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Female hypogonadism (FH) is a relatively common endocrine disorder in women of premenopausal age, but there are significant uncertainties and wide variation in its management. Most current guidelines are monospecialty and only address premature ovarian insufficiency (POI); some allude to management in very brief and general terms, and most rely upon the extrapolation of evidence from the studies relating to physiological estrogen deficiency in postmenopausal women. The Society for Endocrinology commissioned new guidance to provide all care providers with a multidisciplinary perspective on managing patients with all forms of FH. It has been compiled using expertise from Endocrinology, Primary Care, Gynaecology and Reproductive Health practices, with contributions from expert patients and a patient support group, to help clinicians best manage FH resulting from both POI and hypothalamo‐pituitary disorders, whether organic or functional. [ABSTRACT FROM AUTHOR]

Objective: The hypothalamic‐pituitary‐testicular axis is characterised by the existence of major functional changes from its establishment in fetal life until the end of puberty. The assessment of serum testosterone and gonadotrophins and semen analysis, typically used in the adult male, is not applicable during most of infancy and childhood. On the other hand, the disorders of gonadal axis have different clinical consequences depending on the developmental stage at which the dysfunction is established. This review addresses the approaches to evaluate the hypothalamic‐pituitary‐testicular axis in the newborn, during childhood and at pubertal age. Design: We focused on the hormonal laboratory and genetic studies as well as on the clinical signs and imaging studies that guide the aetiological diagnosis and the functional status of the gonads. Results: Serum gonadotrophin and testosterone determination is useful in the first 3–6 months after birth and at pubertal age, whereas AMH and inhibin B are useful biomarkers of testis function from birth until the end of puberty. Clinical and imaging signs are helpful to appraise testicular hormone actions during fetal and postnatal life. Conclusions: The interpretation of results derived from the assessment of hypothalamic‐pituitary‐testicular in paediatric patients requires a comprehensive knowledge of the developmental physiology of the axis to understand its pathophysiology and reach an accurate diagnosis of its disorders. [ABSTRACT FROM AUTHOR]

Background: Inter‐assay variation between different immunoassays and different mass spectrometry methods hampers the biochemical confirmation of male hypogonadism. Furthermore, some laboratories utilise assay manufacturer reference ranges that do not necessarily mirror assay performance characteristics, with the lower limit of normality ranging from 4.9 nmol/L to 11 nmol/L. The quality of the normative data underlying commercial immunoassay reference ranges is uncertain. Design: A working group reviewed published evidence and agreed upon standardised reporting guidance to augment total testosterone reports. Results: Evidence‐based guidance on appropriate blood sampling, clinical action limits, and other major factors likely to affect the interpretation of results are provided. Conclusions: This article aims to improve the quality of the interpretation of testosterone results by non‐specialist clinicians. It also discusses approaches for assay harmonisation which have been successful in some but not all healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Androgen deprivation therapy (ADT) in prostate cancer (PCa) has been associated with development of insulin resistance. However, the predominant site of insulin resistance remains unclear. Methods: The ADT & Metabolism Study was a single‐center, 24‐week, prospective observational study that enrolled ADT‐naive men without diabetes who were starting ADT for at least 24 weeks (ADT group, n = 42). The control group comprised men without diabetes with prior history of PCa who were in remission after prostatectomy (non‐ADT group, n = 23). Prevalent diabetes mellitus was excluded in both groups using all three laboratory criteria defined in the American Diabetes Association guidelines. All participants were eugonadal at enrollment. The primary outcome was to elucidate the predominant site of insulin resistance (liver or skeletal muscle). Secondary outcomes included assessments of body composition, and hepatic and intramyocellular fat. Outcomes were assessed at baseline, 12, and 24 weeks. Results: At 24 weeks, there was no change in hepatic (1.2; 95% confidence interval [CI], −2.10 to 4.43; p =.47) or skeletal muscle (−3.2; 95% CI, −7.07 to 0.66; p =.10) insulin resistance in the ADT group. No increase in hepatic or intramyocellular fat deposition or worsening of glucose was seen. These changes were mirrored by those observed in the non‐ADT group. Men undergoing ADT gained 3.7 kg of fat mass. Conclusions: In men with PCa and no diabetes, 24 weeks of ADT did not change insulin resistance despite adverse body composition changes. These findings should be reassuring for treating physicians and for patients who are being considered for short‐term ADT. In this prospective study of hormone‐naive men who were eugonadal and did not have diabetes, 24 weeks of androgen deprivation therapy (ADT) for prostate cancer (PCa) was not associated with worsening of hepatic or skeletal muscle insulin resistance despite a substantial increase in fat mass. These findings have relevance for both physicians and patients when determining treatment for PCa and suggest that a short course of ADT may not worsen metabolic risk in patients without pre‐existing diabetes. [ABSTRACT FROM AUTHOR]

