Lower Serum Estradiol Levels in Assigned Female at Birth Transgender People with Initiation of Testosterone Therapy: Results from the European Network for the Investigation of Gender Incongruence.

Purpose: Concerns have been raised about undesired estrogenic effects in assigned female at birth (AFAB) transgender people on testosterone therapy. How serum estradiol levels change after initiation of testosterone therapy and if these levels should be monitored remain unclear. Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence. Serum levels of sex steroids were assessed in 746 AFAB transgender people during a 3-year follow-up period, starting at the initiation of hormone treatment. Results: Estradiol levels decreased from median [P25-P75] 45.6 [24.0-102.2] pg/mL to 36.5 [25.0-46.2] pg/mL over 3 years (p < 0.001); a change was already noticeable during the first 3 months (mean -17.1 pg/mL, 95% confidence interval -23.8 to -10.6, p < 0.001). Serum estradiol levels were lower in people without endogenous estradiol production from ovarian source (contraceptive users or post hystero-oophorectomy) at baseline and after 3 months, compared with people with endogenous estradiol production. Using long-acting testosterone undecanoate injections resulted in a more prominent decrease in serum estradiol values over 12 months, compared with short-acting mixed testosterone esters (p < 0.001) or testosterone gel (p = 0.001). Changes in serum estradiol were positively correlated to changes in luteinizing hormone (ρ = 0.107, p < 0.001) and negatively correlated to changes in follicle-stimulating hormone levels (ρ = -0.167, p < 0.001) and body mass index (ρ = -0.082, p < 0.001). Conclusion: Testosterone administration in AFAB transgender people resulted in decreasing serum estradiol levels. Our results suggest that testosterone therapy leads to central suppression of estradiol production, with partial restitution due to aromatization.

Effects of Gender-Affirming Hormones on Lipid, Metabolic, and Cardiac Surrogate Blood Markers in Transgender Persons.

BACKGROUND: Gender-affirming hormonal therapy consists of testosterone in transgender men and estrogens and antiandrogens in transgender women. Research has concluded that gender-affirming therapy generally leads to high satisfaction rates, increased quality of life, and higher psychological well-being. However, given the higher incidence of cardiometabolic morbidity and mortality in cisgender men compared with cisgender women, concerns about the cardiometabolic risk of androgen therapy have been raised. CONTENT: A literature research was conducted on PubMed, Embase, and Scopus, searching for relevant articles on the effects of gender-affirming hormone therapy on cardiometabolic risk and thrombosis. After screening 734 abstracts, 77 full text articles were retained, of which 11 were review articles. SUMMARY: Studies describing a higher risk for cardiometabolic and thromboembolic morbidity and/or mortality in transgender women (but not transgender men) mainly covered data on transgender women using the now obsolete ethinyl estradiol and, therefore, are no longer valid. Currently, most of the available literature on transgender people adhering to standard treatment regimens consists of retrospective cohort studies of insufficient follow-up duration. When assessing markers of cardiometabolic disease, the available literature is inconclusive, which may be ascribed to relatively short follow-up duration and small sample size. The importance of ongoing large-scale prospective studies/registries and of optimal management of conventional risk factors cannot be overemphasized.