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Context: Testosterone therapy has been variably associated with increased thrombotic risk but investigations of global coagulation in this setting are lacking., Objective: This work aimed to compare global coagulation of hypogonadal men before (T0) and 6 months after (T1) starting testosterone replacement therapy (TRT), and healthy controls (HCs)., Methods: An observational prospective cohort study was conducted at 2 tertiary endocrinological ambulatory care centers. Patients included 38 men with hypogonadism (mean age 55 years, SD 13) and 38 age-matched HCs. Thrombin generation assay (TGA) was performed at T0 and T1 in hypogonadal men and in HCs. TGA is an in vitro procedure based on the continuous registration of thrombin generation and decay under conditions mimicking the process that occurs in vivo. The following TGA parameters were recorded: lag time; thrombin-peak concentration; time-to-reach peak, velocity index, and endogenous thrombin potential (ETP), the latter representing the total amount of thrombin generated under the driving forces of procoagulants opposed by the anticoagulants. Protein C, antithrombin, factor (F) VIII, and fibrinogen were assessed., Results: No changes in TGA parameters were observed between T0 and T1. Hypogonadal men displayed significantly higher ETP, fibrinogen, and significantly lower antithrombin levels both at T0 and T1 compared to HCs. Thrombin peak of hypogonadal men was significantly higher than HCs at T0 but not at T1. ETP and antithrombin were correlated with testosterone levels., Conclusion: Hypogonadal men display a procoagulant imbalance detected by increased thrombin generation. Short-term TRT does not worsen global coagulation, suggesting that the treatment can be safely prescribed to men diagnosed with hypogonadism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Monitoring of various clinical outcomes and parameters, such as lipid levels, is recommended in transgender individuals undergoing hormone therapies. However, comprehensive data to inform these recommendations is scarce., Objective: This study aims to conduct a systematic review and meta-analysis to synthesize evidence from existing literature on the effect of exogenous hormone therapy on clinical and biochemical outcomes for transgender adolescents and adults., Methods: We will search multiple electronic databases and will include prospective and retrospective observational studies with and without a control group. The study population will include transgender individuals undergoing hormone therapy with testosterone or estrogen. Comparisons will include age-matched, cisgender individuals and changes from baseline. Primary outcomes include changes in or the development of abnormal lipid parameters. Secondary outcomes include BMI, weight, height, and blood pressure for age, serum testosterone or estrogen levels, and development of disease including hypertension, diabetes, fatty liver disease, obesity, adverse cardiac events, as well as all-cause mortality. The meta-analysis will pool the studies where applicable, and meta-regressions will be conducted to evaluate effect modifiers. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach will be used to evaluate the overall certainty of evidence., Results: We will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. Data collection is ongoing, and the paper is expected to be published in Spring 2025., Conclusions: This systematic review will summarize and evaluate the evidence of the clinical and biochemical outcomes associated with hormone therapies for transgender individuals., Trial Registration: PROSPERO CRD42024483138; https://tinyurl.com/yc4sfvnb., International Registered Report Identifier (irrid): PRR1-10.2196/57931., (©Emily Sattora, Karen Teelin, Christopher Prendergast, Abigail Smith, James Evans, Aamer Imdad. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.11.2024.)

Introduction: Erectile dysfunction (ED) is a neglected complication in patients with pre-diabetes or diabetes mellitus (DM)., Areas Covered: A summary and review of the role of standard ED treatment and the contribution of lifestyle modification and hypoglycemic drugs., Expert Opinion: Oral phosphodiesterase type 5 inhibitors (PDE5i) represent the first-line therapy even in patients with DM. Testosterone replacement therapy (TRT) is mandatory in all hypogonadal (total testosterone < 12 nmol/l) subjects. Alprostadil and/or combined approaches can be considered when PED5i with or without TRT fail. The glycometabolic optimization through lifestyle modification and the use of hypoglycemic drugs represents a crucial step, even for ED treatment. Considering the strong association between ED and forthcoming cardiovascular diseases, the selection of glucagon-like peptide type 1 analogues or sodium glucose cotransporter-2 inhibitors seems to represent the best option due to their long-term effect on chronic complication prevention. Metformin can be considered a possible alternative in less complicated subjects. Penile prostheses (PP) can be offered when all other options are not effective, but the patients should be informed that poor glycometabolic control can increase the risk of PP infection.

