Sexual dimorphism refers to differences between biological sexes that extend beyond sexual characteristics. In humans, sexual dimorphism in the immune response has been well demonstrated, with females exhibiting lower infection rates than males for a variety of bacterial, viral, and parasitic pathogens. There is also a substantially increased incidence of autoimmune disease in females compared to males. Together, these trends indicate that females have a heightened immune reactogenicity to both self and non-self-molecular patterns. However, the molecular mechanisms driving the sexually dimorphic immune response are not fully understood. The female sex hormones estrogen and progesterone, as well as the male androgens, such as testosterone, elicit direct effects on the function and inflammatory capacity of immune cells. Several studies have identified a sex-specific transcriptome and methylome, independent of the well-described phenomenon of X-chromosome inactivation, suggesting that sexual dimorphism also occurs at the epigenetic level. Moreover, distinct alterations to the transcriptome and epigenetic landscape occur in synchrony with periods of hormonal change, such as puberty, pregnancy, menopause, and exogenous hormone therapy. These changes are also mirrored by changes in immune cell function. This review will outline the evidence for sex hormones and pregnancy-associated hormones as drivers of epigenetic change, and how this may contribute to the sexual dimorphism. Determining the effects of sex hormones on innate immune function is important for understanding sexually dimorphic autoimmune diseases, sex-specific responses to pathogens and vaccines, and how innate immunity is altered during periods of hormonal change (endogenous or exogenous).

No abstract

Low testosterone levels are common in men with severe liver disease and predict mortality independent of MELD, the standard score used to prioritize the allocation of liver transplants.

No abstract

Quantification of abdominal visceral adipose tissue (VAT) is important to understand obesity-related comorbidities. We hypothesized that dual X-ray absorptiometry (DXA) measurements of VAT would correlate with traditional gold standards of magnetic resonance imaging (MRI) and computed tomography (CT) in older men. Deming regression and Bland-Altman plots were used to assess the agreement between VAT measured simultaneously by DXA and MRI (n=95) in a cohort of older males participating in a randomized trial of testosterone replacement for diabetes. We also correlated DXA with single-slice CT (n=102) in a cohort of older males undergoing testosterone deprivation for prostate cancer. Lunar Prodigy DXA scanners using enCORE software was used to measure VAT. DXA VAT volume strongly correlated with MRI VAT volume (r=0.90, P<0.0001) and CT VAT area (r=0.83, P<0.0001). As DXA assesses VAT volume in a smaller compartment than MRI, Bland-Altman analysis demonstrated DXA systematically underestimated VAT by an approximately 30% proportional bias. DXA VAT volume measured by Lunar Prodigy DXA scanners correlate well with gold standard MRI and CT quantification methods, and provides a low radiation, efficient, cost-effective option. Future clinical studies examining the effects of interventions on body composition and regional fat distribution may find DXA an appropriate volumetric method to quantify VAT.

Background: Over the last 10 years, increases in demand for transgender health care has occurred worldwide. There are few data on clinical characteristics of Australian adult transgender individuals. Understanding gender identity patterns, sociodemographic characteristics, gender-affirming treatments, as well as medical and psychiatric morbidities, including neurobehavioral conditions affecting transgender and gender-diverse adults will help to inform optimal health service provision.Purpose: In an Australian adult transgender cohort, we aimed to first, assess referral numbers and describe the sociodemographic and clinical characteristics, and second, to specifically assess the prevalence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).Methods: We performed a retrospective audit of deidentified electronic medical records in a primary care and a secondary care gender clinic in Melbourne, Australia. Annual referral rates, sociodemographic data, and prevalence of medical and psychiatric conditions were obtained.Results: Data for 540 transgender individuals were available. Rapid rises were observed in referrals for transgender health services, more than 10 times the number in 2016 compared with 2011. Median age at initial presentation was 27 years (interquartile range (22, 36), range 16–74). Around 21.3% were unemployed and 23.8% had experienced homelessness despite high levels of education. Around 44.1% identified as trans male, 36.3% as trans female, and 18.3% as gender nonbinary. Medical morbidities were rare but mental illness was very common. The prevalence of depression was 55.7%, anxiety in 40.4%, ADHD in 4.3%, and ASD in 4.8%, all higher than reported age-matched general Australian population prevalence.Conclusions: Rising demand for transgender care, socioeconomic disadvantage, and high burden of mental health conditions warrants a comprehensive multidisciplinary approach to provide optimal care for transgender individuals. Given that ASD and ADHD are prevalent, in addition to gender-affirming treatments, psychosocial interventions may assist individuals in navigating health care needs and to support social aspects of gender transition. Further studies are required to understand links between ASD, ADHD, and gender identity and to evaluate optimal models of health service provision for transgender individuals.

