Fertility of tall girls treated with high-dose estrogen, a dose-response relationship

High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life.

The aim was to study the effect of estrogen dose on fertility outcome of these women.

We conducted a retrospective cohort study of university hospital patients.

We studied 125 tall women aged 20-42 yr, of whom 52 women had been treated with 100 μg and 43 with 200 μg of ethinyl estradiol (EE) in adolescence.

Time to first pregnancy, treatment for infertility, and live birth rate were measured.

The time to first pregnancy was increased in treated women. Of untreated women, 80% conceived within 1 yr vs. 69% of women treated with 100 μg EE and 59% of women treated with 200 μg EE. This trend of increased time to pregnancy with increasing estrogen dose was significant (log rank trend test, P = 0.01). Compared with untreated women, fecundability was reduced in women treated with both 100 μg EE [hazard ratio = 0.42; 95% confidence interval (CI), 0.19-0.95] and 200 μg EE (hazard ratio = 0.30; 95% CI, 0.13-0.72). We also observed a significant trend in the incidence of treatment for infertility with increased estrogen dose (P = 0.04). Fecundity was affected in women treated with 200 μg EE who had reduced odds of achieving at least one live birth (odds ratio = 0.13; 95% CI, 0.02-0.81), but not in women treated with 100 μg EE.

We report a dose-response relationship between fertility in later life and estrogen dose used for the treatment of tall stature in adolescent girls; a higher estrogen dose is associated with increased infertility.