The Androgen Society is an international, multidisciplinary medical organization committed to advancing research and education in the field of testosterone deficiency and testosterone therapy (TTh). This position paper is written in response to results of the TRAVERSE study, published in June 2023, which reported no increased risk of major adverse cardiovascular events (MACE) in men who received TTh compared with placebo. In 2013-2014, 2 observational studies reported increased cardiovascular (CV) risks with TTh and received wide media attention. Despite strong criticism of those 2 studies, in 2015, the Food and Drug Administration added a CV warning to testosterone product labels and required pharmaceutical companies to perform a CV safety study, which became the TRAVERSE trial. TRAVERSE enrolled 5246 men at high risk for MACE based on existing heart disease or multiple risk factors. Participants were randomized to daily testosterone gel or placebo gel, with a mean follow-up of 33 months. Results revealed no greater risk of MACE (myocardial infarction, stroke, or CV death) or venothrombotic events in men who received TTh compared with placebo. Review of the prior literature reveals near uniformity of studies reporting no increased MACE with TTh. This includes 2 additional large randomized controlled trials, multiple smaller randomized controlled trials, several large observational studies, and 19 meta-analyses. In view of these findings, it is the position of the Androgen Society that it has now been conclusively determined that TTh is not associated with increased risks of heart attack, stroke, or CV death., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The substitution of testosterone is basic andrological treatment. Beside the "when and how," knowledge of possible side effects is mandatory. Therefore, we highlight the effects of testosterone replacement therapy on bones, cardiac function, sexuality, gynacomatia, fertility, and contraception, but also areas of concern regarding prostate carcinoma and testosterone replacement therapy., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Transgender and gender diverse individuals experience a gender identity that differs from the sex assigned at birth. Some transgender men may request testosterone to induce virilization; however, its impact on bone health remains to be fully elucidated. The objective of this systematic review and meta-analysis was to evaluate the modifications in bone metabolism over a short-term period among transgender men initiating testosterone therapy. A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library. The articles of interest had to report longitudinal evaluation conducted among transgender men, before starting testosterone and after 12 and 24 months of therapy. The analyzed parameters were BMD, calcium, phosphate, 25OHD, PTH, P1NP, BAP, osteocalcin and CTx. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. Fourteen studies met the inclusion criteria, including 1484 subjects. In absence of heterogeneity, BMD did not significantly change at lumbar spine, hip, femoral neck, and whole-body evaluations. Calcium, phosphate, 25OHD and PTH remained stable over time. Regarding bone turnover markers, only P1NP showed a statistically significant increase after 12 months of T therapy, in absence of heterogeneity (SMD 0.61 mcg/l; 95% CI: 0.40-0.83; p < 0.0001; I 2  = 0%, Pforheterogeneity = 0.48). Testosterone therapy among transgender men seems not to disrupt bone health after 12 and 24 months. A statistically significant elevation in P1NP levels after 12 months of therapy may indicate a positive anabolic effect of testosterone in the short-term., (© 2024. The Author(s).)

Background: The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes., Objective: To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer., Methods: In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted., Results: No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups., Conclusion: Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings., (© 2024 American Society of Andrology and European Academy of Andrology.)

Introduction: Rehabilitation medicine in a tertiary care hospital involves attending to many patients affected by intensive care unit (ICU)-associated weakness (ICU-AW) and hospital-associated deconditioning (HAD). These conditions contribute to poor long-term functional outcomes and increased mortality. We explored the role of short-term adjunctive androgen therapy in this group of patients in improving the rehabilitative outcomes., Methods: This was a retrospective analysis of five patients with either ICU-AW or HAD who were given testosterone replacement therapy (TRT) or oxandrolone for a total of 2 weeks during the period from April to November 2020 was undertaken. During the 2-week trial period, the subjects underwent standard rehabilitation therapy., Results: Grip strength was used as the primary outcome measure, and the mean improvement was 4.2 kg (+24.9%), which is encouraging in a 2-week timeframe. This was matched with good functional recovery in terms of distance ambulated and less assistance needed for ambulation. Sex hormone analysis was also done before initiation of TRT, and it showed that four out of five of the subjects were biochemically hypogonadal. None of the subjects dropped out or experienced any significant adverse events over the 2-week trial period. All the subjects except one improved to full independence at 3 months post-discharge., Conclusion: TRT has the potential to be used as a useful adjunct to standard rehabilitation in enhancing functional recovery in critically ill patients. A multidisciplinary approach would ensure that suitable patients benefit from optimal nutrition, optimal rehabilitation and synergistic testosterone therapy in a clinically sound and resource-efficient fashion., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Background and Objective: The longitudinal efficacy and clinical utility of Testosterone Therapy (TTh) in ameliorating functional hypogonadism (FH) remain contentious, with long-term data being scarce. To address this lacuna, a comprehensive long-term registry study, stratifying patients across a spectrum of hypogonadal etiologies, offers a robust investigative paradigm., Materials and Methods: This 9-year registry, encompassing 650 patients (equivalent to 4,362 cumulative years of treatment), included 188 patients diagnosed with FH (mean age 42.3 ± 11.3 years) and 462 individuals with classical hypogonadism (CH). The cohort segregated into 266 men with primary hypogonadism (PH, mean age 34.0 ± 11.7 years) and 196 with secondary hypogonadism (SH, mean age 31.9 ± 12.0 years). Uniform treatment across the cohort involved intramuscular administration of testosterone undecanoate (1,000 mg). A comparative analysis was conducted focusing on anthropometric, metabolic, and safety parameters., Results: Serum testosterone levels increased from 6.6 ± 2.4 to 19.3 ± 2.9 nmol/L (p < 