foragers and pastoralists

    PubMed Central

    Muller, Martin N.; Marlowe, Frank W.; Bugumba, Revocatus; Ellison, Peter T.

    2008-01-01

    The ‘challenge hypothesis’ posits that testosterone facilitates reproductive effort (investment in male–male competition and mate-seeking) at the expense of parenting effort (investment in offspring and mates). Multiple studies, primarily in North America, have shown that men in committed relationships, fathers, or both maintain lower levels of testosterone than unpaired men. Data from non-western populations, however, show inconsistent results. We hypothesized that much of this cross-cultural variation can be attributed to differential investment in mating versus parenting effort, even among married fathers. Here, we directly test this idea by comparing two neighbouring Tanzanian groups that exhibit divergent styles of paternal involvement: Hadza foragers and Datoga pastoralists. We predicted that high levels of paternal care by Hadza fathers would be associated with decreased testosterone in comparison with non-fathers, and that no such difference between fathers and non-fathers would be evident in Datoga men, who provide minimal direct paternal care. Twenty-seven Hadza men and 80 Datoga men between the ages of 17 and 60 provided morning and afternoon saliva samples from which testosterone was assayed. Measurements in both populations confirmed these predictions, adding further support to the hypothesis that paternal care is associated with decreased testosterone production in men. PMID:18826936

  17. Testosterone-secreting adrenal adenoma in a peripubertal girl

    SciTech Connect

    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

  18. 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.

  19. Effects of Testosterone Administration on Strategic Gambling in Poker Play.

    PubMed

    van Honk, Jack; Will, Geert-Jan; Terburg, David; Raub, Werner; Eisenegger, Christoph; Buskens, Vincent

    2016-01-04

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone's primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players' bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one's reputation by revealing deceptive intent, and secondly, not calling the other players' bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous.

  20. 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

  1. Testosterone as a treatment for fatigue in HIV+ men.

    PubMed

    Wagner, G J; Rabkin, J G; Rabkin, R

    1998-07-01

    This study assessed correlates of fatigue and the efficacy of testosterone therapy as a treatment for fatigue in men with symptomatic HIV and clinical hypogonadism. We conducted a 12-week open trial of testosterone for HIV+ men with clinical hypogonadism (low libido plus at least one of the associated symptoms of depressed mood, fatigue, and weight loss), CD4 count below 400 cells/cu.mm, and serum testosterone level below 500 ng/dl. 108 men entered the trial; 50% were nonwhite and 72% had an AIDS diagnosis. Baseline correlates of fatigue, as measured by the self-report Chalder Fatigue Scale (CFS), included elevated laboratory values (hematocrit, hemoglobin), lower overall physical functioning, greater psychological distress, and reduced quality of life. Sixty-six of 72 men who presented with fatigue completed the trial, with 52 (79%) rated as responders (much improved energy level) by the study doctor. Fatigue declined significantly among responders, but not nonresponders.

  2. 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.

  3. 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.

  4. 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.

  5. Phthalate-Induced Pathology in the Foetal Testis Involves More Than Decreased Testosterone Production

    EPA Science Inventory

    Foetal exposure to phthalates is known to adversely impact male reproductive development and function. Developmental anomalies of reproductive tract have been attributed to impaired testosterone synthesis. However, species differences in the ability to produce testosterone have...

  6. Testosterone Stimulates Duox1 Activity through GPRC6A in Skin Keratinocytes*

    PubMed Central

    Ko, Eunbi; Choi, Hyun; Kim, Borim; Kim, Minsun; Park, Kkot-Nara; Bae, Il-Hong; Sung, Young Kwan; Lee, Tae Ryong; Shin, Dong Wook; Bae, Yun Soo

    2014-01-01

    Testosterone is an endocrine hormone with functions in reproductive organs, anabolic events, and skin homeostasis. We report here that GPRC6A serves as a sensor and mediator of the rapid action of testosterone in epidermal keratinocytes. The silencing of GPRC6A inhibited testosterone-induced intracellular calcium ([Ca2+]i) mobilization and H2O2 generation. These results indicated that a testosterone-GPRC6A complex is required for activation of Gq protein, IP3 generation, and [Ca2+]i mobilization, leading to Duox1 activation. H2O2 generation by testosterone stimulated the apoptosis of keratinocytes through the activation of caspase-3. The application of testosterone into three-dimensional skin equivalents increased the apoptosis of keratinocytes between the granular and stratified corneum layers. These results support an understanding of the molecular mechanism of testosterone-dependent apoptosis in which testosterone stimulates H2O2 generation through the activation of Duox1. PMID:25164816

  7. 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 ...

  8. 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.

  9. Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer.

    PubMed

    Golla, Vishnukamal; Kaplan, Alan L

    2017-07-01

    Previously considered an absolute contraindication, the use of testosterone therapy in men with prostate cancer has undergone an important paradigm shift. Recent data has changed the way we approach the treatment of testosterone deficiency in men with prostate cancer. In the current review, we summarize and analyze the literature surrounding effects of testosterone therapy on patients being treated in an active surveillance protocol as well as following definitive treatment for prostate cancer. The conventional notion that defined the relationship between increasing testosterone and prostate cancer growth was based on limited studies and anecdotal case reports. Contemporary evidence suggests testosterone therapy in men with testosterone deficiency does not increase prostate cancer risk or the chances of more aggressive disease at prostate cancer diagnosis. Although the studies are limited, men who received testosterone therapy for localized disease did not have higher rates of recurrences or worse clinical outcomes. Current review of the literature has not identified adverse progression events for patients receiving testosterone therapy while on active surveillance/watchful waiting or definitive therapies. The importance of negative effects of testosterone deficiency on health and health-related quality of life measures has pushed urologists to re-evaluate the role testosterone plays in prostate cancer. This led to a paradigm shift that testosterone therapy might in fact be a viable option for a select group of men with testosterone deficiency and a concurrent diagnosis of prostate cancer.

  10. 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…

  11. 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

  12. The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment.

    PubMed

    Ng Tang Fui, Mark; Hoermann, Rudolf; Zajac, Jeffrey D; Grossmann, Mathis

    2017-10-01

    Testosterone treatment in obese dieting men augments the diet-associated loss of fat mass, but protects against loss of lean mass. We assessed whether body composition changes are maintained following withdrawal of testosterone treatment. We conducted a prespecified double-blind randomized placebo-controlled observational follow-up study of a randomized controlled trial (RCT). Participants were men with baseline obesity (body mass index >30 kg/m 2 ) and a repeated total testosterone level <12 nmol/L, previously enrolled in a 56-week testosterone treatment trial combined with a weight loss programme. Main outcome measures were mean adjusted differences (MAD) (95% confidence interval), in body composition between testosterone- and placebo-treated men at the end of the observation period. Of the 100 randomized men, 82 completed the RCT and 64 the subsequent observational study. Median [IQR] observation time after completion of the RCT was 82 weeks [74; 90] in men previously receiving testosterone (cases) and 81 weeks [67;91] in men previously receiving placebo (controls), P=.51. At the end of the RCT, while losing similar amounts of weight, cases had, compared to controls, lost more fat mass, MAD -2.9 kg (-5.7, -0.2), P=.04, but had lost less lean mass MAD 3.4 kg (1.3, 5.5), P=.002. At the end of the observation period, the former between-group differences in fat mass, MAD -0.8 kg (-3.6, 2.0), P=1.0, in lean mass, MAD -1.3 kg (-3.0, 0.5), P=.39, and in appendicular lean mass, MAD -0.1 kg/m 2 (-0.3, 0.1), P=.45, were no longer apparent. During observation, cases lost more lean mass, MAD -3.7 kg (-5.5, -1.9), P=.0005, and appendicular lean mass, MAD -0.5 kg/m 2 (-0.8, -0.3), P<.0001 compared to controls. The favourable effects of testosterone on body composition in men subjected to a concomitant weight loss programme were not maintained at 82 weeks after testosterone treatment cessation. © 2017 John Wiley & Sons Ltd.

  13. Low Testosterone Correlates with Delayed Development in Male Orangutans

    PubMed Central

    Emery Thompson, Melissa; Zhou, Amy; Knott, Cheryl D.

    2012-01-01

    Male orangutans (Pongo spp.) display an unusual characteristic for mammals in that some adult males advance quickly to full secondary sexual development while others can remain in an adolescent-like form for a decade or more past the age of sexual maturity. Remarkably little is understood about how and why differences in developmental timing occur. While fully-developed males are known to produce higher androgen levels than arrested males, the longer-term role of steroid hormones in male life history variation has not been examined. We examined variation in testosterone and cortisol production among 18 fully-developed (“flanged”) male orangutans in U.S. captive facilities. Our study revealed that while testosterone levels did not vary significantly according to current age, housing condition, and species origin, males that had undergone precocious development had higher testosterone levels than males that had experienced developmental arrest. While androgen variation had previously been viewed as a state-dependent characteristic of male developmental status, our study reveals that differences in the physiology of early and late developing males are detectable long past the developmental transition and may instead be trait-level characteristics associated with a male’s life history strategy. Further studies are needed to determine how early in life differences in testosterone levels emerge and what consequences this variation may have for male behavioral strategies. PMID:23077585

  14. A longitudinal analysis of women's salivary testosterone and intrasexual competitiveness.

    PubMed

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

    2016-02-01

    Research on within-subject changes in women's intrasexual competitiveness has generally focused on possible relationships between women's intrasexual competitiveness and estimates of their fertility. While this approach is useful for testing hypotheses about the adaptive function of changes in women's intrasexual competitiveness, it offers little insight into the proximate mechanisms through which such changes might occur. To investigate this issue, we carried out a longitudinal study of the hormonal correlates of changes in intrasexual competitiveness in a large sample of heterosexual women (N=136). Each woman provided saliva samples and completed an intrasexual competitiveness questionnaire in five weekly test sessions. Multilevel modeling of these data revealed a significant, positive within-subject effect of testosterone on intrasexual competitiveness, indicating that women reported greater intrasexual competitiveness when testosterone was high. By contrast, there were no significant effects of estradiol, progesterone, estradiol-to-progesterone ratio, or cortisol and no significant effects of any hormones on reported relationship jealousy. This is the first study to demonstrate correlated changes in measured testosterone levels and women's reported intrasexual competitiveness, implicating testosterone in the regulation of women's intrasexual competitiveness. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  15. EFFECTS OF ENVIRONMENTAL CHEMICALS ON FETAL TESTES TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Effects of Environmental Chemicals on Fetal Testes Testosterone Production

    Lambright, CS , Wilson, VS , Furr, J, Wolf, CJ, Noriega, N, Gray, LE, Jr.
    US EPA, ORD/NHEERL/RTD, RTP, NC

    Exposure of pregnant rodents to certain environmental chemicals during criti...

  16. Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

    PubMed Central

    Barone, Rosario; Marino Gammazza, Antonella; Sangiorgi, Claudia; Barone, Fulvio; Pitruzzella, Alessandro; Locorotondo, Nicola; Di Gaudio, Francesca; Salerno, Monica; Maglietta, Francesca; Sarni, Antonio Luciano; Di Felice, Valentina; Cappello, Francesco; Turillazzi, Emanuela

    2015-01-01

    Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin‐releasing hormone, luteinizing hormone, and follicle‐stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real‐time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the basal level a 15.6 μM dose of nandrolone. Nandrolone‐induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a‐hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down‐regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects. J. Cell. Physiol. 231: 1385–1391, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:26626779

  17. Low testosterone levels in elderly men with dysthymic disorder.

    PubMed

    Seidman, Stuart N; Araujo, Andre B; Roose, Steven P; Devanand, D P; Xie, Shan; Cooper, Thomas B; McKinlay, John B

    2002-03-01

    A decline in hypothalamic-pituitary-gonadal (HPG) axis function is often seen in elderly men, and dysthymic disorder is common. Symptoms of both HPG axis hypofunction and dysthymic disorder include dysphoria, fatigue, and low libido. The authors compared total testosterone levels in three groups of elderly men. Total testosterone levels were measured in subjects who met DSM-IV criteria for major depressive disorder (N=13) or dysthymic disorder (N=32) and a comparison group (N=175) who had participated in an epidemiological study of male aging and had scored below the median on the Center for Epidemiologic Studies Depression Scale, a well-validated, self-report depression symptom inventory. There were no differences among the three groups in measured demographic variables, including age and weight. Median testosterone levels varied for those with dysthymic disorder (295 ng/dl), major depressive disorder (425 ng/dl), and no depression (423 ng/dl). A test for differences in central tendency showed a statistically significant difference among the three groups. Post hoc pairwise comparisons revealed statistically significant differences between those with dysthymic disorder and those with major depressive disorder and no depression. Total testosterone levels were lower in elderly men with dysthymic disorder than in men with major depressive disorder and men without depressive symptoms. Dysthymic disorder in elderly men may be related to HPG axis hypofunction.

  18. Foetal Testosterone, Social Relationships, and Restricted Interests in Children

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca; Baron-Cohen, Simon; Raggatt, Peter; Taylor, Kevin

    2005-01-01

    Background: Sex-differences exist in some areas of human social behaviour. In animals, foetal testosterone (fT) plays a central role in organising the brain and in later social behaviour. fT has also been implicated in language development, eye-contact, and spatial ability in humans. Methods: Fifty-eight children (35 male and 23 female), whose fT…

  19. IQ, Fetal Testosterone and Individual Variability in Children's Functional Lateralization

    ERIC Educational Resources Information Center

    Mercure, Evelyne; Ashwin, Emma; Dick, Frederic; Halit, Hanife; Auyeung, Bonnie; Baron-Cohen, Simon; Johnson, Mark H.

    2009-01-01

    Previous event-related potential (ERP) studies have revealed that faces and words show a robust difference in the lateralization of their N170. The present study investigated the development of this differential lateralization in school-age boys. We assessed the potential role of fetal testosterone (FT) level as a factor biasing the prenatal…

  20. Second-to-Fourth Digit Length, Testosterone and Spatial Ability

    ERIC Educational Resources Information Center

    Kempel, P.; Gohlke, B.; Klempau, J.; Zinsberger, P.; Reuter, M.; Hennig, J.

    2005-01-01

    Based on stimulating findings suggesting that prenatal levels of steroids may influence cognitive functions, a study with N=40 healthy volunteers of both sexes was conducted. Prenatal levels of testosterone (T) were estimated by use of the second-to-fourth digit ratio (2D:4D) which is supposed to be controlled by the same genes involved in…

  1. Fate of estradiol and testosterone in anaerobic lagoon digestors

    USDA-ARS?s Scientific Manuscript database

    Laboratory-scale lagoon digestors were constructed, and the fate of 14C-labelled 17ß-estradiol (E2) and testosterone (Test) were monitored for 42 d anaerobically under biological and sterile conditions. Hormone levels decreased in the liquid layer and increased in the sludge with time. At 42 d, 16-2...

  2. Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics.

    PubMed

    Collongues, Nicolas; Patte-Mensah, Christine; De Seze, Jérôme; Mensah-Nyagan, Ayikoe-Guy; Derfuss, Tobias

    2018-06-01

    Neuroprotection and remyelination are two unmet needs in the treatment of multiple sclerosis (MS). Therapeutic potential has been identified with sexual hormones, supported in women by a decrease in MS activity during the pregnancy, in men by a greater severity of symptoms and a faster progression than in women. Areas covered: The therapeutic effect of testosterone and estrogens is reviewed. Both hormones have demonstrated an anti-inflammatory effect. Testosterone has an effect in protecting neurons in culture against glutamate-induced toxicity and oxidative stress, and stimulates myelin formation and regeneration mediated through the neural androgen receptor. In experimental autoimmune encephalomyelitis model, estrogens significantly decrease inflammation in the central nervous system via ERα, while its action on ERβ leads to myelin and axon reparation. Estriol therapy in two phase 2 trials showed a decrease in clinical disease activity and inflammatory parameters in MRI. However, evidence of a therapeutic effect of testosterone is scarce. Expert commentary: Phase 3 trials with estriol as an add-on supplementation are now mandatory. Testosterone is another candidate to be tested in phase 2 trials. These hormones should be considered as an adjunctive therapy. New validated tools are needed to assess their effect on neuroprotection and remyelination.

