Examining the influence of the route of administration and dose of estradiol on serum estradiol and testosterone levels in feminizing gender-affirming hormone therapy

Daniel J Slack; Anaïs Di Via Ioschpe; Michael Saturno; Sky Kihuwa-Mani; Uchechukwu O Amakiri; Daniel Guerra; Subha Karim; Joshua D Safer

doi:10.1016/j.eprac.2024.10.002

Examining the influence of the route of administration and dose of estradiol on serum estradiol and testosterone levels in feminizing gender-affirming hormone therapy

Endocr Pract. 2024 Oct 12:S1530-891X(24)00793-6. doi: 10.1016/j.eprac.2024.10.002. Online ahead of print.

Authors

Daniel J Slack¹, Anaïs Di Via Ioschpe², Michael Saturno², Sky Kihuwa-Mani², Uchechukwu O Amakiri², Daniel Guerra², Subha Karim³, Joshua D Safer⁴

Affiliations

¹ Division of Endocrinology, Department of Medicine, Icahn School of Medicine at Mount Sinai. Electronic address: [email protected].
² Icahn School of Medicine at Mount Sinai.
³ Center for Transgender Medicine and Surgery, Mount Sinai Health System.
⁴ Division of Endocrinology, Department of Medicine, Icahn School of Medicine at Mount Sinai; Center for Transgender Medicine and Surgery, Mount Sinai Health System.

PMID: 39401697
DOI: 10.1016/j.eprac.2024.10.002

Abstract

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 ANOVA 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/day increase associated with a reduction in T of 19.03 ng/dL (p=0.005). 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<0.001), with many achieving target hormone levels even at low doses. With higher oral estradiol doses, ANOVA detected dose dependent decreases in mean serum LH and FSH (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 T may be a more reliable biomarker than E2 for managing feminizing GAHT. Serum LH and FSH may also help with the management of feminizing GAHT.