Females whose mothers were prescribed DES while pregnant with them.
Much of the information regarding DES Daughter medical conditions reported here comes from an article published in the New England Journal of Medicine “Adverse Health Outcomes in Women Exposed in Utero to Diethylstilbestrol,” Robert N. Hoover et al., October 6, 2011. The abstract is available online, but only NEJM subscribers have access to the full text. A review of the important NEJM article was done by Medpage Today, an online publication written for healthcare providers. DES Daughters may find it useful to print and share with their doctors.
Respected researchers with the National Cancer Institute (NCI) DES Follow-up Study developed the information in the NEJM article. They identified twelve adverse health outcomes for women exposed to DES before birth. A layman’s explanation of the research can be found in the DES Action VOICE newsletter review of the study.
An article entitled, Prenatal Diethylstilbestrol Exposure and Cancer Risk in Women by Rebecca Troisi, et al of the NCI DES Follow-up Study which appeared in Environmental and Molecular Mutagenesis in 2017 stated: “Taken together, it appears that in-utero exposure to DES is associated with increased risk of malignancy for virtually all of the female lower genital tract, with a relatively small absolute risk that nonetheless, appears to last throughout life.”
***Unless otherwise stipulated, statistics regarding risk factors listed on this page come from this NCI DES Follow-up Study peer-reviewed research.***
Clear Cell Adenocarcinoma (CCA) of the Vagina and Cervix
Various types of cancers affect the vagina and cervix, but only one specific kind is associated with prenatal DES exposure. Clear Cell Adenocarcinoma (CCA) of the vagina/cervix is a rare cancer, even for DES Daughters. The risk is estimated at about 1 in 1,000 DES Daughters.
Years ago there was a mistaken belief that DES Daughters over age 30 were out of danger. But a 2012 population-based analysis done by the Centers for Disease Control and Prevention (CDC) suggests otherwise and raises the specter that there is no upper age limit of this cancer for DES Daughters. Cases have been reported in exposed women older than age 50, so researchers are watching for a possible spike in CCA cases among post-menopausal DES Daughters.
Arthur L. Herbst, MD, Director – University of Chicago CCA Study, who first discovered the link between prenatal DES exposure and vaginal or cervical clear cell adenocarcinoma, recommends: “Even in the absence of a pap smear, the DES exposed woman should have an annual pelvic exam where her physician fully views the vagina and cervix.” Even if the pap smear isn’t done annually, the pelvic exam is the greater priority for these women. It is important that they have these exams annually. Additionally, he says, “we do not have enough data to definitively say or support that there is no upper age limit on CCA diagnoses. Since it is not known yet, this should lead to the continuation of annual exams.”
If you, or someone you know has been diagnosed with clear cell adenocarcinoma (CCA) of the vagina or cervix, you are asked to contact the University of Chicago Registry for Research on Hormonal Transplacental Carcinogenesis, the so-called DES Cancer Registry. Researchers appreciate your help in reporting as they keep track of the CCA vagina/cervix numbers in DES Daughters or suspected DES Daughters.
- DES DAUGHTER PAP/PELVIC EXAM
The screening exam for DES Daughters is similar to a routine one for unexposed women, but it’s more comprehensive. Print the directions for the DES Daughter Annual Exam to bring with you when you go for your appointment. Your health care provider can follow them and you’ll be reassured your exam is done properly. Here is a Pap screening fact sheet specifically for DES Daughters.
Of note is that after a hysterectomy DES Daughters should continue having annual Pap/pelvic exams. Even though the cervix was removed during surgery, DES Daughters remain at risk for CCA of the vagina and should be screened for it every year. DES Daughter Annual Exam directions should be shared with the doctor who will focus on checking the vagina for cancer.
Cervical cancer screening guidelines are evolving, with the latest recommendation (8/2018) from the U.S. Preventive Services Task Force (USPSTF) suggesting that many women can skip years between Pap exams. But the USPSTF explicitly states this guideline does NOT apply to DES Daughters. See Final Recommendation Statement, Cervical Cancer Screening. These recommendations also do not apply to individuals with in utero exposure to diethylstilbestrol or those who have a compromised immune system (eg, women living with HIV). DES Daughters can print the guidelines and highlight the exclusion to show their health care providers. Pointing it out should help in advocating for yearly Pap/pelvic exams.
