Fertility and Ovarian Function in High-Dose Estrogen-Treated Tall Women

Background/Objective: High-dose estrogen treatment to reduce final height of tall girls has been shown to interfere with fertility. Ovarian function has not been studied. We therefore evaluated fertility and ovarian function in tall women who did or did not receive such treatment in adolescence. Methods: This was a retrospective cohort study of 413 tall women aged 23–48 yr, of whom 239 women had been treated. A separate group of 126 fertile, normoovulatory volunteers aged 22–47 yr served as controls. Results: Fertility was assessed in 285 tall women (157 treated, 128 untreated) who had attempted to conceive. After adjustment for age, treated women were at increased risk of experiencing subfertility [odds ratio (OR) 2.29, 95% confidence interval (CI) 1.38–3.81] and receiving infertility treatments (OR 3.44, 95% CI 1.76–6.73). Moreover, fecundity was notably affected because treated women had significantly reduced odds of achieving at least one live birth (OR 0.26, 95% CI 0.13–0.52). Remarkably, duration of treatment was correlated with time to pregnancy (r = 0.23, P = 0.008). Ovarian function was assessed in 174 tall women (119 treated, 55 untreated). Thirty-nine women (23%) exhibited a hypergonadotropic profile. After adjusting for age category, treated women had significantly higher odds of being diagnosed with imminent ovarian failure (OR 2.83, 95% CI 1.04–7.68). Serum FSH levels in these women were significantly increased, whereas antral follicle counts and serum anti-Müllerian hormone levels were decreased. Conclusion: High-dose estrogen-treated tall women are at risk of subfertility in later life. Their fecundity is significantly reduced. Treated women exhibit signs of accelerated ovarian aging with concomitant follicle pool depletion, which may be the basis of the observed subfertility.