Testosterone and resistance training improved physical performance and reduced fatigue in frail older men: 1 year follow-up of a randomized clinical trial.

OBJECTIVE: To improve health conditions among hypogonadal men ≥70 years of age using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium, and protein. METHODS: This study is a 1-year follow-up of a double-blind RCT lasting 20 weeks, including 148 older men ≥70 years old with low testosterone levels and mobility problems. During 52 weeks, 4 groups received either testosterone therapy (TU) or progressive resistance training (Training), both (Combo), or no intervention (Controls). Physiotherapists supported the training groups until week 20, while these participants continued trained on their own during weeks 21 to 52. The main outcome measure was the 30-s chair stand test. RESULTS: The following numbers of participants completed the trial: 20 (Combo), 20 (Controls), 24 (TU), and 14 (Training). When examining 30-s chair stand test performance within each group at baseline, and at weeks 4, 20 and 52, only the Combo group improved (p = 0.001, Friedman Test). Compared to controls, only the Combo group experienced reduced fatigue and tiredness (p < 0.05). CONCLUSIONS: Fifty-two weeks of testosterone supplementation combined with progressive resistance training may enhance physical performance, alleviate fatigue, and had no notable detrimental impacts among males aged ≥70 suffering from mobility issues and testosterone insufficiency.Trial registration - Clinical Trials NCT02873559.

Impaired vascular function among young users of anabolic-androgenic steroids.

Supraphysiological doses of anabolic-androgenic steroids (AAS) is popular among recreational weightlifters and bodybuilders due to the performance-enhancing properties but is also associated with adverse cardiovascular effects. The knowledge about how AAS affect the vasculature is limited, although results from previous studies suggest alterations in vasoreactivity and morphology. In the present study we investigate the association between long-term use of AAS and vascular function. Hundred and twenty-three males were included in the study, 56 of them current AAS users and 67 weightlifting controls. Vascular function was evaluated by carotid artery reactivity and flow-mediated dilation. AAS users had significantly reduced carotid artery reactivity (p < 0.001) and flow-mediated dilation (p < 0.001) compared to weightlifting controls. Results from the present study indicate that long-term use of AAS affect the cardiovascular system negatively, measured as reduced carotid artery reactivity and flow-mediated dilation. These findings could partly explain sudden cardiovascular events among young long-term users of AAS.

Addition of testosterone to endocrine care for transgender women: a dose-finding and feasibility trial.

OBJECTIVE: Transgender women who underwent gonadectomy have lower serum testosterone concentrations than cisgender women. There is uncertainty regarding the dosing and side effects of supplementation of testosterone in transgender women. This study aimed to assess the feasibility of dosing testosterone to the cisgender female physiological range in transgender women. In addition, we explored changes in cardiovascular parameters, virilizing side effects, and clinical symptoms. DESIGN: This is an open-label, single-arm feasibility study. Participants initially went through a dose-titration phase with 2-week intervals of 0.07-0.09-0.13 mL (277-318-403 µg bioavailable testosterone) testosterone 2% gel to establish a dose leading to serum testosterone concentrations between 1.5 and 2.5 nmol/L. This dose was then continued for 8 weeks. METHODS: Participants applied daily transdermal testosterone 2% gel (Tostran®) at the prescribed dosage. Testosterone was measured every 2-4 weeks. Laboratory analyses, side effects, and clinical symptoms were evaluated. RESULTS: In total, 12 participants were included. Most participants required a dose of 0.07 mL (277 µg bioavailable testosterone) or 0.09 mL (318 µg bioavailable testosterone) to reach serum testosterone concentrations of 1.5-2.5 nmol/L. Continuing this dose, testosterone concentrations remained stable throughout the study. Changes in clinical outcomes were in the desired direction, and side effects were mild. CONCLUSIONS: The use of testosterone supplementation in transgender women seems feasible and safe in the short term. Although dosing requires personalized titration, stable testosterone levels can be established. A blinded, placebo-controlled, randomized clinical trial is needed to study the clinical benefit.

Testosterone and other treatments for transgender males and non-binary trans masculine individuals.

Testosterone therapy is the main hormonal treatment offered in transmen to alleviate somatic gender dysphoria. Testosterone can be administered via topical or injectable preparations to achieve physical changes resulting in masculinisation and improve quality of life for the treated individuals. The aim of our paper is to outline methods for testosterone replacement, their impact on main body systems of transmen, potential associated health risks and long term follow up. Androgen use in transgender medicine is safe with appropriate endocrine guidance and monitoring. Studies with longer follow-up period, including those who may prefer low dose testosterone, interested in pregnancy or older people may further improve the management of female-to-male transgender persons.

