Doses Of Testosterone Research Articles

Response to short course androgenisation in late reported cases with micropenis

Background and objectives: Micropenis is an abnormally short penis and its treatment should begin in infancy or in very early childhood. The present study investigated the response of short term testosterone therapy in late reported cases of micropenis.
 Methods: A total of 17 cases of micropenis between the age of 8 and 15 years were included in the study. Standard criteria for the diagnosis of micropenis were followed. All cases were treated with intramuscular testosterone 50 to 75 mg once every 21 days. Response to testosterone treatment was measured by the absolute and percent increment in stretched penile length (SPL). Response was considered adequate if final SPL crosses the average SPL for age. We also compared the response of treatment of cases reported before and after 11 years of age.
 Result: A total of 17 micropenis cases were included in the study. Out of total 17 boys, 10 were between 8 to 11 years (Group 1) and 7 were between 12 to 15 years (Group 2) of age. The mean pre-treatment SPL of 17 micropenis cases was 3.1±0.2 cm (CI: 2.83, 3.43 cm). The mean initial SPL of Gr1 and Gr2 was not significantly different (3.2±0.3 cm vs 3.0±0.1 cm; p>0.248). The mean post treatment SPL of 17 cases increased significantly (p<0.001) compared to their initial SPL. The range of percentage increment in SPL was 100%-400%. Higher testosterone doses were required in Gr2 cases compared to Gr1 (360±20.8 mg vs 260.7±38.5 mg).
 Conclusion: Micropenis in boys with palpable gonads responded to short term testosterone treatment in late reported cases and we termed these cases as simple micropenis.
 Ibrahim Med. Coll. J. 2020; 14(1): 1-4

Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men.

Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations. To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men. 177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls). Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire. Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL. Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed.

Case Report: Homozygous C677T MTHFR Gene Mutation in Male with Hypogonadism

We report a 44-year-old male, who was diagnosed with hypogonadotropic hypogonadism after complaining of erectile dysfunction, depression, and fatigue. He was started on testosterone replacement therapy. He persistently complained of fatigue despite increasing the dose of testosterone over two years and having therapeutic testosterone levels. He was found to have homozygous C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation. After treatment with folate and B12, his symptoms resolve completely. MTHFR is a key enzyme in the folate pathway, and it plays an essential role in homocysteine metabolism. Homozygous C677T individuals have decreased activity of MTHFR enzyme with increased homocysteine levels, which is associated with increased risk of thrombosis. An association has been reported between C677T variant and male infertility. Patients identified to have hyperhomocysteinemia should be treated with B-complex vitamin supplements. Our case emphasizes other possible etiologies for fatigue and erectile dysfunction in a male with hypogonadism on testosterone therapy. Also, it shows possible association between MTHFR gene mutation and male hypogonadism.

SAT-041 Testosterone Reduces Atherosclerosis and Plaque Specific Inflammatory Markers in the ApoE-/- Mouse Model

Low serum testosterone in men is an established cardiovascular risk factor and epidemiological evidence demonstrates an association between low testosterone and with coronary events. Clinical evidence suggests that testosterone therapy (Tth) can improve key cardiovascular risk factors in men and surrogate measures of atherosclerosis, the chronic inflammatory process underlying cardiovascular disease. Atherosclerotic plaque-specific testosterone actions are not fully understood. The present study investigates the influence of testosterone on mediators of vascular inflammation and plaque burden in an in vivo model of atherosclerosis. ApoE-/- mice were either sham operated, castrated or castrated and received fortnightly intramuscular injections of physiological doses of testosterone (mixed testosterone esters, Sustanon 100) to create 3 experimental groups; normal testosterone, testosterone deficient and testosterone replaced respectively. All groups were fed a high-fat ‘Western’ diet for 16 weeks. Lipid deposition in the aortic root was assessed by Oil Red O as an indication of atherosclerotic burden. Plaque composition was assessed immunohistochemically for indicators of stability including collagen content via Masson’s trichrome, and α-smooth muscle actin (αSMA) as well as markers of inflammation including vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule 1 (E-Selectin), and a pan monocyte/macrophage marker (MOMA2). Testosterone deficient castrated mice had significantly increased lipid accumulation in the aortic root compared to testosterone replete sham-operated littermates (48% intima-media area vs 40%, p<0.05). Tth in castrated mice reversed this effect (39%, p<0.05). Plaque stability was not altered between groups. MOMA2 staining indicated increased infiltration and localisation of monocytes/macrophages in the plaques of castrated mice compared to sham-operated (positive staining (% of plaque) 77% vs 59%, P=0.062) and Tth treatment reduced this (77% vs 63%, P=0.1). Vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression were reduced in castrated mice receiving Tth compared to castrated mice receiving saline (33% vs 46%, p<0.05; and 39% vs 58%, P=0.084 respectively). No significant difference in expression of E-Selectin and αSMA were observed between groups. These findings demonstrate that low testosterone increases aortic root lipid deposition and inflammatory composition in a mouse model of atherosclerosis. Increasing testosterone levels through Tth reduces plaque specific inflammatory markers and atherosclerotic burden. This indicates an anti-inflammatory mechanism by which testosterone can protect against the development and progression of atherosclerosis to reduce cardiovascular risk in men.

