Treatment with oestrogen to reduce the adult height of tall girls may cause fertility problems later in life

Research from Australia in this week’s issue of THE LANCET suggests that tall girls given oestrogen therapy in adolescence to reduce adult height are more likely to experience later fertility problems than the general population.

Treatment with oestrogen to reduce the adult height of tall girls has been available since the 1950s. No randomised trials have examined the effect of oestrogen therapy. Such therapy alters the development of the long bones and has been reported to reduce adult height by 2–10 cm.

In a retrospective cohort study, historical data from paediatric endocrinologists and self-referrals identified around 1400 women who were assessed for oestrogen therapy from 1959 onwards. 780 of these women completed a survey about their fertility in later life, half of whom actually received therapy (the treatment group); the other half were assessed but not given hormone treatment (the control group).

After adjustment for age, treated women were more likely to have ever tried for a year or more to become pregnant without success (80% increase compared with women in the control group), more likely to have seen a doctor because they were having difficulty becoming pregnant (80% increase), and were twice as likely to have ever taken fertility drugs compared with women not given hormone therapy. In terms of the time to first pregnancy, women who had received oestrogen therapy in adolescence were 40% less likely to conceive in any given menstrual cycle of unprotected intercourse.

Lead investigator Alison Venn (Menzies Research Institute, University of Tasmania, Australia) comments: “Although the possibility of adverse reproductive effects of oestrogen treatment for tall stature in girls has been acknowledged for many years, we believe ours is the first study to report long-term follow-up of the reproductive experiences of a large cohort of treated girls. Our findings indicate that exposure to high-dose oestrogens in adolescence is associated with impaired fertility in later life. This effect was seen as both a reduced per cycle rate of conception in those who conceived, and as an increase in the risk of experiencing infertility. The availability of infertility treatments is likely to have contributed to the finding that women who were treated for tall stature had only a small decrease in the probability of eventually conceiving and having a live birth compared with untreated women.”