0.001). TTh was linked with weight reduction and decreased waist circumference (WC) in both CH and FH cohorts (both p < 0.001). Cox regression and Kaplan-Meier analyses delineated disparities: men with FH demonstrated a higher propensity for losing > 10% body weight and > 5% WC compared to CH (hazard ratio [HR] 1.3 [1.1-1.4], p = 0.008 and HR 1.4 [1.3-1.5], p = 0.001). Increases in hematocrit > 50% were uniform across groups, albeit amelioration of anemia was more pronounced in FH versus CH (p = 0.002). Increments of prostate-specific antigen (PSA) levels were more likely to occur in FH (HR 1.3 [1.1-1.6], p = 0.003). FH patients exhibited pronounced improvements in metabolic parameters and in aging male symptom score (AMS) and IIEF-EF questionnaire scores. These effects were markedly modulated by age and initial weight. Subgroup analysis of age-matched obese patients revealed an accentuated impact of TTh in CH compared to FH., Discussion and Conclusion: The therapeutic outcomes of TTh across distinct hypogonadal populations demonstrate heterogeneous responses, significantly influenced by diagnostic categorization, age, and baseline risk factor profiles., (© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

The menopause transition and post-menopause period marks a time of dynamic physiological and hormonal change. Cisgender women commonly experience vasomotor symptoms, genitourinary symptoms, and changes in bone health. The transgender population, including those assigned female at birth (AFAB) and those assigned male at birth (AMAB), has been understudied in terms of experiences through the menopause transition and midlife. Additionally, there is no formal recommendation or guidance on continuation of gender-affirming hormone therapy (GAHT) through midlife. While gender-affirming therapies for transgender patients are well defined and supported by organizational guidelines, including from the World Professional Association for TGD Health (WPATH) (Standards of Care 8, SOC8) and from the Endocrine Society (2017), evidence on continuation of therapy and dose adjustments into mid-life are lacking. Data from a few large cohort studies and small cross-sectional studies suggest increased risk of venous thromboembolism (VTE), stroke and myocardial infarction in those AMAB on GAHT. For those AFAB on testosterone therapy, risks of cardiovascular disease and stroke and to bone health are not well defined, given inconsistent findings from large cohort studies. Currently, the decision to continue GAHT for transgender patients is guided by patient preference along with clinician guidance. Further research is warranted regarding risks of continuing GAHT into mid-life for both AMAB and AFAB patients. Given the significant benefit of GAHT in this population, however, this data would be most helpful for counseling on risks along with appropriate monitoring and prevention for related morbidities during mid-life in the setting of GAHT use., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: While many transgender and gender diverse individuals rapidly achieve amenorrhea on testosterone, emerging data have identified that breakthrough bleeding can occur in up to one-third of individuals with long-term use. Breakthrough bleeding can worsen dysphoria and patients may seek management to reattain amenorrhea. Because of this, there is a need to assess efficacy of management approaches., Objective: The primary aim of the study was to evaluate methods used by patients and their providers to manage breakthrough bleeding which arises after 1 year of testosterone use. Secondary aims included describing the diagnostic approaches to breakthrough bleeding, and proposing an algorithm for classification and management of breakthrough bleeding in this patient population., Study Design: This was an institutional review board-approved single tertiary center, retrospective chart review of transgender and gender diverse individuals on testosterone gender affirming hormone therapy who experienced breakthrough bleeding after 1 year of use. Charts were reviewed to determine patient characteristics, testosterone use, and breakthrough bleeding management approaches., Results: Of the 96 individuals who had been on testosterone for 1 year and experienced breakthrough bleeding, 97% (n=93) engaged in at least 1 approach to management. The mean age at initiation of testosterone was 21.9 (standard deviation 5.4) and the median duration of time on testosterone was 54.5 months (interquartile range 33.5, 82). Only 16% (n=15) were using menstrual suppression at the time of their breakthrough bleeding episode. Breakthrough bleeding was successfully managed in 77 (79%), following between 1 and 4 attempted approaches. More than half of management attempts (63%) were successful on the first try. When management approaches were analyzed independently, the range of success associated with any particular approach was between 33% and 100%. Other than hysterectomy, which was fully successful at managing breakthrough bleeding, no approach was significantly better than no intervention. This was true both for individuals who did and did not bleed with missed testosterone doses. Regardless of what approach was used, after a failed attempt, the next attempt was successful in more than half of individuals. Of the 16 who underwent hysterectomy, 1 did so in part as a first line approach to manage breakthrough bleeding., Conclusion: In this study, use of medical management methods was not found to be superior to observation alone in the management of breakthrough bleeding. In the absence of data supporting superiority of any method, we recommend tailoring method attempts to patients' goals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In Brief: Animal studies are needed to inform clinical guidance on the effects of testosterone gender-affirming hormone therapy (T-GAHT) on fertility. This review summarizes current animal models of T-GAHT and identifies gaps in knowledge for future study., Abstract: Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and pre-pubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations.

This review assesses the evidence of the physiological effects of testosterone on cardiovascular health, the association between male hypogonadism and cardiovascular health, and the effects of testosterone therapy on cardiovascular health in male hypogonadism. Preclinical studies suggest complex effects of testosterone on cardiovascular risk by acting on skeletal muscle, cardiomyocytes, vasculature, adipocytes, insulin action, and erythropoiesis. Furthermore, low testosterone has a bi-directional association with cardiometabolic risk. Observational studies have reported worse metabolic profiles in men with organic hypogonadism. However, a consistent association between major cardiovascular events and male hypogonadism has not been established. Hematocrit increases with testosterone therapy; however, most studies do not report an increase in venous thromboembolism risk. Although some observational studies and a small randomized controlled study reported an increased risk of cardiovascular disease, recent data confirm the medium-term cardiovascular safety of testosterone therapy in middle-aged and older men with low testosterone., (© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)