  3. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  4. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  5. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  6. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  7. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  8. Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells.

    PubMed

    Pomara, Cristoforo; Barone, Rosario; Marino Gammazza, Antonella; Sangiorgi, Claudia; Barone, Fulvio; Pitruzzella, Alessandro; Locorotondo, Nicola; Di Gaudio, Francesca; Salerno, Monica; Maglietta, Francesca; Sarni, Antonio Luciano; Di Felice, Valentina; Cappello, Francesco; Turillazzi, Emanuela

    2016-06-01

    Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real-time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the basal level a 15.6 μM dose of nandrolone. Nandrolone-induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a-hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down-regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  9. Effects of Testosterone Administration on Strategic Gambling in Poker Play

    PubMed Central

    van Honk, Jack; Will, Geert-Jan; Terburg, David; Raub, Werner; Eisenegger, Christoph; Buskens, Vincent

    2016-01-01

    Testosterone has been associated with economically egoistic and materialistic behaviors, but -defensibly driven by reputable status seeking- also with economically fair, generous and cooperative behaviors. Problematically, social status and economic resources are inextricably intertwined in humans, thus testosterone’s primal motives are concealed. We critically addressed this issue by performing a placebo-controlled single-dose testosterone administration in young women, who played a game of bluff poker wherein concerns for status and resources collide. The profit-maximizing strategy in this game is to mislead the other players by bluffing randomly (independent of strength of the hand), thus also when holding very poor cards (cold bluffing). The profit-maximizing strategy also dictates the players in this poker game to never call the other players’ bluffs. For reputable-status seeking these materialistic strategies are disadvantageous; firstly, being caught cold bluffing damages one’s reputation by revealing deceptive intent, and secondly, not calling the other players’ bluffs signals submission in blindly tolerating deception. Here we show that testosterone administration in this game of bluff poker significantly reduces random bluffing, as well as cold bluffing, while significantly increasing calling. Our data suggest that testosterone in humans primarily motivates for reputable-status seeking, even when this elicits behaviors that are economically disadvantageous. PMID:26727636

  10. [Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

    PubMed

    Gonzales, Gustavo F

    2011-03-01

    The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

  11. 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

  12. Testosterone deficiency prevents left ventricular contractility dysfunction after myocardial infarction.

    PubMed

    Ribeiro Júnior, R F; Ronconi, K S; Jesus, I C G; Almeida, P W M; Forechi, L; Vassallo, D V; Guatimosim, S; Stefanon, I; Fernandes, A A

    2018-01-15

    Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups. Eight weeks after MI, papillary muscle contractility was analyzed under increasing calcium (0.62, 1.25, 2.5 and 3.75 mM) and isoproterenol (10 -8 to 10 -2  M) concentrations. Ventricular myocytes were isolated for intracellular calcium measurements and assessment of Ca 2+ handling proteins. Contractility was preserved in the orchidectomized animals after myocardial infarction and was reduced when testosterone was replaced (Ca 2+ 3.75 mM: Sham: 608 ± 70 (n = 11); OCT: 590 ± 37 (n = 16); MI: 311 ± 33* (n = 9); OCT + MI: 594 ± 76 (n = 7); OCT + MI + T: 433 ± 38* (n=4), g/g *p < 0.05 vs Sham). Orchidectomy also increased the Ca 2+ transient amplitude of the ventricular myocytes and SERCA-2a protein expression levels. PLB phosphorylation levels at Thr 17 were not different in the orchidectomized animals compared to the Sham animals but were reduced after testosterone replacement. CAMKII phosphorylation and protein nitrosylation increased in the orchidectomized animals. Our results support the view that testosterone deficiency prevents MI contractility dysfunction by altering the key proteins involved in Ca 2+ handling. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Marketing and Testosterone Treatment in the USA: A Systematic Review.

    PubMed

    Bandari, Jathin; Ayyash, Omar M; Emery, Sherry L; Wessel, Charles B; Davies, Benjamin J

    2017-10-01

    Testosterone replacement therapy (TRT) is currently approved by the Food and Drug Administration only for classic hypogonadism, although off-label indications have resulted in a dramatic expansion in prescriptions in the USA. Marketing may significantly affect prescriber behavior. To systematically review all available evidence on marketing and TRT in the USA. PubMed, Embase, and Scopus were searched up to July 2017 for all relevant publications reporting on assessments of the TRT market size, economic costs associated with hypogonadism, trends in TRT prescriptions, drug discontinuation rates, and advertising and sales efforts in the USA. Twenty retrospective studies were included in the final analysis. The market size for hypogonadism constitutes 5.6-76.8% of men in the USA, with the lower end of the range representing the strictest criteria for diagnosis. Men with a diagnosis of hypogonadism consume $14 118 in direct and indirect costs to the payer. Over the last 2 decades, TRT prescriptions have increased between 1.8- and 4-fold. After 1 yr, 80-85% of men discontinue TRT. There is an association between direct-to-consumer advertising and testosterone testing, TRT prescriptions, and TRT without testosterone testing. There is a high prevalence of misinformation on Internet advertising. Off-label indications have driven the dramatic expansion of TRT prescriptions over the last 2 decades. Direct-to-consumer advertising poses a unique challenge in the USA. Overtreatment can be avoided by applying strict diagnostic criteria for hypogonadism, which limits the addressable market for TRT. In this report, we reviewed the relationship between marketing and testosterone therapy in the USA. We found that many patients are prescribed testosterone without an appropriate diagnosis of hypogonadism, which may be related to the marketing efforts for off-label prescribing. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores.

    PubMed

    Key, T J; Roe, L; Thorogood, M; Moore, J W; Clark, G M; Wang, D Y

    1990-07-01

    Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

  15. Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men.

    PubMed

    Roy, Tracey Ann; Blackman, Marc R; Harman, S Mitchell; Tobin, Jordan D; Schrager, Matthew; Metter, E Jeffery

    2002-08-01

    Muscle mass and strength losses during aging may be associated with declining levels of serum testosterone (T) in men. Few studies have shown a direct relationship between T and muscle mass and strength. Subjects were 262 men, aged 24-90 yr, from the Baltimore Longitudinal Study of Aging, who had T and sex hormone-binding globulin sex hormone-binding globulin (SHBG) measurements, from which the free T index (FTI) was calculated (T/SHBG) from serum samples collected longitudinally since 1963, total body fat mass and arm and leg fat-free mass (FFM) by dual-energy X-ray absorptiometry and arm and leg strength by dynanomometry. Mixed-effects models estimated T and FTI at the time of mass and strength measurements. Age, total body fat, arm and leg FFM, T, and FTI were significantly associated with concentric and eccentric strength. FTI, not T, was modestly, but directly, related to arm and leg strength after fat, arm and leg FFM, height, and age were accounted for and indirectly through body mass. FTI is a better predictor of arm and leg strength than T in aging men.

  16. 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.

  17. 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

  18. Exogenous testosterone decreases men's personal distance in a social threat context.

    PubMed

    Wagels, Lisa; Radke, Sina; Goerlich, Katharina Sophia; Habel, Ute; Votinov, Mikhail

    2017-04-01

    Testosterone can motivate human approach and avoidance behavior. Specifically, the conscious recognition of and implicit reaction to angry facial expressions is influenced by testosterone. The study tested whether exogenous testosterone modulates the personal distance (PD) humans prefer in a social threat context. 82 healthy male participants underwent either transdermal testosterone (testosterone group) or placebo application (placebo group). Each participant performed a computerized stop-distance task before (T1) and 3.5h after (T2) treatment, during which they indicated how closely they would approach a human, animal or virtual character with varying emotional expression. Men's PD towards humans and animals varied as a function of their emotional expression. In the testosterone group, a pre-post comparison indicated that the administration of 50mg testosterone was associated with a small but significant reduction of men's PD towards aggressive individuals. Men in the placebo group did not change the initially chosen PD after placebo application independent of the condition. However comparing the testosterone and placebo group after testosterone administration did not reveal significant differences. While the behavioral effect was small and only observed as within-group effect it was repeatedly and selectively shown for men's PD choices towards an angry woman, angry man and angry dog in the testosterone group. In line with the literature, our findings in young men support the influential role of exogenous testosterone on male's approach behavior during social confrontations. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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.

  20. Longitudinal synergies between cortisol reactivity and diurnal testosterone and antisocial behavior in young adolescents.

    PubMed

    Susman, Elizabeth J; Peckins, Melissa K; Bowes, Jacey L; Dorn, Lorah D

    2017-10-01

    The aims were to identify the correspondence between simultaneous, longitudinal changes in cortisol reactivity and diurnal testosterone and to test the hypothesis that cortisol reactivity and diurnal testosterone interact so as to influence antisocial behavior. Participants were 135 children and young adolescents assessed at 6-month intervals over 1 year. Upon enrollment girls were age 8, 10, or 12 years (N = 69, M = 10.06 years) and boys were age 9, 11, or 13 years (N = 66, M = 10.94 years). Assessments included Tanner staging by a nurse, cortisol reactivity (Trier Social Stress Test for Children), diurnal testosterone, and interviews and questionnaires. Growth models showed that cortisol reactivity and diurnal testosterone basal levels (intercept) and rate of change (slopes) were not related, suggesting different mechanisms of growth. Longitudinal regression analyses assessed cortisol reactivity and diurnal testosterone longitudinally. The interactions of cortisol reactivity and diurnal testosterone showed that when diurnal testosterone was low, boys with low cortisol reactivity were reported to have more behavior problems (i.e., oppositional defiant disorder symptoms and attention problems) than when testosterone was high. In addition, when diurnal testosterone was high, boys with high or moderate cortisol reactivity were significantly higher on total antisocial behavior, attention behavior problems, and oppositional defiant disorder symptoms than when testosterone was low or moderate. The results were similar but less frequent for girls. These findings advance the science of young adolescence by showing the interaction between preexisting sensitivity to stressors and the normative testosterone changes of puberty and antisocial behavior.

  1. "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.

  2. “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

  3. [The importance of testosterone in the treatment of metabolic syndrome in men].

    PubMed

    Kempisty-Zdebik, Ewa; Zdebik, Aleksander

    2012-01-01

    Testosterone deficiency syndrome is being seen in increasing percentage of men with middle and old age. Besides the typical deterioration of sexual function there is predisposition to metabolic syndrome and increased risk of cardiovascular diseases. The similarity of the effects of testosterone substitution and the dietary treatment led the authors to a retrospective analysis of patient data treated for testosterone deficiency syndrome. Data on 341 patients aged over 45 years with metabolic syndrome and diabetes, meeting criteria for the diagnosis of testosterone deficiency syndrome were divided into 5 groups: T--testosterone substitution without additional diet, T-Low-Carb--testosterone and low carbohydrate diet, T-Fat-Low--testosterone and low fat diet, Carb-Low--only low carbohydrate diet, Fat-Low--only low fat diet. We analyzed change in body weight, waist circumference, blood pressure, fasting glucose, HbAlc, HDL cholesterol and triglyceride levels within 6 months from the start of observation. The best results of all investigated parameters were obtained in patients treated with testosterone and low-carbohydrate diet and in the group treated with testosterone and low-fat diet. Slightly worse results in the group received the same diets and the worst in the group treated only with testosterone. The improvement obtained in the total testosterone therapy and diet was much greater than the simple sum of the effects of both methods witch suggests the existence of synergies.

  4. 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

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

    PubMed Central

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

    2015-01-01

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

  6. Quantitative determination of testosterone levels with biolayer interferometry.

    PubMed

    Zhang, Hao; Li, Wei; Luo, Hong; Xiong, Guangming; Yu, Yuanhua

    2017-10-01

    Natural and synthetic steroid hormones are widely spread in the environment and are considered as pollutants due to their endocrine activities, even at low concentrations, which are harmful to human health. To detect steroid hormones in the environment, a novel biosensor system was developed based on the principle of biolayer interferometry. Detection is based on changes in the interference pattern of white light reflected from the surface of an optical fiber with bound biomolecules. Monitoring interactions between molecules does not require radioactive, enzymatic, or fluorescent labels. Here, 2 double-stranded DNA fragments of operator 1 (OP1) and OP2 containing 10-bp palindromic sequences in chromosomal Comamonas testosteroni DNA (ATCC11996) were surface-immobilized to streptavidin sensors. Interference changes were detected when repressor protein RepA bound the DNA sequences. DNA-protein interactions were characterized and kinetic parameters were obtained. The dissociation constants between the OP1 and OP2 DNA sequences and RepA were 9.865 × 10 -9  M and 2.750 × 10 -8  M, respectively. The reactions showed high specifically and affinity. Because binding of the 10-bp palindromic sequence and RepA was affected by RepA-testosterone binding, the steroid could be quantitatively determined rapidly using the biosensor system. The mechanism of the binding assay was as follows. RepA could bind both OP1 and testosterone. RepA binding to testosterone changed the protein conformation, which influenced the binding between RepA and OP1. The percentage of the signal detected negative correlation with the testosterone concentration. A standard curve was obtained, and the correlation coefficient value was approximately 0.97. We could quantitatively determine testosterone levels between 2.13 and 136.63 ng/ml. Each sample could be quantitatively detected in 17 min. These results suggested that the specific interaction between double-stranded OP1 DNA and the RepA protein

  7. Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men.

    PubMed

    Dalmasso, Carolina; Patil, Chetan N; Yanes Cardozo, Licy L; Romero, Damian G; Maranon, Rodrigo O

    2017-10-17

    The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. ORAL INTERPRETATION.

    ERIC Educational Resources Information Center

    CAMPBELL, PAUL N.

    THE BASIC PREMISE OF THIS BOOK IS THAT LEARNING TO READ ORALLY IS OF FUNDAMENTAL IMPORTANCE TO THOSE WHO WOULD FULLY APPRECIATE OR RESPOND TO LITERATURE. BECAUSE READERS MUST INTERPRET LITERATURE ALWAYS FOR THEMSELVES AND OFTEN FOR AN AUDIENCE, THREE ASPECTS OF ORAL INTERPRETATION ARE EXPLORED--(1) THE CHOICE OF MATERIALS, WHICH REQUIRES AN…

  9. Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels.

    PubMed

    Cunningham, Glenn R; Stephens-Shields, Alisa J; Rosen, Raymond C; Wang, Christina; Bhasin, Shalender; Matsumoto, Alvin M; Parsons, J Kellogg; Gill, Thomas M; Molitch, Mark E; Farrar, John T; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A; Cifelli, Denise; Crandall, Jill P; Ensrud, Kristine E; Gallagher, Laura; Zeldow, Bret; Lewis, Cora E; Pahor, Marco; Swerdloff, Ronald S; Hou, Xiaoling; Anton, Stephen; Basaria, Shehzad; Diem, Susan J; Tabatabaie, Vafa; Ellenberg, Susan S; Snyder, Peter J

    2016-08-01

    The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function. To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes. A placebo-controlled trial. Twelve academic medical centers in the United States. A total of 470 men ≥65 years of age with low libido, average T <275 ng/dL, and a partner willing to have sexual intercourse at least twice a month. Men were assigned to take T gel or placebo for 1 year. Sexual function was assessed by three questionnaires every 3 months: the Psychosexual Daily Questionnaire, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function. Compared with placebo, T administration significantly improved 10 of 12 measures of sexual activity. Incremental increases in total and free T and estradiol levels were associated with improvements in sexual activity and desire, but not erectile function. No threshold T level was observed for any outcome, and none of the 27 baseline characteristics predicted responsiveness to T. In older men with low libido and low T levels, improvements in sexual desire and activity in response to T treatment were related to the magnitude of increases in T and estradiol levels, but there was no clear evidence of a threshold effect.

