The following section provides summaries of selected DES research undertaken within the past two to three years, as printed in the DES Action Canada Newsletter.

Endometriosis in DES daughters
“In utero exposures and the incidence of endometriosis.” Stacy A. Missmer et al., Fertility and Sterility, Vol.82, No. 6, December 2004 (Supplemental notes from DES Action Voice)

This cohort study took place from 1989 to 1999 at Brigham and Women's Hospital and Harvard Medical School in Boston and involved a total of 84,446 female registered nurses—ranging in age from 25 to 42. Researchers studied the rate of endometriosis according to birth weight, premature birth, multiple gestation (twins, triplets, or more), DES exposure and having been breastfed. All cases of endometriosis were confirmed by laparoscopy. The study found that DES daughters in the study had an 80% greater risk of endometriosis compared with the women not exposed to DES. Lower birth weight (below 5.5 lbs) was inversely associated with endometriosis (i.e. as birth weight decreased, the risk of endometriosis increased); and women from multiple births had a 70% greater risk of endometriosis. Neither premature birth nor breastfeeding showed significant risk. According to the researchers: “The relation between DES exposure and endometriosis may result from a combined effect of increased retrograde menstruation, immune dysfunction, and exogenous estrogen exposure.”

“Risk of benign gynecologic tumors in relation to prenatal diethylstilbestrol exposure,” L.A. Wise et al., Obstetrics & Gynecology January 2005, Vol. 105, No. 1.
As part of the National Cancer Institute’s DES Follow-up Study, researchers at Boston University reported that in utero DES exposure is associated with paraovarian cysts (noncancerous cysts adjacent to the ovaries). Researchers studied the incidence of noncancerous ovarian cysts, paraovarian cyst and uterine leiomyomata (fibroids). The study showed a link between in utero DES exposure and paraovarian cysts but no link with ovarian cysts or uterine fibroids. These cysts may have no symptoms and may need no treatment unless they are causing problems such as pain or infertility. Researchers noted the potential bias of self reporting in the study and the “detection bias” because DES daughters are more likely to be screened for reproductive problems. “Our findings for paraovarian cysts are consistent with animal studies showing that developing reproductive organs are a potential in utero target for the long-term toxic effects of DES.”

“Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development,” D.D. Baird and R. Newbold, Reproductive Toxicology May-June 2005, Vol. 20, No. 1.
Animal studies have shown a definite association between in utero DES exposure and the development of uterine leiomyomata (noncancerous fibroids that can cause pain, bleeding, complications in pregnancy and infertility). In this study, researchers at the National Institute of Environmental Health Services of the National Institutes of Health in the U.S. investigated this potential link in the human population. The study participants were randomly selected women aged 35 to 49 separated into two sub-groups – 819 black women and 504 white women – to account for the increased risk of uterine fibroids in black women. In contrast to the study by Wise et al. in January (see above), this study found a higher incidence of uterine fibroids in DES-exposed women – for white women, 15% of unexposed and 26% of DES-exposed women developed large tumours; for black women, 32% of unexposed and 60% of DES-exposed women developed large fibroids. Of the five black women who reported prenatal DES exposure; all five (100%) developed fibroids. By randomly selecting women and using ultrasound screening for fibroids, the researchers attempted to reduce detection bias. “Our overall results showed increased risk of uterine fibroids in women prenatally exposed to DES, and DES-exposed women tended to have larger fibroids. The number of women who were certain that they were DES daughters was small, but the association with fibroids was robust... Our findings suggest that uterine fibroids should be added to the list of long-term health problems they [DES-exposed women] may experience.”

New name for ‘third generation’
With a growing body of research into the effects of DES exposure on the third generation, DES researchers and representatives in the U.S. recently agreed that a more precise term than “third generation” was necessary. To be consistent with other DES-exposed groups, the “third generation” of DES-exposed people will now be referred to as “DES grandchildren” or “DES grandsons and DES granddaughters.” The new name is also more inclusive of the potential harm caused by indirect DES exposure – for example, injuries to DES grandchildren caused by premature birth due to the DES-associated reproductive tract abnormalities of DES daughters. This is an important legal distinction for cases brought forward by DES grandchildren and their families.