Non-surgical (reversible) male contraception methods, when approved for general clinical application, should be made available to all interested men aged 18 50 years in good general health regardless of their semen parameters. In the preliminary workup, a complete personal and family history aimed at identifying specific conditions that may potentially increase the risks for adverse effects (associated with testosterone replacement) is advisable but a general or andrological examination is not required, unless indicated by the history. Baseline body weight, blood pressure and haemoglobin should be recorded for the purpose of future monitoring. While risks and benefits of vasectomy have been well established, appropriately nuanced patient counselling and assessment are essential for ensuring a satisfactory outcome of vasectomy., (© 2024 The Author(s). Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning., Objectives: To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel., Discussion: Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product's efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy., Conclusion: There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background and Objective: Darolutamide is an androgen receptor inhibitor that increases overall survival in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer (PCa). This phase 2 study assessed the efficacy and safety of darolutamide as monotherapy without ADT in patients with eugonadal testosterone levels., Methods: This was a 24-wk, open-label, randomized study of patients with hormone-sensitive, histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH); an Eastern Cooperative Oncology Group performance status score of 0/1; and life expectancy >1 yr. All patients received darolutamide 600 mg bid or a commercially available GnRH analog. The primary endpoint is a prostate-specific antigen (PSA) response, defined as a ≥80% decline at week 24 relative to baseline in the darolutamide study arm. The GnRH arm is used as an internal control. The secondary endpoints included changes in T levels, safety/tolerability, and quality of life., Key Findings and Limitations: Among 61 men enrolled, the median (range) age was 72 yr (53-86 yr); 42.6% of them had metastases. In the darolutamide arm, the evaluable population with available PSA values at baseline and week 24 consisted of 23 patients. Twenty-three (100%) evaluable darolutamide patients achieved a PSA decline of >80% at week 24 (primary endpoint), with a median (range) decrease of -99.1% (-91.9%, -100%). Serum T levels increased by a median (range) of 44.3 (5.7-144.0) at week 24, compared with baseline. In the darolutamide arm, 48.4% of men reported drug-related adverse events (AEs; mostly grade 1 or 2). The most frequent treatment-emergent AEs included gynecomastia (35.5%), fatigue (12.9%), hot flush (12.9%), and hypertension (12.9%). Health-related quality of life measures are descriptive, and GnRH arm results will be presented as an internal reference., Conclusions and Clinical Implications: Darolutamide monotherapy was associated with a significant PSA response in nearly all men with hormone-naïve PCa. Testosterone-level changes and most common AEs (gynecomastia, fatigue, hypertension, and hot flush) were consistent with potent androgen receptor inhibition., Patient Summary: In this study, we report the first use of darolutamide, a novel antiandrogen, as monotherapy without androgen deprivation therapy (ADT). The study shows that darolutamide induce a profound suppression of prostate-specific antigen in all patients, with a safety profile different from that of ADT., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Organic male hypogonadism due to irreversible hypothalamic-pituitary-testicular (HPT) pathology is easily diagnosed and treated with testosterone-replacement therapy. However, controversy surrounds the global practice of prescribing testosterone to symptomatic men with low testosterone and non-gonadal factors reducing health status, such as obesity, type 2 diabetes, and ageing (ie, functional hypogonadism), but without identifiable HPT axis pathology. Health optimisation remains the gold-standard management strategy. Nevertheless, in the last decade large clinical trials and an individual patient data meta-analysis of smaller clinical trials confirmed that testosterone therapy induces modest, yet statistically significant, improvements in sexual function without increasing short-term to medium-term cardiovascular or prostate cancer risks in men with functional hypogonadism. Although testosterone improves bone mineral density and insulin sensitivity in these men, trials from the last decade suggest insufficient evidence to determine the safety and effectiveness of use of this hormone for the prevention of fractures or type 2 diabetes. This Review discusses the pathogenesis and diagnosis of male hypogonadism and appraises the evidence underpinning the management of this condition., Competing Interests: Declaration of interests MG has received research funding from Bayer and Otsuka; and speaker's honoraria from Besins, Health Care, and Novartis. LA participated in advisory boards for Androlabs, Merck, and Galapagos; and receives a senior clinical research fellowship from Research foundation Flanders (1800923N). RQ participated in an advisory board for Roche Diagnostics. CNJ received investigator-led grants from Logixx Pharma; and received a National Institute for Health and Care Research post-doctoral fellowship. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose of Review: The goal of this paper is to review the most recent studies evaluating treatments for female sexual dysfunction (FSD), including distressing symptoms of desire, arousal, and orgasm disorder. We divide the sections into psychological and pharmacological., Recent Findings: There is excellent evidence in favour of mindfulness, cognitive behavioural therapy, and psychoeducation for improving low sexual desire in women, and less evidence in support of these approaches to address other sexual dysfunctions in women. There are two US Food and Drug Administration (FDA) approved pharmacological treatments for low desire in premenopausal women that have modest benefits above placebo, and a significant proportion of users will experience side effects. Evidence also supports the use of transdermal testosterone for low desire in postmenopausal women., Summary: Sexual dysfunction in women is common and distressing, and there are a variety of psychological and pharmacological treatments. More research is needed to better understand the predictors of a positive treatment response in order to deliver