  10. Male osteoporosis and androgenic therapy: from testosterone to SARMs

    PubMed Central

    Cilotti, Antonio; Falchetti, Alberto

    2009-01-01

    As in the women, male osteoporosis represents an important social problem, amplified by the increasing life expectance. Differently from women, 50% of male osteoporosis is secondary to treatments and/or diseases that make mandatory their search through an accurate clinical investigations in every newly diagnosed osteoporotic men. Male osteoporosis is frequently underdiagnosed and consequently undertreated, and too often it is revealed only after the occurrence of a fragility fracture. Androgens may prevent the loss of cancellous bone and stimulate periosteal cortical bone apposition. The anabolic effect of testosterone on both bone and muscle, is limited by the high incidence of androgenic side effects. Hypogonadism is the only situation where the benefits of the use of testosterone formulations exceed the side effects. Selective androgen receptor modulators can dissociate androgenic and anabolic effect on different tissues with various strategies. Many compounds have been studied with positive results in vivo and in clinical trials. PMID:22461251

  11. Protective effects of new Wenshen Shengjing Decoction on cyclosporine-induced impairment of testosterone synthesis and spermatogenic apoptosis.

    PubMed

    Pan, Xiaoyan; Wang, Xiyan; Wang, Xuenan; Zhang, Wansheng; Sun, Zhanxuan; Liang, Xuanxuan; Zhang, Xue; Li, Wenjun; Li, Zhixin

    2018-01-01

    The aim of the present study was to investigate the potential protective effects of new Wenshen Shengjing Decoction (new WSSJD; including Cornu Cervi Nippon Parvum , Panax ginseng, Cynomorium songaricum, Cistanche deserticola, Radix Astragali, Epimedium brevicornum and Angelica sinensis) on cyclosporine-induced impairment of testosterone synthesis and spermatogenic apoptosis in mice. A total of 90 adult male Kunming mice were divided into the following 6 groups: Control (no intervention), dimethylsulfoxide (DMSO; received only DMSO), cyclosporine A (CsA), clomifene citrate (CC; CsA + CC, 15 mg/kg/day), WSSJD (CsA + WSSJD, crude drug 12 g/kg/day) and new WSSJD (CsA + new WSSJD, crude drug 12 g/kg/day). All mice were treated for 30 days via oral gavage. The testes were subsequently fixed and stained with hematoxylin & eosin to assess the development of seminiferous epithelia. Immunohistochemical techniques were used to detect the expression of luteinizing hormone receptor (LHR) and P450 side chain cleavage (P450scc) in testicular Leydig cells. In addition, the apoptosis of spermatogenic cells in the testes was detected using a terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling assay, and flow cytometry was used to analyze the survival rate and early apoptosis of sperm in the epididymis. Compared with the CsA and CC groups, new WSSJD administration significantly increased levels of serum testosterone and the expressions of LHR and P450scc in testicular Leydig cells (P<0.05), while the apoptosis of spermatogenic cells in the seminiferous tubules and early apoptosis of mature sperm were significantly decreased (P<0.05). These results suggest that new WSSJD may ameliorate CsA-induced spermatogenic damage in male mice by enhancing testosterone synthesis and the secretion of testicular Leydig cells, and by reducing the apoptosis of spermatogenic cells.

  12. Use of Exogenous Testosterone for the Treatment of Male Factor Infertility: A Survey of Nigerian Doctors.

    PubMed

    Omisanjo, Olufunmilade Akinfolarin; Ikuerowo, Stephen Odunayo; Abdulsalam, Moruf Adekunle; Ajenifuja, Sheriff Olabode; Shittu, Khadijah Adebisi

    2017-01-01

    Though exogenous testosterone is known for its contraceptive effects in men, it is sometimes prescribed by medical practitioners for the treatment of male factor infertility in the mistaken belief that exogenous testosterone improves sperm count. The aim of this study was to evaluate the scope of testosterone use in the treatment of male factor infertility by medical practitioners in Lagos, Nigeria. A survey using a structured questionnaire was carried out amongst doctors attending a regular Continuing Medical Education (CME) programme in Lagos, Nigeria. There were 225 respondents. Most of the respondents (69.8%, n = 157) indicated that exogenous testosterone increases sperm count. Only 22 respondents (9.8%) indicated (correctly) that exogenous testosterone decreases sperm count. Seventy-seven respondents (34.2%) had prescribed some form of exogenous testosterone in the treatment of male factor infertility. The vast majority of respondents who had prescribed testosterone (81.8%, n = 63) thought exogenous testosterone increases sperm count. There was no statistically significant difference in the pattern of prescription across the respondents' specialty ( p = 0.859) or practice type ( p = 0.747). The misuse of exogenous testosterone for the treatment of male infertility was common amongst the respondents, with most of them wrongly believing that exogenous testosterone increases sperm count.

  13. Sexually stimulated testosterone release in male mice (Mus musculus): roles of genotype and sexual arousal.

    PubMed

    James, Peter J; Nyby, John G; Saviolakis, George A

    2006-09-01

    In virtually every mammalian species examined, some males exhibit reflexive testosterone release upon encountering a novel female (or female-related stimulus). At the same time, not every individual male (or every published study) provides evidence for reflexive testosterone release. Four experiments using house mice (Mus musculus) examined the hypothesis that both the male's genotype and his degree of sexual arousal (as indexed by ultrasonic mating calls) are related to such variability. In Experiment 1, CF-1 males exhibited reflexive testosterone elevations 30 min after encountering female urine. CK males, on the other hand, did not exhibit testosterone elevations 20, 30, 50, 60, or 80 min after encountering female urine (Experiments 1 and 2) suggesting this strain incapable of reflexive release. In Experiment 3, we measured both mating calls and reflexive testosterone release in response to female urine in CF-1 and CK males. Most males of both strains called vigorously to female urine but not to water. But, only CF-1 males exhibited significant testosterone elevations to female urine. In Experiment 4, DBA/2J males called vigorously to females followed by testosterone elevations 30 min later. The first 3 experiments support the hypothesis that male genotype is an important variable underlying mammalian reflexive testosterone release. Statistically significant correlations between mating calls in the first minute after stimulus exposure and testosterone elevations 30 min later (Experiments 3 and 4) support the hypothesis that, in capable males, reflexive testosterone release is related to the male's initial sexual arousal.

  14. Biochemical Mechanisms and Microorganisms Involved in Anaerobic Testosterone Metabolism in Estuarine Sediments

    PubMed Central

    Shih, Chao-Jen; Chen, Yi-Lung; Wang, Chia-Hsiang; Wei, Sean T.-S.; Lin, I-Ting; Ismail, Wael A.; Chiang, Yin-Ru

    2017-01-01

    Current knowledge on the biochemical mechanisms underlying microbial steroid metabolism in anaerobic ecosystems is extremely limited. Sulfate, nitrate, and iron [Fe (III)] are common electron acceptors for anaerobes in estuarine sediments. Here, we investigated anaerobic testosterone metabolism in anaerobic sediments collected from the estuary of Tamsui River, Taiwan. The anaerobic sediment samples were spiked with testosterone (1 mM) and individual electron acceptors (10 mM), including nitrate, Fe3+, and sulfate. The analysis of androgen metabolites indicated that testosterone biodegradation under denitrifying conditions proceeds through the 2,3-seco pathway, whereas testosterone biodegradation under iron-reducing conditions may proceed through an unidentified alternative pathway. Metagenomic analysis and PCR-based functional assays suggested that Thauera spp. were the major testosterone degraders in estuarine sediment samples incubated with testosterone and nitrate. Thauera sp. strain GDN1, a testosterone-degrading betaproteobacterium, was isolated from the denitrifying sediment sample. This strain tolerates a broad range of salinity (0–30 ppt). Although testosterone biodegradation did not occur under sulfate-reducing conditions, we observed the anaerobic biotransformation of testosterone to estrogens in some testosterone-spiked sediment samples. This is unprecedented since biotransformation of androgens to estrogens is known to occur only under oxic conditions. Our metagenomic analysis suggested that Clostridium spp. might play a role in this anaerobic biotransformation. These results expand our understanding of microbial metabolism of steroids under strictly anoxic conditions. PMID:28848528

  15. Cognitive effects of testosterone and finasteride administration in older hypogonadal men

    PubMed Central

    Borst, Stephen E; Yarrow, Joshua F; Fernandez, Carmen; Conover, Christine F; Ye, Fan; Meuleman, John R; Morrow, Matthew; Zou, Baiming; Shuster, Jonathan J

    2014-01-01

    Serum concentrations of neuroactive androgens decline in older men and, in some studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor), in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥60 years with a serum testosterone concentration of ≤300 ng/dL or bioavailable testosterone ≤70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week) versus vehicle, paired with finasteride (5 mg/day) versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies are warranted to determine if testosterone replacement may improve cognition in other domains. PMID:25143719

  16. Testosterone replacement therapy and the heart: friend, foe or bystander?

    PubMed Central

    Canfield, Steven; Wang, Run

    2016-01-01

    The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, “beneficial (friendly use)”, “detrimental (foe)” and “no effects at all (bystander)”, based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT’s). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT’s does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not. PMID:28078222

  17. Testosterone replacement therapy and the heart: friend, foe or bystander?

    PubMed

    Lopez, David S; Canfield, Steven; Wang, Run

    2016-12-01

    The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, "beneficial (friendly use)", "detrimental (foe)" and "no effects at all (bystander)", based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT's). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT's does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.

  18. Choosing Fighting Competitors Among Men: Testosterone, Personality, and Motivations.

    PubMed

    Borráz-León, Javier I; Cerda-Molina, Ana Lilia; Rantala, Markus J; Mayagoitia-Novales, Lilian

    2018-01-01

    Higher testosterone levels have been positively related to a variety of social behaviors and personality traits associated with intrasexual competition. The aim of this study was to evaluate the role of testosterone levels and personality traits such as aggressiveness, competitiveness, and self-esteem on the task of choosing a fighting competitor (a rival) with or without a motivation to fight. In Study 1, a group of 119 men participated in a task for choosing a rival through pictures of men with high-dominant masculinity versus low-dominant masculinity. Participants completed three personality questionnaires and donated two saliva samples (pre-test and post-test sample) to quantify their testosterone levels. We found that the probability of choosing high-dominant masculine men as rivals increased with higher aggressiveness scores. In Study 2, the task of choosing rivals was accompanied by motivations to fight (pictures of women with high or low waist-to-hip ratio [WHR]). In this context, we observed that the probability of choosing dominant masculine men as rivals depended on the WHR of the women. Overall, average levels of post-test testosterone, aggressiveness, and high self-esteem increased the probability to fight for women with low WHR independently of the dominance masculinity of the rivals. Our results indicate that human decisions, in the context of intrasexual competition and mate choice, are regulated by physiological and psychological mechanisms allowing men to increase their biological fitness. We discuss our results in the light of the plasticity of human behavior according to biological and environmental forces.

  19. Direct total and free testosterone measurement by liquid chromatography tandem mass spectrometry across two different platforms.

    PubMed

    Rhea, Jeanne M; French, Deborah; Molinaro, Ross J

    2013-05-01

    To develop and validate liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the direct measurement of total and free testosterone in patient samples on two different analytical systems. An API 4000 and 5000 triple quadropoles were used and compared; the former is reported to be 3-5 times less sensitive, as was used to set the quantitation limits. Free testosterone was separated from the protein-bound fraction by equilibrium dialysis followed by derivatization. Either free or total testosterone, and a deuterated internal standard (d3-testosterone) were extracted by liquid-liquid extraction. The validation results were compared to two different clinical laboratories. The use of d2-testosterone was found to be unacceptable for our method. The total testosterone LC-MS/MS methods on both systems were linear over a wide concentration range of 1.5-2000ng/dL. Free testosterone was measured directly using equilibrium dialysis coupled LC-MS/MS and linear over the concentration range of 2.5-2500pg/mL. Good correlation (total testosterone, R(2)=0.96; free testosterone, R(2)=0.98) was observed between our LC-MS/MS systems and comparator laboratory. However, differences in absolute values for both free and total testosterone measurements were observed while a comparison to a second published LC-MS/MS method showed excellent correlation. Free and total testosterone measurements correlated well with clinical observations. To our knowledge, this is the first published validation of free and total testosterone methods across two analytical systems of different analytical sensitivities. A less sensitive system does not sacrifice analytical or clinical sensitivity to directly measure free and total testosterone in patient samples. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. Emerging medication for the treatment of male hypogonadism.

    PubMed

    Aydogdu, Aydogan; Swerdloff, Ronald S

    2016-09-01

    Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. The available literature of T and alternative treatments for male hypogonadism are discussed. Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.

  1. CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

    PubMed

    Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

    2017-01-01

    Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

  2. Successful hunting increases testosterone and cortisol in a subsistence population

    PubMed Central

    Trumble, Benjamin C.; Smith, Eric A.; O'Connor, Kathleen A.; Kaplan, Hillard S.; Gurven, Michael D.

    2014-01-01

    Controversy over the adaptive significance of male hunting in subsistence societies hinges on the relative importance of familial provisioning and mate-quality signalling. This paper examines the proximate and ultimate motivations of hunting behaviour from a neuroendocrine perspective, using salivary testosterone and cortisol data collected before, during and after hunting focal follows from 31 Tsimane hunters aged 18–82 years. Despite circadian declines in hormone levels, testosterone and cortisol of Tsimane hunters increased at the time of a kill, and remained high as successful hunters returned home. Previous studies of hormonal changes during competitions find that high-stakes and success in the presence of relevant audiences result in increased neuroendocrine arousal. If men hunt primarily to provision their families, then an additional audience would not be expected to impact testosterone or cortisol, nor would the size of the animal killed. However, if signalling male quality by ‘showing off’ was a larger relative driver of men's hunting behaviour, one would expect greater hormonal response in cases where men returned with large sharable kills, especially in the presence of community members. Consistent with provisioning models of male hunting motivation, neither kill size nor encountering an audience of villagers while returning from hunting was associated with hormonal changes for successful hunters. PMID:24335989

  3. Association of subcutaneous testosterone pellet therapy with developing secondary polycythemia

    PubMed Central

    Rotker, Katherine Lang; Alavian, Michael; Nelson, Bethany; Baird, Grayson L; Miner, Martin M; Sigman, Mark; Hwang, Kathleen

    2018-01-01

    A variety of methods for testosterone replacement therapy (TRT) exist, and the major potential risks of TRT have been well established. The risk of developing polycythemia secondary to exogenous testosterone (T) has been reported to range from 0.4% to 40%. Implantable T pellets have been used since 1972, and secondary polycythemia has been reported to be as low as 0.4% with this administration modality. However, our experience has suggested a higher rate. We conducted an institutional review board-approved, single-institution, retrospective chart review (2009–2013) to determine the rate of secondary polycythemia in 228 men treated with subcutaneously implanted testosterone pellets. Kaplan–Meyer failure curves were used to estimate time until the development of polycythemia (hematocrit >50%). The mean number of pellets administered was 12 (range: 6–16). The mean follow-up was 566 days. The median time to development of polycythemia whereby 50% of patients developed polycythemia was 50 months. The estimated rate of polycythemia at 6 months was 10.4%, 12 months was 17.3%, and 24 months was 30.2%. We concluded that the incidence of secondary polycythemia while on T pellet therapy may be higher than previously established. PMID:29205178

  4. The effects of prenatal testosterone on wages: Evidence from Russia.

    PubMed

    Nye, John V C; Bryukhanov, Maksym; Kochergina, Ekaterina; Orel, Ekaterina; Polyachenko, Sergiy; Yudkevich, Maria

    2017-02-01

    Is in utero exposure to testosterone correlated with earnings? The question matters for understanding determinants of wage differences that have attracted so much attention among economists in the past decade. Evidence indicates that markers for early testosterone exposure are correlated with traits like risk-taking and aggressiveness. But it is not at all clear how such findings might map into labor market success. We combine unique data from the Russian Longitudinal Monitoring Survey with measured markers (2D:4D ratios) for testosterone exposure and find that lower digit ratios (higher T) correlate with higher wages for women and for men, when controlling for age, education and occupation. There is also some evidence of a potential non-linear, inverse U-effect of digit ratios on wages but this is sensitive to choice of specification. These findings are consistent with earlier work on prenatal T and success in careers (Coates et al., 2009) but inconsistent with the work of Gielen et al. (2016) who find differing effects for men and women. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies.

