Injectable Estradiol Monotherapy Effectively Suppresses Testosterone in Gender-Affirming Hormone Therapy.

OBJECTIVE: To evaluate the association between injectable estradiol and serum total testosterone (TT) concentrations and determine additional associations between covariates (age, intramuscular vs subcutaneous administration, ester [cypionate vs valerate], injection timing relative to laboratory draw, antiandrogen use, and progestogen use) and TT concentration. METHODS: Cross-sectional retrospective multisite study including adult transgender and gender-diverse patients without a history of gonadectomy or concurrent gonadotropin-releasing hormone agonist use prescribed weekly injectable estradiol at a stable dose for >75 days between 2019 and 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 with those who did not. A weighted linear mixed model evaluated relationship between TT concentration and covariates. RESULTS: Of the 357 patients included, the median estradiol dose, estradiol concentration, and TT concentration were 4 mg (interquartile range [IQR], 3-6 mg), 232 pg/mL (IQR, 134-371 pg/mL), and 17 ng/dL (IQR, 10-33 ng/dL), respectively. There was no significant difference in TT concentration or proportion reaching TT suppression between patients using estradiol monotherapy and 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 were associated with a lower TT concentration. CONCLUSION: Injectable estradiol, even as monotherapy, was effective at TT suppression in 82.6% of patients and comparable with combination therapy with an antiandrogen(s) or progestogen. Progestogen use was independently associated with a lower TT concentration, whereas spironolactone had no significant effect.

Duke Scholars

Author Carly Elizabeth Kelley Medicine, Endocrinology, Metabolism, and Nutrition