SUN-133 Injectable Estradiol for Gender-Affirming Hormone Therapy Effectively Suppresses Testosterone Concentrations

Abstract Disclosure: A.L. Misakian: None. D. Ariel: None. E.A. Sullivan: None. G. Singh: None. D. Loeb: None. T. Strickland: None. S.J. Iwamoto: None. M.S. Rothman: None. B. Botzheim: None. J.W. Liang: None. C. Kelley: None. O.R. Hamnvik: None. Introduction: Injectable estradiol (E2) is popular among transgender and gender diverse (TGD) individuals, but little is known about its effects on testosterone (T) suppression. Specific aims: 1. Determine the effect of injectable E2 use on serum T concentration ([T]). 2. Evaluate the effect of covariates (age, E2 dose, E2 concentration ([E2]), route [IM vs SC], ester [cypionate vs valerate], timing of injection relative to lab draw, anti-androgen use, and progestogen use) on [T]. Material and methods: This cross-sectional retrospective study across 6 U.S. academic medical centers included adult TGD patients prescribed weekly injectable E2 at a stable dose for >75 d between 2019-2023, who had an available serum [T] and [E2] with confirmed timing relative to the last injection, and who had not undergone gonadectomy or GnRH agonist treatment. Those who achieved the guideline-recommended [T] goal <50 ng/dL were compared to those who did not. We modeled the relationship between [T] and [E2] by fitting a weighted linear mixed model with [T] as the outcome and the above covariates as fixed effects. Results: 359 patients were included, with a median age of 29 years (interquartile range [IQR] 25,35). Most took E2 valerate (93%) via IM route (75%). The median E2 dose was 4 mg (IQR 3,6), median [E2] 232 pg/mL (IQR 133,370), and median [T] 17 ng/dL (IQR 10,33). The 297 patients (82.7%) who achieved [T] <50 ng/dL were taking a higher median E2 dose compared to those with a [T] ≥ 50 ng/dL (5 mg/wk vs. 3 mg/wk) and had a higher [E2] (246 pg/mL vs. 169 pg/mL), both p<0.001. The proportion achieving [T] <50 ng/dL was similar (85-90%) in those with an [E2] of 100-200, >200, >250, and >300 pg/mL. There was no significant difference in [T] or the proportion achieving [T] <50 ng/dL between patients on E2 monotherapy vs. those taking E2 together with an antiandrogen and/or a progestogen. In the linear mixed model, higher [E2], fewer days since injection, and use of a progestogen was associated with lower [T], while finasteride use was associated with higher [T]. The other variables, including spironolactone use, were not associated with [T]. Conclusions: Most (>80%) patients using injectable E2 achieved guideline-recommended [T] at a median dose of 5 mg/wk with a median [E2] of 246 pg/mL. Route of administration and type of ester had no significant impact on [T]. The most commonly used antiandrogen in the U.S., spironolactone, was not associated with [T] while progestogen use (primarily micronized progesterone) was associated with a lower [T]. Our study demonstrates that injectable E2 effectively suppresses [T], even with a guideline-recommended [E2] of 100-200 pg/mL, with no significant impact of antiandrogens on [T]. We also found that progestogen use was independently associated with lower [T]. Prospective studies are needed to elucidate the optimal role of injectable E2 and progestogens on T suppression in TGD patients. Presentation: Sunday, July 13, 2025