    PubMed

    Saad, F; Yassin, A; Doros, G; Haider, A

    2016-01-01

    Long-term testosterone replacement therapy (TRT) up to 5 years has been shown to produce progressive and sustainable weight loss (WL) in hypogonadal men. This study investigated effects of long-term TRT up to 8 years in hypogonadal men with different obesity classes. From two independent observational registries we identified a total of 411 obese, hypogonadal men receiving TRT in urological clinics. The effects of TRT on anthropometric as well as metabolic parameters were studied for a maximum duration of 8 years, mean follow-up: 6 years. All men received long-acting injections of testosterone undecanoate in 3-monthly intervals. In all three classes of obesity, T therapy produced significant WL, decrease in waist circumference (WC) and body mass index (BMI). In patients with class I obesity, mean weight decreased from 102.6±6.4 to 84.1±4.9 kg, change from baseline: -17.4±0.5 kg and -16.8±0.4%. WC in this group of patients decreased from 106.8±7.4 to 95.1±5.3 cm, change from baseline: -10.6±0.3 cm. BMI decreased from 32.69±1.4 to 27.07±1.57, change from baseline: -5.52±0.15 kg m(-2). In patients with class II obesity, weight decreased from 116.8±6.9 to 91.3±6.3 kg, change from baseline: -25.3±0.5 kg and -21.5±0.4%. WC decreased from 113.5±7.5 to 100.0±5.4 cm, change from baseline: -13.9±0.4 cm. BMI decreased from 37.32±1.45 to 29.49±1.71, change from baseline: -8.15±0.17 kg m(-2). In patients with class III obesity, weight decreased from 129.0±5.6 to 98.9±4.8 kg, change from baseline: -30.5±0.7 kg and -23.6±0.5%. WC decreased from 118.5±5.6 to 103.8±4.9 cm, change from baseline: -14.3±0.4 cm. BMI decreased from 41.93±1.48 to 32.46±1.59, change from baseline -9.96±0.29 kg m(-2). Testosterone therapy appears to be an effective approach to achieve sustained WL in obese hypogonadal men irrespective of severity of obesity. Based on these findings we suggest that T therapy offers safe and effective

  6. The History of Testosterone and the Evolution of its Therapeutic Potential.

    PubMed

    Morgentaler, Abraham; Traish, Abdulmaged

    2018-04-13

    Testosterone therapy has been controversial since its synthesis in the 1930s to the present day. Testosterone's history provides depth and context for current controversies. To review the history of testosterone therapy from its initial synthesis in the 1930s to the modern day. Expert review of the literature. Impactful events in the history of testosterone. By the 1940s there was already a fascinating literature that described the many symptomatic benefits of testosterone therapy that are recognized today. Numerous early reports suggested testosterone therapy improved angina pectoris and peripheral vascular disease. The assertion by Huggins and Hodges (Cancer Res 1941;1:293-297) in 1941 that testosterone activated prostate cancer (PCa) cast a pall for the next 70 years. The introduction of the radioimmunoassay in the 1970s shifted the diagnosis of testosterone deficiency from signs and symptoms to an undue emphasis on blood test results. The fear of PCa was the primary obstacle to the adoption of testosterone therapy for decades. Prescription rates increased as accumulated evidence showed testosterone therapy was not associated with increased PCa risks. The observation that androgenic stimulation of PCa reaches a maximum at relatively low testosterone concentrations-the saturation model-provided the theoretical framework for understanding the relation between androgens and PCa and led to multiple case series documenting reassuring results of testosterone therapy in men with PCa. Recent concerns regarding cardiovascular risks also have diminished because new evidence suggests testosterone therapy might actually be cardioprotective. In 2016 the Testosterone Trials provided high-quality evidence of multiple benefits of testosterone therapy, nearly all of which had been recognized by clinicians by 1940. If the past has any lessons for the future, it is likely that research will continue to demonstrate health benefits of testosterone therapy, while it remains one of

  7. Oral cancer.

    PubMed

    Gerson, S J

    1990-01-01

    In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.

  8. Preliminary evidence that testosterone's association with aggression depends on self-construal.

    PubMed

    Welker, Keith M; Norman, Rachel E; Goetz, Stefan; Moreau, Benjamin J P; Kitayama, Shinobu; Carré, Justin M

    2017-06-01

    A contribution to a special issue on Hormones and Human Competition. Previous research and theory suggest testosterone is an important hormone for modulating aggression and self-regulation. We propose that self-construal, a culturally-relevant difference in how individuals define the self in relation to others, may be an important moderator of the relationship between testosterone and behaviors linked to aggression. Within two studies (Study 1 N=80; Study 2 N=237) and an integrated data analysis, we find evidence suggesting that acute testosterone changes in men are positively associated with aggressive behavior for those with more independent self-construals, whereas basal testosterone is negatively associated with aggression when individuals have more interdependent self-construals. Although preliminary, these findings suggest that self-construal moderates the association between testosterone and aggression, thereby paving the way toward future work examining the potential cultural moderation of the behavioral effects of testosterone. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Factors influencing annual fecal testosterone metabolite profiles in captive male polar bears (Ursus maritimus).

    PubMed

    Curry, E; Roth, T L; MacKinnon, K M; Stoops, M A

    2012-12-01

    The objectives of this study were to assess the effects of season, breeding activity, age and latitude on fecal testosterone metabolite concentrations in captive, adult male polar bears (Ursus maritimus). Fourteen polar bears from 13 North American zoos were monitored for 12-36 months, producing 25-year-long testosterone profiles. Results indicated that testosterone was significantly higher during the breeding season (early January through the end of May) compared with the non-breeding season with the highest concentrations excreted from early January through late March. Variations in excretion patterns were observed among individuals and also between years within an individual, with testosterone peaks closely associated with breeding activity. Results indicate that fecal testosterone concentrations are influenced by season, breeding activity and age, but not by latitude. This is the first report describing longitudinal fecal testosterone metabolite concentrations in individual adult male polar bears. © 2012 Blackwell Verlag GmbH.

  10. Genetic and Environmental Influences on Testosterone in Adolescents: Evidence for Sex Differences

    PubMed Central

    Harden, K. Paige; Kretsch, Natalie; Tackett, Jennifer L.; Tucker-Drob, Elliot M.

    2015-01-01

    The current study investigated the genetic and environmental etiology of individual differences in salivary testosterone during adolescence, using data from 49 pairs of monozygotic twins and 68 pairs of dizygotic twins, ages 14–19 years (M = 16.0 years). Analyses tested for sex differences in genetic and environmental influences on testosterone and its relation to pubertal development. Among adolescent males, individual differences in testosterone were substantially heritable (55%), and significantly associated with self-reported pubertal status (controlling for age) via common genetic influences. In contrast, there was no heritable variation in testosterone for females, and testosterone in females was not significantly associated with pubertal status after controlling for age. Rather, environmental influences shared by twins raised together accounted for all of the familial similarity in female testosterone (53%). This study adds to a small but growing body of research that investigates genetic influences on individual differences in behaviorally-relevant hormones. PMID:24523135

  11. 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.

  12. Oral sex.

    PubMed

    1996-04-05

    The Gay and Lesbian Medical Association urges HIV prevention specialists to regard male-to-male oral-genital sex as a low-risk activity and concentrate instead on the danger of unprotected anal intercourse. According to the association, the confusion and mixed messages surrounding oral sex are harming efforts to encourage gay men to make rational choices about truly risky behavior. The recommendations appear in the association's position paper issued March 19, 1996.

  13. Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism: A Real-Life Observational Registry Study Setting Comparing Treated and Untreated (Control) Groups.

    PubMed

    Traish, Abdulmaged M; Haider, Ahmad; Haider, Karim Sultan; Doros, Gheorghe; Saad, Farid

    2017-09-01

    In the absence of large, prospective, placebo-controlled studies of longer duration, substantial evidence regarding the safety and risk of testosterone (T) therapy (TTh) with regard to cardiovascular (CV) outcomes can only be gleaned from observational studies. To date, there are limited studies comparing the effects of long-term TTh in men with hypogonadism who were treated or remained untreated with T, for obvious reasons. We have established a registry to assess the long-term effectiveness and safety of T in men in a urological setting. Here, we sought to compare the effects of T on a host of parameters considered to contribute to CV risk in treated and untreated men with hypogonadism (control group). Observational, prospective, cumulative registry study in 656 men (age: 60.7 ± 7.2 years) with total T levels ≤12.1 nmol/L and symptoms of hypogonadism. In the treatment group, men (n = 360) received parenteral T undecanoate (TU) 1000 mg/12 weeks following an initial 6-week interval for up to 10 years. Men (n = 296) who had opted against TTh served as controls. Median follow-up in both groups was 7 years. Measurements were taken at least twice a year, and 8-year data were analyzed. Mean changes over time between the 2 groups were compared by means of a mixed-effects model for repeated measures, with a random effect for intercept and fixed effects for time, group, and their interaction. To account for baseline differences between the 2 groups, changes were adjusted for age, weight, waist circumference, fasting glucose, blood pressure, and lipids. There were 2 deaths in the T-treated group, none was related to CV events. There were 21 deaths in the untreated (control) group, 19 of which were related to CV events. The incidence of death in 10 patient-years was 0.1145 in the control group (95% confidence interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95% CI: 0.0023-0.0368; P < .000); the estimated difference between groups was 0.0804 (95

  14. 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

  15. 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

  16. 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

  17. Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway

    PubMed Central

    Pei, Luo; Shaozhen, Hou; Gengting, Dong; Tingbo, Chen; Liang, Liu; Hua, Zhou

    2013-01-01

    Mechanisms for Panax ginseng's cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury. PMID:24282438

  18. 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.

  19. Testosterone, Plumage Colouration and Extra-Pair Paternity in Male North-American Barn Swallows

    PubMed Central

    Eikenaar, Cas; Whitham, Megan; Komdeur, Jan; van der Velde, Marco; Moore, Ignacio T.

    2011-01-01

    In most monogamous bird species, circulating testosterone concentration in males is elevated around the social female's fertile period. Variation in elevated testosterone concentrations among males may have a considerable impact on fitness. For example, testosterone implants enhance behaviours important for social and extra-pair mate choice. However, little is known about the relationship between natural male testosterone concentration and sexual selection. To investigate this relationship we measured testosterone concentration and sexual signals (ventral plumage colour and tail length), and determined within and extra-pair fertilization success in male North American barn swallows (Hirundo rustica erythrogaster). Dark rusty coloured males had higher testosterone concentrations than drab males. Extra-pair paternity was common (42% and 31% of young in 2009 and 2010, respectively), but neither within- nor extra-pair fertilization success was related to male testosterone concentration. Dark rusty males were less often cuckolded, but did not have higher extra-pair or total fertilization success than drab males. Tail length did not affect within- or extra-pair fertilization success. Our findings suggest that, in North American barn swallows, male testosterone concentration does not play a significant direct role in female mate choice and sexual selection. Possibly plumage colour co-varies with a male behavioural trait, such as aggressiveness, that reduces the chance of cuckoldry. This could also explain why dark males have higher testosterone concentrations than drab males. PMID:21853105

  20. 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.

  1. 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

  2. Anxiolytic-like Effect of Testosterone in Male Rats: GABAC Receptors Are Not Involved

    PubMed Central

    Roohbakhsh, Ali; Moghaddam, Akbar Hajizadeh; Delfan, Karim Mahmoodi

    2011-01-01

    Objective(s) The effect of testosterone on anxiety-like behaviors has been the subject of some studies. There is evidence that testosterone modulates anxiety via GABA (gama aminobutyric acid) and GABAergic system. The involvement of GABAC receptors in those effects of testosterone on anxiety-like behaviors of the rats was investigated in the present study. Materials and Methods A group of rats received subcutaneous injections of testosterone (5, 10 and 20 mg/kg). Two groups of rats received intracerebroventricular injections of either CACA (GABAC agonist, 0.125 μg/rat) or TPMPA (GABAC antagonist, 3 microg/rat) following administration of testosterone (5, 10 and 20 mg/kg). After the injections, the rats were submitted to the elevated plus-maze test of anxiety. Results The rats received testosterone alone, showed a decreased in anxiety-like behaviors (P< 0.01). Administration of either CACA or TPMPA did not modify animals’ behavior compared to the rats received testosterone alone. Conclusion The results of the present study showed that administration of testosterone induces anxiolytic-like behaviors in the rats and GABAC receptors possibly are not involved in the anxiolytic effect of testosterone. PMID:23493519

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Effect of application site, clothing barrier, and application site washing on testosterone transfer with a 1.62% testosterone gel.

    PubMed

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

    2012-02-01

    To evaluate the effect of application site location, clothing barrier, and application site washing on testosterone transfer from males dosed with 1.62% testosterone gel to female partners. Open-label, randomized, parallel group, crossover study performed in 24 healthy male/female couples. 2.5 or 5.0 g of gel was applied to upper arms and shoulders or abdomens of male subjects. Skin contact occurred 2 hours after gel application between male and female subjects to compare the effect of wearing or not wearing a t-shirt, washing or not washing before contact, and the effect of differing application sites. Treatments were separated by a 1-week washout period. On each dosing day, 15 minutes of supervised skin contact occurred between the dosed male and female partner. Contact was either abdomen to abdomen (male to female), or upper arms/shoulders (male) to upper arms/shoulders, wrists and hands (female), depending on the male application site. Serum samples were collected from females at baseline and after contact to assess secondary testosterone exposure. C(max) (maximum serum concentration), AUC(0-24) (area under serum concentration-time curve from 0-24 hours), and C(av) (time-averaged concentration over 24-hour post-contact period) were assessed. Subjects were monitored for adverse events. Testosterone exposure (C(av) and C(max)) in females increased by up to 27% (2.5 g) or up to 280% (5.0 g) from baseline after direct skin contact at 2 hours after gel application, although C(av) remained within the female eugonadal range. Transfer from the abdomen was prevented when a t-shirt was worn (2.5-g dose). When the application site was washed before contact, mean C(av) was comparable to baseline, and C(max) was slightly higher (14%). Transfer was higher after direct skin-to-skin contact when the application and contact sites were upper arms/shoulders versus the abdomen. Testosterone concentrations returned to baseline within 48 hours after last skin contact. There is

  9. Oral biopsy: oral pathologist's perspective.

    PubMed

    Kumaraswamy, K L; Vidhya, M; Rao, Prasanna Kumar; Mukunda, Archana

    2012-01-01

    Many oral lesions may need to be diagnosed by removing a sample of tissue from the oral cavity. Biopsy is widely used in the medical field, but the practice is not quite widespread in dental practice. As oral pathologists, we have found many artifacts in the tissue specimen because of poor biopsy technique or handling, which has led to diagnostic pitfalls and misery to both the patient and the clinician. This article aims at alerting the clinicians about the clinical faults arising preoperatively, intraoperatively and postoperatively while dealing with oral biopsy that may affect the histological assessment of the tissue and, therefore, the diagnosis. It also reviews the different techniques, precautions and special considerations necessary for specific lesions.

