Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility

Background Treatment with oestrogen to reduce the adult height of tall girls has been available since the 1950s. We undertook a retrospective cohort study to assess the long-term effects of this treatment on fertility. Methods Eligible participants were identified from the records of Australian paediatric endocrinologists who assessed tall girls from 1959 to 1993, and from self-referrals. Individuals included girls who had received oestrogen treatment (diethylstilboestrol or ethinyl oestradiol) (treated group) and those who were assessed but not treated (untreated group). Information about reproductive history was sought by telephone interview. Findings 1432 eligible individuals were identified, of whom 1243 (87%) could be traced. Of these, 780 (63%) completed interviews: 651 were identified from endocrinologists' records, 129 were self-referred. Treated (n=371) and untreated (n=409) women were similar in socioeconomic and other characteristics. After adjustment for age, treated women were more likely to have ever tried for 12 months or more to become pregnant without success (relative risk [RR] 1·80, 95% CI 1·40-2·30) ; more likely to have seen a doctor because they were having difficulty becoming pregnant (RR 1·80, 1·39-2·32); and more likely to have ever taken fertility drugs (RR 2·05, 1·39-3·04). Time to first pregnancy analysis showed that the treated group was 40% less likely to conceive in any given menstrual cycle of unprotected intercourse (age-adjusted fecundability ratio 0·59, 95% CI 0·46-0·76). These associations persisted when self-referred women were excluded. Interpretation High-dose oestrogen treatment in adolescence seems to reduce female fertility in later life. This finding has implications for current treatment practices and for our understanding of reproductive biology.