Long-term Effects of Pre-operative Testosterone and Dihydrotestosterone on Glans Width in Boys With Hypospadias.

BACKGROUND: Small glans width is a risk factor for urethroplasty complications. This study aimed to assess and compare short- and long-term effects of two pre-operative topical androgen treatment protocols on maximum glans width. Furthermore, to evaluate post-operative complications when surgery was delayed >3 months following hormonal treatment completion. METHODS: Topical 2.5% dihydrotestosterone (February 2016-July 2018) and 5% testosterone (August 2018-December 2022) treatment protocols, completed >3 months before surgery, were offered to all children with proximal hypospadias and small glans width requiring urethroplasty. Serial glans width measurements were collected prospectively pre- and post-androgen treatment. Demographic data and complications were collected retrospectively. RESULTS: A significant increase in mean glans width was observed following both dihydrotestosterone (6.1 mm [95% CI 4.3-7.9 mm] pre-dihydrotestosterone to 14.9 mm [13.2-16.6 mm, p < 0.0001] post-dihydrotestosterone in 11 children) and testosterone (10.5 mm [9.9-11.1 mm] pre-testosterone to 14.6 mm [13.7-15.5 mm, p < 0.0001] post-testosterone in 32 children). Serial post-treatment measurements showed no loss of gained width >1 year after treatment completion. Mean increase in glans width from pre-treatment measurement at 0-3 months, 4-12 months and >12 months following treatment was 7 mm (95% CI 3.8-10.2), 9 mm (7.2-10.8) and 10 mm (7.3-12.7) post-dihydrotestosterone and 4.4 mm (95% CI 3.4-5.4 mm), 4.3 mm (3.5-5.2) and 5.1 mm (4-6.2) post-testosterone respectively. Complications were noted in 4/22 patients who received topical androgen prior to initial hypospadias surgery and had completed all surgical stages. CONCLUSIONS: Both treatment protocols produced a significant, sustained increase in glans width. Delaying hypospadias surgery for >3 months following androgen application may circumvent androgen induced vascularity and poor wound healing. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Treatment study.

[Efficacy of oral testosterone undecanoate in children with androgen insensitivity syndrome].

Objective: To investigate the efficacy and safety of oral testosterone therapy in individuals diagnosed with androgen insensitivity syndrome (AIS). Methods: A self-controlled study design was utilized, focusing on individuals with AIS who were genetically diagnosed at the Department of Endocrinology, Genetics, and Metabolism of Beijing Children's Hospital between 2009 and 2021. These patients underwent treatment involving the administration of testosterone. The primary observed indexes include the measurement of penis length, which should meet the minimal surgical standard (penis length≥2.5 cm) or greater than or equal to -2.5 s (lower limit of normal). Secondary observed indexes include penile length standard deviation score (PL-SDS), an increase in penis longitude (ΔPL), medication dosage, the course of therapy, and safety indicators, among others. There were 4 courses of treatment. After each course, patients were evaluated to determine whether termination of treatment was appropriate. Patients who exhibited inadequate post-treatment penile length growth were advised to continue with further treatment. The statistical methodology included t-test, and a Wilcoxon rank sum test to describe efficacy and safety. The patients were followed up until 2023. Results: The study comprised a total of 51 individuals with AIS, comprising 33 males and 18 females (gender of registered permanent residence). Among these patients, 10 were diagnosed with complete androgen insensitivity syndrome (CAIS) and 41 were diagnosed with partial androgen insensitive syndrome (PAIS). There were 2 children with CAIS were diagnosed by doctors and prescribed testosterone undecanoate, but the children did not really take medicine.The penile length of CAIS patients could not be measured (penile length<0.5 cm) before and after treatment. For PAIS patients, baseline penile length and PL-SDS were (2.3±0.6) cm and -3.7±1.3, respectively. The measurements for penile length and PL-SDS after each treatment course were recorded as follows: (2.7±0.8), (2.8±0.6), (2.6±0.4), (2.6±0.4) cm and -2.8±1.6, 2.5±1.6, 2.9±1.2, -3.2±0.9, respectively. Both penile length and PL-SDS interventions showed statistically significant gains when compared to the baseline performance of the 4 courses (t=4.05、3.56、2.55、2.23 and 3.88、3.50、2.50、2.19, all P<0.05). Before treatment, 13 PAIS patients (32%) reached 2.5 cm and seven (17%) reached greater than or equal to -2.5 s. Following the initial, subsequent, third, and fourth therapeutic interventions, 18 cases (44%), 24 cases (59%), 25 cases (61%), and 26 cases (63%) reached 2.5 cm, respectively. Additionally, A total of 12 cases (29%), 15 cases (37%), 20 cases (49%), and 21 cases (51%), respectively, were found to reach greater than or equal to -2.5 s. The study involved the longitudinal monitoring of patients with the highest recorded age being 13.7 years. The weight, height, body mass index, bone age/age, cholesterol, hemoglobin and so on were all within the normal range and the difference were not statistically significant (all P>0.05). All 49 patients were no abnormalities in blood electrolyte, liver and kidney function and thyroid function and no changes in precocious puberty, pubic hair growth, aggressive behavior, vulvar skin darkening, diarrhea or other conditions. Conclusions: Testosterone undecanote in children with CAIS was no effective. The initial course of treatment for patients with PAIS demonstrates observable enhancements in penile length and PL-SDS. For patients with inadequate penile length growth, continued treatment in subsequent courses (such as the second, third, and fourth courses) is recommended toenhance outcomes gradually. Testosterone undecanoate was safe and effective for the majority of individuals with PAIS patients, with few adverse effects and good treatment tolerance.