While the need for annual Pap smears for cervical cancer screening is under discussion, the need for the yearly pelvic part of the exam is also being questioned for all women. But again, special consideration should be given to the needs of DES Daughters, and some might say the pelvic portion of the Pap/pelvic exam is the most important part of the screening for CCA of the vagina and cervix. Annual pelvic exams may be questioned for some women but not for DES Daughters.
For some DES Daughters being told a Pap smear is abnormal became a common occurrence, but by around age 40 many DES Daughters report their Pap results started coming back as normal. However, no matter what the age, there should be follow-up with a doctor after every abnormal pap.
Breast cancer has many risk factors and DES exposure is one of them. Previous studies have shown a small increase in risk among DES Daughters throughout their lifetime. However, in the latest analysis by the National Cancer Institute, there was up to a 30% increase in breast cancer risk in DES Daughters in their 40s.
To put this in context, the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program estimates the risk of breast cancer as 1.5% at age 40 to 2.4% at age 50. A 30% increased risk for the DES exposed means approximately 2% to 3.1% from 40 to 50. Much of the increase in risk appears to be caused by the effects of DES on fertility, mainly later age at first childbirth. More research is being done to study how DES Daughters metabolize estrogen and if this relates to the excess breast cancer risk as well. The excess risk appears to begin lessening after age 50 even though breast cancer risk in general – independent of DES exposure – tends to increase with age. Please see the most recent study, and login to see the report on this study in the Winter Voice 2018, #155.
- Breast Cancer Screening
DES Action encourages all DES Daughters to remind their health care providers of their increased breast cancer risk and discuss an appropriate screening protocol, which likely will include annual breast screenings and yearly clinical breast exams. DES Daughters should also pay attention to the normal appearance and feel of their breasts and report any changes to their doctors. Any woman with dense breast tissue (DES exposed or not) is higher risk for breast cancer and needs a 3D mammogram which looks through layers of breast tissue. This should be followed 6 months later by a either a breast ultrasound, or a breast MRI. If you have dense breast tissue, please discuss the appropriate screening with your doctor. (Members login to see this discussion in our video interview with Dr. Gary Levine, Radiologist and Breast Screening Specialist-Memorial Care Breast Centers, CA).
- Breast Cancer Type
There is no specific malignant tumor type of breast cancer associated with the increased risk for breast cancer among DES Daughters over the age of forty. Rather, prenatal DES exposure may increase the growth of any cells that develop into breast cancer. It is this potential for a more rapid growth rate that results in the increased risk for DES Daughters.
Once given a diagnosis of breast cancer the treatment for DES Daughters is the same as that for unexposed women.
- How DES Causes Harm
A study by Yale University researchers found that DES does not mutate a DES Daughter’s DNA sequence. Rather, prenatal DES exposure appears to alter the regulating system that influences how genes operate by turning on and off. It’s believed DES may cause changes in the operation of tumor suppressing genes that can lead to breast cancer formation.
Structural Changes of the Reproductive Tract
DES Daughters have an increased incidence of structural changes in their reproductive organs, among them a T-shaped uterus (See illustration below). The uterine lining of a T-shaped uterus appears to be the same as for an unexposed woman, so researchers suggest the fundamental difference (except for the shape) is in the underlying structure of the fibromuscle. Of note is that pregnant DES Daughters with a T-shaped uterus and those with a normally shaped uterus are both at increased risk for premature delivery. Prenatal DES exposure can adversely affect the shape and functioning of virtually the entire reproductive tract, including the vagina, cervix, uterus, fallopian tubes, and ovaries. Some DES Daughters report having an incompetent cervix, which can be the cause for some second-trimester pregnancy losses.
