Background: Testosterone therapy in transgender men (TM) is aimed at achieving serum testosterone levels in the male reference range. It remains unknown if serum oestradiol levels in TM should be evaluated and/or adjusted. Although reported serum oestradiol levels in TM are variable in the current literature, these values may be affected through two possible mechanisms: serum oestradiol levels may increase through aromatization of exogenous testosterone, while the effects of exogenous testosterone on endogenous oestradiol and gonadotropins remain unknown.
Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Serum levels of sex steroids, gonadotropins and body composition were prospectively assessed in 746 TM during a three-year follow-up period, starting at the initiation of testosterone. BMI, body fat%, sex steroids, gonadotrophines were measured at each visit. Data were analyzed cross-sectionally and prospectively (Δ).
Results: Testosterone therapy resulted in a decrease in oestradiol levels over thirty-six months (−34.2, 95% CI −41.1 −27.3, P<0.001), and this was already apparent after the first three months (−17.13, 95% CI −23.82 −10.56, P<0.001). Serum LH levels did not change over the course of testosterone therapy (P=1.000), although serum FSH levels remained stable over the first nine months (P=0.997), with an increase between nine and thirty-six months (+12.1, 95% CI 4.3 19.9). Mean BMI values increased during the first year (+0.744, 95% CI 0.1 1.3, P=0.024), returning to values comparable to baseline at 18 months (P=0.880), and remaining stable thereafter (P=0.557). Mean total body fat percentage decreased over the first two years (−11.6, 95% CI −14.3 −8.8, P<0.001), remaining stable thereafter (P=0.618). Δ (serum oestradiol) was positively correlated to Δ (serum LH) (ρ=0.107, P< 0.001) and negatively to Δ (serum FSH) (ρ=−0.167, P<0.001) and Δ (BMI) (ρ=−0.082, P<0.001) over the entire follow-up period. Δ (serum oestradiol) was not correlated to Δ (serum testosterone) (P=0.973) nor to Δ (total body fat percentage) (P=0.688).
Conclusions: Testosterone administration in TM is associated with a decrease in serum oestradiol levels, already apparent at three months follow-up. The observed decrease could not be explained by changes in serum gonadotropins nor by changes in body composition. It remains to be determined to which extent the observed decrease is due to suppression of endogenous oestradiol production and/or decreased aromatase activity. As serum oestradiol levels decrease in TM, we do not suggest monitoring and/or adjusting oestradiol levels for clinical practice.
18 - 21 May 2019
European Society of Endocrinology