The relationship between anabolic androgenic steroid use and body image, eating behavior, and physical activity by gender: A systematic review.

The prevalence of anabolic androgenic steroids (AAS) is rising, especially in recreational sports and the general population. While body image significantly influences AAS use, gender differences remain unclear. We examined gender-related connections between AAS use, body image, eating behavior, and physical activity. Following PRISMA guidelines, we analyzed 22 studies: 14 with male-only samples, 5 mixed-gender, 2 with sexual and gender minorities, and 1 with a female-only sample. FINDINGS: confirm body image as a key predictor of AAS use. Though AAS use correlates with eating disorders, outcomes vary by context; for instance, no discernible difference in eating behavior was observed between AAS users and non-users in bodybuilding. Physical activity findings varied, with some studies showing no significant differences between AAS users and non-users. Due to limited gender-comparison studies, conclusive gender-related differences cannot be drawn. This systematic review underscores the complex interplay between AAS use, body image, eating behavior, and physical activity, emphasizing the necessity for further research to develop targeted interventions for diverse populations, addressing AAS-related concerns and promoting overall well-being.

Pharmacological management of testosterone deficiency in men current advances and future directions.

INTRODUCTION: Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering. AREAS COVERED: This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data. EXPERT OPINION: During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.

Cardiovascular safety of testosterone replacement therapy in men: an updated systematic review and meta-analysis.

INTRODUCTION: The cardiovascular (CV) safety of testosterone (T) replacement therapy (TRT) is still conflicting. Recent data suggested a TRT-related increased risk of atrial fibrillation (AF). The aim of this study was to systematic review and meta-analyze CV risk related to TRT as derived from placebo controlled randomized trials (RCTs). AREAS COVERED: An extensive Medline, Embase, and Cochrane search was performed. All placebo-controlled RCTs reporting data on TRT-related CV safety were considered. To better analyze the role of T on AF, population-based studies investigating the relationship between endogenous circulating T levels and AF incidence were also included and analyzed. EXPERT OPINION: Out of 3.615, 106 studies were considered, including 8.126 subjects treated with TRT and 7.310 patients allocated to placebo. No difference between TRT and placebo was observed when major adverse CV events were considered. Whereas the incidence of non-fatal arrhythmias and AF was increased in the only trial considering CV safety as the primary endpoint, this was not confirmed when all other studies were considered (MH-OR 1.61[0.84;3.08] and 1.44[0.46;4.46]). Similarly, no relationship between endogenous T levels and AF incidence was observed after the adjustment for confounders Available data confirm that TRT is safe and it is not related to an increased CV risk.

Effect of Pre-operative Parenteral Testosterone on Penile Dimensions and Vascularity in Proximal Hypospadias: A Prospective Observational Study.