DES Daughters have an increased risk for infertility with studies showing DES Daughters dealing with infertility at a rate 2.4 times higher than unexposed women. Of note is that for DES Daughters exposed before 9 weeks of pregnancy, the never achieved-pregnancy rate was 30.2% compared with a rate of 20.5% among DES Daughters whose exposure occurred later than 13 weeks into gestation. This is not unexpected given that the reproductive tract develops during early stages of fetal-life. This NCI research into reasons for infertility among DES Daughters is interesting reading for those who’ve dealt with the condition and those just embarking on their family planning journey.
In general, infertility treatments for DES Daughters are the same as for other women. Working with a doctor you like and trust is important.
- Clomid and Uterine Cancer
Widely used for women undergoing infertility treatments, clomiphene citrate (also known as Clomid or Serophene), is implicated in an increased risk for uterine cancer. The study was not DES specific; however, its finding suggests all women should have a conversation with their doctors before taking it. Clomid is often prescribed early in treatment protocols, meaning many DES Daughters have been prescribed the drug through the years.
Notably, the uterine cancer risk increased with total Clomid dose and was highest among women who never became pregnant. If applicable, it may be worth having Clomid use noted on your patient history so that health care providers can be alert for the uterine cancer possibility.
DES Daughters should get early confirmation of pregnancy to be certain the fetus is not developing outside of the uterus, which could cause serious complications. Ectopic (or tubal) pregnancy rates for DES Daughters were 14.6% compared with only 2.9% in the unexposed population, as found by the NCI DES Follow-up Study.
Miscarriage, Stillbirth and Preterm Labor
Because of their increased risks for miscarriage, stillbirth and preterm labor, all DES Daughters, even if they’ve had previous normal pregnancies, should be given high-risk obstetric care starting at the earliest stage of pregnancy. Sadly, most early miscarriages are not preventable; however, careful monitoring of the cervix is warranted.
Several of the twelve adverse health impacts identified by NCI researchers involve DES Daughters having higher rates for complications during pregnancy compared with unexposed women. The NCI researchers found the incidence of preterm delivery at 53.3% in DES Daughters, as opposed to 17.8% in unexposed women. Miscarriage figures among DES Daughters compared to unexposed women are 50.3% versus 38.6%. Stillbirth numbers in DES Daughters are also higher, pegged at 8.9% compared with 2.6% in women not exposed to DES.
Understanding the cause of a threatened second trimester pregnancy loss is important. Some second-trimester losses may occur in DES-exposed women because of incompetent cervices, while others are the result of premature labor. This is an important distinction, since treatments used in these conditions are different. A cerclage (stitch) may be inserted to keep the cervix closed if an incompetent cervix is the problem. In the case of premature labor a cerclage would be of little use and after careful consideration the doctor may recommend bed rest, drugs or both to suppress labor.
DES Daughters have a 1.4 times higher risk for this pregnancy complication involving a form of high blood pressure and edema (fluid retention) than unexposed women. That translates into 26.4% of DES Daughters dealing with preeclampsia during their pregnancies compared with 13.7% of unexposed women. Another reason why pregnant DES Daughters should be carefully monitored as high-risk obstetric patients, even after a previous successful birth.
DES Daughters are at increased risk for this painful chronic disease in which endometrial tissue is found outside the uterus in the pelvic cavity. Data from the Nurses’ Health Study II shows a staggering 80% higher incidence of endometriosis in DES Daughters compared with unexposed women. The numbers were even greater among DES Daughters who reported dealing with infertility.
DES Daughters often have anatomical complications such as cervical stenosis (narrowing of the cervical canal, sometimes to the point of closure) that may increase the likelihood of retrograde menstruation. Other anatomical malformations common to DES Daughters may also increase the endometriosis risk. A review of this study, including additional information, can be read in the DES Action VOICE newsletter.
The good news is that for most women, including DES Daughters, the pain of endometriosis disappears after menopause.
These benign tumors (officially called leiomyomata) can cause pain, bleeding, infertility and pregnancy complications. They are the leading cause of hysterectomies nationwide. When responses to the Nurses’ Health Study II were analyzed, the results showed DES Daughters had a 12% increased incidence of uterine fibroids with the strongest correlation occurring in those who were exposed to DES during the first three months of gestation. An article about this study ran in the Summer 2014 DES Action VOICE newsletter.