SAT-LB6 First Human Trial of an Oral Native Testosterone Shows Physiological Levels of Testosterone and Dht in Both Fasted and Fed State in Hypogonadal Men

Introduction: The prevalence of male hypogonadism is estimated to be 6% in the USA (1). Current therapies have limited acceptability: gels can be messy and risk inadvertent dosing of others; injections are painful; and oral testosterone undecanoate (TU) delivers variable testosterone levels, requires concurrent ingestion of a fatty meal and may produce supraphysiological dihydrotestosterone (DHT) levels. We present the first human trial of an oral native testosterone preparation formulated to deliver physiological levels of testosterone irrespective of food intake. Aim: To compare the pharmacokinetics of DITEST (Diurnal Ltd Cardiff, UK) to an oil based oral TU formulation (Andriol Testocaps MSD, UK) and explore the effect of food on DITEST bioavailability. Methods: Single centre, phase 1b study of DITEST in 25 adult males with hypogonadism, one subject withdrawn after single period and only included in safety analysis (Clinicaltrials.gov: NCT02966652). Part 1 compared the pharmacokinetics of 80mg TU with 120mg DITEST after a high fat meal. Part 2 the pharmacokinetics of 200mg of DITEST administered in either fed or fasted states. Results are baseline adjusted. Results: DITEST showed a testosterone dose response between 120mg and 200mg with Cmax 550 (19.1) and 877 (30.4) ng/dl (nmol/l) and AUC0-10h 59.5 and 88.6 h*nmol/L. DITEST 200mg gave an equivalent Cmax and AUC0-10h to TU 80mg: Cmax 877 (30.4) vs 906 (31.4) ng/dl (nmol/l) and AUC0-10h 88.6 vs 102 h*nmol/L. Fed and fasted DITEST had similar pharmacokinetics: Cmax 764 (26.5) vs 877 (30.4) ng/dl (nmol/L), AUC0-10h 87.0 vs 88.6. DITEST resulted in lower levels of DHT than TU: Cmax 84 (2.9), 131 (4.5) & 194 (6.7) ng/dl (nmol/l); AUC0-10h 11.0, 16.7 & 36.3 h*nmol/L for DITEST 120mg, 200mg & 80mg TU, respectively. There was one serious adverse event (urinary retention) in the study during TU dosing. There were no emerging safety concerns, and adverse event frequency and severity was similar between the two treatments. Discussion: These results demonstrate that 200mg DITEST provides similar testosterone exposure with more physiological DHT exposure than 80mg TU given with a high fat meal. Administration of DITEST in fed and fasted states provides similar testosterone and DHT exposure. Compared to published literature on a self-emulsifying formulation of TU at 200mg, DITEST at 200mg provides a similar testosterone Cmax and no requirement for a fatty meal (2). Conclusion: DITEST is an oral native testosterone formulation with anticipated advantages over current oral therapy of dosing without food and a lower risk of supraphysiological DHT levels.

