Fertility, ovarian function may be affected by high-dose estrogen used to stunt growth

Hendriks AE. J Clin Endocrinol Metab. 2011;doi:10.1210/jc.2010-2244.

Issue: April 2011

Tall girls who were treated with high-dose estrogen to inhibit height growth in the past appear to be at greater risk for subfertility and imminent ovarian failure, results from a Dutch study indicate.

During the 1950s, estrogen was a popular treatment for tall girls in Europe, Australia and the United States. The short-term side effects of this therapy are well-documented, but only one study has reported on long-term outcomes.

Researchers in the Netherlands sought to supplement these data by conducting a retrospective cohort study of 413 tall women (expected height of more than 184 cm) aged 23 to 48 years. Of these participants, 239 received treatment with high-dose estrogen. Information was also collected from a control group of 126 fertile, normo-ovulatory women aged 22 to 47 years.

Two hundred eighty-five women — 66% treated and 74% untreated — attempted conception. After adjustment for age, treated women were less likely to conceive than untreated women (OR=0.22; 95% CI, 0.09-0.55) and were more likely to receive fertility treatments (OR=3.44; 95% CI, 1.76-6.73). The researchers also said treated women had lower odds of achieving at least one live birth than untreated women (OR=0.26; 95% CI, 0.13-0.52), with involuntary childlessness lasting a median of 40 months.

Data linked duration of treatment with time to pregnancy (P=.008). On average, treated women with a time to pregnancy lasting more than 12 months received estrogen treatment for 3.2 months longer than women who achieved their first pregnancy before 12 months of unprotected intercourse (95% CI, 0.38-5.96), the researchers said.

Among the 119 treated and 55 untreated tall women with data on ovarian function, 23% were hypergonadotropic. The researchers found that, after adjustment for age, treated women were more likely to be diagnosed with imminent ovarian failure (OR=2.83; 95% CI, 1.04-7.68). These women also demonstrated significantly increased follicle-stimulating hormone (FSH) and luteinizing hormone levels while simultaneously having lower antimüllerian hormone and inhibin B levels. Lower antral follicle counts were also observed in this population.

“Our results indicate that treated women experience more difficulties getting pregnant compared with untreated women and more often receive infertility treatments,” the researchers wrote. “We show for the first time that abnormal serum levels of hormones related to the hypothalamus-pituitary-gonadal axis, especially FSH, may be involved in the observed subfertility.”

Disclosure: Several researchers report receiving research grants from various pharmaceutical companies. For the full list of disclosures, see the study.

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