Context 17β-estradiol (E2) is increasingly administered subcutaneously (SC) to transgender women, but questions remain regarding dosing and efficacy. Objectives Primary aims: 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 (PO) therapy. Secondary aim: To determine if serum estrone (E1) and sex-hormone binding globulin (SHBG) levels were lower with SC compared to PO administration, possibly reflecting less first-pass hepatic effects. Methods This retrospective cohort study evaluated records of transgender women receiving either SC or PO E2 in the Reproductive Endocrinology and Gender Clinic at Maine Medical Center. Serum levels of E2, TT, E1 and SHBG were extracted from charts. Results Demographics were similar in SC (n=25) and PO (n=20) groups. Serum E2 reached the target therapeutic range (75-250 pg/mL) and TT was suppressed to <50ng/mL in all patients and were not statistically different between groups. In five patients in the SC group, E2 was measured before and after dosing, with mean values within the target range. The median [IQR] E1 level was higher in the PO E2 group than in the SC E2 group (907 [737-1576] and 76 [49-96] pg/mL, p<0.001). SHBG levels did not differ between groups. Conclusions SC E2 administration is effective in transgender women for achieving target serum E2 and TT levels. Both SC and PO E2 achieved similar E2 and TT levels, but PO E2 resulted in much higher E1 levels.
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Moreau et al. (2025) studied this question.