Examining the Influence of the Route of Administration and Dose of Estradiol on Serum Estradiol and Testosterone Levels in Feminizing Gender-Affirming Hormone Therapy.

Introduction: Individuals may seek gender-affirming hormone therapy (GAHT) to align their physical appearance with their gender identity. Feminizing GAHT typically involves the use of estrogen. This study investigates the effect of route of administration (ROA) and dose of estradiol on estradiol (E2) and testosterone (T) levels in transfeminine individuals.

Methods: We conducted a chart review of 573 patients with an active prescription for estradiol for feminizing GAHT and serum hormone levels available. Multiple linear regression and analysis of variance were used to analyze the effect of dose and ROA of estradiol on serum E2 and T.

Results: Oral estradiol was the only ROA demonstrating a linear dose-response, with each 1 mg/d increase associated with a reduction in T of 19.03 ng/dL (P = .005). Lower T levels were seen with higher doses of transdermal estradiol but a significant dose-response was not demonstrated. Intramuscular estradiol was associated with lower T and higher E2 compared to oral and transdermal ROAs (P < .001), with many achieving target hormone levels even at low doses. Higher doses of oral estradiol were associated with lower mean serum leutenizing hormone and follicle stimulating hormone levels (P < .05).

Conclusion: Oral estradiol can be titrated to achieve a stepwise decrease in serum T. The intramuscular ROA appears to be the most potent delivery of estradiol with impact on serum hormone levels with doses on the low end of guideline-suggested ranges. Serum leutenizing hormone and follicle stimulating hormone may also help with the management of feminizing GAHT.