Background: Long-term use of supraphysiologic doses of anabolic-androgenic steroids (AAS) has been associated with impaired visuospatial memory in young men but little is known about its cognitive effects in middle-aged men.Objectives: We compared cognition in middle-aged men with histories of long-term AAS use and age-matched non-users.Methods: We administered cognitive tests from the CANTAB battery to 76 weightlifters aged 37–60 years (mean [SD] 48.5 [6.5] years), of whom 51 reported at least 2 years of cumulative AAS use and 25 reported no AAS exposure.Results: We found no significant AAS user versus non-user group differences on visuospatial, verbal memory, emotional recognition, or executive function tasks (corrected p’s ≥ .00089; effect sizes ≤ .5).Conclusions: Our null visuospatial task findings contrast with our prior younger cohort study (mean age 37.1 [7.1] years), in which we found impaired visuospatial task performance in people who use AAS, and with other reports of cognitive impairments in younger men use AAS. Men who use AAS may develop early visuospatial memory deficits that stabilize by middle age while middle-aged non-users’ performance may “catch up” due to normal age-related visuospatial declines. Similar effects could contribute to our null findings on other tasks. Between-study cohort substance use differences or environmental factor differences that modify cognition, such as study geographical location and time of year, also could contribute to our discordant findings. Since young adult male AAS users experience increased mortality from unnatural causes, improving our understanding of AAS cognitive effects in this age group is important. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA.The cross‐sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30–51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin‐like growth factor‐1 (IGF‐1). Blood glucose, insulin, and beta‐hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated.In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF‐1 negatively correlated with FM.Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA). A cohort study. University-affiliated male reproductive health center. A total of 616 consecutive patients with NOA and hypogonadism (total testosterone [T] levels <350 ng/dL) underwent micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history. Patients aged 23–55 years underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts on the basis of pre-SR hormonal stimulation. A multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success, defined as the presence of viable spermatozoa in extracted specimens. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to assess the relationship between SR success and relevant predictors. Sperm retrieval rates were compared between patients receiving or not hormonal stimulation, and logistic regression analysis evaluated the effect of baseline follicle-stimulating hormone levels (i.e., normogonadotropic vs. hypergonadotropic classes) on SR success. The overall micro-TESE success rate was 56.6%. Baseline follicle-stimulating hormone levels (aOR, 0.97; 95% CI, 0.94–0.99), pre-SR hormonal stimulation (aOR, 2.54; 95% CI, 1.64–3.93), presence of clinical varicocele (aOR, 0.05; 95% CI, 0.01–0.51), history of previous varicocelectomy (aOR, 2.55; 95% CI, 1.26–5.16), and testicular histopathology were independent predictors of SR success. Among hormone-pretreated patients, pre-micro-TESE T levels and delta T (an absolute increase in T levels from baseline) were associated with SR success. A pre-micro-TESE T level of 418.5 ng/dL (area under the curve value: 0.78) and a delta T of 258 ng/dL (area under the value: 0.76) distinguished patients with positive and negative SR outcomes. Subgroup analysis showed that pre-SR hormonal stimulation yielded a greater benefit for normogonadotropic patients than for those who were hypergonadotropic. This study underscores the association between clinical factors and micro-TESE success in hypogonadal men with NOA. Although causality is not established, our findings suggest that these patients may benefit from pre-SR interventions, particularly hormonal stimulation and varicocele repair. NCT05110391. [ABSTRACT FROM AUTHOR]