Gender-affirming hormone therapy (GAHT) guidelines describe estradiol doses for intramuscular (IM), but not subcutaneous (SC) routes. Objective was to compare SC and IM estradiol doses and hormone concentrations in transgender and gender diverse (TGD) individuals.

There was no statistical difference in age, BMI or anti-androgen use between patients on SC estradiol (n = 74) vs IM estradiol (n = 56). Median weekly doses of SC estradiol, 3.75 mg [IQR 3-4 mg] were statistically significantly lower than IM estradiol, 4 mg [IQR 3-5.15 mg] (p = 0.005), but estradiol concentrations achieved by both groups were not significantly different, (p = 0.69) and median testosterone concentrations were in the cisgender female range and were not significantly different between routes (p = 0.92). Subgroup analysis demonstrated significantly higher doses in the IM group when estradiol > 100 pg/mL, testosterone < 50 ng/dL, with gonads present, or use of anti-androgens. Multiple Regression Analysis demonstrated that estradiol dose was significantly associated with estradiol concentrations after adjusting for injection route, BMI, anti-androgen use, and gonadectomy status.