Objective: While androgen deprivation therapy (ADT) has been associated with insulin resistance and frailty, controlled prospective studies are lacking. We aimed to examine the relationships between insulin resistance and frailty with body composition and testosterone. Design: Case-control prospective study. Methods: Sixty three men with non-metastatic prostate cancer newly commencing ADT (n = 34) and age-matched prostate cancer controls (n = 29) were recruited. The main outcomes were insulin resistance (HOMA2-IR), Fried's frailty score, body composition by dual x-ray absorptiometry and short physical performance battery (SPPB) measured at 0, 6 and 12 months. A generalised linear model determined the mean adjusted difference (95% CI) between groups. Results: Compared with controls over 12 months, men receiving ADT had reductions in mean total testosterone level (14.1-0.4 nmol/L, P < 0.001), mean adjusted gain in fat mass of 3530 g (2012, 5047), P < 0.02 and loss of lean mass of 1491 g (181, 2801), P < 0.02. Visceral fat was unchanged. HOMA2-IR in the ADT group increased 0.59 (0.24, 0.94), P = 0.02, which was most related to the increase in fat mass (P = 0.003), less to lean mass (P = 0.09) or total testosterone (P = 0.088). Frailty increased with ADT (P < 0.0001), which was related to decreased testosterone (P = 0.028), and less to fat mass (P = 0.056) or lean mass (P = 0.79). SPPB was unchanged. Conclusions: ADT is associated with increased insulin resistance and frailty within 12 months of commencement, independently of confounding effects of cancer or radiotherapy. Insulin resistance appears to be mediated by subcutaneous or peripheral sites of fat deposition. Prevention of fat gain is an important strategy to prevent adverse ADT-associated cardiometabolic risks.

Introduction Rising demand for gender‐affirming hormone therapy mandates a need for more formalised care of transgender and gender diverse (TGD) individuals in Australia. Estimates suggest that 0.1–2.0% of the population are TGD, yet medical education in transgender health is lacking. We aim to provide general practitioners, physicians and other medical professionals with specific Australian recommendations for the hormonal and related management of adult TGD individuals. Main recommendations Hormonal therapy is effective at aligning physical characteristics with gender identity and in addition to respectful care, may improve mental health symptoms. Masculinising hormone therapy options include transdermal or intramuscular testosterone at standard doses. Feminising hormone therapy options include transdermal or oral estradiol. Additional anti‐androgen therapy with cyproterone acetate or spironolactone is typically required. Treatment should be adjusted to clinical response. For biochemical monitoring, target estradiol and testosterone levels in the reference range of the affirmed gender. Monitoring is suggested for adverse effects of hormone therapy. Preferred names in use and pronouns should be used during consultations and reflected in medical records. While being TGD is not a mental health disorder, individualised mental health support to monitor mood during medical transition is recommended. Changes in management as result of this position statement Gender‐affirming hormone therapy is effective and, in the short term, relatively safe with appropriate monitoring. Further research is needed to guide clinical care and understand long term effects of hormonal therapies. We provide the first guidelines for medical practitioners to aid the provision of gender‐affirming care for Australian adult TGD individuals.