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.

Endocrine consequences of breast cancer therapy and survivorship.

Breast cancer survivorship is increasing, due to earlier diagnosis of the disease and more effective therapies. Long-term endocrine sequelae, including early menopause, bone health, fertility implications and menopausal symptoms, are important survivorship issues. Ovarian failure is common with chemotherapy and options for preserving fertility in young women include ovarian suppression during chemotherapy and oocyte or embryo cryopreservation before chemotherapy.

From cardiovascular protection to cardiovascular risk: the metamorphosis of menopausal hormone therapy.

Over the last 70years, oestrogen therapy for the management of menopausal symptoms has undergone a metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk. The former perception is based on the convincing evidence from the Nurses' Health Study cohorts and the epidemiological data surrounding early menopause. The latter, and later, perception is based on the disquieting results from two randomised controlled studies, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative study (WHI).

Abiraterone in Classic Congenital Adrenal Hyperplasia: Results of Medical Therapy Before Adrenalectomy.

We present the case of a 20-year-old woman with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, with uncontrolled hyperandrogenemia despite supraphysiological glucocorticoid therapy. We used abiraterone acetate, an inhibitor of the 17-hydroxylase/17,20-lyase enzyme, to suppress adrenal androgen synthesis and allow physiological glucocorticoid and mineralocorticoid therapy, as a proof-of-concept, before proceeding to bilateral adrenalectomy. We report the patient's clinical course, the changes in adrenal steroids, and the immunohistochemistry of the adrenals.

Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry.

Background: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case-control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes.

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.

A case of catamenial erythema multiforme major successfully treated with goserelin.

Summary: We report a case of catamenial erythema multiforme major in a 46-year-old female. She was treated successfully with goserelin, a GnRH agonist, until the expected age of menopause; however, its therapeutic effects persisted for longer than expected, possibly due to accumulation in adipose tissue.

Learning Points: A group of menstrual cycle-related dermatoses and hypersensitivity syndromes exist but are rarely reported in the literature.

Induction of lactation in a patient with complete androgen insensitivity syndrome.

Summary: With rising rates of adoption and surrogacy, induced lactation is likely to become increasingly relevant, allowing women who did not undergo pregnancy to breastfeed. We describe the case of a woman with complete androgen insensitivity syndrome (CAIS) on conventional oestrogen therapy who was expecting a child via surrogacy and who wished to breastfeed. The woman was commenced on supplementary oestrogen therapy, domperidone and breast stimulation by mechanical breast pump 8 weeks prior to the delivery of her child.

A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal RinGSM) over 12 weeks in healthy postmenopausal women.

Objectives: The exploratory objectives of this study were to evaluate the usability and acceptability and to conduct a preliminary evaluation of the efficacy of DARE-HRT1. DARE-HRT1 is an intravaginal ring (IVR) that releases 17β2-estradiol (E2) with progesterone (P4) over 28 days. It is the first combination E2 and P4 IVR being developed for the treatment of vasomotor symptoms (VMS) in healthy postmenopausal women with an intact uterus.

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.

Congenital hypogonadotrophic hypogonadism, induction of minipuberty, and future fertility.

Summary: A 33-year-old man with Kallmann syndrome had received pulsatile GnRH as an infant for the treatment of cryptorchidism. As an adult, his treatment for fertility with gonadotrophins was unusually rapid compared with expectations, with a total sperm count of 25 million after only 12 months of gonadotrophin therapy. We propose that pulsatile GnRH treatment as an infant induced minipuberty and facilitated his successful, rapid response to therapy.

Mediation analysis of the testosterone treatment effect to prevent type 2 diabetes in the Testosterone for Prevention of Type 2 Diabetes Mellitus trial.

Objective: To determine if testosterone treatment effect on glycaemia is mediated through changes in total fat mass, abdominal fat mass, skeletal muscle mass, non-dominant hand-grip, oestradiol (E2), and sex hormone-binding globulin (SHBG).

Design: Mediation analysis of a randomised placebo-controlled trial of testosterone.