  10. The hidden dimensions of the competition effect: basal cortisol and basal testosterone jointly predict changes in salivary testosterone after social victory in men.

    PubMed

    Zilioli, Samuele; Watson, Neil V

    2012-11-01

    Dominance struggles appear to affect hormone concentrations in many mammalian species, such that higher concentrations of testosterone are seen in winners of competitions, compared to losers. This so-called, "competition effect" has received inconsistent empirical support, suggesting that additional psychological (e.g., mood), situational (i.e., nature of the competition) and physiological (e.g., cortisol) variables might intervene in modulating testosterone fluctuations after social contests. We investigated possible interactions between the hypothalamic-pituitary-gonadal (HPG) axis and the hypothalamic-pituitary-adrenal (HPA) stress axis in predicting transient changes in testosterone after social victory or defeat on a familiar competitive task. In particular, the present study examined the dual-hormone hypothesis - proposing that baseline cortisol potently modulates the competition effect (Mehta and Josephs, 2010) - in a sample of healthy young men engaged in head-to-head competition on a widely played commercial videogame, Tetris. We found a significant interaction between HPG and HPA axes status and the competition effect on testosterone in the randomly assigned videogame winners, such that winners with a pre-competition combination of high baseline testosterone and low baseline cortisol exhibited significantly greater post-competition testosterone concentrations. The randomly assigned videogame losers showed significantly decreased post-competition levels of testosterone. Possible biological and evolutionary mechanisms underlying this phenomenon are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

    PubMed

    Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

    2016-04-01

    Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research

  12. Effect of PCB and DES on rat monoamine oxidase, acetylcholinesterase, testosterone, and estradiol ontogeny

    SciTech Connect

    Vincent, D.R.; Bradshaw, W.S.; Booth, G.M.

    1992-06-01

    Diethylstilbestrol (DES) and polychlorinated biphenyl (PCB) have been documented as potentially hazardous environmental agents. In utero exposure to DES produces human vaginal adenocarcinoma, male reproductive tract lesions in mice, and has been correlated with personality changes in human males. PCB (Kanechlor) was found to be the major toxin in the {open_quotes}Yusho{close_quotes} rice oil poisoning in Japan in 1968. Other investigators have shown in rats that PCB (Arochlor) causes liver adenofibrosis, thyroid dysfunction, atypical mitochondria, and dilation of both smooth and rough endoplasmic reticulum. Matthews et al. (1978) also reported that 4, 4{prime} chlorinated biphenyl was the most potent inducer ofmore » monooxygenases, irrespective of chlorination at other sites. Although these compounds have been studied extensively in mammals, there is a paucity of data examining their effects when non-fetotoxic amounts are administered chronically and orally during gestation. The present study is part of a larger effort designed to establish a protocol for testing the developmental effects of xenobiotics such as DES and PCB. Levels of acetylcholinesterase (AChE) were measured as an indicator of the integrity of nerve transmission in the central nervous system. Monoamine oxidase (MAO) is a marker for the outer mitochondrial membrane and is an important amine metabolizing enzyme. Testosterone and estradiol are important sex steroids in mammals, and effects upon levels of the two hormones may signal anomalies in development of sex characteristics. 35 refs., 3 figs., 1 tab.« less

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

    PubMed

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

    2000-06-01

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

  14. The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy.

    PubMed

    Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

    2015-02-01

    For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer. We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance. We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines

  15. Intensive exercise training suppresses testosterone during bed rest

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Stanford, K. I.; Stein, T. P.; Greenleaf, J. E.

    2005-01-01

    Spaceflight and prolonged bed rest (BR) alter plasma hormone levels inconsistently. This may be due, in part, to prescription of heavy exercise as a countermeasure for ameliorating the adverse effects of disuse. The initial project was to assess exercise programs to maintain aerobic performance and leg strength during BR. The present study evaluates the effect of BR and the performance of the prescribed exercise countermeasures on plasma steroid levels. In a 30-day BR study of male subjects, the efficacy of isotonic (ITE, n = 7) or isokinetic exercise (IKE, n = 7) training was evaluated in contrast to no exercise (n = 5). These exercise countermeasures protected aerobic performance and leg strength successfully. BR alone (no-exercise group) did not change steroidogenesis, as assessed by the plasma concentrations of cortisol, progesterone, aldosterone, and free (FT) and total testosterone (TT). In the exercise groups, both FT and TT were decreased (P < 0.05): FT during IKE from 24 +/- 1.7 to 18 +/- 2.0 pg/ml and during ITE from 21 +/- 1.5 to 18 +/- 1 pg/ml, and TT during IKE from 748 +/- 68 to 534 +/- 46 ng/dl and during ITE from 565 +/- 36 to 496 +/- 38 ng/dl. The effect of intensive exercise countermeasures on plasma testosterone was not associated with indexes of overtraining. The reduction in plasma testosterone associated with both the IKE and ITE countermeasures during BR supports our hypothesis that intensive exercise countermeasures may, in part, contribute to changes in plasma steroid concentrations during spaceflight.

  16. Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species.

    PubMed

    Jena, Ashish Kumar; Vasisht, Karan; Sharma, Neetika; Kaur, Ramdeep; Dhingra, Mamta Sachdeva; Karan, Maninder

    2016-08-22

    Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species. In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents. The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC. The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH. These findings are

  17. Unsuspected Clenbuterol Toxicity in a Patient Using Intramuscular Testosterone

    PubMed Central

    Griswold, Matthew K.; Blohm, Eike; Cross, Roderick; Boyer, Edward W.; Carey, Jennifer L.

    2017-01-01

    Clenbuterol is a beta-agonist that has been abused by fitness-oriented individuals for muscle growth and weight loss. We report a case of a 46-year-old man who presented tachycardic, hypokalemic, and hyperglycemic after injecting testosterone obtained from Brazil. He developed refractory hypotension and was started on an esmolol infusion for suspected beta-agonist toxicity. Laboratory analysis showed a detectable clenbuterol serum concentration. Analysis of an unopened ampule contained boldenone undecylenate, clenbuterol, and vitamin E. This case illustrates a novel exposure that caused beta-agonist toxicity and was treated successfully with rapid-onset beta blocker. PMID:29849287

  18. 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

  19. Detection of nandrolone, testosterone, and their esters in rat and human hair samples.

    PubMed

    Höld, K M; Borges, C R; Wilkins, D G; Rollins, D E; Joseph, R E

    1999-10-01

    Nandrolone and testosterone are anabolic androgenic steroids occasionally abused by athletes. A sensitive, specific, and reproducible gas chromatography-mass spectrometry method for the quantitative determination of nandrolone, testosterone, and their esters in hair has been developed. The limits of quantitation of this method, based on 20 mg of hair, were 50 pg/mg for nandrolone and testosterone, 100 pg/mg for testosterone acetate, and 200 pg/mg for nandrolone-decanoate. Nandrolone-d3 and testosterone-d3 were used as internal standards. This method has been applied to the analysis of these compounds incorporated into rat and human hair. Male Long-Evans rats were given nandrolone decanoate 60 mg/kg intraperitoneally (i.p.) once daily for 10 days over a time period of 14 days. Two of the three rats contained nandrolone in the pigmented hair collected at day 21 at a concentration of 63 and 76 pg/mg, respectively. No drug was found in the corresponding nonpigmented hair. The rat hair samples that tested positive for nandrolone contained also nandrolone decanoate in concentrations of 0.9 and 1.2 ng/mg, respectively. In a separate experiment rats were given testosterone acetate 10 mg/kg i.p. once daily for five days. No testosterone or testosterone acetate was detected in the rat hair samples. Hair specimens were also obtained from four self-reported steroid users. The hair of two subjects were determined to be positive for testosterone in concentrations of 54 and 81 pg/mg. These data demonstrate that it is possible to detect the steroids nandrolone, testosterone, and nandrolone decanoate in hair after systemic administration.

  20. 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

  1. 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

  2. The impact of drug reimbursement policy on rates of testosterone replacement therapy among older men.

    PubMed

    Piszczek, Jolanta; Mamdani, Muhammad; Antoniou, Tony; Juurlink, David N; Gomes, Tara

    2014-01-01

    Despite a lack of data describing the long-term efficacy and safety of testosterone replacement therapy (TRT), prescribing of testosterone to older men has increased with the availability of topical formulations. The magnitude of this increase and the impact of formulary restrictions on testosterone prescribing are poorly characterized. We conducted a time series analysis using the linked health administrative records of men aged 66 years or older in Ontario, Canada between January 1, 1997 and March 31, 2012. We used interventional autoregressive integrated moving average models to examine the impact of a restrictive drug reimbursement policy on testosterone prescribing and examined the demographic profile of men initiating testosterone in the final 2 years of the study period. A total of 28,477 men were dispensed testosterone over the study period. Overall testosterone prescribing declined 27.9% in the 6 months following the implementation of the restriction policy (9.5 to 6.9 men per 1000 eligible; p<0.01). However, the overall decrease was temporary and testosterone use exceeded pre-policy levels by the end of the study period (11.0 men per 1000 eligible), largely driven by prescriptions for topical testosterone (4.8 men per 1000 eligible). Only 6.3% of men who initiated testosterone had a documented diagnosis of hypogonadism, the main criteria for TRT reimbursement according to the new policy. Government-imposed restrictions did not influence long-term prescribing of testosterone to older men. By 2012, approximately 1 in every 90 men aged 66 or older was being treated with TRT, most with topical formulations.

  3. 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

  4. 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.

  5. Oral candidiasis.

    PubMed

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial.

    PubMed

    Zitzmann, M; Rohayem, J; Raidt, J; Kliesch, S; Kumar, N; Sitruk-Ware, R; Nieschlag, E

    2017-05-01

    Although several progestins have been tested for hormonal male contraception, the effects of dosage and nature of various progestins on gonadotropin suppression combined with and without additional testosterone has not been performed in a comparative trial. The aim of this study was to evaluate the differential impact of four oral or transdermal progestins on the suppression of gonadotropins in healthy men: oral: cyproterone acetate (CPA), levonorgestrel (LNG), norethisterone acetate (NETA), and transdermal: Nestorone ® (NES), all in combination with transdermal testosterone (T). Randomized clinical trial testing was performed with four progestins at two doses each. After a 2-week progestin-only treatment, transdermal T was added for further 4 weeks and was followed by a 3-week recovery period. Progestin-dose per day: CPA 10 mg/20 mg, NES 2 mg/3 mg/dose e.g. 200/300 μg/day absorbed, NETA 5 mg/10 mg, LNG 120 μg/240 μg. From an andrology outpatient clinic, 56 healthy men aged 18-50 years, with body mass index ≤33 kg × m -2 were included in the study. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied. Secondary outcome measure included were serum testosterone concentrations, sperm concentrations, and safety parameters. Intergroup comparisons demonstrated that CPA and LNG had the strongest effect on LH/FSH suppression. Nevertheless, every substance showed significant inhibitory effects on gonadotropin secretion, especially in combination with transdermal T. A decrease in hematocrit and insulin sensitivity as well as cholesterol subfractions and triglycerides was uniformly seen for every group. The combination of oral or transdermal progestins with a transdermal testosterone preparation is able to suppress gonadotropins. Further dose titration studies with sperm suppression as an end-point should be conducted to determine the lowest effective dose for hormonal male contraception. © 2017 American

  7. Low-dose spironolactone ameliorates insulin resistance and suppresses elevated plasminogen activator inhibitor-1 during gestational testosterone exposure.

    PubMed

    Olatunji, Lawrence A; Usman, Taofeek O; Akinade, Aminat I; Adeyanju, Oluwaseun A; Kim, InKyeom; Soladoye, Ayodele O

    2017-12-01

    Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life. We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects. Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19. Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone. These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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…

  13. 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)

  14. Sex-Specific Associations between Umbilical Cord Blood Testosterone Levels and Language Delay in Early Childhood

    ERIC Educational Resources Information Center

    Whitehouse, Andrew J. O.; Mattes, Eugen; Maybery, Murray T.; Sawyer, Michael G.; Jacoby, Peter; Keelan, Jeffrey A.; Hickey, Martha

    2012-01-01

    Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time-points. Methods: Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When…

  15. 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.

  16. Single dose testosterone administration modulates emotional reactivity and counterfactual choice in healthy males.

    PubMed

    Wu, Yin; Clark, Luke; Zilioli, Samuele; Eisenegger, Christoph; Gillan, Claire M; Deng, Huihua; Li, Hong

    2018-04-01

    Testosterone has been implicated in the regulation of emotional responses and risky decision-making. However, the causal effect of testosterone upon emotional decision-making, especially in non-social settings, is still unclear. The present study investigated the role of testosterone in counterfactual thinking: regret is an intense negative emotion that arises from comparison of an obtained outcome from a decision against a better, non-obtained (i.e. counterfactual) alternative. Healthy male participants (n = 64) received a single-dose of 150 mg testosterone Androgel in a double-blind, placebo-controlled, between-participants design. At 180 min post-administration, participants performed the counterfactual thinking task. We applied a computational model derived from behavioral economic principles to uncover latent decision-making mechanisms that may be invisible in simple choice analyses. Our data showed that testosterone increased the ability to use anticipated regret to guide choice behavior, while reducing choice based on expected value. On affective ratings, testosterone increased sensitivity to both obtained and counterfactual outcomes. These findings provide evidence that testosterone causally modulates emotional decision-making, and highlight the role of testosterone in affective sensitivity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Aggressive behavior and change in salivary testosterone concentrations predict willingness to engage in a competitive task.

    PubMed

    Carré, Justin M; McCormick, Cheryl M

    2008-08-01

    The current study investigated relationships among aggressive behavior, change in salivary testosterone concentrations, and willingness to engage in a competitive task. Thirty-eight male participants provided saliva samples before and after performing the Point Subtraction Aggression Paradigm (a laboratory measure that provides opportunity for aggressive and defensive behavior while working for reward; all three involve pressing specific response keys). Baseline testosterone concentrations were not associated with aggressive responding. However, aggressive responding (but not point reward or point protection responding) predicted the pre- to post-PSAP change in testosterone: Those with the highest aggressive responding had the largest percent increase in testosterone concentrations. Together, aggressive responding and change in testosterone predicted willingness to compete following the PSAP. Controlling for aggression, men who showed a rise in testosterone were more likely to choose to compete again (p=0.03) and controlling for testosterone change, men who showed the highest level of aggressive responding were more likely to choose the non-competitive task (p=0.02). These results indicate that situation-specific aggressive behavior and testosterone responsiveness are functionally relevant predictors of future social behavior.

  18. 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.

  19. Testosterone and sexual risk among transmen: A mixed methods exploratory study

    PubMed Central

    Dadasovich, Rand; Auerswald, Coco; Wilson, Erin C.; Minnis, Alexandra M.; Raymond, H. Fisher; McFarland, Willi

    2017-01-01

    Little research has explored the link between the behavioural effects of testosterone use among transmen and HIV risk. We conducted a mixed methods study to explore testosterone use among transmen and the behavioural effects on HIV risk. A sample of 122 transmen from San Francisco participated in a cross-sectional quantitative survey and 14 transmen participated in 2 focus group discussions. Most participants (81.9%) were currently taking hormones. Participants attributed testosterone use to new sexual behaviours among 69% of transmen, changes in sexual attractions (49%), and increased frequency of sexual activity (72%). Among current testosterone users, 3.3% had cisgender men as partners before starting testosterone, whereas after starting testosterone, 25.4 % did. Similarly, 4.1% had a transgender woman as a sexual partner before starting testosterone and 13.9% after starting testosterone. Findings suggest that testosterone’s side effects were associated with transmen’s desires for sex with cisgender men who have sex with men. The reported increase in attraction to and sex with partners from populations with a high HIV prevalence may have important implications for HIV risk among transmen, especially as the availability of transgender health services may draw transmen to an area where HIV prevalence is high. PMID:27552941

  20. Paternal and Maternal Testosterone in Parents of NICU Infants Transitioning Home.

    PubMed

    Garfield, Craig F; Simon, Clarissa D; Rutsohn, Joshua; Lee, Young S

    Lower testosterone during the transition to new parenthood is considered beneficial to help parents better engage with their infants. No data currently exist studying salivary testosterone of parents with infants in neonatal intensive care units (NICUs) during the transition to home. We examine testosterone levels for parents of very low-birth-weight infants, including links between salivary testosterone and infant factors (such as breast-feeding), psychosocial stress, and changes over time.Testosterone salivary samples were assayed after self-collection by 86 parents (43 fathers and 43 mothers) with NICU infants at wakeup and bedtime prior to discharge and at 3 additional times at home. Self-reported survey measures, including psychosocial reports, were also collected at these times.Using multilevel modeling approaches, we report significant associations between paternal testosterone by time and psychosocial adjustment and between both paternal and maternal testosterone and infant feeding mode (P < .05). Results were significant after accounting for covariates. Our study is the first to examine the time course of diurnal testosterone for parents of premature infants over the transition home; as such, we suggest further research into better understanding parental physiology in this vulnerable parent population.

  1. 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

  2. Gender differences in testosterone and cortisol response to competition.

    PubMed

    Kivlighan, Katie T; Granger, Douglas A; Booth, Alan

    2005-01-01

    This study examined intra-individual change in testosterone, cortisol, and hormone-behavior relationships in response to a rowing ergometer competition. Forty-six members (23 females) of a university crew team provided saliva samples before, 20- and 40-min post-competition, as well as baselines on a non-competition day. Behavioral assessments included measures of previous rowing experience, dominance, competitiveness, bonding with teammates, pre- and post-competition mental state and performance. Men's and women's endocrine responses to this competitive setting were more different than alike and varied by level of competitive experience, the specific phase of the competitive event, and the particular hormone measured. Inter-individual differences in testosterone and cortisol were differentially associated with social affiliation with teammates but rarely with dominance or competitiveness. Theoretically, the findings support the integration of features of the 'tend and befriend' model with the biosocial model of status, and suggest future research directions that may lead to clarification and refinement of those ideas.

  3. Exercise training improves free testosterone in lifelong sedentary aging men.

    PubMed

    Hayes, Lawrence D; Herbert, Peter; Sculthorpe, Nicholas F; Grace, Fergal M

    2017-07-01

    As the impact of high-intensity interval training (HIIT) on systemic hormones in aging men is unstudied to date, we investigated whether total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (free-T) and cortisol (all in serum) were altered following HIIT in a cohort of 22 lifelong sedentary (62 ± 2 years) older men. As HIIT requires preconditioning exercise in sedentary cohorts, participants were tested at three phases, each separated by six-week training; baseline (phase A), following conditioning exercise (phase B) and post-HIIT (phase C). Each measurement phase used identical methods. TT was significantly increased following HIIT (~17%; P  < 0.001) with most increase occurring during preconditioning (~10%; P  = 0.007). Free-T was unaffected by conditioning exercise ( P  = 0.102) but was significantly higher following HIIT compared to baseline (~4.5%; P  = 0.023). Cortisol remained unchanged from A to C ( P  = 0.138). The present data indicate a combination of preconditioning, and HIIT increases TT and SHBG in sedentary older males, with the HIIT stimulus accounting for a small but statistically significant increase in free-T. Further study is required to determine the biological importance of small improvements in free-T in aging men. © 2017 The authors.

  4. Testosterone sorption and desorption: effects of soil particle size.

    PubMed

    Qi, Yong; Zhang, Tian C; Ren, Yongzheng

    2014-08-30

    Soils contain a wide range of particles of different diameters with different mobility during rainfall events. Effects of soil particles on sorption and desorption behaviors of steroid hormones have not been investigated. In this study, wet sieve washing and repeated sedimentation methods were used to fractionate the soils into five ranges. The sorption and desorption properties and related mechanisms of testosterone in batch reactors filled with fractionated soil particles were evaluated. Results of sorption and desorption kinetics indicate that small soil particles have higher sorption and lower desorption rates than that of big ones. Thermodynamic results show the sorption processes are spontaneous and exothermal. The sorption capacity ranks as clay>silt>sand, depending mainly on specific surface area and surface functional groups. The urea control test shows that hydrogen bonding contributes to testosterone sorption onto clay and silt but not on sand. Desorption tests indicate sorption is 36-65% irreversible from clay to sand. Clays have highest desorption hysteresis among these five soil fractions, indicating small particles like clays have less potential for desorption. The results provide indirect evidence on the colloid (clay)-facilitated transport of hormones (micro-pollutants) in soil environments. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. A concise review of testosterone and bone health

    PubMed Central

    Mohamad, Nur-Vaizura; Soelaiman, Ima-Nirwana; Chin, Kok-Yong

    2016-01-01

    Osteoporosis is a condition causing significant morbidity and mortality in the elderly population worldwide. Age-related testosterone deficiency is the most important factor of bone loss in elderly men. Androgen can influence bone health by binding to androgen receptors directly or to estrogen receptors (ERs) indirectly via aromatization to estrogen. This review summarized the direct and indirect effects of androgens on bone derived from in vitro, in vivo, and human studies. Cellular studies showed that androgen stimulated the proliferation of preosteoblasts and differentiation of osteoblasts. The converted estrogen suppressed osteoclast formation and resorption activity by blocking the receptor activator of nuclear factor k-B ligand pathway. In animal studies, activation of androgen and ERα, but not ERβ, was shown to be important in acquisition and maintenance of bone mass. Human epidemiological studies demonstrated a significant relationship between estrogen and testosterone in bone mineral density and fracture risk, but the relative significance between the two remained debatable. Human experimental studies showed that estrogen was needed in suppressing bone resorption, but both androgen and estrogen were indispensable for bone formation. As a conclusion, maintaining optimal level of androgen is essential in preventing osteoporosis and its complications in elderly men. PMID:27703340

  6. The Effect of Special Operations Training on Testosterone, Lean Body Mass, and Strength and the Potential for Therapeutic Testosterone Replacement: A Review of the Literature

    DTIC Science & Technology

    2016-07-01

    Effects of Testosterone or Anabolic Androgenic Steroid on Body Mass, Lean Body Mass, and Strength in Patients with Disease or Muscle Wasting...of Ranger training reportedly decreased body mass, fat mass, and lean body mass (LBM), with reductions in field measures of strength and power of...Table 3. Effects of Testosterone or Anabolic Androgenic Steroid with Resistance Training on Lean Body Mass and Strength Source Subjects Treatment

  7. Oral care.

    PubMed

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. Copyright © 2011 S. Karger AG, Basel.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

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

    PubMed Central

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

    2016-01-01

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

  15. Effects of testosterone on spatial learning and memory in adult male rats

    PubMed Central

    Spritzer, Mark D.; Daviau, Emily D.; Coneeny, Meagan K.; Engelman, Shannon M.; Prince, W. Tyler; Rodriguez-Wisdom, Karlye N.

    2011-01-01

    A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting seven days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects. PMID:21295035

  16. 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

  17. 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.

  18. 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.

  19. The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency.

    PubMed

    Chin, Kok-Yong; Gengatharan, Dhivakaran; Mohd Nasru, Fadlin Sakina; Khairussam, Rehan Amalia; Ern, Sherlyn Lai Hui; Aminuddin, Siti Aina Wahidah; Ima-Nirwana, Soelaiman

    2016-12-14

    Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content ( p < 0.05) but it did not affect femoral biomechanical strength ( p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength.

  20. The Effects of Annatto Tocotrienol on Bone Biomechanical Strength and Bone Calcium Content in an Animal Model of Osteoporosis Due to Testosterone Deficiency

    PubMed Central

    Chin, Kok-Yong; Gengatharan, Dhivakaran; Mohd Nasru, Fadlin Sakina; Khairussam, Rehan Amalia; Ern, Sherlyn Lai Hui; Aminuddin, Siti Aina Wahidah; Ima-Nirwana, Soelaiman

    2016-01-01

    Osteoporosis reduces the skeletal strength and increases the risk for fracture. It is an underdiagnosed disease in men. Annatto tocotrienol has been shown to improve bone structural indices and increase expression of bone formation genes in orchidectomized rats. This study aimed to evaluate the effects of annatto tocotrienol on biomechanical strength and calcium content of the bone in orchidectomized rats. Thirty three-month-old male Sprague-Dawley rats were randomly assigned to five groups. The baseline control (BC) group was sacrificed at the onset of the study. The sham-operated group (SHAM) received olive oil (the vehicle of tocotrienol) orally daily and peanut oil (the vehicle of testosterone) intramuscularly weekly. The remaining rats were orchidectomized and treated with three different regimens, i.e., (1) daily oral olive oil plus weekly intramuscular peanut oil injection; (2) daily oral annatto tocotrienol at 60 mg/kg plus weekly intramuscular peanut oil injection; (3) daily oral olive oil plus weekly intramuscular testosterone enanthate injection at 7 mg/kg. Blood, femur and tibia of the rats were harvested at the end of the two-month treatment period for the evaluation of serum total calcium and inorganic phosphate levels, bone biomechanical strength test and bone calcium content. Annatto-tocotrienol treatment improved serum calcium level and tibial calcium content (p < 0.05) but it did not affect femoral biomechanical strength (p > 0.05). In conclusion, annatto-tocotrienol at 60 mg/kg augments bone calcium level by preventing calcium mobilization into the circulation. A longer treatment period is needed for annatto tocotrienol to exert its effects on bone strength. PMID:27983628

  1. 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

  2. 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

  3. Marijuana use and serum testosterone concentrations among U.S. males.

    PubMed

    Thistle, J E; Graubard, B I; Braunlin, M; Vesper, H; Trabert, B; Cook, M B; McGlynn, K A

    2017-07-01

    Marijuana has been reported to have several effects on the male reproductive system. Marijuana has previously been linked to reduced adult testosterone, however, a study in Denmark reported increased testosterone concentrations among marijuana users. This study was performed to estimate the effect of marijuana use on testosterone in U.S. males. Data on serum testosterone, marijuana use, and covariates for 1577 men from the 2011-2012 U.S. National Health and Nutrition Examination Survey (NHANES) were analyzed. Information on marijuana use was collected by a self-administered computer-assisted questionnaire. Serum testosterone was determined using isotope dilution liquid chromatography tandem mass spectrometry. The effects of marijuana use on serum testosterone concentrations were examined by frequency, duration, and recency of use. Adjusted means and 95% confidence intervals (CI) of serum testosterone across levels of marijuana use were estimated using multiple linear regression weighted by the survey weights. The majority (66.2%) of the weighted study population reported ever using marijuana with 26.6% reporting current marijuana use. There was no difference in serum testosterone between ever users (adjusted mean = 3.69 ng/mL, 95% CI: 3.46, 3.93) and never users (adjusted mean = 3.70 ng/mL, 95% CI: 3.45, 3.98) upon multivariable analysis. However, serum testosterone was inversely associated with time since last regular use of marijuana (p-value for trend = 0.02). When restricted to men aged 18-29 years, this relationship strengthened (p-value for trend <0.01), and serum testosterone was also inversely associated with time since last use (p-value for trend <0.01), indicating that recency of use, and not duration or frequency, had the strongest relationship with testosterone levels. Serum testosterone concentrations were higher in men with more recent marijuana use. Studies are needed to determine the extent to which circulating testosterone concentrations

  4. Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

    PubMed

    Goetz, Laura G; Mamillapalli, Ramanaiah; Sahin, Cagdas; Majidi-Zolbin, Masoumeh; Ge, Guanghao; Mani, Arya; Taylor, Hugh S

    2018-02-01

    The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no preclinical research has assessed atherosclerosis risk after XHT. We examined the effects of testosterone XHT after ovariectomy on atherosclerosis plaque formation in female mice and evaluated whether adding low-dose estradiol to cross-sex testosterone treatments after ovariectomy reduced lesion formation. Six-week-old female ApoE-/- C57BL/6 mice underwent ovariectomy and began treatments with testosterone, estradiol, testosterone with low-dose estradiol, or vehicle alone until euthanized at 23 weeks of age. Atherosclerosis lesion progression was measured by Oil Red O stain and confirmed histologically. We found reduced atherosclerosis in the estradiol- and combined testosterone/estradiol-treated mice compared with those treated with testosterone or vehicle only in the whole aorta (-75%), aortic arch (-80%), and thoracic aorta (-80%). Plaque size was similarly reduced in the aortic sinus. These reductions in lesion size after combined testosterone/estradiol treatment were comparable to those obtained with estrogen alone. Testosterone/estradiol combined therapy resulted in less atherosclerosis plaque formation than either vehicle or testosterone alone after ovariectomy. Testosterone/estradiol therapy was comparable to estradiol replacement alone, whereas mice treated with testosterone only fared no better than untreated controls after ovariectomy. Adding low-dose estrogen to cross-sex testosterone therapy after oophorectomy could improve cardiovascular outcomes for transgender patients. Additionally, these results contribute to understanding of the effects of estrogen and testosterone on atherosclerosis progression. Copyright © 2018 Endocrine Society.

  5. Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

    NASA Astrophysics Data System (ADS)

    Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

    2014-02-01

    The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

  6. 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

  7. Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study.

    PubMed

    Stout, Martin; Tew, Garry A; Doll, Helen; Zwierska, Irena; Woodroofe, Nicola; Channer, Kevin S; Saxton, John M

    2012-12-01

    This study assessed the feasibility of a 12-week program of exercise, with and without intramuscular testosterone supplementation, in male patients with chronic heart failure (CHF) and low testosterone status and collected preliminary data for key health outcomes. Male patients with CHF (n = 41, age 67.2 years, range 51-84 years) with mean ± SD testosterone levels of 10.7 ± 2.6 nmol/L (309 ± 76 ng/dL) were randomly allocated to exercise with testosterone or placebo groups. Feasibility was assessed in terms of recruitment, intervention compliance, and attrition. Outcomes included an incremental shuttle walk test, peak oxygen uptake, muscular strength, echocardiographic measures, N-terminal pro-brain natriuretic peptide, inflammatory markers, depression (Beck Depression Inventory), and health-related quality of life (Minnesota Living with Heart Failure Questionnaire and Medical Outcomes Study Short-Form). Attrition was 30% but with 100% compliance to exercise and injections in patients who completed the study. Similar improvements in shuttle walk test (18% vs 19%), body mass (-1.3 kg vs -1.0 kg), and hand grip strength (2.1 kg vs 2.5 kg) from baseline were observed in both groups. The exercise with testosterone group showed improvements from baseline in peak oxygen uptake (P < .01), Beck Depression Inventory (P < .05), leg strength (P < .05), and several Medical Outcomes Study Short-Form quality of life domains (P < .05), which were generally not apparent in the exercise with placebo group. Echocardiographic measures, N-terminal pro-brain natriuretic peptide, and inflammatory markers were mostly unchanged. This study shows for the first time that testosterone supplementation during a program of exercise rehabilitation is feasible and can positively impact on a range of key health outcomes in elderly male patients with CHF who have a low testosterone status. Copyright © 2012 Mosby, Inc. All rights reserved.

