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

Area of Science:

• Endocrinology
• Reproductive Health
• Transgender Healthcare

Background:

• Current guidelines recommend 2-20 mg of injectable estradiol weekly for gender-affirming hormone therapy.
• The Endocrine Society suggests a target estradiol range of 100-200 pg/mL.

Purpose of the Study:

• To evaluate if lower doses of injectable estradiol valerate (3-4 mg weekly) result in physiologic estradiol concentrations.
• To assess the impact of these doses on total testosterone levels.

Main Methods:

• Retrospective chart review of 526 adult patients receiving 3 or 4 mg of injectable estradiol valerate weekly.
• Estradiol concentrations were measured mid-way between injections, with a target range of 100-357 pg/mL.
• Data on anti-androgen use, progesterone, weight, and hormone levels were extracted.

Main Results:

• In the per-protocol analysis (n=459), 78.3% (3 mg group) and 76.0% (4 mg group) achieved estradiol levels of 100-357 pg/mL.
• 46.0% (3 mg) and 42.0% (4 mg) achieved levels within the 100-200 pg/mL range.
• Total testosterone was <50 ng/dL in 83.6% (3 mg) and 90.0% (4 mg) of patients, with lower levels when spironolactone was used.

Conclusions:

• Injectable estradiol doses at the lower end of current guidelines (3-4 mg weekly) can achieve physiologic estradiol concentrations.
• Most patients reached estradiol levels within or above the suggested 100-200 pg/mL range.
• Current guidelines for injectable estradiol valerate may need adjustment to recommend lower doses.