NZ women may face similar issues to USA court case

About 600 New Zealand women — and potentially as many as 1000 to 2000 — prescribed a synthetic estrogen decades ago, may have daughters facing the same issues as 53 American women who have gone to court in Boston to sue drug companies who made and promoted the drug.

Professor Charlotte Paul

A study in the New England Journal of Medicine last year indicated an increased risk of 12 medical conditions for  women who were exposed in the womb to diethylstilbestrol (DES). In many cases it was was prescribed in the mistaken belief it could reduce pregnancy complications.

Researchers at the National Cancer Institute (US) and other medical centers followed 4600 women who were exposed to DES before it was discontinued in 1971 found that these “exposed” daughters were twice as likely to be infertile and at five times the risk as of having a preterm delivery, compared with women not exposed in the womb. The daughters also had 40 times the risk of developing a rare cancer of the vagina among young women, called clear cell adenocarcinoma (CCA), and nearly double the risk of breast cancer, the researchers said. DES was known as Stilboestrol when it was given to NZ women.

The USA court case,  in Boston is believed to be the first major litigation alleging a link between DES and breast cancer in “DES daughters” over the age of 40, and the  women’s lawyers say their case is supported by last year’s study  that suggests that breast cancer risk is nearly doubled in DES daughters over this  age.

In New Zealand, Professor Charlotte Paul wrote a paper in 2006 which said  that the longterm adverse effects of Stilboestrol prescribed for pregnant women in New Zealand  were still being clarified. She  said DES was used as a post-coital contraceptive in NZ and was given to women to suppress lactation. It was prescribed to some pregnant women in the 1960s, though the main use was in the 1940s and 1950s.  She was not aware of anyone prescribed it during pregnancy after 1971.

Professor Paul,  Professor of Preventive and Social Medicine, at Otago University — a member of National Ethics Advisory Committee (NEAC)  from 2002 to 2008 and was a medical advisor to the Cartwright Inquiry —   responded to questions from the SMC as the Boston case got underway:

What estimate would you make for the numbers of women in NZ who were exposed (directly or in the womb), and what proportion of those likely suffered from health effects linked to the exposure?  

“We estimated 600 exposed women in 1984 and considered that a major underestimate. It may be 1000 to 2000. It is a guess now. The mothers have an increased risk of breast cancer, the daughters of CCA and breast cancer, and very commonly structural abnormalities of the reproductive tract and hence difficulty with childbearing. The sons have some reproductive tract abnormalities”.

Why do you think there has never been a systematic attempt to identify exposed women in New Zealand?

“The first work my colleagues and I did was in 1983 when we approached obstetricians and gynaecologists to ask about their use of DES in New Zealand. The results were published as a letter to the NZMJ in 1984 (interesting a longer paper reporting the results was rejected by three medical journals). And we got the sense that publicity for this episode was not actively sought (indeed the opposite) by doctors.  I approached the Department of Health about publicising the issue for women after the study was done. The Department did a small survey of general practitioners to gauge GP prescribing and mentioned DES in a clinical services letter in 1989. I persuaded them to fund a pamphlet on DES for exposed mothers, daughters and sons which was published in 1994 and sent to all general practitioners. Following the release of that pamphlet there was a TV programme about DES and subsequently I received many letters from women. For most of them, when they enquired about their records, they were unavailable.
“I remember discussion about a register in the 1980s but the Department of Health were not keen and most of the records were already unavailable.  The current regulations require health records to be held for only 10 years after the last consultation. These regulations date from 1996 and submissions recommending a longer time were unsuccessful. I think some DHBs do keep mother/infant records for longer”.

To what extent has the fact that women who were not exposed to DES had a second peak in the incidence of CCA around age 70 been reflected in the exposed population?

“There has been no information published yet to definitely suggest a second peak [in exposed women]. The Herbst Registry in Chicago stated in 2007:  ‘The Registry, as of December 2007, has accessioned approximately 760 cases of clear cell adenocarcinoma (CCA)….  The initial age-incidence curve showed a peak between ages 15-25 years among the DES-exposed.  Currently cases up to age 55 have been accessioned and there is a suggestion of a possible increase in frequency among DES-exposed beginning to appear in those over 40 years of age’.”

What is the current understanding of the cumulative excess risk for CCA in women exposed to DES while in the womb?

“The cumulative excess risk for CCA would be the same as the cumulative risk of CCA, as the cancer is so rare (30 to 40 times less) in unexposed (women). The cumulative risk is in the order of 1 in 1000 to age 40 years”

What are the implications for sons exposed to DES in the womb?

“Some studies have suggested an increased risk of testicular cancer in sons, but this is not confirmed. The latest study to assess risk of testicular cancer  in a combined cohort analysis of four cohorts of men was published in 2001. The authors found an elevation in risk of testicular cancer, relative risk for exposed versus unexposed men was 3.05 but the 95% confidence interval included 1.0 (0.65 – 22.0), so this could have been a chance finding. Indeed there were only 6 cases in the exposed group and 2 in the unexposed. The combined cohort is too small for robust assessment of risk.

Your 2006 paper mentioned grandchildren of DES-exposed women may also have a potential for DES-linked cancers: has there been any indication of possible health effects on  DES granddaughters?

“The concern about grandchildren is based on animal models.  It is suggested to be an epigenetic effect. A recent study of birth defects in the third generation did find an excess overall among daughters and a significant increase in heart defects. As these were self reported (by parents) reporting bias was considered a possibility”.