  8. Testosterone-induced development of the rat levator ani muscle.

    PubMed

    Tobin, C; Joubert, Y

    1991-07-01

    The perinatal development of the levator ani (LA) muscle in male and female rats was investigated by measuring the total number of muscle units (MU) (i.e., mononucleate cells, clustered or independent myotubes, and muscle fibers) in transverse semithin sections of the entire muscle and the MU cross-sectional area in 22-day-old fetuses (F22), 1-day-old (D1 = day of birth), 3-day-old (D3), and 6-day-old (D6) newborns. Male muscle contained 350 +/- 64 MU on F22, twice that of the female. The number of MU increased markedly in males from F22, but changed little in females; the number of MU in males was 760% that of females on D6. The MU cross-sectional area was greater in males on F22 (120.8 micron(s)2 +/- 7.5) and D1 (155.2 micron(s)2 +/- 64.8) than in females (F22: 89.2 micron(s) +/- 14.2, D1: 64.1 micron(s)2 +/- 19.7) and dropped to about 30 X micron(s)2 in both sexes on D6. Female rats given a single injection of testosterone propionate (TP) before D7 showed a significant increase in the number of fibers, but no increase in cross-sectional area. TP given after D7 had no effect on the fiber number, but increased the average cross-sectional area. The increase in fiber number induced by postnatal TP treatment was a permanent effect, still quantifiable in 15-month-old females. We conclude that the sexual dimorphism of the rat LA muscle is principally due to a dramatic increase in the MU number in male muscles during the perinatal period, rather than to involution of the fibers in female muscles as it is widely accepted. This increase seems to be, at least partly, under the control of testosterone.

  9. 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.

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

    PubMed

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

    2012-01-01

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

  11. Testosterone reactivity to facial display of emotions in men and women.

    PubMed

    Zilioli, Samuele; Caldbick, Evan; Watson, Neil V

    2014-05-01

    Previous studies have examined testosterone's role in regulating the processing of facial displays of emotions (FDEs). However, the reciprocal process - the influence of FDEs, an evolutionarily ancient and potent class of social signals, on the secretion of testosterone - has not yet been studied. To address this gap, we examined the effects of emotional content and sex of facial stimuli in modulating endogenous testosterone fluctuations, as well as sex differences in the endocrine responses to faces. One hundred and sixty-four young healthy men and women were exposed, in a between-subjects design, to happy or angry same-sex or opposite-sex facial expressions. Results showed that in both men (n=85) and women (n=79), extended exposure to faces of the opposite sex, regardless of their apparent emotional content, was accompanied by an accumulation in salivary testosterone when compared to exposure to faces of the same sex. Furthermore, testosterone change in women exposed to angry expressions was greater than testosterone change in women exposed to happy expressions. These results add emotional facial stimuli to the collection of social signals that modulate endocrine status, and are discussed with regard to the evolutionary roles of testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. 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.

  13. Exogenous testosterone enhances cortisol and affective responses to social-evaluative stress in dominant men.

    PubMed

    Knight, Erik L; Christian, Colton B; Morales, Pablo J; Harbaugh, William T; Mayr, Ulrich; Mehta, Pranjal H

    2017-11-01

    Stress often precedes the onset of mental health disorders and is linked to negative impacts on physical health as well. Prior research indicates that testosterone levels are related to reduced stress reactivity in some cases but correlate with increased stress responses in other cases. To resolve these inconsistencies, we tested the causal influence of testosterone on stress reactivity to a social-evaluative stressor. Further, prior work has failed to consider status-relevant individual differences such as trait dominance that may modulate the influence of testosterone on responses to stressors. Participants (n=120 males) were randomly assigned to receive exogenous testosterone or placebo (n=60 testosterone treatment group) via topical gel prior to a well-validated social-evaluative stressor. Compared to placebo, testosterone significantly increased cortisol and negative affect in response to the stressor, especially for men high in trait dominance (95% confidence intervals did not contain zero). The findings suggest that the combination of high testosterone and exposure to status-relevant social stress may confer increased risk for stress-mediated disorders, particularly for individuals high in trait dominance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Effects of testosterone administration on threat and escape anticipation in the orbitofrontal cortex.

    PubMed

    Heany, Sarah J; Bethlehem, Richard A I; van Honk, Jack; Bos, Peter A; Stein, Dan J; Terburg, David

    2018-05-30

    Recent evidence suggests that the steroid hormone testosterone can decrease the functional coupling between orbitofrontal cortex (OFC) and amygdala. Theoretically this decoupling has been linked to a testosterone-driven increase of goal-directed behaviour in case of threat, but this has never been studied directly. Therefore, we placed twenty-two women in dynamically changing situations of escapable and inescapable threat after a within-subject placebo controlled testosterone administration. Using functional magnetic resonance imaging (fMRI) we provide evidence that testosterone activates the left lateral OFC (LOFC) in preparation of active goal-directed escape and decouples this OFC area from a subcortical threat system including the central-medial amygdala, hypothalamus and periaqueductal gray. This LOFC decoupling was specific to threatening situations, a point that was further emphasized by an absence of such decoupling in a second experiment focused on resting-state connectivity. These results not only confirm that testosterone administration decouples the LOFC from the subcortical threat system, but also show that this is specifically the case in response to acute threat, and ultimately leads to an increase in LOFC activity when the participant prepares a goal-directed action to escape. Together these results for the first time provide a detailed understanding of functional brain alterations induced by testosterone under threat conditions, and corroborate and extend the view that testosterone prepares the brain for goal-directed action in case of threat. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. 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.

  17. 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.

  18. 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.

  19. Accuracy-based proficiency testing for testosterone measurements with immunoassays and liquid chromatography-mass spectrometry.

    PubMed

    Cao, Zhimin Tim; Botelho, Julianne Cook; Rej, Robert; Vesper, Hubert

    2017-06-01

    Accurate testosterone measurements are needed to correctly diagnose and treat patients. Proficiency Testing (PT) programs using modified specimens for testing can be limited because of matrix effects and usage of non-reference measurement procedure (RMP)-defined targets for evaluation. Accuracy-based PT can overcome such limitations; however, there is a lack of information on accuracy-based PT and feasibility of its implementation in evaluation for testosterone measurements. Unaltered, single-donor human serum from 2 male and 2 female adult donors were analyzed for testosterone by 142 NYSDH-certified clinical laboratories using 16 immunoassays and LC-MS/MS methods. Testosterone target values were determined using an RMP. The testosterone target concentrations for the 4 specimens were 15.5, 30.0, 402 and 498ng/dl. The biases ranged from -17.8% to 73.1%, 3.1% to 21.3%, -24.8% to 8.6%, and -22.1% to 6.8% for the 4 specimens, respectively. Using a total error target of ±25.1%, which was calculated using the minimum allowable bias and imprecision, 73% of participating laboratories had ≥3 of the 4 results within these limits. The variability in total testosterone measurements can affect clinical decisions. Accuracy-based PT can significantly contribute to improving testosterone testing by providing reliable data on accuracy in patient care to laboratories, assay manufacturers, and standardization programs. Copyright © 2017. Published by Elsevier B.V.

  20. 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.

  1. Exogenous testosterone affects early threat processing in socially anxious and healthy women.

    PubMed

    van Peer, Jacobien M; Enter, Dorien; van Steenbergen, Henk; Spinhoven, Philip; Roelofs, Karin

    2017-10-01

    Testosterone plays an important role in social threat processing. Recent evidence suggests that testosterone administration has socially anxiolytic effects, but it remains unknown whether this involves early vigilance or later, more sustained, processing-stages. We investigated the acute effects of testosterone administration on social threat processing in 19 female patients with Social Anxiety Disorder (SAD) and 19 healthy controls. Event-related potentials (ERPs) were recorded during an emotional Stroop task with subliminally presented faces. Testosterone induced qualitative changes in early ERPs (<200ms after stimulus onset) in both groups. An initial testosterone-induced spatial shift reflected a change in the basic processing (N170/VPP) of neutral faces, which was followed by a shift for angry faces suggesting a decrease in early threat bias. These findings suggest that testosterone specifically affects early automatic social information processing. The decreased attentional bias for angry faces explains how testosterone can decrease threat avoidance, which is particularly relevant for SAD. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Salivary testosterone is related to self-selected training load in elite female athletes.

    PubMed

    Cook, Christian J; Beaven, C Martyn

    2013-05-27

    Testosterone has been related to improved acute neuromuscular performance in athletic populations. It is our contention that testosterone may also contribute to improved volitional motivation and, when monitored longitudinally, may provide one proxy marker for readiness to perform. Twelve female netball players provided saliva samples prior to five standardized training sessions in which they completed a maximal-distance medicine ball throw, and then 3 sets of bench press and then back squat using a self-selected load perceived to equal a 3-repetition maximum load. Additional repetitions were encouraged when possible and total voluntary workload was calculated from the product of the load lifted and repetitions performed. Relative salivary testosterone levels as a group were correlated with bench press (r=0.8399; p=0.0007) and squat (r=0.6703; p=0.0171) self-selected workload, as well as maximal medicine ball throw performance (r=0.7062; p=0.0103). Individual salivary testosterone, when viewed relatively over time, demonstrated strong relationships with self-selected workloads during an in-season training period in female netball players. As such, daily variations in testosterone may provide information regarding voluntary training motivation and readiness to perform in elite athletic populations. Psychological and behavioral aspects of testosterone may have the potential to enhance training adaptation by complementing the known anabolic and permissive properties of testosterone. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. 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.

  8. Average Associations Between Sexual Desire, Testosterone, and Stress in Women and Men Over Time.

    PubMed

    Raisanen, Jessica C; Chadwick, Sara B; Michalak, Nicholas; van Anders, Sari M

    2018-05-29

    Sexual desire and testosterone are widely assumed to be directly and positively linked to each other despite the lack of supporting empirical evidence. The literature that does exist is mixed, which may result from a conflation of solitary and dyadic desire, and the exclusion of contextual variables, like stress, known to be relevant. Here, we use the Steroid/Peptide Theory of Social Bonds as a framework for examining how testosterone, solitary and partnered desire, and stress are linked over time. To do so, we collected saliva samples (for testosterone and cortisol) and measured desire as well as other variables via questionnaires over nine monthly sessions in 78 women and 79 men. Linear mixed models showed that testosterone negatively predicted partnered desire in women but not men. Stress moderated associations between testosterone and solitary desire in both women and men, but differently: At lower levels of stress, higher average testosterone corresponded to higher average solitary desire for men, but lower solitary desire on average for women. Similarly, for partnered desire, higher perceived stress predicted lower desire for women, but higher desire for men. We conclude by discussing the ways that these results both counter presumptions about testosterone and desire but fit with the existing literature and theory, and highlight the empirical importance of stress and gender norms.

  9. Marked testosterone deficiency-related symptoms may be associated to higher metabolic risk in men with low testosterone levels.

    PubMed

    García-Cruz, Eduard; Leibar-Tamayo, Asier; Romero-Otero, Javier; Asiaín, Ignacio; Carrión, Albert; Castañeda, Roberto; Mateu, Laura; Luque, Pilar; Cardeñosa, Oscar; Alcaraz, Antonio

    2014-09-01

    Testosterone deficiency syndrome (TDS) is usually suspected on the basis of signs/symptoms. However, some men with low testosterone levels (low T) are asymptomatic or present mild, unnoticed symptoms. Would they have the same cardiovascular risk as symptomatic men? This study aims to assess the relationship between presence/severity of low T-related symptoms and the likelihood of metabolic syndrome (MetS). Data were taken from a multicenter, cross-sectional study conducted in Spain among men visiting men's healthcare offices aged ≥45 with low T (total T <8 nmol/L or <12 nmol/L and calculated free T <250 nmol/L). Only subjects whose MetS components and symptoms had been assessed were selected. Data available included anthropometrics, toxic habits, comorbidities, and total testosterone (TT) levels. MetS was defined using the harmonized definition. Erectile dysfunction was classified using the International Index of Erectile Function questionnaire. The Ageing Male Symptoms (AMS) scale assessed symptoms. Symptom severity was classified as "none/mild" and "moderate/severe." Bivariate and multivariate logistic regression analyses were performed to calculate the effect of moderate/severe symptoms on the odds ratio (OR) for MetS. Mean age (SD) was 61.2 (8.1) years. Erectile dysfunction (ED), AMS, and MetS prevalence were 97.4%, 94.9%, and 69.6%. Prevalence of MetS was higher in men with moderate/severe symptoms vs. men with no/mild ones (75.3% vs. 57.9%, P < 0.001). Age and prevalence of TT <8 nmol/L, moderate/severe ED, and obesity were significantly higher in men with moderate/severe symptoms. Multivariate analysis showed that besides obesity and moderate/severe ED, moderate/severe symptoms increased the likelihood of MetS. This effect disappeared in men with severe ED and in the nonobese. Three symptoms showed relationship with MetS after adjusting for all confounding factors. Severity of TDS symptoms may indicate higher cardiovascular risk in men with low

  10. Validity of midday total testosterone levels in older men with erectile dysfunction.

    PubMed

    Welliver, R Charles; Wiser, Herbert J; Brannigan, Robert E; Feia, Kendall; Monga, Manoj; Köhler, Tobias S

    2014-07-01

    Based on studies showing the circadian rhythmicity of testosterone the optimal time of day to draw total testosterone in men has classically been reported as between 8 and 11 a.m. However, further studies demonstrated that the testosterone circadian rhythmicity becomes blunted with age. We retrospectively reviewed the charts of 2,569 men who presented with erectile dysfunction for total testosterone and draw times. We compared the men by age group, including less than 40 years and 5-year groupings after age 40 years. Total testosterone was analyzed for variability during the most common draw time hours (7 a.m. to 2 p.m.). Mean total testosterone at 7 to 9 a.m. and 9 a.m. to 2 p.m. clinically and statistically differed only in men younger than 40 vs 40 to 44 years old (mean difference 207 ng/dl, 95% CI 98-315, p = 0.0004 vs 149 ng/dl, 95% CI 36-262, p = 0.01). No other group showed a clinically and statistically significant difference between those periods. Total testosterone in men with erectile dysfunction who are younger than 45 years should be drawn as close to 7 a.m. as possible because a statistically and clinically relevant decrease in testosterone will occur during the course of the day. Men older than 45 years with erectile dysfunction can have total testosterone drawn at any time before 2 p.m. without misleading results. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Increased Testosterone Decreases Medial Cortical Volume and Neurogenesis in Territorial Side-Blotched Lizards (Uta stansburiana)

    PubMed Central

    LaDage, Lara D.; Roth, Timothy C.; Downs, Cynthia J.; Sinervo, Barry; Pravosudov, Vladimir V.

