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

J Clin Endocrinol Metab. 2012 Sep;97(9):3107-14. doi: 10.1210/jc.2012-1078. Epub 2012 Jun 20.


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

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

Design/setting: We conducted a retrospective cohort study of university hospital patients.

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.

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

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Body Height
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Estrogens / pharmacology*
  • Ethinyl Estradiol / pharmacology
  • Female
  • Fertility / drug effects*
  • Humans
  • Infertility, Female / drug therapy
  • Infertility, Female / epidemiology
  • Kaplan-Meier Estimate
  • Live Birth
  • Pregnancy
  • Proportional Hazards Models
  • Young Adult


  • Estrogens
  • Ethinyl Estradiol