Efficacy and Safety of Pubertal Induction Using 17β-Estradiol in Transgirls

Puberty suppression using gonadotropin-releasing hormone agonists, followed by induction of the desired sex characteristics using sex steroids, has been recommended by the current guidelines as the treatment of choice for gender dysphoric adolescents, although little evidence is available.

To evaluate the efficacy and safety of estrogen treatment for pubertal induction in transgirls (female-identifying adolescents assigned male at birth).

Twenty-eight adolescents treated with oral estrogen for ≥1 year were included. The Tanner stage, anthropometry, laboratory parameters, bone age, and body composition were evaluated.

Breast development started within 3 months in 83% of adolescents, and after 3 years, 86% had Tanner breast stage 4 to 5. The hip circumference increased and the waist/hip ratio decreased. The median serum estradiol was 100 pmol/L (range, 24 to 380) at the standard adult dose of 2 mg of 17β-estradiol. The adult height standard deviation score was +1.9 (for females). The body mass index standard deviation score, lean body mass percentage, fat percentage, and blood pressure did not change. No abnormalities of creatinine or liver enzymes were detected, and the hematocrit and hemoglobin A1c did not change. One individual developed hyperprolactinemia during high-dose ethinylestradiol treatment to limit growth.

Pubertal induction using estradiol is effective; however, an adult dose of 2 mg does not always result in appropriate serum estradiol levels. Monitoring renal function, liver enzymes, hematocrit, and hemoglobin A1c during pubertal induction with estradiol is not necessary. Further studies are needed to establish effective and safe methods to limit growth.