Reducing the Adult Height of Tall Girls with DES: Effects on Fertility

image of tall-girls
Estrogens have been used to reduce the height of unusually tall girls since the 1950s based upon the concept that, during normal puberty, increased estrogen levels lead to epiphyseal fusion in the long bones. DES treatment in adolescence seems to reduce female fertility in later life by 40%.

Abstract

Oestrogen treatment to reduce the adult height of tall girls: long-term effects on fertility, Lancet (London, England), NCBI PubMed PMID 15500896, 2004 Oct.

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.

More DES DiEthylStilbestrol Resources

Five Scary and Shocking Facts about Diethylstilbestrol

1. As early as 1939, researchers had shown that DES Diethylstilbestrol could cause cancer and changes in the reproductive tracts of mice and rats, but drug companies ignored these results ; they also tested DES on pregnant women without consent.

Image from A Healthy Baby Girl, a 1996 documentary in which filmmaker Judith Helfand chronicles the health consequences of her in utero exposure to diethylstilbestrol
DES did not lead to healthier babies, nor did it prevent miscarriages, according to research that began appearing in 1953

2. In 1953, a study of 2000 women at the University of Chicago showed that DES did not prevent miscarriage; on the contrary, it was associated with increases in premature labor and a higher rate of abortions.

3. Despite this study, the drug continued to be used.  It wasn’t until 1971 that American drug companies were legally obliged to label DES “unsuitable for pregnant women”.  The FDA did not ban the drug but issued a contraindication which means that the drug DES continued to be prescribed to pregnant women even after the link between a rare form of vaginal cancer in young women and prenatal exposure to DES was established.

4. A whole generation of new medical students and doctors don’t know about Diethylstilbestrol, yet a study published in 2011 confirmed lifetime risk of adverse health effect in DES daughters (the youngest are in their mid 30’s early 40’s).  DES is one of those cases where the patients often know more about its effects than the doctors.

5. DES is a multi-generational tragedy.  Research by the Netherlands Cancer Institute in 2002 suggests that hypospadias a misplaced opening of the penis occurred 20 times more frequently among third-generation sons.  In laboratory studies of elderly third-generation DES-exposed mice born to DES daughter mice, an increased risk of uterine cancers, benign ovarian tumors and lymphomas were found.  Third-generation male mice were shown to be at risk for certain reproductive tract tumors.

Are we going to ignore these results like we did in 1939?

Third-generation children, the offspring of DES daughters and DES sons, are just beginning to reach the age when relevant health problems can be studied.  Funding for more research is critically needed to continue to look for evidence of reproductive abnormalities and cancers among third-generation DES women and men to ensure they receive appropriate follow-up care.