Feminizing hormone therapy using GnRH agonists as antiandrogens is not associated with adverse metabolic and bone effects in adult transgender women

Introduction Gender-affirming hormone therapy (GAHT) effectively alleviates gender dysphoria. However, its effect on metabolic and bone health is not well-established. The goal of this retrospective longitudinal study was to evaluate the effects of standardized feminizing GAHT using GnRH agonists and estrogens on metabolic and bone parameters in assigned male at birth (AMAB) individuals. Methods Clinical and biochemical data of 40 AMAB individuals were collected at baseline, 6, 12, and 24 months of GAHT. A Dual X-ray absorptiometry to assess bone mineral density (BMD) and body composition was done at 12 months on GAHT. Primary outcomes included changes in BMI and body composition indexes. Potential predictors such as age and BMI at baseline, estradiol (E2) route, delta E2 rise, as well as the obtention of plasma E2 concentrations target (> 300 pmol/L), were explored. Results Body mass index, fat mass index and visceral adipose tissue did not change ( p = 0.14; p = 0.14; p = 0.73, respectively) under GAHT. However, GAHT resulted in a reduction in lean mass indices (-0.66 kg/m2, 95% CI [-0.96, -0.36], p < 0.001) at 12 months of treatment. Further, GAHT led to a consistent increase in plasma HDL-cholesterol (0.18 mmol/L, 95% CI [0.12, 0.24], p < 0.001). At baseline, 41% of participants had low BMD (Z-score < -2.0 SD); this declined to 27% by 12 months, accompanied by an increased BMD at lumbar spine [+0.03 g/cm 2 , 95%CI (0.02, 0.05), p =<0.001]. A greater E2 rise, as well as the attainment of the target of > 300 pmol/l for plasma E2 concentrations were not significantly associated with changes in metabolic outcomes at 12 months follow-up. Conclusions Despite prior concerns, GAHT did not adversely affect surrogate markers of cardiovascular and bone health.