Investigations into the possible link between DES exposure and uterine fibroids are ongoing because other studies have shown conflicting results. One done by the NCI DES Follow-up Study did not find an increased incidence of uterine fibroids, while research conducted by the National Institute of Environmental Health Sciences (NIEHS) Sister Study did show a DES link, with larger fibroids reported by DES Daughters than women who weren’t exposed. That has led to the speculation that in DES Daughters the benign tumors may have either started at an earlier age, or grown faster, or both. As with endometriosis, for many women uterine fibroids regress after menopause.
Prenatal DES exposure is associated with an increased risk for these benign gynecologic tumors, or non-cancerous fluid-filled sacs adjacent to the ovaries. Researchers with the NCI DES Follow-up Study worked with data generated in the 1990s and point out that while the risk for paraovarian cysts in DES Daughters is increased, they found no heightened risk for ovarian cysts among DES Daughters. But studies are continuing.
Paraovarian cysts are common among all women in the U.S., and treatment is generally surgery, depending on the symptoms of discomfort being experienced, whether DES-exposed or not. Details about this study were shared in the DES Action VOICE newsletter.
- Early Menopause
DES Daughters, as a group, seem to begin menopause slightly earlier than unexposed women, with the earliest being in those exposed to the highest cumulative doses of DES in the womb. However, it appears the experience of menopause for DES Daughters is no different from that of women who were not exposed to DES. A review of this study in the DES Action VOICE newsletter has a thorough explanation.
- DES Daughters and HRT
Studies have not been done specifically concerning DES exposure and the use of hormone replacement therapy (HRT). But since DES Daughters were exposed, in many cases to a high level of a synthetic hormone before birth, the precautionary principle suggests DES Daughters should avoid extra hormonal exposures. Writing in the DES Action VOICE newsletter, DES Daughter Carol O’Leary shared her tips for surviving menopause without HRT. Menopause can be debilitating for some women, whose quality of life is seriously diminished by the symptoms. In that case, if HRT is absolutely necessary, and only then, should they consider using the lowest HRT dose possible for the shortest length of time. But caution is advised. This should be discussed with a health care provider to determine the safest and best course of action.
Autoimmune Disease – No DES Link Except For Rheumatoid Arthritis
Despite animal research in the 1990s that found an association between DES and autoimmune issues, there has been no confirmation of that finding in human studies, with the exception of Rheumatoid Arthritis (RA). This is vexing because DES mouse studies are usually a good predictor of the human experience.
Researchers speculate that perhaps the human cohort (group) wasn’t large enough to tease out additional autoimmune diseases. Another theory is that those exposed to DES may develop autoimmune disorders at earlier ages than the general population, but the overall rate of autoimmune disease may be the same among the DES exposed and unexposed. Read more in an article from the DES Action VOICE newsletter.
It appears that DES exposure before birth may be linked to an increased risk for adult depression and anxiety. Results from the Nurses’ Health Study II published in the American Journal of Epidemiology in 2010 (with more than 76,000 participants) indicate a history of depression reported by 19.7% of DES Daughters compared with 15.9% of unexposed women. The study was reviewed in the DES Action VOICE newsletter.
Since that review a September 2019 study in the journal Epidemiology surveyed nearly 5,000 DES-exposed and over 2,700 unexposed participants in the NCI’s DES Combined Cohort Follow-up Study (DOI: 10.1097/EDE.0000000000001048). Among women, 26% of DES Daughters and 23% of unexposed women reported depression, and 17% of both DES Sons and unexposed men reported depression. The researchers found no statistically significant increased risk of depression in DES Children, even when limited to those taking antidepressants. They controlled for various factors, including physical health problems, but not family history of depression. However, the authors did find a weak association between DES and depression for only DES Daughters with a low exposure dose or exposure before 8 weeks gestation: They were 1.2 times more likely to have depression than unexposed women. The depression diagnoses weren’t related to whether the DES Daughters had abnormal findings in the vaginal lining or any other DES-related problems. The researchers concluded “We found a potentially slightly increased risk of depression in women who were exposed very early in gestation. Also noted was a weak link in women and men exposed to a low cumulative prenatal dose of DES, but among men this was apparent only after accounting for other factors.” Together, this research shows that a link between DES exposure and depression cannot be completely ruled out, but there isn’t enough evidence to suggest depression is any more likely in DES Daughters and Sons than in the general population.
Cardiovascular Disease, Diabetes and Osteoporosis
DES studies continue with additional medical issues now possibly linked to exposure. These conditions have been found to occur in higher rates for DES Daughters and DES Sons compared with individuals who were not exposed.
- high cholesterol
- cardiovascular disease (stroke, coronary artery disease and myocardial infarction)
Specifics on the findings developed from NCI DES Follow-up Study research are in a DES Action VOICE newsletter article.
Scientists had been seeing mounting evidence that endocrine disruptors, of which DES is one, are implicated in increased risks for cardiovascular disease. Therefore, this study’s results were not totally unexpected.
These results were reconfirmed in a study published in October 2017. No special screenings or treatments have been identified, but DES Daughters should stay aware of potential increased risks.
Endocrine disrupting compounds are being examined in gender identity studies, but so far DES research has not found a conclusive DES link. One confounding thought now under investigation regards the layering of endocrine disruptive exposures, both prenatally and perinatally. Researchers want to understand if there is an association and then whether DES exposure might itself be a cause or, perhaps combined with other exposures, be a trigger for variations.
Questions have been routinely raised in the DES community regarding the possibility that prenatal DES exposure may be linked to increased rates for homosexuality, transgender and transsexual conditions. Animal studies point in that direction yet, so far, no evidenced-based research in human populations has been able to confirm it. This article on DES and sexuality ran in the DES Action VOICE newsletter describing what researchers are seeing in human studies.
To understand the struggles faced by transgender individuals read a letter that was sent to DES Action. But note that some statements may not hold up to scientific scrutiny.
In a VOICE newsletter commentary the late DES Action USA Co-founder Pat Cody examined why it is difficult for researchers to study behavioral and sexual questions and develop definitive answers.
DES creates emotional trauma for all who come in contact with it: DES Mothers (and Fathers), DES Daughters, DES Sons, and DES Grandchildren and beyond. It is truly a family issue.
Upon first learning of exposure, some DES Daughters react with shock, disbelief, and even a sense of betrayal. It can strain the mother-daughter relationship even though both parties involved are victims.
Some DES Daughters want to brush off the known risks as “not a concern” to them, only to grow more interested when/if DES health problems develop. Meanwhile, others investigate all possible consequences as soon as they learn of their exposure. Other responses reported by DES Daughters are fear and anxiety when new health problems are identified.
Then there are anger issues. Sadly, some DES Mothers feel the brunt of that emotion from their daughters. But more commonly the anger is turned against doctors, drug companies and the world in general.
Experience shows that keeping lines of communication open can be helpful. Staying current on the latest DES findings and health screening recommendations can open discussions with family members. Taking action can reduce feelings of helplessness as well – including being vigilant in getting proper medical care. Climbing on our soapbox now – joining DES Action can be another step toward healing. Members get new information throughout the year and feel good about doing something positive by supporting an organization actively pushing for more DES research.
DES As An Endocrine Disruptor
Of note is that DES is an endocrine disrupting chemical. The DES community is described as the “poster population” for what can happen when individuals are exposed to these chemicals before birth. The DES experience triggered research into endocrine disruptors and how hormonally active substances interfere with prenatal development and can cause adverse health outcomes later in life.
Another such chemical is bisphenol A (BPA), a synthetic estrogen that has a chemical structure very similar to that of DES. Health impacts linked to BPA are remarkably familiar to those known to be associated with DES exposure but occur at much lower doses.
This is an important distinction between the two that must be taken into account: Pay attention to the exposure dose. Here’s an explanation of the similarities, and differences between the two endocrine disruptors: DES and BPA.
Also, because many of these exposures are common in our environment, rather than exposure through a drug like DES, identifying and eliminating the exposure potential can be challenging. Here’s a link with ways to reduce environmental exposures in our daily lives.