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


METHODS
We conducted a retrospective cohort study of university hospital patients.


METHODS
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.


RESULTS
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.
Department of Pediatrics, Division of Endocrinology, Erasmus Medical Center-Sophia, Room Sp3435, Dr. Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. a.e.j.hendriks@erasmusmc.nl
A E J
AE
Hendriks
S L S
SL
Drop
J S E
JS
Laven
A M
AM
Boot
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001827:Body Height; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D050498:Live Birth; D011247:Pregnancy; D016016:Proportional Hazards Models; D055815:Young Adult
D004967:Estrogens; D004997:Ethinyl Estradiol