more personalized care., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objective: To evaluate operative complications and healthcare utilization in transgender patients on testosterone undergoing minimally invasive gender-affirming hysterectomy compared to control patients., Design: We performed a retrospective cohort study. Operative reports were used to gather information on intraoperative complications. We collected information on postoperative complications, electronic medical record (EMR) messages, phone calls, emergency department utilization, and clinic visits through a 90-day postoperative period. Healthcare utilization reasons were categorized as vaginal bleeding, pain, vaginal discharge, dysuria, urinary retention, bowel concern, incision concern, or other., Setting: Tertiary care academic medical center., Patients: Patients aged 18 to 55 who underwent a benign minimally invasive hysterectomy with or without oophorectomy performed between January 2014 and December 2022. The testosterone-using cohort consisted of patients who had a gender identity of male, transgender male, genderqueer, or nonbinary with documented testosterone use prior to surgery (n = 88). The control cohort consisted of patients who identified as female, genderqueer, or nonbinary with no documented testosterone use (n = 242)., Interventions: Not applicable., Measurements and Main Results: Patients using testosterone were younger, had a lower body mass index, lower American Society of Anesthesiologists class, and were more likely to be nulliparous. The median time patients used testosterone was 2.5 years (1.5-5.0). Patients on testosterone are at increased risk of intraoperative perineal lacerations requiring repair (RR 3.3, CI 95% [1.03-10.5]). A higher number of patients on testosterone reported vaginal bleeding via EMR message or phone call (RR 1.74 CI 95% [1.1-2.7]) compared to controls. No difference in reasons for emergency department visits was noted. The use of postoperative vaginal estrogen started at the postoperative visit was more frequent in the testosterone-using patients (7 [8.0%] vs 4 [1.7%], p = .01)., Conclusion: This study demonstrates that testosterone use preoperatively may increase risk of intraoperative vaginal laceration requiring repair. Testosterone use also correlates with increased reports of vaginal bleeding through EMR message, phone call, and clinic visit. These results contribute new evidence to include in preoperative counseling and support existing evidence surrounding the safety of gender-affirming hysterectomy., Competing Interests: Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: In male congenital hypogonadotropic hypogonadism (CHH), it was observed that lower dose human gonadotropic hormone (hCG) can maintain normal intratesticular testosterone levels. We propose this study to compare the low-dose hCG, follicle stimulating hormone (FSH), and Testosterone (T) [LFT Regimen] to conventional treatment to induce virilization and fertility., Design: This open-label randomized pilot study was conducted from June 2020 to December 2021., Subjects and Outcome Measures: CHH were randomly assigned to either the LFT regimen (Group A)-low-dose hCG (500U thrice per week), FSH (150U thrice per week), and T(100 mg biweekly) or conventional therapy(GroupB) with high hCG dose(2000U thrice per week) and the same FSH dose. The hCG dosage was titrated to reduce anti-mullerian hormone (AMH) by 50% and normalization of plasma T in groups A and B, respectively. The primary objective was to compare the percentage of individuals who achieved spermatogenesis between the two groups., Results: Out of 30 patients, 23 (76·7%) subjects achieved spermatogenesis, and the median time was 12 (9-14·9) months. There was no difference in achieving spermatogenesis between the two groups (64·3% vs 7·5%,P = 0·204), and even the median time for spermatogenesis was similar (15months vs 12months,P = 0·248). Both groups had nonsignificant median plasma AMH at spermatogenesis, [6·6 ng/ml (3·3-9·76) vs4·41 ng/ml (2·3-6·47), P = 0·298]. Similarly, the median plasma Inhibin B at spermatogenesis between groups were comparable [152·4 pg/ml (101·7-198·0) vs49·1 pg/ml (128·7-237·3), P = 0·488]., Conclusions: A reasonable approach to induce fertility in male CHH is to initiate combination therapy using FSH, low-dose hCG targeting AMH <6·9 ng/ml, along with T to achieve normal range. Monitoring AMH could serve as a proxy indicator of spermatogenesis., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Purpose: In men with prolactinoma treated with dopamine agonists (DA), the extent, timeline, and predictive factors of gonadotropic axis recovery are still unclear., Methods: We analyzed data of 97 men with a prolactinoma treated with DA (77/97 macroprolactinomas). We excluded patients with primary hypogonadism, surgery < 12 months after DA initiation, and patients with tumors < 5 mm or prolactin < 45 µg/l at diagnosis., Results: Among the 97 patients, 12 had normal total testosterone (NT group) and 85 had low testosterone at diagnosis (LT group). In the NT group, testosterone rose from a mean of 13.5 nmol/l to 17.1nmol/l at 6 months (n = 11; p < 0.05) then remained stable at 12 months (n = 8). In the LT group, testosterone rose from a mean of 5.2 nmol/l to 9.6 nmol/l at 6 months (n = 66; p < 0.001) and further to 13.1nmol/l at 12 months (n = 40; p < 0.001) then remained stable. Recovery from hypogonadism occurred in 43%, 50%, and 54% of patients at 6, 12 and 24 months, respectively (61%, 69 and 69% if prolactin was normal). Factors independently associated with persistent hypogonadism at 12 months were at baseline the presence of visual field deficit and lower testosterone levels, while the most significant independent predictor of persistent hypogonadism at one year was a testosterone level < 7.4 nmol/l at 6 months, with 91% sensitivity and 94% specificity., Conclusion: Testosterone levels recover in a small majority of men with prolactinoma mostly during the first year of DA treatment. However, testosterone replacement could be considered earlier in patients with large and compressive tumors, and in whom testosterone remains below 7.4 nmol/l after 6 months of DA treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This perspective provides an overview of issues needed to bring a testosterone-progestogen combined transdermal male hormonal contraceptive to the market. Large-scale phase 2b trials are near completion and a pivotal trial to confirm efficacy and safety has been designed. We believe we are close to accomplishing the steps necessary to bring the first male-directed effective, safe, and reversible pharmaceutical contraceptive approach to the public. If successful, we believe it will provide a new option for couples to consider in their family planning., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Hypoactive Sexual Desire Disorder (HSDD) is a frequent sex-related problem in women; however, a specific tool to characterize HSDD