INTRODUCTION: Severe or proximal hypospadias is associated with inadequate local tissue and small phallus size. Pre-operative androgens have been used to increase phallus size, but there are very few studies on its role in proximal hypospadias. This study aimed to assess the effects of pre-operative intramuscular (IM) testosterone on proximal penile hypospadias in terms of penile morphology and tissue characteristics of penile skin. MATERIALS AND METHODS: This prospective observational study was conducted on 27 patients of proximal hypospadias over a period from June 2017 to July 2018. The patients were sequentially enrolled into two groups: Group A and Group B. Group A patients received IM testosterone before surgery, whereas Group B patients were operated without pre-operative testosterone. Outcomes were analysed in terms of change in penile dimensions and effect on vascularity of penile skin. RESULTS: Pre-operative IM testosterone in Group A caused a significant increase in stretched penile length from a mean of 3.058 cm (±0.691) to 3.9 cm (±0.875) ( P = 0.002), penile circumference from a mean of 4.142 cm (±0.772) to 4.667 cm (±1.174) ( P = 0.029) and glans width from a mean of 1.225 cm (±0.245) to 1.750 cm (±0.571) ( P = 0.002). There was higher microvessel density in the preputial skin of Group A (mean: 12.212 [±4.745] blood vessels/high-power field [HPF]) compared to Group B (8.867 [±3.258] blood vessels/HPF) ( P = 0.043). CONCLUSION: Pre-operative testosterone in proximal hypospadias causes significant changes in penile dimensions and tissue characteristics. Improvement in penile dimensions leads to ease in operability and better tissue handling. However, more studies with large sample size are required to establish the beneficial effects of pre-operative hormone stimulation on urethroplasty.

Persistent vaginal bleeding during gender-affirming hormone therapy in transgender men.

PURPOSE: While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition. METHODS: In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months. RESULTS: A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019). CONCLUSION: Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.

Early Life Androgen Administration Attenuates Aging Related Declines in Muscle Protein Synthesis.

PURPOSE: This study examined the acute and long-term effects of nandrolone decanoate (ND) on fractional synthetic rates (FSR). METHODS: Male C57BL/6 mice were randomized into ND ( n = 20) or sham ( n = 20) groups. ND injections (10 g·kg -1 ·wk -1 ) started at 7 months of ages and continued for 6 wk. Ten animals from each group were randomly separated and examined 1 wk following drug cessation. The remaining animals were examined at 16 months of age. Animals were injected IP with 1.5 mL of deuterated water 24 h before euthanasia. The kidney, liver, heart, gastrocnemius, and soleus were extracted. Samples were analyzed for deuterated alanine enrichment in the bound protein and intracellular fraction by liquid chromatography tandem mass spectrometry to measure estimated FSR (fraction/day (F/D)) of mixed tissue. RESULTS: One-way ANOVA, with treatment and age as fixed factors, indicated that kidney FSR was greater ( P = 0.027) in ND (0.41 ± 0.02 F/D) than sham (0.36 ± 0.014F/D) and higher ( P = 0.003) in young (0.42 ± 0.2 F/D) than old (0.35 ± 0.01 F/D). Liver and heart FSR values were greater ( P ≤ 0.001) in young (0.79 ± 0.06 F/D and 0.13 ± 0.01 F/D, respectively) compared with old (0.40 ± 0.01 F/D and 0.09 ± 0.01 F/D, respectively), but not between ND and sham. Gastrocnemius FSR was ( P ≤ 0.001) greater in young (0.06 ± 0.01 F/D) compared with old (0.03 ± 0.002 F/D), and greater ( P = 0.006) in ND (0.05 ± 0.01 F/D) compared with sham (0.04 ± 0.003 F/D). Soleus FSR rates were greater ( P = 0.050) in young (0.13 ± 0.01 F/D) compared with old (0.11 ± 0.003 F/D), but not between ND (0.12 ± 0.01 F/D) and sham (0.12 ± 0.01 F/D). Old animals who had received ND displayed elevated FSR in the gastrocnemius ( P = 0.054) and soleus ( P = 0.024). CONCLUSIONS: ND use in young adult animals appeared to maintain long-term elevations in FSR in muscle during aging.

Androgen deficiency in hypopituitary women: its consequences and management.

