Evaluation of 17β-Estradiol Administration by Subcutaneous Injections in Transgender Women

17β-Estradiol (E2) is increasingly administered subcutaneously (SC) to transgender women, but questions remain regarding dosing and efficacy.

The primary aims of this work were to determine if SC E2 could consistently achieve serum E2 and total testosterone (TT) levels within target therapeutic ranges and if TT and E2 levels were comparable to those achieved with standard oral therapy. The secondary aim was to determine if serum estrone (E1) and sex hormone-binding globulin (SHBG) levels were lower with SC compared to oral administration, possibly reflecting fewer first-pass hepatic effects.

This retrospective cohort study evaluated records of transgender women receiving either SC or oral E2 in the Reproductive Endocrinology and Gender Clinics at Maine Medical Center. Serum levels of E2, TT, E1, and SHBG were extracted from charts.

Demographics were similar in SC (n = 25) and oral (n = 20) groups. Serum E2 reached the target therapeutic range (75-250 pg/mL) and TT was suppressed to less than 50 ng/mL in all patients and were not statistically different between groups. In 5 patients in the SC group, E2 was measured before and after dosing, with mean values within the target range. The median (interquartile range) E1 level was higher in the oral E2 group than in the SC E2 group (907 pg/mL [737-1576 pg/mL] and 76 pg/mL [49-96 pg/mL]; P < .001). SHBG levels did not differ between groups.

SC E2 administration is effective in transgender women for achieving target serum E2 and TT levels. Both SC and orally administered E2 achieved similar E2 and TT levels, but orally administered E2 resulted in much higher E1 levels.