genotype influences androgen response in developing murine skeletal muscle.

Androgens act through androgen receptor (AR) to maintain muscle mass. Evidence suggests that this pathway is influenced by "the gene for speed," (α-actinin-3). Given that one in five people lack α-actinin-3, it is possible that they may respond to androgens differently.

Testicular Function After Immune-Checkpoint Inhibitors Treatment.

Objective: To investigate the effects of immune-checkpoint inhibitors (ICIs) on spermatogenesis and testicular endocrine function in reproductive-age men with melanoma.

Design: Prospective, mixed longitudinal and cross-sectional cohort study.

Patients: Twenty-nine men aged 19-46 years undergoing ICI therapy for melanoma at two Australian centres between 2019 and 2024.

Debate about the Free Testosterone Hypothesis: Useful Tool or Misguided Mirage?

In this debate, two clinicians discuss the merits and demerits of the free testosterone hypothesis. Although most clinical guidelines recommend the measurement of free testosterone in the evaluation for male hypogonadism (at least in men with suspected low serum sex hormone binding globulin), there remains controversy about underlying hypothesis that serum free testosterone is a significant contributor to androgen effect. In this debate, Dr.

Evaluation of reference ranges of four circulating sex steroids from dried blood spots in women aged 18-40 years.

Capillary dried blood spot collection offers an excellent less invasive alternative to serum or plasma collection by venesection. This study aimed to generate reference ranges for four sex steroids in capillary whole blood samples collected from healthy premenopausal women as dried blood spots as a screening method to detect disorders of sex development. Using this method we evaluated variations according to age, body mass index, menstrual cycle, and hormonal contraceptive use.

Defining sex in the sporting world.

At an elite international level, professional sports have a well-established fairness-based binary sex classification which is challenged by male-bodied athletes with female gender identity, notably male-to-female transgender and XY Disorders of Sex Development (DSD) individuals seeking to compete in female events. For sports where success depends on power and/or endurance, physical advantages stemming from male puberty, which produces men's circulating testosterone concentrations 20-30 times those of children or women at any age, leading to larger and stronger muscles, bones, cardiorespiratory functions and blood hemoglobin. Yet complete suppression of endogenous testosterone after male puberty leaves a legacy of reduced but not eliminated physical advantages.

Functional Analysis of HSD17B3-Deficient Male Mice Reveals Roles for HSD17B7 and HSD17B12 in Testosterone Biosynthesis.

Historically, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) was thought to be the key enzyme responsible for testicular testosterone production. In humans, loss-of-function mutations in HSD17B3 impair testosterone production during prenatal life leading to impaired development of androgen-dependent tissues in 46,XY individuals. However, male mice with HSD17B3 deficiency exhibit normal testicular testosterone concentrations, normal development of reproductive organs and are fertile, suggesting that mice express other hydroxysteroid dehydrogenase enzymes capable of testicular testosterone synthesis.

Treatment With a Nonaromatizable Androgen for Transgender Man With a Hormone-sensitive Ovarian Cancer.

Gender-affirming hormone therapy (GAHT) is increasingly prescribed to transgender men and gender diverse individuals to better align their affirmed gender identity and somatic phenotype, aiming to improve psychosocial well-being. However, the long-term outcomes of GAHT, especially risk of hormone-related malignancy, remains unclear. We report a case of transgender man on long-term GAHT with testosterone who developed recurrent hormone-sensitive endometrioid ovarian cancer.

Impact of Excess Activin A on the Lipids, Metabolites, and Steroids of Adult Mouse Reproductive Organs.

Bioactivity of the hormone and growth factor activin A is central to fertility and health. Dysregulated circulating activin levels occur with medication usage and multiple pathological conditions. The inhibin-alpha knockout mouse (InhaKO) models chronic activin elevation and unopposed activin A bioactivity.

Approach to the Patient: Low Testosterone Concentrations in Men With Obesity.

Pathologic hypogonadism occurs when serum testosterone is significantly and persistently reduced by irreversible organic (structural, genetic) disorders of the hypothalamic pituitary testicular axis. Men with pathologic hypogonadism require lifelong testosterone replacement. In contrast, mild or moderate reductions in serum testosterone frequently accompany obesity, and its numerous comorbidities in men are best considered nongonadal illness syndromes, wherein reduction in serum testosterone is usually reversible upon amelioration of the underlying nongonadal illness.

Biology and Management of Male-Bodied Athletes in Elite Female Sports.