Please note that the Third Generation Network has changed its name to the DES Action Generations Network in response to this recent decision (the new e-mail address is

HRT risks

Research into the risks associated with Hormone Replacement Therapy (HRT) continues to surface since the Women’s Health Initiative study was stopped in 2002 due to increased risk of invasive breast cancer. For DES-exposed women, the extra breast cancer risk associated with HRT is of particular concern. However, it was not the most common serious harm revealed by the WHI study. The study shows that HRT increases the risk of heart attacks, stroke, blood clots, breast cancer and dementia. There were some benefits: fewer cases of colorectal cancer and fewer hip fractures. The latter had not previously proven for HRT. However, even the women at highest risk for hip fractures experienced more harm than benefit. In total, over a 5-year period, an additional 1 in 100 women taking HRT were harmed. This may seem like a small additional risk, but it translates into many thousands of extra women suffering unnecessary harm among the millions of women who have taken HRT during the last 30 years.

Using HRT for disease prevention is unadvisable. Women should first seek other safer approaches to relieve menopausal symptoms. And for those who cannot find relief otherwise, HRT should still only be prescribed to women at low risk of heart disease and breast cancer. The advice that short-term use is much safer than long-term use is based only on breast cancer risks. Other harmful effects – heart disease, blood clots and stroke – can occur at any time. The bottom line is to try other approaches to deal with menopausal symptoms first and to proceed with extra caution if you have been exposed to DES.

“Tall girls” and fertility
“Estrogen treatment to reduce the adult height of tall girls: long-term effects on fertility,” A Venn et al., Lancet, October 2004, Volume 364, Issue 9444

Despite no randomized, controlled trials evaluating effectiveness, the use of estrogen as a treatment to prevent girls from growing too tall dates back to the 1950s. Until 1971, DES was one of the most common drugs used for this purpose. In this study at the University of Tasmania, researchers investigated the long-term effects of this treatment on fertility. Through medical records and self-referrals, 1432 eligible individuals were identified, all of whom had been assessed for height using hand and wrist x-rays during or prior to adolescence. Some of the women who self-referred were from the Australian advocacy group Tall Girls Inc. Of the total number of eligible individuals, 780 completed questionnaires and telephone interviews – 371 had been treated with DES or ethinyl estradiol or both and 409 had been assessed and not treated. Data from medical records were also used. Researchers found that, after adjusting for age, the treated women were more likely to have tried for 12 months or more to become pregnant without success (35.9% of treated women compared with 18.6% for untreated women); more likely to have seen a doctor because they were having difficulty becoming pregnant (34.2% treated, 17.9% untreated) and more likely to have ever taken fertility drugs (18.3% treated, 8.3% untreated). The number of eventual pregnancies and live births was similar for both groups. The authors state: “High dose estrogen in adolescence seems to reduce female fertility in later life...For women who had estrogen treatment for tall stature, it is reassuring that the likelihood of eventually conceiving and having a live birth was only slightly lower than that for untreated women, though treated women took longer to conceive and more required fertility services.”

More research needed on third generation effects.
“Ovarian carcinoma in an adolescent with transgenerational exposure to diethylstilbestrol,” J. Blatt et al., Journal of Pediatric Hemotology/Oncology, August 200, Vol 25, Issue 8

This case concerns a 15-year old girl whose mother was exposed to DES in utero. The girl was experiencing several stomach pain and, when examined, was diagnosed with small-cell ovarian carcinoma (rarely seen in adolescence). She was treated with chemotherapy but experienced a recurrence one year later at which time she was treated with surgery and radiation. The authors stated: “Several reports suggest that transgenerational exposure to diethylstilbestrol (DES) may have deleterious effects on the genitourinary tract. This case, while anecdotal, suggests that a transgenerational history of DES exposure should be noted, and that granddaughters with persistent abdominal pain even during childhood may need evaluation for genital tract abnormalities.” While this one case does not make a causal link, it does point to the need for further investigation into third generation effects of DES exposure.