Pre-operative hormone stimulation in hypospadias repair: A facilitator or a confounder

Preoperative hormone stimulation (PHS) is popular in hypospadias reconstructive surgery. While still controversial, it is performed to have a more developed gross anatomy of the glans and penis for improvement of the surgical condition and outcome. In this study we assessed morphometric and histologic effects of pre-operative testosterone therapy on the penis and prepuce in patients with hypospadias. 18 patients with hypospadias who received 3 monthly doses of 25mg testosterone injections were compared with 23 patients with hypospadias who were managed without pre-operative androgen therapy. Penile morphometry and hormone side effects were assessed in monthly pre-operative visits. Intra operative observations and preputial histopathology were also compared between the groups. Glans diameter enlarged significantly after the first dose of testosterone. (P<0.001) while morphologic changes were not significant by further injections. 72.2% showed one or more hormone related side effects that were mostly mild. Severe side effects such as thick pubic hair growth, frequent erections or considerable penis hyper-sensation were observed in 27.8%. Glans to corpus ratio was 0.2±0.75 in PHS group compare to 0.3±0.17 in control group. (P<0.001). Hemorrhage needing tourniquet placement was reported in 44.4% of the PHS patients compared to 26.1% among the control group. Histopathologic studies revealed increased vascularity and less inflammation of the prepuce in PHS group compared to controls. The glans and penis enlargement wasn't significant in 22.2% of patients who underwent PHS. We identified the first dose of testosterone as the most effective one. This finding supports the idea of close clinical monitoring to stop PHS when a significant response is observed and the expected goals are reached. Androgen side effects were not uncommon among our patients although they were mainly mild. Intraoperative assessments showed a decreased glans wing thickness to corporal body ratio in PHS group compared to controls. This finding caused more complex glanuloplasty while wrapping the glans wings over neo urethra and enlarged corporal bodies. We suggest limiting PHS to carefully selected cases considering the observed anatomical and histological changes and the side effects. Monthly monitoring during PHS is recommended to stop androgen therapy as soon as the minimum defined targets are reached. This may decrease the rate of androgen side effects while providing better surgical conditions.

Prenatal low-dose methyltestosterone, but not dihydrotestosterone, treatment induces penile formation in female mice and guinea pigs†.

Genital tubercle has bisexual potential before sex differentiation. Females exposed to androgen during sex differentiation show masculinized external genitalia, but the effects of different androgens on tubular urethral and penile formation in females are mostly unknown. In this study, we compared the masculinization effects of commonly used androgens methyltestosterone, dihydrotestosterone, and testosterone on the induction of penile formation in females. Our results suggested that prenatal treatment with low doses of methyltestosterone, but not same doses of dihydrotestosterone or testosterone, could induce penile formation in female mice. The minimum dose of dihydrotestosterone and testosterone for inducing tubular urethral formation in female mice was, respectively, 50 and 20 times higher than that of methyltestosterone. In vivo methyltestosterone treatment induced more nuclear translocation of androgen receptors in genital tubercles of female mice, affected Wnt signaling gene expressions, and then led to similar patterns of cell proliferation and death in developing genital tubercles to those of control males. We further revealed that low-dose methyltestosterone, but not same dose of dihydrotestosterone or testosterone, treatment induced penile formation in female guinea pigs. Exposure of female mouse genital tubercle organ culture to methyltestosterone, dihydrotestosterone, or testosterone could induce nuclear translocation of androgen receptors, suggesting that the differential effect of the three androgens in vivo might be due to the hormonal profile in mother or fetus, rather than the local genital tissue. To understand the differential role of these androgens in masculinization process involved is fundamental to androgen replacement therapy for diseases related to external genital masculinization.

Fiber type-specific hypertrophy and increased capillarization in skeletal muscle following testosterone administration in young women.

