Comparison of the Subcutaneous and Intramuscular Estradiol Regimens as Part of Gender-Affirming Hormone Therapy

Objective: Gender-affirming hormone therapy guidelines describe the estradiol (E2) doses for intramuscular (IM), but not subcutaneous (SC), routes. The objective was to compare the SC and IM E2 doses and hormone levels in transgender and gender diverse individuals. Methods: This is a retrospective cohort study at a single-site tertiary care referral center. Patients were transgender and gender diverse individuals who received injectable E2 with at least 2 E2 measurements. The main outcomes were the dose and serum hormone levels between the SC and IM routes. Results: There were no statistically significant differences in age, body mass index, or antiandrogen use between patients on SC (n = 74) and those on IM (n = 56). The weekly doses of SC E2, 3.75 mg (IQR, 3-4 mg), were statistically significantly lower than those of IM E2, 4 mg (IQR, 3-5.15 mg) (P =.005); however, the E2 levels achieved were not significantly different (P =.69), and the testosterone levels were in the cisgender female range and not significantly different between routes (P =.92). Subgroup analysis demonstrated significantly higher doses in the IM group when the E2 and testosterone levels were >100 pg/mL and <50 ng/dL, respectively, with the presence of the gonads or use of antiandrogens. Multiple regression analysis demonstrated that the dose was significantly associated with the E2 levels after adjusting for injection route, body mass index, antiandrogen use, and gonadectomy status. Conclusion: Both the SC and IM E2 achieve therapeutic E2 levels without a significant difference in the dose (3.75 vs 4 mg). SC may achieve therapeutic levels at lower doses than IM.