Case report of CCA recurrence1
“Endobronchial clear cell adenocarcinoma occurring in a patient 15 years after treatment for DES-associated vaginal clear cell adenocarcinoma,” WB Hall et al., Gynecologic Oncology, June 2004, Vol 93, Issue 3

This report from the University of North Carolina describes the case of a DES daughter who was successfully treated for clear cell adenocarcinoma of the vagina and cervix fifteen years earlier. While, metastases in the bronchial tubes or bronchi is known to occur after removal of the primary tumour, most recurrences are within 2 to 3 years of the initial diagnosis. In this case, endobronchial (within the brochi or bronchial tubes) CCA was diagnosed 15 years after the initial CCA diagnosis associated with DES exposure. The authors state: “This case suggests that management of clear cell cancer survivors should involve long-term follow-up because of the potential for the appearance of a new focus of clear cell adenocarcinoma.”

Cerclage for preterm birth
“Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial,” V Berghella, American Journal of Obstetrics and Gynecology, October 2004, Vol. 191, No. 4

This trial compares the effectiveness of cerclage and bed rest with bed rest only in the prevention of preterm birth in women with a short cervix. Sixty-one women who were identified at high risk for preterm birth took part in the study, including one DES daughter. The women were randomly assigned either cerclage and bed rest (31 women) or bed rest only (30 women). The DES daughter was in the group that received bed rest only. Both groups received similar counselling and treatment. Preterm birth (defined as less than 35 weeks gestation) occurred in 14 women from each group and no difference was found in obstetric or neonatal outcomes. In preliminary results, the researchers conclude: “Cerclage did not prevent preterm birth in women with a short cervix. These results should be confirmed by larger trials.”

DES and sexual behaviour
“Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol,” Titus-Ernstoff et al., Epidemiology March 2003, Vol. 14, No. 2

Animal studies on DES exposure have suggested that DES may affect the part of the brain that controls sexual behaviour and right/left handedness. However, human studies looking at these same effects have been inconclusive and limited in size. In this study, researchers sent questionnaires to a large cohort of 2,600 DES sons and 5,600 DES daughters (all with documented exposure to DES), asking questions about marital status, sexual behaviour, and left or right handedness. Researchers concluded that there was a lack of evidence to prove psychosexual behaviour is affected by prenatal exposure to DES. Through self-reporting, 95% of women and men reported exclusively heterosexual partners and 1% of all respondents reported “mostly same sex.” The study also looked at incidences of mental illness (mainly depression) and both the exposed group and control group were similar. One difference the study found was that DES sons were more likely to be left handed; this was not found in DES daughters. The authors cautioned that the self-reporting format was a limitation, especially in reporting of mental illness: “Although we found no association between DES exposure and mental illness in women, the question is not easily addressed in these data because survey respondents may under-represent those affected by mental illness and may misclassify outcomes in these self-reported data.”

Herbst urges DES daughters to continue annual exams

Dr. Arthur Herbst, lead author of the 1971 study linking DES exposure to clear-cell adenocarcinoma, set up a DES registry following the discovery in the 70s. In recent years, health guidelines have suggested that women may only need pelvic examinations every 2 to 3 years if they have not had an abnormal result. And the exams are not considered necessary for women who have had hysterectomies. In 2002, Herbst reminded DES daughters that they should continue annual pelvic exams, despite these recommendations. Quoted in the The Voice (Fall 2002, #94), Herbst stated: “The oldest DES exposed patient to develop CCA had reached an age in her early 50s diagnosed, I believe, earlier this year. There are a number of CCA patients who are DES exposed and who were over age 50 years at the time of diagnosis. I believe the evidence from our Registry is quite clear and that these cancers will continue to develop, rarely, among the exposed. There clearly is no safe period. The DES exposed without CCA at a minimum need an annual pelvic examination.” DES Action/USA recommends that DES daughters keep a copy of Herbst’s statement in their medical records as a reminder to their physician.