It is well established that testosterone administration induces muscle fiber hypertrophy and myonuclear addition in men; however, it remains to be determined whether similar morphological adaptations can be achieved in women. The aim of the present study was therefore to investigate whether exogenously administered testosterone alters muscle fiber morphology in skeletal muscle of young healthy, physically active women. Thirty-five young (20-35 yr), recreationally trained women were randomly assigned to either 10-wk testosterone administration (10 mg daily) or placebo. Before and after the intervention, hormone concentrations and body composition were assessed, and muscle biopsies were obtained from the vastus lateralis. Fiber type composition, fiber size, satellite cell and myonuclei content, as well as muscle capillarization were assessed in a fiber type-specific manner by immunohistochemistry. After the intervention, testosterone administration elevated serum testosterone concentration (5.1-fold increase, P = 0.001) and induced significant accretion of total lean mass (+1.9%, P = 0.002) and leg lean mass (+2.4%, P = 0.001). On the muscle fiber level, testosterone increased mixed-fiber cross-sectional area (+8.2%, P = 0.001), an effect primarily driven by increases in type II fiber size (9.2%, P = 0.006). Whereas myonuclei content remained unchanged, a numerical increase (+30.8%) was found for satellite cells associated with type II fibers in the Testosterone group. In parallel with fiber hypertrophy, testosterone significantly increased capillary contacts (+7.5%, P = 0.015) and capillary-to-fiber ratio (+9.2%, P = 0.001) in type II muscle fibers. The present study provides novel insight into fiber type-specific adaptations present already after 10 wk of only moderately elevated testosterone levels in women.NEW & NOTEWORTHY We have recently demonstrated performance-enhancing effects of moderately elevated testosterone concentrations in young women. Here we present novel evidence that testosterone alters muscle morphology in these women, resulting in type II fiber hypertrophy and improved capillarization. Our findings suggest that low doses of testosterone potently impact skeletal muscle after only 10 wk. These data provide unique insights into muscle adaptation and support the performance-enhancing role of testosterone in women on the muscle fiber level.

Single dose testosterone administration increases men’s facial femininity preference in a Chinese population

Sex hormones are thought to influence human mate preferences. Previous studies have reported mixed results regarding the association between men’s testosterone levels and their mate preferences. The present study investigated the effect of testosterone administration on men’s facial femininity preference. Heterosexual Chinese male participants (n = 140) received a single dose of 150 mg testosterone or placebo gel in a double-blind, placebo-controlled, between-participant design. Results showed that Chinese men demonstrated general preferences for feminized women’s faces, consistent with previous results from the Western population. More importantly, men showed stronger attraction to femininity in women’s faces three hours after testosterone administration than at the beginning of the session. In the placebo group, no significant change in facial femininity preferences was found between time points. These results indicate that exogenous testosterone increases men’s facial femininity preferences in a Chinese population.

Vaginal bleeding and spotting in transgender men after initiation of testosterone therapy: A prospective cohort study (ENIGI)

Background: Previous studies have cross-sectionally described amenorrhea in cohorts of transgender men on intramuscular or subcutaneous testosterone injections. It remains uncertain which testosterone preparations most effectively suppress vaginal bleeding and when amenorrhea occurs after testosterone initiation.Aim:To investigate the clinical effects of various testosterone preparations on vaginal bleeding and spotting in transgender men.Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Data on the persistence and intensity of vaginal bleeding and spotting, serum sex steroid levels and body composition were prospectively and cross-sectionally assessed in 267 transgender men during a three-year follow-up period, starting at the initiation of various testosterone preparations.Results: After three months of testosterone, 17.9% of transgender men reported persistent vaginal bleeding and 26.8% reported spotting. The percentages reporting vaginal bleeding and spotting decreased over the first year of testosterone (bleeding 4.7% and spotting 6.9% at 12 months, respectively), with no participants reporting vaginal bleeding or spotting after 18 months of testosterone. Factors associated with vaginal bleeding or spotting included lower serum testosterone levels and being on testosterone gel as compared to injections (e.g., esters or undecanoate preparations). If vaginal bleeding persisted, starting progestogens at three months resulted in a decrease in the intensity of vaginal bleeding and spotting.Discussion: Transgender men and hormone-prescribing providers can be reassured that vaginal bleeding and spotting usually stop within three months after testosterone initiation. If not, serum testosterone levels should be measured and testosterone dose adjusted to achieve serum testosterone levels in the physiologic male range. Adding a progestin can be considered after three to six months if bleeding persists. Providers should be aware that cessation of bleeding can be more difficult to achieve in transgender men with lower serum testosterone levels or those on testosterone gel.

Hormonal Male Contraception.