    2017-01-01

    Variation in an animal's spatial environment can induce variation in the hippocampus, an area of the brain involved in spatial cognitive processing. Specifically, increased spatial area use is correlated with increased hippocampal attributes, such as volume and neurogenesis. In the side-blotched lizard (Uta stansburiana), males demonstrate alternative reproductive tactics and are either territorial—defending large, clearly defined spatial boundaries—or non-territorial—traversing home ranges that are smaller than the territorial males' territories. Our previous work demonstrated cortical volume (reptilian hippocampal homolog) correlates with these spatial niches. We found that territorial holders have larger medial cortices than non-territory holders, yet these differences in the neural architecture demonstrated some degree of plasticity as well. Although we have demonstrated a link among territoriality, spatial use, and brain plasticity, the mechanisms that underlie this relationship are unclear. Previous studies found that higher testosterone levels can induce increased use of the spatial area and can cause an upregulation in hippocampal attributes. Thus, testosterone may be the mechanistic link between spatial area use and the brain. What remains unclear, however, is if testosterone can affect the cortices independent of spatial experiences and whether testosterone differentially interacts with territorial status to produce the resultant cortical phenotype. In this study, we compared neurogenesis as measured by the total number of doublecortin-positive cells and cortical volume between territorial and non-territorial males supplemented with testosterone. We found no significant differences in the number of doublecortin-positive cells or cortical volume among control territorial, control non-territorial, and testosterone-supplemented non-territorial males, while testosterone-supplemented territorial males had smaller medial cortices containing fewer

  12. 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.

  13. 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.

  14. 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.

  15. Testosterone causes both prosocial and antisocial status-enhancing behaviors in human males

    PubMed Central

    Dreher, Jean-Claude; Pazderska, Agnieszka; Frodl, Thomas; Nolan, John J.; O’Doherty, John P.

    2016-01-01

    Although popular discussion of testosterone’s influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status. Here, we tested these hypotheses in healthy young males by injecting testosterone enanthate or a placebo in a double-blind, between-subjects, randomized design (n = 40). Participants played a version of the Ultimatum Game that was modified so that, having accepted or rejected an offer from the proposer, participants then had the opportunity to punish or reward the proposer at a proportionate cost to themselves. We found that participants treated with testosterone were more likely to punish the proposer and that higher testosterone levels were specifically associated with increased punishment of proposers who made unfair offers, indicating that testosterone indeed potentiates aggressive responses to provocation. Furthermore, when participants administered testosterone received large offers, they were more likely to reward the proposer and also chose rewards of greater magnitude. This increased generosity in the absence of provocation indicates that testosterone can also cause prosocial behaviors that are appropriate for increasing status. These findings are inconsistent with a simple relationship between testosterone and aggression and provide causal evidence for a more complex role for testosterone in driving status-enhancing behaviors in males. PMID:27671627

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

    SciTech Connect

    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

  17. Investigating the binding behaviour of two avidin-based testosterone binders using molecular recognition force spectroscopy.

    PubMed

    Rangl, Martina; Leitner, Michael; Riihimäki, Tiina; Lehtonen, Soili; Hytönen, Vesa P; Gruber, Hermann J; Kulomaa, Markku; Hinterdorfer, Peter; Ebner, Andreas

    2014-02-01

    Molecular recognition force spectroscopy, a biosensing atomic force microscopy technique allows to characterise the dissociation of ligand-receptor complexes at the molecular level. Here, we used molecular recognition force spectroscopy to study the binding capability of recently developed testosterone binders. The two avidin-based proteins called sbAvd-1 and sbAvd-2 are expected to bind both testosterone and biotin but differ in their binding behaviour towards these ligands. To explore the ligand binding and dissociation energy landscape of these proteins, we tethered biotin or testosterone to the atomic force microscopy probe while the testosterone-binding protein was immobilized on the surface. Repeated formation and rupture of the ligand-receptor complex at different pulling velocities allowed determination of the loading rate dependence of the complex-rupturing force. In this way, we obtained the molecular dissociation rate (k(off)) and energy landscape distances (x(β)) of the four possible complexes: sbAvd-1-biotin, sbAvd-1-testosterone, sbAvd-2-biotin and sbAvd-2-testosterone. It was found that the kinetic off-rates for both proteins and both ligands are similar. In contrast, the x(β) values, as well as the probability of complex formations, varied considerably. In addition, competitive binding experiments with biotin and testosterone in solution differ significantly for the two testosterone-binding proteins, implying a decreased cross-reactivity of sbAvd-2. Unravelling the binding behaviour of the investigated testosterone-binding proteins is expected to improve their usability for possible sensing applications. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Testosterone prevents protein loss via the hepatic urea cycle in human.

    PubMed

    Lam, Teresa; Poljak, Anne; McLean, Mark; Bahl, Neha; Ho, Ken K Y; Birzniece, Vita

    2017-04-01

    The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied. To determine whether testosterone reduces hepatic urea production. An open-label study. Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day). The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with 15 N 2 -urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated. Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min; P  < 0.01), which was paralleled by a significant reduction in serum urea concentration. Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% ( P  < 0.05). There was a positive association between Lox and hepatic urea production at baseline ( r 2  = 0.60, P  < 0.05) and after testosterone administration ( r 2  = 0.59, P  < 0.05). Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle. © 2017 European Society of Endocrinology.

  19. 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.

  20. 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

  1. Testosterone-mineralizing culture enriched from swine manure: characterization of degradation pathways and microbial community composition.

    PubMed

    Yang, Yun-Ya; Pereyra, Luciana P; Young, Robert B; Reardon, Kenneth F; Borch, Thomas

    2011-08-15

    Environmental releases and fate of steroid sex hormones from livestock and wastewater treatment plants are of increasing regulatory concern. Despite the detection of these hormones in manures, biosolids, and the environment, little attention has been paid to characterization of fecal bacteria capable of hormone degradation. The enrichments of (swine) manure-borne bacteria capable of aerobic testosterone degradation were prepared and the testosterone mineralization pathway was elucidated. Six DNA sequences of bacteria from the Proteobacteria phylum distributed among the genera Acinetobacter, Brevundimonas, Comamonas, Sphingomonas, Stenotrophomonas, and Rhodobacter were identified in a testosterone-degrading enriched culture with testosterone as the sole carbon source. Three degradation products of testosterone were identified as androstenedione, androstadienedione, and dehydrotestosterone using commercially available reference standards, liquid chromatography-UV diode array detection, and liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS). Three additional degradation products of testosterone were tentatively identified as 9α-hydroxytestosterone, 9α-hydroxyandrostadienedione or 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione, and 9α-hydroxydehydrotestosterone or 9α-hydroxyandrostenedione using LC-TOF/MS. When (14)C-testosterone was introduced to the enriched culture, 49-68% of the added (14)C-testosterone was mineralized to (14)CO(2) within 8 days of incubation. The mineralization of (14)C-testosterone followed pseudo-first-order reaction kinetics in the enriched culture with half-lives (t(1/2)) of 10-143 h. This work suggests that Proteobacteria play an important environmental role in degradation of steroid sex hormones and that androgens have the potential to be mineralized during aerobic manure treatment or after land application to agricultural fields by manure-borne bacteria.

  2. Age Differences in Prenatal Testosterone's Protective Effects on Disordered Eating Symptoms: Developmental Windows of Expression?

    PubMed Central

    Culbert, Kristen M.; Breedlove, S. Marc; Sisk, Cheryl L.; Keel, Pamela K.; Neale, Michael C.; Boker, Steven M.; Burt, S. Alexandra; Klump, Kelly L.

    2015-01-01

    Prenatal testosterone exposure may be protective against disordered eating. However, prior studies have produced mixed results. Developmental differences in prenatal testosterone's protective effects on disordered eating may explain these discrepancies. Indeed, studies have differed in the age of participants assessed, with data supporting prenatal testosterone effects on disordered eating in early adolescent and young adult samples but not in late adolescence. The present series of studies are the first to investigate age differences in prenatal testosterone's protective effects on disordered eating. Two indirect markers of higher prenatal testosterone were examined: 1) lower finger-length ratios [index (2D)/ring (4D) finger] (Study 1), and 2) lower disordered eating in females from opposite-sex twin pairs (who are thought to be exposed to higher prenatal testosterone from their male co-twin) relative to female controls (Study 2). Participants were twins from the Michigan State University Twin Registry (Study 1: n = 409; Study 2: n = 1,538) in early adolescence, late adolescence, or young adulthood. Disordered eating was assessed with well-validated questionnaires. Finger-length ratios were measured from hand scans, using electronic computer calipers. Findings were consistent across both studies. Higher prenatal testosterone (lower 2D:4D; females from opposite-sex twin pairs vs. controls) predicted lower disordered eating in early adolescence and young adulthood only. Prenatal testosterone-disordered eating associations were not observed during late adolescence. Results point to the possibility of developmental windows of expression for prenatal testosterone's protective effects on disordered eating and suggest that prior discrepant results may reflect age differences across samples. PMID:25621790

  3. 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.

  4. 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

  5. Changes in testosterone related to body composition in late midlife: Findings from the 1946 British birth cohort study

    PubMed Central

    Wu, Frederick C. W.; Keevil, Brian; Lashen, Hany; Adams, Judith; Hardy, Rebecca; Muniz, Graciela; Kuh, Diana; Ben‐Shlomo, Yoav; Ong, Ken K.

    2015-01-01

    Objective Randomized trials in men with testosterone deficiency have provided evidence of short‐term effects of testosterone therapy on muscle and fat mass but it is unclear whether this persists over a longer period or how testosterone affects women. We examined whether the midlife decline in testosterone relates to fat and lean mass in both sexes. Methods Data were collected from 440 men and 560 women participating in the 1946 British birth cohort study with testosterone measured at 53 and/or 60‐64 years. Fat and appendicular lean mass were measured at 60‐64 years using dual‐energy X‐ray absorptiometry. Results Mean free testosterone concentrations were lower at 60‐64 than 53 years, by 26% in both sexes. At both ages testosterone was negatively associated with fat mass in men and positively associated in women. A larger decline in free testosterone was associated with higher fat mass in men but with lower fat mass among women. In contrast, declines in testosterone were not associated with lean mass in either sex. Conclusions Our findings suggest sex‐divergent relationships between testosterone and fat mass and their distribution but do not support the hypothesis that midlife declines in testosterone lead to lower lean mass. PMID:26053924

  6. 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

  7. 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.

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

    PubMed

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

    2001-01-01

    Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive

  9. Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep.

    PubMed

    Veiga-Lopez, Almudena; Lee, James S; Padmanabhan, Vasantha

    2010-08-01

    Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30-90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (>/=18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome.

  10. [Oral Anatomy.

    PubMed

    Abe, Shinichi

    With regard to oral cavity, it is known that jaw bone morphology greatly changes with tooth loss. Therefore, it is necessary to consider the muscles attached to the jaw bone and the surrounding vessels and nerves, in connection with the jaw bone morphology after tooth loss. As an example, the height of the mandibular bone decreases to the position of the mylohyoid line after tooth loss. By this marked morphological change in the alveolar area, the lingual nerve and the lingual artery branches running in the sublingual area on the mandibular inner surface becomes located in the area almost the same as the alveolar crest.

  11. 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

  12. Combined administration of levonorgestrel and testosterone induces more rapid and effective suppression of spermatogenesis than testosterone alone: a promising male contraceptive approach.

    PubMed

    Bebb, R A; Anawalt, B D; Christensen, R B; Paulsen, C A; Bremner, W J; Matsumoto, A M

    1996-02-01

    Studies using high dose testosterone (T) administration in normal men as a male contraceptive have resulted in azoospermia rates of only 50-70%. Previous studies of T and progestogen combinations have shown comparable rates of azoospermia, but have been uncontrolled or used T in doses less than that associated with maximal suppression of sperm production. We conducted a randomized, placebo-controlled, single blind trial comparing 6 months of T enanthate administration (100 mg, im, weekly) with the same dose of T enanthate in conjunction with the progestogen levonorgestrel (LNG; 500 micrograms, orally, daily) in 36 normal men, aged 20-42 yr (n = 18 in each group). The primary end points were induction of azoospermia or severe oligospermia (< 3 million sperm/mL). The combination of T plus LNG was much more effective in suppressing sperm production than T alone. Sixty-seven percent of the T plus LNG group (12 of 18) and 33% of the T alone group (6 of 18) achieved azoospermia by 6 months (P = 0.06). Severe oligospermia or azoospermia developed in 94% of the T plus LNG (17 of 18) group compared to 61% of the T alone group (11 of 18; P < 0.05). T plus LNG also suppressed sperm production more rapidly than T alone. Time to azoospermia was 9.9 +/- 1.0 vs. 15.3 +/- 1.9 weeks in the T plus LNG and T alone groups, respectively (mean +/- SEM; P < 0.05). Serum high density lipoprotein cholesterol decreased 21.7 +/- 3.6% in men given T plus LNG (P < 0.05), compared to only a 1.8 +/- 3.8% decrease in men in the T alone group. Average weight gain was 5.3 +/- 0.8 kg in the T plus LNG group and 2.3 +/- 0.9 kg in the T alone group (P < 0.05). Acne and increase in hemoglobin were similar in the two groups. We conclude that combination hormonal therapy with T plus a progestogen might offer a reversible male contraceptive approach with a more rapid onset of action and more reliable induction of both azoospermia and severe oligospermia than T alone.

  13. 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, ...

  14. 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.

  15. Testosterone administration does not affect men's rejections of low ultimatum game offers or aggressive mood.

    PubMed

    Cueva, Carlos; Roberts, R Edward; Spencer, Tom J; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N; Herbert, Joe; Rustichini, Aldo

    2017-01-01

    Correlative evidence suggests that testosterone promotes dominance and aggression. However, causal evidence is scarce and offers mixed results. To investigate this relationship, we administered testosterone for 48h to 41 healthy young adult men in a within-subjects, double-blind placebo-controlled balanced crossover design. Subjects played the role of responders in an ultimatum game, where rejecting a low offer is costly, but serves to destroy the proposer's profit. Such action can hence be interpreted as non-physical aggression in response to social provocation. In addition, subjects completed a self-assessed mood questionnaire. As expected, self-reported aggressiveness was a key predictor of ultimatum game rejections. However, while testosterone affected subjective ratings of feeling energetic and interested, our evidence strongly suggests that testosterone had no effect on ultimatum game rejections or on aggressive mood. Our findings illustrate the importance of using causal interventions to assess correlative evidence. Copyright © 2016. Published by Elsevier Inc.

  16. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness

    PubMed Central

    Pan, Michael M.

    2016-01-01

    Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required. PMID:27141449

  17. The effects of nandrolone, testosterone and their decanoate esters on murine lupus.

    PubMed Central

    Verheul, H A; Stimson, W H; den Hollander, F C; Schuurs, A H

    1981-01-01

    Treatment of NZB/NZW F1 (B/W) female and castrated male mice with testosterone or 19-nortestosterone (nandrolone), either by implantation in silastic tubing or by subcutaneous injections of their decanoate esters, reduced in a dose-dependent manner symptoms associated with murine lupus (proteinuria, IgG antibodies to DNA) and prolonged survival. These phenomena were observed under both prophylactic (start at 3-4 weeks) and therapeutic treatments (start 27-29 weeks). Nandrolone and its decanoate ester were at least as potent as testosterone and testosterone decanoate. As the unwanted androgenic properties of nandrolone and its ester are significantly less pronounced than those of testosterone and its ester, also in these NZB/NZW mice, the beneficial effect on murine lupus does not seem to be associated with these properties. PMID:6973425

  18. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness.

    PubMed

    Pan, Michael M; Kovac, Jason R

    2016-04-01

    Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required.

  19. 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, e