Methods: Six Australian tertiary care centres recruited 1007 males, aged 50-74 years, with waist circumference ≥95 cm, serum total testosterone ≤14 nmol/L (immunoassay), and either impaired glucose tolerance or newly diagnosed type 2 diabetes on an oral glucose tolerance test (OGTT).

Digenic Congenital Hypogonadotropic Hypogonadism Due to Heterozygous p.R31C and p.G445_L453del Variants.

A 28-year-old man with congenital hypogonadotropic hypogonadism (CHH) was found to be heterozygous for the p.R31C mutation, reported in the literature as pathogenic and dominant. The same mutation was found in his son at birth, but the testing of the infant at 64 days confirmed the hormonal changes associated with minipuberty.

Serum 21-Deoxycortisol for Diagnosis of Nonclassic Congenital Adrenal Hyperplasia in Women With Androgen Excess.

Context: Nonclassic congenital adrenal hyperplasia (NCCAH) requires exclusion before diagnosing polycystic ovary syndrome (PCOS). Increasing use of liquid chromatography and tandem mass spectrometry (LC-MS/MS) necessitates revision of immunoassay-based criteria for NCCAH. Measurement of 21-deoxycortisol (21DF) may simplify the diagnosis of heterozygosity (HTZ), the presence of 1 affected CYP21A2 allele, which currently relies on complex molecular studies.

A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women.

Objectives: Primary objectives were to evaluate the safety and systemic pharmacokinetics (PK) of DARE-HRT1, an intravaginal ring (IVR), which releases 17β2-Estradiol (E2) with progesterone (P4) for 28 days in healthy postmenopausal women.

Methods: This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women with an intact uterus. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d).

Evaluation of 28-day estradiol and progesterone vaginal rings in a phase 1 clinical pharmacokinetic study.

Objective: The aim of this work is to develop a combination of 17β-estradiol (E2) and progesterone (P4) in a single-dose intravaginal ring (IVR) for the treatment of vasomotor symptoms (VMS) and genitourinary syndrome of menopause while providing endometrial protection. The objective of this study was to evaluate DARE-HRT1, a 28-day IVR that continuously delivers E2 and P4, in a phase 1 clinical trial to assess its pharmacokinetics.

Methods: This was an open-label, three-arm (group) study.

Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: a phase 2, randomised, double-blind, placebo-controlled trial.

Background: Vasomotor symptoms (hot flushes and night sweats) are experienced by more than two-thirds of women with breast cancer taking oral adjuvant endocrine therapy. Safe and effective treatments are lacking. Q-122 is a novel, non-hormonal compound that has shown promise for reducing vasomotor symptoms by modulation of oestrogen-responsive neurons in the hypothalamus.

Establishing a Total Hip T-Score Threshold to Measure Contralateral Hip Bone Mineral Density: Avoiding Missed Diagnosis of Osteoporosis.

Bone mineral density (BMD) of the hip is routinely measured unilaterally, but can differ between left and right. This study aimed to establish total hip T-score thresholds for measuring contralateral hip BMD, to avoid missing the diagnosis of osteoporosis. In 4914 participants (2709 females) in the Busselton Healthy Ageing Study, BMD of both hips and lumbar spine (L1-L4) was measured by dual-energy x-ray absorptiometry (DXA) using a GE Lunar Prodigy Pro densitometer.

Recovery of male reproductive endocrine function after ceasing prolonged testosterone undecanoate injections.

Context: The time course of male reproductive hormone recovery after stopping injectable testosterone undecanoate (TU) treatment is not known.

Objective: The aim of this study was to investigate the rate, extent, and determinants of reproductive hormone recovery over 12 months after stopping TU injections.

Materials And Methods: Men (n = 303) with glucose intolerance but without pathologic hypogonadism who completed a 2-year placebo (P)-controlled randomized clinical trial of TU treatment were recruited for further 12 months while remaining blinded to treatment.

Effect of Testosterone Treatment on Bone Microarchitecture and Bone Mineral Density in Men: A 2-Year RCT.

Context: Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown.

Objective: We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT).