Revisiting Injectable Estradiol Valerate Dosing for Gender-Affirming Hormone Therapy: A Retrospective Cohort Review

Current guidelines for estrogen-based gender-affirming hormone therapy regimens suggest 2-20 mg injectable estradiol weekly. We hypothesized that using doses on the lower end of current guidelines would result in physiologic estradiol concentrations.

We performed a retrospective chart review of adults prescribed 3 or 4 mg of injectable estradiol valerate weekly through a statewide clinic network, whose protocol deemed estradiol concentrations of 100-357 pg/mL mid-way between injections acceptable-with the cap based on the lab's reference range for estradiol. We extracted data on route of injection, antiandrogen, and progesterone prescriptions, weight, and serum estradiol and total testosterone concentrations.

We analyzed 526 patients who met inclusion criteria. In the per protocol analysis (n = 459), which excluded 67 patients with identified lab timing, dosing, or other errors, 78.3% of those taking 3 mg of injectable estradiol valerate weekly and 76.0% of those taking 4 mg had serum estradiol concentrations 100-357 pg/mL, while 46.0% and 42.0% respectively had concentrations in the 100-200 pg/mL range. Total testosterone values were <50 ng/dL among 83.6% of patients prescribed 3 mg and 90.0% of patients prescribed 4 mg, with lower testosterone levels among those taking spironolactone.

Despite using injectable estradiol doses on the lower end of the current guidelines, most estradiol concentrations outside the range suggested by the Endocrine Society (100-200 pg/mL) were above the suggested range. The majority of patients obtained physiologic estradiol concentrations, as approximated by lab reference ranges. Guidelines for physiologic estradiol concentrations should recommend lower doses for injectable estradiol valerate.