Comparison of Subcutaneous Versus Intramuscular Estradiol Administration for Feminizing Gender-Affirming Hormone Therapy

This single health system, retrospective cohort study compared subcutaneous (SC) versus intramuscular (IM) estradiol administration in 70 adult patients with a diagnosis of gender incongruence or gender dysphoria seen in an LGBTQ Specialty Clinic within a safety-net institution between October 2018 and December 2024. The primary endpoint was patients who reached therapeutic estradiol levels at 6 months. Secondary endpoints included the incidence of sub- and supra-therapeutic and actual estradiol levels at months 3, 6, 9, and 12 and patients who received pharmacist-led injection technique education. At 6 months, the proportion of patients achieving therapeutic estradiol levels did not differ between IM and SC administration. In exploratory analyses of continuous estradiol concentrations, IM administration was associated with higher measured estradiol levels.