Tolvaptan versus fluid restriction in moderate-profound hyponatremia: An open-label randomized clinical trial.

Context: Current first-line therapy for hyponatremia, fluid restriction (FR), is often unsuccessful. Tolvaptan, an arginine vasopressin V2-receptor antagonist, is effective however concerns about plasma sodium (pNa) overcorrection risk have limited uptake.

Objective: To compare the efficacy of tolvaptan and fluid restriction, with a pre-specified protocol for dextrose 5% intervention if sodium correction targets were exceeded.

Bone Health Management in Men Commencing Androgen Deprivation Therapy for Prostate Cancer and Women Commencing Anti-Oestrogen Therapy for Breast Cancer.

Background: Survival of patients with prostate and breast cancer, the commonest cancer in men and women, respectively, has markedly improved with advances in early diagnosis, treatment and multi-disciplinary care by the oncology and surgical community. However, the use of increasingly potent endocrine therapies may cause bone loss, resulting in secondary osteoporosis.

Review: This review summarises the current management of cancer treatment-induced bone loss in this group of patients at high risk of osteoporotic fractures with their attendant morbidity and mortality.

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.

Increased Ambient Temperature and Hyponatremia Presentations: A 10-Year Retrospective Study at an Australian Hospital.

Objective: To determine the relationship between ambient air temperature and the incidence of hyponatremia in a heat-prone region.

Methods: We conducted a retrospective study that correlated serum sodium concentrations documented at the Austin Hospital in Melbourne over 10 years from January 2014 to December 2023 with publicly available temperature data from the Australian Bureau of Meteorology. The main outcome measures were serum sodium concentrations and incidence of hyponatremia admissions when correlated to temperature, and, following heatwave events, defined as temperature above 30 °C over 5 consecutive days.

The Effects of Aerobic Exercise Training on Testosterone Concentration in Individuals Who are Obese or Have Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Background: Obesity and type 2 diabetes (T2D) are associated with alterations in testosterone concentrations. While evidence indicates that aerobic training can influence testosterone in healthy populations or females with hyperandrogenism, its impact in individuals with obesity or T2D remains unclear. Thus, the aim of this study was to investigate whether aerobic training can influence circulating testosterone concentrations in individuals with obesity or T2D.

Indications for testosterone therapy in men.

Purpose Of Review: Testosterone replacement therapy for men with organic hypogonadism due to medical disease of the hypothalamic-pituitary-testicular (HPT) axis is uncontroversial. In these men, testosterone replacement replaces the deficient hormone and relieves the signs and symptoms of androgen deficiency. In contrast, the role of testosterone treatment in middle-aged or older men who have clinical features consistent with androgen deficiency accompanied by reductions in serum testosterone but lack identifiable HPT axis disease, a scenario sometimes referred to as 'functional' or 'late onset' hypogonadism, has been uncertain.

Male hypogonadism: pathogenesis, diagnosis, and management.

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.

Testosterone in prevention and treatment of type 2 diabetes in men: Focus on recent randomized controlled trials.

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.

Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial.

Purpose: Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women.

Methods: In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months).

Testosterone therapy in older men: clinical implications of recent landmark trials.

Testosterone therapy for men with hypogonadism due to identifiable hypothalamic-pituitary-testicular (HPT) pathology is uncontroversial. However, the risks and benefits of testosterone for men with clinical features of hypogonadism in the absence of identifiable HPT axis pathology have been uncertain. Recent landmark placebo-controlled trials assessed the benefits and risks of testosterone therapy (≤3 years) for middle-aged and older men with symptoms and possible signs of hypogonadism or end-organ androgen deficiency, low or low-normal serum testosterone concentrations, but no HPT pathology: Testosterone therapy (1) had modest-but clinically significant-benefits on average self-reported energy and mood, sexual function, and satisfaction; (2) in conjunction with a lifestyle programme, reversed or reduced incident type 2 diabetes mellitus (T2D) in men at high risk of or newly diagnosed with T2D; (3) modestly improved objectively assessed muscle strength and timed walking distance; (4) increased bone density and strength, but did not reduce falls or typical osteoporotic fractures and surprisingly increased the risk of fractures typically attributable to trauma; and (5) did not significantly increase the risk of myocardial infarction, stroke, or prostate cancer.

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.

Focal Seizures in a Patient With Chronic Basal Ganglia Calcifications Secondary to Idiopathic Primary Hypoparathyroidism.

Patients with hypoparathyroidism can present with concurrent basal ganglia calcifications (BGCs). The exact pathogenesis is unknown, although it is thought to relate to calcium-phosphate deposition from chronic hypocalcemia and hyperphosphatemia. We present the case of a 65-year-old man with known idiopathic primary hypoparathyroidism and concurrent extensive BGC.

Dysnatremia in a changing climate: A global systematic review of the association between serum sodium and ambient temperature.

Objective: Both hyponatremia and hypernatremia have been reported to occur more frequently with higher ambient temperatures, although the underlying mechanisms are not well understood. Global temperatures are rising due to climate change, which may impact the incidence of dysnatremia worldwide. We aimed to identify, collate and critically appraise studies analyzing the relationship between climate measures (outdoor temperature, humidity) and serum sodium concentrations.

Testosterone Treatment, Weight Loss, and Health-related Quality of Life and Psychosocial Function in Men: A 2-year Randomized Controlled Trial.

Objective: To determine the effect of testosterone vs placebo treatment on health-related quality of life (HR-QOL) and psychosocial function in men without pathologic hypogonadism in the context of a lifestyle intervention.

Design, Setting, Participants: Secondary analysis of a 2-year randomized controlled testosterone therapy trial for prevention or reversal of newly diagnosed type 2 diabetes, enrolling men ≥ 50 years at high risk for type 2 diabetes from 6 Australian centers.

Interventions: Injectable testosterone undecanoate or matching placebo on the background of a community-based lifestyle program.

Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy.

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age.

Cardiometabolic Effects of Denosumab in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression: RCT.

Context: Menopause is associated with changes in musculoskeletal, body composition, and metabolic parameters that may be amplified in premenopausal women receiving estradiol suppression for breast cancer. Denosumab offsets deleterious skeletal effects of estradiol suppression and has been reported to have effects on body composition and metabolic parameters in preclinical and observational studies, but evidence from double-blind randomized controlled trials is limited.

Objective: To assess the effect of denosumab on body composition and metabolic parameters.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

Background: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment.

The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.

Purpose Of Review: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models.

Recent Findings: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance.

Long-term Outcomes of Testosterone Treatment in Men: A T4DM Postrandomization Observational Follow-up Study.

Context: The T4DM study randomized 1007 men with impaired glucose tolerance or newly diagnosed diabetes to testosterone undecanoate (TU, 1000 mg) or matching placebo (P) injections every 12 weeks for 24 months with a lifestyle program with testosterone (T) treatment reducing diabetes diagnosis by 40%.

Background: The long-term effects on new diagnosis of diabetes, cardiovascular and prostate disease, sleep apnea, weight maintenance trajectory and androgen dependence were not yet described.

Methods: A follow-up email survey after a median of 5.