subtypes based on sexual inhibitory and excitatory factors is still lacking., Aim: (1) To find a cutoff value in Sexual Inhibition Scale (SIS)/Sexual Excitation Scale (SES) scores predicting a diagnosis of HSDD in women consulting for sexual symptoms, (2) to explore the sexual inhibitory and excitatory profiles in women referred to a clinic for female sexual dysfunction by stratifying the sample according to the newfound cutoffs, and (3) to identify biopsychosocial factors significantly associated with the 2 profiles., Methods: An overall 133 women consulting for sexual symptoms were retrospectively evaluated for clinical, biochemical, and psychosexologic data collected at the first visit. A subgroup of 55 women treated with transdermal testosterone was retrospectively analyzed at baseline and the 6-month visit., Outcomes: Patients underwent physical and laboratory examinations and completed the SIS/SES, Female Sexual Function Index, Female Sexual Distress Scale-Revised, Emotional Eating Scale, and Middlesex Hospital Questionnaire., Results: Specific cutoffs for SIS1 (≥32.5; indicating threat of performance failure) and SES (≤46.5) predicted HSDD diagnosis with an accuracy of 66.4% (P = .002) and 68.7% (P < .0001), respectively. Patients with impaired SIS1 scores showed higher distress and psychopathologic symptoms, while those with impaired SES scores demonstrated lower desire and arousal and a negative association with some metabolic and hormonal parameters. SES score also showed a significant predictive value on testosterone treatment efficacy for HSDD., Clinical Translation: A better characterization of HSDD would enable individualized treatment based on the main underlying etiologies., Strengths and Limitations: Limitations of the study include the small sample size and cross-sectional retrospective design, with the choice of treatment for HSDD limited to transdermal testosterone. Strengths comprise the thorough and multifactorial evaluation of every aspect potentially affecting inhibitory and excitatory components of sexual desire., Conclusion: Validated cutoffs of SIS/SES scores could allow deep characterization of women diagnosed with HSDD, thus ensuring better tailoring of therapy and prediction of the probability of response to specific treatments., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Results of recent studies suggest that high levels of endogenous testosterone decrease the risk of diabetes. Testosterone therapy may delay the transition from prediabetes to diabetes and accelerate healing of diabetic foot ulcers in hypogonadal men. We investigated whether testosterone therapy in this population decreases the occurrence of diabetic foot complications within 1 and 5 years of diabetes diagnosis., Methods: Optum's deidentified Clinformatics Data Mart database was searched for male patients with diabetes. Associations between testosterone therapy and the occurrence of ulceration or the use of wound care were explored in the entire population and in those with and without hypogonadism using both bivariate and multivariate analyses., Results: Contrary to the hypotheses, testosterone therapy seems to confer increased risk of diabetic foot complications. In hypogonadal men with at least 1 year of follow-up after diabetes diagnosis, any use of testosterone therapy increased the odds of wound care utilization by a factor of 1.10 (95% confidence interval, 1.03-1.17), and the odds of ulceration by a factor of 1.13 (95% confidence interval, 1.03-1.24). Similar results are seen in all men, both with and without hypogonadism. Further exploration reveals that hypogonadism also increases the risk of wounds among people with diabetes with care utilization in the entire population., Conclusions: Further research is needed to elucidate the mechanisms by which hypogonadism and testosterone therapy impact diabetic foot complications, and whether these mechanisms are mediated by vascular or neurologic factors.

Infectious, inflammatory and autoimmune conditions present differently in males and females. SARS-CoV-2 infection in naive males is associated with increased risk of death, whereas females are at increased risk of long COVID 1 , similar to observations in other infections 2 . Females respond more strongly to vaccines, and adverse reactions are more frequent 3 , like most autoimmune diseases 4 . Immunological sex differences stem from genetic, hormonal and behavioural factors 5 but their relative importance is only partially understood 6-8 . In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. Here we performed longitudinal systems-level analyses in 23 trans men and found that testosterone modulates a cross-regulated axis between type-I interferon and tumour necrosis factor. This is mediated by functional attenuation of type-I interferon responses in both plasmacytoid dendritic cells and monocytes. Conversely, testosterone potentiates monocyte responses leading to increased tumour necrosis factor, interleukin-6 and interleukin-15 production and downstream activation of nuclear factor kappa B-regulated genes and potentiation of interferon-γ responses, primarily in natural killer cells. These findings in trans men are corroborated by sex-divergent responses in public datasets and illustrate the dynamic regulation of human immunity by sex hormones, with implications for the health of individuals undergoing hormone therapy and our understanding of sex-divergent immune responses in cisgender individuals., (© 2024. The Author(s).)

The interplay between endogenous testosterone (Te) and prostate cancer (PCa) has long been recognized, with androgen deprivation therapy (ADT) being a cornerstone of advanced and metastatic PCa management. However, the association between Te levels and PCa risk remains complex and not fully understood. This review delves into the complex relationship between adult-onset hypogonadism (AOH) and PCa, shedding light on the complexities surrounding PCa risk and disease aggressiveness. Despite the significant prevalence of PCa among men, particularly as they age, and the emergence of AOH as a prevalent health concern, data regarding their association remains heterogeneous and inconsistently documented. While some studies suggest a potential correlation between low Te levels and decreased PCa detection rates, others indicate a higher risk of aggressive pathological features, primarily observed in prostatectomy cohorts. It's noteworthy that there's evidence indicating hypogonadal men might face an increased risk of reclassification during active surveillance (AS) of low-risk disease. This is supported by the observation of elevated rates of disease upgrading in historical cohorts of low-risk prostatectomies. These contradictory findings are poorly reflected in treatment guidelines. Further research is imperative to comprehensively understand the clinical and associative correlations between AOH and PCa risk and biology, thereby informing more effective management strategies in the future.

