Hypothalamic Amenorrhea and Leptin
© 2005 Prime Health Consultants, Inc.
Venn and colleagues identified from medical records 1248 Australian women who had been assessed and/or treated with estrogens (3mg DES or 150µg ethinyl estradiol daily) for tall stature during the years 1959 to 1993, to assess the effects of this treatment on long-term fertility. A group of 184 self-referrals (members of Tall Girls Inc an Australian advocacy group) were included in the study. To be included subjects had to have had a bone age determination at the time of assessment. Subjects were invited to complete a written questionnaire and computer-assisted telephone interview. The interview included questions regarding reproductive history including whether or not they had ever seen a doctor due to difficulty becoming pregnant, whether they had ever tried unsuccessfully for more than 12 months to become pregnant, and whether or not they had ever taken fertility drugs as treatment for infertility. The time to pregnancy was analyzed for each month of attempting pregnancy. Data from the medical records included age at menarche, treatment type, duration of treatment, and first and last assessment of estimated mature height by Bailey and Pinneau method.
The final sample size included 618 women (75% of the treated and 95% of the untreated). The mean age of these women was 39.8 years (treated) and 37.7 years (untreated). Both groups were similar in terms of marital status and highest level of education. Self-reported current height was greater in the treated women (179.0cm vs 176.8cm). Both groups were similar in terms of history of smoking, oral contraceptive use, age of first sexual intercourse and lifetime number of male sexual partners. There were no differences between the women treated with DES or ethinyl estradiol on any parameter. Women who had been treated with estrogen were more likely to report problems with fertility. When the data were adjusted for age, the women who had been treated were less likely to have ever been pregnant and to have ever had a live birth. Treated women were more likely to have tried unsuccessfully for 12 months to become pregnant, to have seen a doctor because of difficulty becoming pregnant, and to have taken fertility drugs. Height was not related to fertility problems and the differences between the 2 groups remained when the self-referred women were excluded from the analysis. A significant, but weak duration of treatment effect was observed.
The authors state that the data were not sufficient to establish a pathophysiological cause for the reduced fertility. They also state that the likelihood of ever becoming pregnant and having a live birth, although statistically reduced for women who had been treated for tall stature, was only slightly lower than that for untreated women and that newer treatments for infertility may reduce that difference.
Editor’s Comment: Clearly there has been a significant drop in the number of girls seeking treatment to reduce mature height potential over the past 20 years. However, the authors note that a recent survey of pediatric endocrinologists in the United States reveals that 23% have treated such girls over the past 5 years. Thus, although the absolute number of girls seeking treatment is low, such treatment is still being sought and is available. The current study, although not the first to show the possibility of adverse reproductive effects of estrogen treatment for tall stature, is perhaps the largest long-term follow-up to date. The information is interesting and important. Pediatric endocrinologists need to be able to discuss these facts with each family seeking to reduce their daughter’s mature height potential. It is reassuring that no obvious safety concerns were identified through these interviews and chart data.
William L. Clarke, MD