Women with hypopituitarism have various degrees of androgen deficiency, which is marked among those with combined hypogonadotrophic hypogonadism and secondary adrenal insufficiency. The consequences of androgen deficiency and the effects of androgen replacement therapy have not been fully elucidated. While an impact of androgen deficiency on outcomes such as bone mineral density, quality of life, and sexual function is plausible, the available evidence is limited. There is currently no consensus on the definition of androgen deficiency in women and it is still controversial whether androgen substitution should be used in women with hypopituitarism and coexisting androgen deficiency. Some studies suggest beneficial clinical effects of androgen replacement but data on long-term benefits and risk are not available. Transdermal testosterone replacement therapy in hypopituitary women has shown some positive effects on bone metabolism and body composition. Studies of treatment with oral dehydroepiandrosterone have yielded mixed results, with some studies suggesting improvements in quality of life and sexual function. Further research is required to elucidate the impact of androgen deficiency and its replacement treatment on long-term outcomes in women with hypopituitarism. The lack of transdermal androgens for replacement in this patient population and limited outcome data limit its use. A cautious and personalized treatment approach in the clinical management of androgen deficiency in women with hypopituitarism is recommended while awaiting more efficacy and safety data.

Efficacy and safety of bipolar androgen therapy in mCRPC after progression on abiraterone or enzalutamide: A systematic review.

PURPOSE: To further determine the efficacy and safety of bipolar androgen therapy (BAT) on patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone (ABI) or enzalutamide (ENZA). MATERIALS AND METHODS: We systematically searched the Pubmed, Web of Science and ClinicalTrials.gov up to June 2021. Literature review, study selection, and data extraction were conducted by 2 reviewers. Risk of bias was assessed according to the methodology of the European Association of Urology (EAU). A systematic review and pooled analysis were performed. The primary outcomes were PSA50 after BAT and AR-targeted therapy rechallenge, objective response rate (ORR) after BAT, and AEs after BAT. The definition of PSA50 was that participants achieving a PSA decline ≥50% according to Prostate Cancer Working Group (PCWG2) criteria. The ORR determined by determined by Response Evaluation Criteria in Solid Tumors (RECIST) included patients experienced partial response (PR) or complete response (CR). RESULTS: In a total of 74 unique records, 5 studies were eligible for inclusion. Participants who underwent BAT achieved PSA50 of 0.26 (95% CI [0.20, 0.32]) and objective response rate (ORR) of 0.32 (95% CI [0.21, 0.44]). Patients completed BAT proceeded to AR-target therapy (ABI or ENZA) achieved moderate response (PSA50 0.54, 95% CI [0.30, 0.76]). Based on our multiple subgroup analysis, type of post-BAT AR-target therapy had a strong impact on PSA50 of AR-target therapy rechallenge. Most of adverse events (AEs) were low grade. CONCLUSIONS: The present study indicated that BAT could induce clinical responses in mCRPC patients after progression on ABI or ENZA, with an acceptable side effects profile. BAT could also be able to restore sensitivity to ABI and ENZA rechallenge in a subset of patients.

Long-term testosterone undecanoate treatment in the elderly testosterone deficient male: An observational cohort study.

BACKGROUND: Quarterly intramuscular injections with long-acting testosterone undecanoate (TU) provide stable serum testosterone concentrations over time and are therefore preferred by many testosterone-deficient patients. However, the use of long-acting TU in elderly patients is limited due to lack of safety and feasibility studies. OBJECTIVE: To investigate long-acting TU pharmacokinetics and assess differences in treatment regimens and risk of adverse outcomes in younger versus elderly testosterone-deficient patients. MATERIALS AND METHODS: Single-center longitudinal observational study. Patients who initiated long-acting TU treatment between 2005 and 2010 were included. Elderly patients were born before 1956 and younger patients between 1965 and 1985. TU dose was adjusted yearly through shortening or prolongation of time between injections. Treatment targets were as follows: (1) free testosterone between 0 and -1 SD from the age-adjusted mean, (2) no symptoms of testosterone deficiency, and (3) hematocrit within the normal range. RESULTS: The study population consisted of 63 elderly and 63 younger patients. Median follow-up time during testosterone replacement was 12.1 years. Increasing intervals between TU injections were performed 44% more often in the elderly compared to younger patients and time between TU injections were prolonged 4% more in the elderly patients. The hematocrit, as well as the hematocrit for a given serum testosterone (hematocrit: testosterone ratio), increased with treatment time but did not differ between age groups. During follow-up, 40% of patients-both elderly and younger-experienced polycythemia. Risk of polycythemia did not differ with age. DISCUSSION AND CONCLUSION: An increased number of adjustments of TU dose are necessary in elderly patients in order to reach treatment targets. TU treatment in elderly testosterone-deficient patients is not associated with an increased risk of polycythemia compared to younger patients if age-adjusted treatment targets are reached.