The demand for availability of efficient and safe contraceptive methods is strengthened by the predictions made by the United Nations regarding the future growth of the human population. So far, women are not only the main victims of the unsafe procedures related to terminating unwished pregnancies but do also carry the main responsibility for family planning. There is a significant desire among men for sharing this responsibility and a substantial proportion of females are willing to trust their male partners in regard to the use of contraception. Therefore, there is a need for developing new reversible, safe, effective, acceptable, affordable and available methods of male contraception. Thus, hormonal manipulation resulting in the suppression of sperm production seems, so far, to be the most feasible approach to achieve the above-mentioned goal. Several strategies of such hormonal manipulation have been tested. Most of them are based on the administration of more or less supra-physiological doses of exogenous testosterone, alone or in combination with other means of endocrine suppression of gonadotropin secretion. Although, so far, the goal of hormonal male contraception fulfilling the above-mentioned criteria, has not yet been achieved; continuing development of new molecules, gives hope for the near future.

2020 CPT Codes Include Electronic Visits

High doses of testosterone might lead to mood improvements in men, but hormone replacement could also increase the risk of other health problems.

Review of the salivary dosage of insulin, testosterone and cortisol

Review of the salivary dosage of insulin, testosterone and cortisol

The Effect of Testosterone Replacement on Intramedullary, Inguinal and Visceral Fat in Ovariectomized Rats.

The present article aims to evaluate the impact of testosterone treatment on the expansion of visceral, subcutaneous and intramedullary adipose tissue of ovariectomized rats and the visceral and subcutaneous fat expression of peroxisome proliferator-activated receptors (PPARs) gamma. METHODS: In total 48 female Wistar rats were castrated and randomly divided into 6 treatment groups: group E2 was submitted to estradiol 5 μg/day; group T, to testosterone 5 μg/day; group E2 + T, to estradiol 5 μg/day + testosterone 5 μg/day; group TT, to testosterone 30 μg/day; group E2 + TT, to estradiol 5 μg/day + testosterone 30 μg/day; and placebo was administered to group P. After 5 weeks, the rats were euthanized, the inguinal and visceral adipose tissues were harvested, weighted, and had their PPAR gamma expression evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The right femurs were harvested and histologically prepared to perform the number count of the intramedullary adipocytes. The expansion of visceral fat tissue was much higher in the TT group when compared with other treated groups (p < 0.001). The TT group also showed a higher expansion of inguinal fat (p < 0.01), and groups E2 + T and E2 + TT presented lower growth compared to the P group (p < 0.01). The number of femur intramedullary adipocytes only showed significant differences between groups TT and E2 + TT (p < 0.05). The expression of PPAR gamma showed no differences among the groups. The use of testosterone in high doses leads to an important expansion in both visceral and inguinal adipose tissues. Association with estradiol exerts an expansion-repressive effect on the visceral and inguinal adipose tissues.

Consumption of avocado oil (Persea americana) improves the biochemical profile of rats submitted to long-term androgenic stimulation.

Introduction: indiscriminate use of anabolic steroids is associated with cardiovascular diseases, renal damage, and hepatic toxicity. Contrastingly, nutraceutical foods such as avocados prevent and control several diseases, as they can reduce the effects of oxidative stress. Objective: this study evaluates the benefits of consuming an avocado oil-based diet to attenuate the systemic damage caused by supraphysiological doses of testosterone, by analyzing the biochemical profile of 28 42-day-old male Wistar rats. Methods: silicone pellets containing testosterone were surgically implanted, and they received control or avocado oil-based feed. After 20 weeks, all the male rats were anesthetized and their blood samples collected. Results: although the high hormone concentration had a negative influence on the biochemical profile of these animals, the groups that consumed avocado oil exhibited a reduction in serum triacylglycerols (-21 %; p = 0.0001), VLDL (-20 %; p = 0.0085), LDL (-78 %; p < 0.0001), and total cholesterol (-12 %; p < 0.0001), along with positive changes in their HDL concentrations (+7 %; p = 0.001). The avocado oil groups also manifested a reduction in the total concentration of serum proteins (-24 %; p = 0.0357), albumin (-26 %; p = 0.0015), urea (-14 %; p = 0.04), and creatinine (-33 %; p < 0.0001). The concentration of liver transaminases was found to be higher in the animals included in the induced group (ALT, +66 %; p = 0.0005, and AST, +23 %; p = 0.0021), whereas they remained stable in the avocado oil group. Conclusion: from the above, it may be concluded that supraphysiological doses of testosterone are related to increased risk factors for cardiovascular, renal, and hepatic diseases, and that the consumption of avocado oil shields the biochemical profile, thus reducing the associated risk factors.

Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats

Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500–1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.

