Effects of DES - DES Action Australia

The Politics of Funding

Before we look at the health outcomes of DES exposure that have emerged so far, it is necessary to spell out just how little research has been done over the years. With the exception of The Tall Girl study, no research has been carried out in Australia.

In the United States it was only after consumer advocacy groups, including the newly formed DES Action USA, put pressure of the US government that a FDA DES Task Force was established in 1978. Right from the early days, it was a fight to get any funding for DES research. The relatively limited research funds available to study the DES population were constantly under threat. By the early 1980s research funding was more or less restricted to studies of DES daughters. DES sons were ignored, as were DES mothers.

Equally depressing is the realisation of just how much of the funding for medical research and ongoing drug education is linked directly or indirectly to the pharmaceutical industry.

The Effects of DES

Latent, Invisible, Unexpected… & Deadly

In 1971 it was discovered that DES caused clear cell cancer of the vagina/cervix in DES daughters. Although rare, all DES daughters have a life time risk of the cancer and require annual screening. This involves a specific screening test, as a normal Pap smear will not detect the cancer.

This finding sent shock waves through the medical science community. Up until this time, based on the Thalidomide tragedy, it was believed that any adverse outcomes to a drug would be evident soon after the exposure, as in “birth defects”. With DES and clear cell adenocarcinoma, it was a whole new ball game with the adverse outcome being expressed decades after the exposure.

Timing rather than Dose

It was found that the timing of the DES exposure was more important than the dose.

The “dose” of DES is impossible to measure, as there was great diversity in both the strength of dose and duration. Many women were prescribed DES in large, increasing doses over the pregnancy. Others, due to nausea, only took it for two or three days. DES daughters who develop clear cell cancer cover the full gamut of exposures – from only two or three days of exposure to huge doses for the whole pregnancy. What is critical is the timing of exposure, i.e. exposure in the first trimester.

Multiple Adverse Effects

During the following years, more and more adverse health outcomes emerged, rather like a stone thrown into a pond, with the ripples slowly moving out in ever-widening circles.

Many DES daughters have tissue and structural changes to the reproductive tract because of their DES exposure. They have increased rates of a range of conditions such as dysplasia, endometriosis, ovarian cysts, and early menopause. In addition many daughters experience infertility and pregnancy complications, such as ectopic pregnancy, first and second trimester miscarriage and pregnancy loss, and premature birth.

Many DES sons also have cellular and structural abnormalities of the reproductive tract, an increased risk of reproductive tract cancers, and impaired fertility. As with DES daughters, the severity and incidence of these adverse health effects appear to be related to the timing of the initial exposure.

A 1984 medical journal article published the finding that DES mothers have an increased risk of breast cancer, and noted that they tended to develop the disease at a younger age than the non-exposed control group.

Animal Studies & Animal Modelling

Whereas human research into the effects of DES exposure was essentially “reactive” and severely restricted due to funding constraints, animal studies have allowed proactive research into DES. Using mice, researchers were able to examine more precisely the effect of timing and dose. The mouse is a valid model as the differentiation stages of the reproductive tract is similar and comparable to that of a human. By correlating both dose and time of exposure, researchers were able to replicate in mice the adverse health outcomes found in the human DES population. That is, DES daughter mice developed clear cell cancer, had structural damage to the reproductive tract, and had high rates of infertility and adverse pregnancy outcomes. Similarly, DES son mice experienced structural damage to the reproductive tract, cancer, sterility and impaired fertility.

A 1981 landmark publication, ‘Developmental Effects of DES in Pregnancy’ edited by Arthur L Herbst and Howard A. Bern, brought together leading experimental researchers and expert clinicians on DES and this close collaboration between the two disciplines has continued.

Immune System Compromised

Another benefit of animal research is that, as the mouse has a much shorter life span, researchers can “look into the future” and predict what may emerge as the DES population ages. One such study reported in Herbst & Bern showed that, in later life, the immune system of DES exposed mice was suddenly compromised.

Preliminary studies of DES daughters in the early 1980s indicated that DES exposure is linked with immune system problems, including a higher incidence of autoimmune disease, such as asthma, arthritis, diabetes, systemic lupus and thyroid dysfunction.

Taking the initiative, DES Action USA collaborated in a Health Survey of its members, surveying a wide range of health conditions. The findings indicated that the DES population has a higher than expected incidence of depression, stress-related conditions, thyroid dysfunction and metabolic disorders.

It appears that DES exposure affects not only the reproductive system but other body systems such as the immune, muscular-skeletal, and cardio-vascular systems; as well as the nervous system, including the brain.

Unfortunately at this time all medical research funding into DES was stopped.