Teleconferences on DES research

Since 2003, the CDC DES Update has sponsored a number of teleconferences on various aspects of DES research. DES experts such as Dr. Julie Palmer (lead author on the 2002 study of breast cancer risk in DES daughters) and Dr. John McLachlan (30-year veteran of research on DES as an “endocrine disrupter”) present their research findings on DES and field questions from the public. There has been a teleconference on cancer risks for DES daughters, one on the effects on DES sons and one on animal research and the implications for the future health care of those exposed. The public is welcome to register for the teleconferences and, for an excellent overview and update on current DES research, the conference transcripts are posted on the DES Update Web site at DES Action/USA’s quarterly newsletter The Voice also provides summaries of the conference discussions.

DES Sons’ International Network

Scott Kerlin, founder of the DES Sons’ International Network, recently celebrated the fifth anniversary of the online discussion group for DES sons. Since July 1999, Kerlin has been compiling research from the 500-member Network who self-reported “either confirmed or strongly suspected” prenatal exposure to DES. In October 2004, Kerlin was invited by Dr. John McLachlan, founder of the Center for Bioenvironmental Research at Tulane and Xavier Universities, to present his paper, “The Presence of Gender Dysphoria, Transsexualism, and Disorders of Sexual Differentiation in Males Prenatally Exposed to Diethylstilbestrol: Initial Evidence from a 5-Year Study” at the 6th Annual E-Hormone Conference in New Orleans. Over the five-year period, Network members reported their health concerns through the discussion group and personal interviews. The top three health concerns were: 1) hormonal/endocrine health issues; 2) gender identity and sexual health issues; and 3) mental health issues, including anxiety and depression. Other reported effects included: autoimmune disorders, infertility, reproductive tract abnormalities, ambiguous or underdeveloped genitalia, epididymal cysts and erectile dysfunction. Only a small number of members reported developing any form of cancer (primarily testicular cancer). For more information about the research or to read the paper, visit: or contact Scott Kerlin at

Breast cancer risk for DES daughters
“Risk of Breast Cancer in Women Exposed to Diethylstilbestrol in Utero: Preliminary Results,” Palmer et al., Cancer Causes Control October 2002, Vol. 13, No. 8

This follow up study at the National Cancer Institute surveyed 3,916 women exposed to DES in utero and 1,746 unexposed women to determine if DES daughters have an increased risk of breast cancer. While the authors caution that the results are preliminary, the study suggests that DES daughters over the age of 40 may be 2.5 times more likely to develop breast cancer compared with the unexposed women. The risk for DES daughters under 40 was not statistically significant. The median age of DES daughters in this study was 43 years, which the authors point out is an age when “cancer incidence is still relatively low in the general population.” It is therefore important to continue this area of investigation among the population of DES daughters as they grow older. According to the study’s lead author, Julie Palmer, almost all of the DES daughters diagnosed with breast cancer developed estrogen receptor-positive tumors. Treatment for this type of breast cancer often includes Tamoxifen but the potential effects of using this hormonal treatment for DES daughters is unknown. During a CDC teleconference in 2003, Dr Palmer spoke about an ongoing follow-up study looking at the 4 to 5 years since the last analysis: “We expect there to be an appreciable number of new breast cancer cases reported since the last questionnaire. Enough cases so that future analysis is likely to provide more definitive results...Thus we hope to have more informed results for you in the next year or two.” In the same teleconference, Dr Titus-Ernstoff stated that their research also confirmed a 30% greater risk of breast cancer in DES mothers. She stated: “In all likelihood this will prove to be the final and definitive investigation of breast cancer risk in the DES mothers.”

For further information about research on DES exposure, visit DES Action USA website at where you can also subscribe to the DES Action Voice.