The effects of testosterone administration on muscle areas of the trunk and pelvic floor in hysterectomized women with low testosterone levels: proof-of-concept study.

The aim of this study was to determine the effect of testosterone administration on trunk and pelvic floor muscle area in women with low testosterone levels. Participants were hysterectomized women with total testosterone<31 ng/dL and/or free testosterone<3.5 pg/mL; participating in the Testosterone Dose Response in Surgically Menopausal Women (TDSM) trial. All participants received a standardized transdermal estradiol regimen during the 12-week run-in period, and were then randomized to receive weekly intramuscular injections of placebo, or 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Muscle areas of the trunk and pelvis were measured at baseline and end of treatment using 1.5 Tesla magnetic resonance imaging. Total and free testosterone levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Testosterone effect on muscle areas was analyzed using linear regression models. A total of 24 women who had available baseline and posttreatment magnetic resonance imaging were included in the analysis. Increased cross-sectional areas of the paraspinal, psoas, and abdominal wall muscles were seen after testosterone administration. The estimated mean change (95% CI; P value) between treatment groups was 4.07 cm (1.26-6.88; P = 0.007) for paraspinal, 1.60 cm (0.10-3.09; P = 0.038) for psoas major, and 7.49 cm (1.96-13.02; P = 0.011) for abdominal wall muscles. Increases in psoas muscle area were significantly associated with changes in free testosterone concentrations. No significant changes in obturator internus and pelvic floor muscle areas were observed. Short-term testosterone administration in women with low testosterone levels was associated with increased trunk muscle area.

Single dose testosterone administration increases impulsivity in the intertemporal choice task among healthy males

Circulating levels of testosterone have been positively associated with impulsivity. The present study investigates the effect of testosterone administration on impulsivity in an intertemporal choice task, where participants are given a choice between smaller-sooner rewards and larger-later rewards. Healthy young male participants (n = 111) received a single-dose of 150 mg testosterone gel in a double-blind, placebo-controlled, between-subjects design. At 180 min post-administration, participants performed the decision-making task. Both model-free (i.e., higher indifference point) and model-based (i.e., steeper discounting rate) parameters revealed that testosterone administration increased impulsive choice. This finding supports the hypothesis that exogenous testosterone increases impulsivity among healthy young males in a laboratory task.

Serum Testosterone and Cortisol Concentrations After Single-Dose Administration of 100-Mg Transdermal Testosterone in Healthy Men.

The growing interest in testosterone's effects on men's social behaviors, in particular aggressive, risk-taking, or status maintenance behaviors, is accompanied by a paucity of dose-dependent pharmacokinetic data. Examining the neurophysiological effects of transdermal testosterone typically includes a 4h delay before further brain-behavior measurements. Nevertheless, high heterogeneity regarding the timing of follow-up measurements and dosage remains. In a double-blind placebo-controlled design, we examined the short-term pharmacokinetic profile of 100-mg transdermal testosterone (Testotop®) to determine the optimal time for detecting testosterone-mediated effects. Across two studies, 35 healthy men received a single dose of testosterone and placebo in two separate sessions. In study one (n = 16), serum testosterone and cortisol were assessed serially every 30 min up to 2 h posttreatment. In study two (n = 19), we assessed serum testosterone and cortisol at baseline, 2 h, and 4.15 h (255 min) posttreatment. Relative to baseline and placebo, transdermal testosterone significantly increased total serum testosterone concentrations 90 min posttreatment, reaching maximum concentration between 2 h and 3 h posttreatment. Albeit elevated, serum testosterone levels gradually decreased between 2 h and 4 h following treatment. Transdermal testosterone did not suppress cortisol release. Instead, cortisol concentrations decreased according to cortisol's known circadian rhythm. Unlike previous findings showing significant testosterone concentration increases as soon as 60 min and as late as 3 h post 150-mg testosterone treatment, our 100-mg testosterone manipulation significantly increased testosterone concentrations 90 min following treatment. These pharmacokinetic data are important in facilitating the optimization of timing parameters for future testosterone challenge studies.

Neonatal Inhibition of DNA Methylation Disrupts Testosterone-Dependent Masculinization of Neurochemical Phenotype.

Many neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ERα) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ERα and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ERα cell number in the VMH, in this case by increasing ERα neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ERα cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types.