Gender-affirming hormone therapy (GAHT) is used by many transgender and gender-diverse adults to align physical characteristics with their gender identity, reduce gender incongruence and improve psychological functioning. This narrative review provides an overview of the initiation and monitoring of GAHT in an Australian context. Trans individuals treated with testosterone typically receive standard testosterone doses and formulations recommended for cisgender men, whereas those receiving estradiol GAHT are typically treated with estradiol in combination with an anti-androgen in those without orchidectomy. Proactive monitoring and mitigation of cardiovascular risk factors is pertinent in all transgender and gender-diverse adults and bone health is an important consideration in those using estradiol GAHT., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction/aims: Recent clinical guidelines recommend that adolescents with Duchenne muscular dystrophy (DMD) who are on daily glucocorticoid treatment should be offered pubertal induction in order to ensure adult levels of sex hormones as they reach adulthood. However, it remains unclear how gonadal status, including androgen concentrations, impacts physical function and future fertility. The aim of this study was to give a voice to adults with DMD, exploring their perspectives around sexual health, hormone treatment, and fertility., Methods: Qualitative data was collected from six adults with DMD through two online focus groups. Participants were recruited through Pathfinders Neuromuscular Alliance and Duchenne UK and invited to take part if they had DMD and were 18 years of age or older. Conversations were transcribed verbatim and an interpretivist paradigm was used with thematic analysis., Results: The main themes identified were (1) the need for communication and information about sexual health, (2) dealing with the potential fear of rejection, (3) physical barriers to relationships including sex, (4) testosterone supplementation in DMD, and (5) parenthood and fertility., Discussion: We recommend that clinicians work with young people with DMD individually, to explore the benefits of testosterone treatment for them and their personal sexual health needs. If they are offered treatment, this should always be accompanied by the opportunity for psychological support. This work highlights the need for further research to establish the role of testosterone supplementation in adults with DMD and its effects on fertility and the value of specific emotional and practical support for sexual health., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used to understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer (IRR 0.46, 95% CI 0.43-0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45-0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19-0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18-0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based analysis suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between hypogonadism and TRT in hypogonadal men on the risk of subsequent prostate cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Studies are needed to examine the effects of testosterone replacement therapy on ambulatory blood pressure (BP) parameters. This study assessed a testosterone transdermal system (TTS) using 24-hour ambulatory BP monitoring., Methods: In a single-arm, noninferiority trial conducted at 41 US sites, 168 men (mean age: 56.2 years) with hypogonadism not receiving testosterone replacement therapy in the past 6 months were enrolled and received ≥1 study drug dose. Nightly TTS treatment was administered for 16 weeks (starting dose: 4 mg/d; min, max dose: 2, 6 mg/d) to achieve testosterone concentration of 400-930 ng/dL. The primary endpoint was mean change from baseline to week 16 in 24-hour systolic BP (SBP). Noninferiority was determined based on the upper bound of the 2-sided 95% CI <3.0 mmHg., Results: Sixty-two men had ≥85% study drug compliance and a valid week 16 ambulatory BP monitoring session. Mean change from baseline to week 16 in 24-hour average SBP was 3.5 mmHg (95% CI, 1.2-5.8 mmHg; n = 62). Since the upper limit of the CI was >3 mmHg, an effect of TTS could not be ruled out. Mean changes were larger at daytime vs nighttime and in subgroups of men with vs without hypertension. Cardiovascular adverse events were rare (<2%) and nonserious; no major cardiovascular adverse events were reported., Conclusion: A meaningful effect of 16-week TTS treatment on 24-hour average SBP among men with hypogonadism could not be ruled out based on the study's noninferiority criterion. The magnitude of mean changes observed may not be clinically meaningful regarding cardiovascular events., Competing Interests: Disclosure Financial support for the study was provided by AbbVie, Inc (North Chicago, IL). AbbVie, Inc, participated in study design, research, data collection, analysis, and interpretation of data, and writing, reviewing, and approving the publication. All authors contributed to the development of the manuscript and maintained control over the final content. No authors received payment or other compensation related to the development of the manuscript. Anna Chan and James W. Thomas are employees of AbbVie, Inc, and own AbbVie, Inc stock or stock options. Mitchell D. Efros, Jed C. Kaminetsky, and Neil D. Sherman have no relevant disclosures., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Objectives: We describe studies determining the association between testosterone therapy (TTh) and mortality., Materials & Methods: We used a registry database of 737 men with adult-onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10-year follow-up. We compared associations between testosterone undecanoate (TU), cardio-metabolic risk factors and mortality using non-parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio-metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio-metabolic risk., Results: During a median follow-up interquartile range (IQR) of 114 (84-132) months, 94 of the 737 men died. TU (ref: non-treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14-0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high-risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the "law of initial value," where greater improvements are evident following treatment in patients with worse baseline values., Conclusions: This study with long follow-up confirms that TTh is associated with lower mortality in men with adult-onset TD. This association was evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Purpose: To explore the potential of testosterone therapy in managing cytopenias in myelodysplastic neoplasm and investigate the link between hypogonadism and hematologic malignancies., Methods: A case of a patient with intermediate-risk myelodysplastic neoplasm and hypogonadism treated with testosterone replacement therapy is presented. Testosterone, prostate specific antigen, and erythropoietin levels were checked prior to therapy initiation and 3 months after. Blood counts were monitored over time. This is followed by a literature review of testosterone use in myelodysplastic neoplasm and the prevalence of hypogonadism in hematologic malignancies., Results: The patient showed sustained improvement in anemia with testosterone therapy and reported subjective improvement in his weakness and fatigue. This improvement occurred even in the setting of an undetectable follow up erythropoietin level. His repeat prostate specific antigen levels remained low, while testosterone levels showed marked improvement. The literature review demonstrated positive response rates for testosterone in treating myelodysplastic neoplasm-related cytopenias, and showed a higher incidence of hypogonadism in hematologic malignancies., Conclusion: Our review suggests that the use of testosterone in low and intermediate-risk myelodysplastic neoplasm is underexplored and poses to have significant potential as a future therapeutic agent, after careful consideration of risks and benefits. In addition, the incidence of hypogonadism in myelodysplastic neoplasm and its potential impact on exacerbating cytopenias in myelodysplastic neoplasm warrants further investigation., (© 2024. The Author(s).)

