Metabolic safety of gender-affirming hormonal treatment in transgender females

Background Gender incongruence results from the mismatch between gender identity and thesex assigned at birth. The process of gender affirmation includes a series of procedures during which the transgender individual acquires phenotypic features of the desired sex. Hormonal therapy for transgender women aims to suppress endogenous androgens and replace them with estrogens. The present study sought to investigate the safety of feminizing therapy in transgender women in relation to somatometric and metabolic parameters. Methods The medical records of transgender women who received oral estradiol valerate and a gonadotropin-releasing hormone (GnRH) agonist for at least 18 months were reviewed. The study population had estradiol levels within the normal limits of the follicular phase of cisgender women of reproductive age and suppressed blood testosterone levels after 18 months of treatment. Changes in body mass index, glycemic and lipid profiles, hemoglobin and hematocrit, and liver function tests were examined. The paired t-test was used for statistical analysis. Results The mean blood estradiol and testosterone levels after approximately 18 months of treatment were 85.65 pg/mL and 24 ng/dL, respectively. There was a statistically significant increase in blood triglycerides as well as a statistically significant decrease in hemoglobin and hematocrit. However, none of the participants developed severe hypertriglyceridemia or anemia. No significant changes were found in blood cholesterol (total, high-density lipoprotein, and low-density lipoprotein cholesterol), glucose, and liver enzymes. Conclusions Treatment with oral estradiol valerate and an intramuscular GnRH agonist is used in daily clinical practice to promote feminizing physical changes in transgender women. However, the possibility of side effects is not well documented. The present study demonstrated that achieving estradiol and testosterone levels within therapeutic targets is important for the safety of gender-affirming therapy.