High-dose estrogen therapy for tall stature in adolescent girls appears to reduce fertility later in life, according to a retrospective cohort study.
Estrogen has been used for years in the United States, Europe, and Australia to limit the adult height of tall girls, but little has been known about its long-term effects, said Alison Venn, Ph.D., of the Menzies Research Institute at the University of Tasmania in Australia, and associates.
Medical record reviews and interviews with women who were assessed for height from 1959 on showed that women who were treated with estrogen as growth-suppressant therapy were significantly more likely to have experienced infertility and were more than twice as likely to have ever taken fertility drugs than were women who were not treated (Lancet 2004;364:1513-8).
The number of girls treated in recent years is lower than in the 1960s to 1980s, the investigators said. However, growth-suppressant therapy is still prescribed. A survey of U.S. pediatric endocrinologists published in 2002 found that 96 (23%) of 411 respondents had treated tall girls in the preceding 5 years. Most said they had treated fewer than five girls.
The practice is based on the knowledge that in healthy pubertal development, estrogen leads to the epiphyseal fusion of the long bones. There have been no randomized controlled trials of treatment effectiveness, but height reductions of 2-10 cm have been reported, the investigators said.
Study participants were identified mainly from the medical records of Australian pediatric endocrinologists who assessed tall girls from 1959 to 1993; other participants self-referred in response to publicity about the study.
A cohort of 1,432 eligible women was identified; 1,243 were located and invited to participate. Of the women who were contacted, 780 completed interviews.
Women who had been treated (371 women, mean age of 40 years) and those who were assessed but not treated (409 women, mean age of 38 years) were similar in terms of socioeconomic status, sexual history, and other characteristics.
The type of estrogen treatment was unknown for 25 women, but in all other cases the treated women had been prescribed diethylstilbestrol (DES) or ethinyl estradiol; DES was in use before 1971.
Women treated with DES and ethinyl estradiol were similar in terms of their age at the start of treatment (approximately 13 years), the estimated mature height predicted before treatment (approximately 182 cm), and the duration of treatment (26 months for DES, 24 months for ethinyl estradiol).
Treated women were 80% more likely to have tried for at least 12 months to become pregnant without success; 36% of treated women and 19% of untreated women reported such difficulties.
Treated women were also 80% more likely to have ever seen a doctor because of trouble becoming pregnant, and they were more than twice as likely to have ever taken fertility drugs; 18% of treated women and 8% of untreated women reported taking the drugs.
An analysis of the reported time to first pregnancy showed that the treated group was 40% less likely to conceive in any given menstrual cycle of unprotected intercourse.
Investigators found the same associations when self-referred women were excluded from the analyses.