Background: For two decades preceding the COVID-19 pandemic, testosterone therapy (TT) became more prevalent in the US. Given the forced shift in practice patterns and healthcare accessibility during the pandemic, it was unclear how TT utilization would change., Objective: To assess the change in testosterone prescriptions nationally., Design: Cross-sectional study., Data Sources: State prescription drug monitoring program data between 2018 and 2022., Participants: All individuals filling testosterone prescriptions in participating states., Measurements: Unique people filling testosterone prescriptions annually, demographic information on gender and age as available., Results: In 2022 there was a 27% relative increase of subjects treated with TT (+439,659 cases compared with 2018). The increase was more evident in the pandemic period with a rise in prevalence most notable for people 45-54 (114,114 people, 35% increase) and 35-44 (97,263 people, 58% increase). All regions except the Midwest increased the total population treated, led by the South (52%) followed by the West (28%) and Northeast (23%). Available data indicated men accounted for most patients treated in all age groups except under 24 years., Limitations: Study population limited to those in participating states with no diagnostic information and limited demographics available., Conclusion: Between 2018 and 2022, and primarily after the start of the pandemic in 2020, nationally there was a substantial increase in the number of people using TT. The largest increases occurred in a younger demographic, primarily men, than have previously been reported or studied. These results echo other findings showing increased use of controlled substances during the pandemic period and warrant further study regarding the factors behind this rise., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Selinger, Thallapureddy. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Abstract: Testosterone replacement therapy (TRT) is a crucial intervention for men diagnosed with hypogonadism, a condition characterized by inadequate testosterone production. As primary care NPs play an essential role in managing patients with hypogonadism, they must comprehensively understand TRT. This article serves as a primer for primary care NPs, based on current guidelines, to provide evidence-based care for men with hypogonadism. It offers an overview of the etiology, clinical presentation, diagnostic criteria, and treatment options for hypogonadism, focusing on using TRT appropriately in primary care settings., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ectopic prostatic tissue in female patients is rare. It is theorized that the presence of prostatic tissue in female patients is likely a Wolffian remnant or transformation of hormonally mediated tissue of the uterus, cervix, Skene's gland, and, rarely, periurethral tissue. Due to the increase in the use of testosterone and gender-affirming therapies, it is important to understand the role of testosterone in mediating the presence of ectopic prostatic tissue., Case: We present a case of ectopic prostatic tissue in a urethral diverticulum in a female patient with exposure to testosterone hormone therapy and review the literature on this finding., Conclusion: Although rare, ectopic prostatic tissue should be considered in the differential diagnosis of anterior vaginal cysts, especially in the setting of testosterone supplementation., Competing Interests: Financial Disclosure J. Eric Jelovsek reports money was paid to his institution from the NIDDK, FDA, and the NICHD. He received payment from UpToDate. He participates in an advisory board for Collamedix. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Due to increasing older populations worldwide, injuries, disabilities and deaths caused by falls among the elderly represent a growing human and societal problem. We aimed to improve health among men of at least 70 years of age with low-normal to low testosterone and mobility problems by using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium and protein., Methods: This was a single-centre, randomized, placebo-controlled, double-blind trial with 148 older men with a median age of 77 (73-81) years, testosterone levels at median 8 (5-9) nmol/L (full range from 1.1 to 12.9 nmol/L) and mobility problems, recruited at University Hospital of Copenhagen, Herlev Hospital, Denmark. Participants were randomized into four arms for 20 weeks: (1) TU therapy (n = 37); (2) progressive resistance training with supplements of calcium, vitamin D and protein (n = 36); (3) both interventions combined (n = 36); or (4) no intervention (n = 39). The main outcome measure was the 30-s chair stand test, due to test performance correlating with the risk of serious fall injuries and lower extremity muscle strength. Outcome measurements were performed at baseline and after 20 weeks., Results: After the intervention, the combination group receiving progressive resistance training, TU and supplements achieved a median score of 13 (11-15) compared to the control group at 10 (0-14) in the 30-s chair stand test (P = 0.003). This median improvement of 3.0 was clinically important. Compared to the control group, participants in the combination group also increased quality of life (P < 0.05) and reduced both tiredness (P < 0.05) and leg fat (P < 0.05) and had higher variability in the RR interval (P < 0.01). The group receiving TU reduced gynoid and leg fat compared to the control group (both P < 0.05). Blood tests improved for several variables, especially in the combination group. There was no statistically significant increase in adverse effects from either the supplements or training., Conclusions: In men ≥70 years old with low-normal to low testosterone and mobility problems, supplements of testosterone, calcium, vitamin D and protein combined with progressive resistance training improved 30-s chair stand test performance, muscle strength and quality of life. Both tiredness and leg fat were reduced, and RR interval variability was increased. Significant adverse effects were not observed., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS)., Methods: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS)., Results: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis., Conclusion: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

In epidemiological studies, lowered serum testosterone concentrations are common in men with obesity, prediabetes, and established type 2 diabetes (T2D). In men with prediabetes, lowered serum testosterone also predicts a future risk of T2D in men. Administration of testosterone consistently reduces fat mass and increases skeletal muscle mass-body compositional changes expected to be metabolically favorable. In men with established T2D, the effects of testosterone treatment on glycemic measures are inconsistent. Irrespective of baseline serum testosterone concentration in men with prediabetes or newly diagnosed early-onset T2D, testosterone treatment prescribed in conjunction with a lifestyle program has been reported to reduce the risk of T2D by 40% after 2 years, suggesting that either a lifestyle program is required to facilitate the glycemic benefit of testosterone treatment and/or that testosterone treatment has more favorable effects on glycemia in men early in the evolution or onset of the disease. The durability of the benefit and longer-term safety of testosterone treatment have not been established. Therefore, more studies are required before testosterone treatment can be recommended for the prevention and/or treatment of men with or at elevated risk of T2D who do not have hypogonadism due to an established disease of the hypothalamic-pituitary-testicular axis., (© 2024 The New York Academy of Sciences.)

Competing Interests: Conflicts of interest: none to declare.