Aim: The changes in serum oestradiol levels in assigned female at birth (AFAB) transgender people receiving testosterone therapy have not been elucidated. How serum oestradiol levels change after initiation of testosterone therapy, if these levels should be monitored and whether altered oestradiol levels will result in adverse health outcomes, remains unclear.
Methods: This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Serum levels of sex steroids and body composition were prospectively and cross-sectionally assessed in 746 AFAB transgender people during a three-year follow-up period, starting at the initiation of hormone treatment.
Results: Oestradiol levels decreased from 45.49 [24.00102.15] pg/mL (baseline, median [percentile 25percentile 75]) to 36.5 [25.046.2] pg/mL over three years (P<0.001), a change was already noticeable during the first three months (mean 17.13 pg/ml, 95% CI −23.82 −10.56, P<0.001). Serum oestradiol levels were lower in people without endogenous oestradiol production (contraceptive users or people who underwent gonadectomy) at baseline and after three months, compared to people with endogenous oestradiol production (contraceptives: P<0.001, gonadectomy: P=0.007). The use of long acting testosterone undecanoate injections resulted in a more prominent decrease in serum oestradiol values over twelve months, compared to short acting mixed testosterone esters injections (P<0.001) or testosterone gel (P=0.001). Changes in serum oestradiol were positively correlated to changes in LH (ρ=0.107, P<0.001) and negatively correlated to changes in FSH levels (ρ=−0.167, P<0.001) and BMI (ρ= −0.082, P<0.001).
Conclusion: Testosterone administration in AFAB transgender people results in decreasing serum oestradiol levels. Although an underlying mechanism is difficult to fathom, our results suggest that testosterone administration may suppress endogenous oestradiol production. However, serum oestradiol levels in AFAB people receiving testosterone therapy remain higher than levels observed in males, which may be attributed to aromatization of exogenous testosterone.