The physical advantages in elite power sports that allow men to surpass women are derived from the experience of male puberty. By creating testicular testosterone production 20-30-fold over women at any age, sustained exposure over years to adult male testosterone concentrations produces larger and stronger muscles, bones, and the cardiorespiratory system with a higher blood hemoglobin explaining those advantages. While genetic advantages in exercise performance unrelated to sex are accepted in elite sports, adults who have experienced male puberty but have female gender identity, such as male-to-female transgender or intersex (XY Disorders of Sexual Development, DSD), create a category-defeating conflict if they compete in female power sports.

Testosterone Treatment and Sexual Function in Men: Secondary Analysis of the T4DM (Testosterone for Diabetes) Trial.

Context: The combined effects of testosterone treatment and lifestyle intervention on sexual function in men at high risk of type 2 diabetes are unclear.

Objective: To assess the effect of testosterone treatment with a lifestyle intervention in men aged 50 to 74 years at high risk of, or newly diagnosed with, type 2 diabetes (via oral glucose tolerance test).

Design: A secondary analysis of the Testosterone for the Prevention of Type 2 Diabetes trial, a double-blind, placebo-controlled trial conducted across 6 Australian centers.

Predicting type 2 diabetes and testosterone effects in high-risk Australian men: development and external validation of a 2-year risk model.

Objective: We have shown that men aged 50 years+ at high risk of type 2 diabetes treated with testosterone together with a lifestyle program reduced the risk of type 2 diabetes at 2 years by 40% compared to a lifestyle program alone. To develop a personalized approach to treatment, we aimed to explore a prognostic model for incident type 2 diabetes at 2 years and investigate biomarkers predictive of the testosterone effect.

Design: Model development in 783 men with impaired glucose tolerance but not type 2 diabetes from Testosterone for Prevention of Type 2 Diabetes; a multicenter, 2-year trial of Testosterone vs placebo.

Molecular mechanism of androgen receptor mutation in multigenerational mild androgen insensitivity syndrome.

Objective: Androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations creates a spectrum of clinical presentations based on residual AR function with the mildest impairment creating mild AIS (MAIS) whose undefined molecular mechanism and subtle clinical features leave it less understood and underdiagnosed.

Design: In silico modeling and in vitro androgen bioassay of the mutated AR are used to identify its structural and physiological mechanism. Clinical features and responses to high-dose testosterone treatment of three cases of MAIS across a six-generation family pedigree are described.

Successful colonization of the testicular germinal epithelium by bone marrow stem cells producing spermatozoa of donor genotype is rare.

Background: It is not known whether bone marrow stem cells when injected intravenously for a bone marrow transplant colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.

Objectives: To differentiate host from donor genotype in spermatozoa of men who have undergone successful bone marrow transplants.

Efficacy of Gonadotropin Treatment for Induction of Spermatogenesis in Men With Pathologic Gonadotropin Deficiency: A Meta-Analysis.

Introduction: Hypogonadotropic hypogonadism (HH) is a treatable cause of nonobstructive azoospermic male infertility. Gonadotropin treatment can successfully induce spermatogenesis in most patients, although comprehensive quantitative summary data on spermatogenic outcomes like those required to induce pregnancy is lacking in the literature.

Materials And Methods: Systematic review and meta-analysis of outcomes related to male reproductive function following gonadotropin treatment.

Testosterone and Erythrocyte Lifespan.

Context: Endogenous and exogenous androgens increase circulating erythrocytes and hemoglobin but their effects on erythrocyte lifespan is not known.

Objective: To investigate androgen effects on immature and mature erythrocyte lifespan in humans and mice using novel nonradioactive minimally invasive methods.

Design: Human erythrocyte lifespan was estimated using alveolar carbon monoxide concentration and blood hemoglobin in Levitt's formula in hypogonadal or transgender men before and up to 18 weeks after commencing testosterone (T) treatment.

High circulating concentrations of estradiol are anabolic for bone mass and strength in an adult male to female transgender mouse model.

The effects of gender affirming hormone therapy (GAHT) on bone microarchitecture and fracture risk in adult transgender women is unclear. To investigate the concept that skeletal integrity and strength in trans women may be improved by treatment with a higher dose of GAHT than commonly prescribed, we treated adult male mice with a sustained, high dose of estradiol. Adult male mice at 16 weeks of age were administered ~1.

Cross-Sectional Associations between Nutrient Intake and Tooth Decay in Older Australian Men: The Concord Health and Ageing in Men Project.

Poor nutrition is a risk factor for dental decay in younger people. However, except for sugar, it is unclear if this is true in older age groups. The aim of this study was to analyze the possible associations between overall dietary intake of nutrients and diet quality and the presence of dental decay in community-dwelling older men.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

Background: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial.

Purpose: To clarify associations of sex hormones with these outcomes.

Data Sources: Systematic literature review to July 2019, with bridge searches to March 2024.