Injectable estradiol monotherapy effectively suppresses testosterone in gender-affirming hormone therapy.

Abstract

Objectives: 1. Evaluate association between injectable estradiol and serum TT concentrations. 2. Determine additional associations between covariates (age, intramuscular vs subcutaneous administration, ester [cypionate vs valerate], injection timing relative to lab draw, antiandrogen use, progestogen use) and TT concentration.

Methods: Cross-sectional retrospective multisite study including adult TGD patients without history of gonadectomy or concurrent GnRH agonist use prescribed weekly injectable estradiol at a stable dose for >75 days between 2019-2023 with confirmed timing of estradiol and TT concentrations relative to last injection. Those who reached guideline-recommended TT suppression (<50 ng/dL) were compared to those who did not. A weighted linear mixed model evaluated relationship between TT concentration and covariates.

Results: Of the 357 patients included, median estradiol dose was 4 mg (interquartile range [IQR] 3-6), estradiol concentration 232 pg/mL (IQR 134-371), and TT concentration 17 ng/dL (IQR 10-33). There was no significant difference in TT concentration or proportion reaching TT suppression between patients using estradiol monotherapy vs estradiol with an antiandrogen(s) and/or a progestogen. In the weighted linear mixed model, higher estradiol concentration, fewer days since injection, and progestogen use was associated with lower TT concentration.

Conclusions: Injectable estradiol, even as monotherapy, was effective at TT suppression in 82.6% of patients and comparable to combination therapy with an antiandrogen(s) or progestogen. Progestogen use was independently associated with lower TT concentration while spironolactone had no significant effect.