The impact of testosterone therapy on quality of life in adolescents with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in childhood. It is associated with progressive muscle function decline and premature death. Long-term oral glucocorticoid use slows muscle weakness but is associated with several side effects including delayed puberty. This study assessed the impact of a 2-year incremental intramuscular testosterone regimen on quality of life (QoL) in a cohort of 15 adolescents with DMD. The Pediatric Quality of Life Inventory (PedsQL) Neuromuscular module was used to assess QoL and was completed by parent-child dyads. Semi-structured interviews were carried out to understand patient views on testosterone therapy. QoL scores increased in 10 of the 15 participants during treatment, with a mean total PedsQL score of 74.6 pre-treatment v 80.2 post treatment (p = 0.04). This was supported by comments in the semi-structured interviews. Parent-reported PedsQL scores were lower than their child's post treatment (p = 0.007). Testosterone therapy for pubertal induction was associated with an improvement in QoL and the observed physical changes during puberty played an important role. Low self-esteem was also a prevailing theme. This data supports the inclusion of testosterone therapy for pubertal induction as a Standard of Care.

The Prevalence of Hypogonadism and the Effectiveness of Androgen Administration on Body Composition in HIV-Infected Men: A Meta-Analysis.

BACKGROUND: Hypogonadism is a common comorbidity in human immunodeficiency virus (HIV)-infected men, although the real prevalence is difficult to be estimated. Moreover, in HIV settings, the efficacy of exogenous testosterone (Te) administration at improving body composition remains unclear. AIM OF THE STUDY: This review has a double aim. First, to estimate the prevalence of pituitary-testis axis abnormality in HIV-infected patients compared to uninfected subjects. Second, to evaluate the effect of androgen administration on body composition in HIV-infected men. MATERIALS AND METHODS: A systematic review of the literature and meta-analysis was carried out. Two separated literature searches were performed, the first to evaluate the prevalence of Te deficiency in HIV-infected men and the second one to evaluate effects of androgen administration on body composition. RESULTS: The overall prevalence of Te deficiency in HIV-infected men was calculated from 41 studies, showing a 26% prevalence, which was even higher when free T (fT) levels, more than total T, were considered. Indeed, TT serum levels were similar between HIV patients and controls, although higher SHBG and lower fT were detected in HIV populations. When HIV-infected men were treated with exogenous Te, a significant increase in body weight, lean body mass and fat free mass was detected. CONCLUSION: The systematic review confirms the high prevalence of Te deficiency in HIV-infected men, particularly when fT has been considered. Moreover, chronic androgen supplementation improves body composition, affecting the lean mass compartment. However, considering the general frailty of HIV patients, a tailored indication for Te therapy should be advocated.

Reversing the effects of androgen-deprivation therapy in men with metastatic castration-resistant prostate cancer.

OBJECTIVE: To investigate whether bipolar androgen therapy (BAT), involving rapid cyclic administration of high-dose testosterone, as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC) promotes improvements in body composition and associated improvements in lipid profiles and quality of life. PATIENTS AND METHODS: Men from two completed trials with computed tomography imaging at baseline and after three cycles of BAT were included. Cross-sectional areas of psoas muscle, visceral and subcutaneous fat were measured at the L3 vertebral level. Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire and 36-item short-form health survey were used to assess quality of life. RESULTS: The 60 included patients lost a mean (sd) of 7.8 (8.2)% of subcutaneous fat, 9.8 (18.2)% of visceral fat, and gained 12.2 (6.7)% muscle mass. Changes in subcutaneous and visceral fat were positively correlated with each other (Spearman's correlation coefficient 0.58, 95% confidence interval 0.35-0.71) independent of the effects of age, body mass index, and duration of androgen-deprivation therapy. Energy, physical function, and measures of limitations due to physical health were all significantly improved at 3 months. The improvements in body composition were not correlated with decreases in lipid levels or observed improvements in quality of life. CONCLUSIONS: In the present study, BAT was associated with significant improvements in body composition, lipid parameters, and quality of life. This has promising implications for the long-term health of men with mCRPC.

A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.

BACKGROUND: Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. METHODS: The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. RESULTS: Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. CONCLUSIONS: Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients.