DES Grandchildren

Offspring of a DES Daughter or a DES Son

Legacy of DES: Navigating the Health Landscape as a DES Grandchild

Are You a DES Granddaughter or Grandson?

Updated September 2025

You may not be able to tell. Hopefully, your parents told you about DES being part of your family health history. If so, they deserve credit because it is a challenging discussion to have.

What might make you suspect a history of DES exposure? If there was any family discussion about a drug given to your grandmother while she was pregnant, or if your mom mentioned a history of difficulty getting pregnant, miscarriages, or reproductive tract cancer (all possible in DES Daughters), then you may be a DES Grandchild and should pay attention to that possibility.

Unfortunately, obtaining medical records from past years to confirm your suspicion is nearly impossible, so that avenue of confirmation may not be available to you.

What is the concern?

Mice are recognized as good predictors of the human experience related to DES exposure. Pregnant mice given DES led to health problems in their offspring similar to those seen in human DES Daughters and DES Sons. When the third generation of DES-exposed mice offspring exhibited health problems, researchers raised a warning flag.

Scientists are applying what they learned from animal studies to investigate whether a drug given to grandmothers has affected their grandchildren. As study results come in, there is growing evidence of an adverse impact on the generation of DES Grandchildren.

How that could happen is explained in an article on transgenerational epigenetics published in 2022 by researchers from the Center for Reproductive Biology. The article reviews how exposure to a toxic substance could carry its effects through genes to one, two, or more generations. An earlier article from Mother Jones magazine has a simpler explanation, addressing the DES experience in the last paragraph.

Briefly, these toxic exposures do not mutate DNA. Instead, they alter how specific genes turn themselves on and off to do the work they are programmed to do in the body. If DES exposure in a previous generation interferes with the regulation of certain genes, then health problems may develop in the offspring of subsequent generations.

Preterm Birth, Stillbirth, and Low Birth Weight

DES Grandchildren appear to have an increased risk of being born prematurely and of low birth weights compared to children whose mothers were not exposed prenatally to DES, according to a study conducted by a team of researchers at Harvard University School of Public Health, Harvard Medical School, and Columbia University. The results were published in 2021 in the International Journal of Epidemiology. The DES Grandchildren studied were three times more likely to have been born with a low birth weight than those whose mothers had not been exposed to DES in utero. DES Grandchildren were also 2.8 times more likely to be born premature. Finally, DES Daughters were almost 1.6 times more likely to have a stillbirth than their nonexposed counterparts. Even for DES grandchildren born at full term, there was a 1.6 times greater risk of having a low birth weight.

Low birth weight is important because it affects the newborn immediately and potentially for decades. In addition to the possibility of breathing issues and low oxygen right at the time of birth, other risks include nervous system problems, digestive system issues, and infection. As they grow, babies with low birth weight face increased risks for developmental and behavioral difficulties, which often lead to learning challenges in school. Health concerns seen later in life can include diabetes, hypertension, and mental health problems.

Delayed Menstrual Regularity, Skipping Periods, and Preterm Deliveries

DES Granddaughters participating in the long-running National Cancer Institute (NCI) DES Follow-up Study reported menstruation starting at about the same age as women without a history of DES exposure in their families. The study found that it took longer for DES Granddaughters to develop regular menstrual periods. However, the researchers acknowledged that the number of female participants was small and stressed that further studies are needed. Read a review of this research in the VOICE Winter 2007 newsletter.

A more recent study that appeared in Reproductive Toxicology in December 2018 reported that DES Granddaughters had a higher risk of irregular menstruation as adults and of having a preterm delivery than their unexposed counterparts. This article was reviewed in the VOICE Winter 2019.

Uterine Defects (indicated but not confirmed)

A French study on defects of the genital tract in DES Grandchildren was covered in the VOICE Winter 2020. The main finding of the study, published in the journal Therapie, was that abnormalities in the uterus were more common among DES granddaughters than in the general population.

The three defects found were doubling of the uterus, bicornuate (heart-shaped) uterus, and Mayer-Rokintansky-Küster-Hauser (MRKH) syndrome (the vagina and uterus are underdeveloped or completely absent).

It is not yet possible to say definitively that a parent’s prenatal DES exposure caused the uterine defects. Because this was a retrospective, observational study, the DES parent participants might have had other risk factors that were unknown and unknowable from the study design. It must also be noted that this is an initial study with a small number of patients, and it has not yet been replicated.

Grandson’s Higher Risk of Genital Abnormalities (indicated but not confirmed)

Boys born to DES Sons appear to have an increased risk of micropenis and undescended testicles, according to the findings from a small study in France. The study population was small, including just over 200 DES Grandsons born to fathers prenatally exposed to DES, and only six of the DES Grandson participants developed these problems.

 

The study was published in 2018 in the French journal Therapie. The 209 DES Grandsons were compared to Europe’s general population, to children born to DES Daughters, and to sons of women not prenatally exposed to DES. The researchers did not have a group of boys born to unexposed men to use as a comparison group, which was a weakness in the study.

Congenital abnormalities occurred in 3.5% of boys born to DES Sons, including three cases of cryptorchidism (undescended testes), two cases of hypospadias, and three cases of hypoplasia of the penis (micropenis). However, the authors stated the results showed no increased incidence of hypospadias in DES Grandsons.

If future studies confirm these findings, it suggests the physical effects of DES on genitourinary development may continue into the third generation, depending on the biological sex of the DES-exposed parent and the DES Grandchild. Perhaps surprisingly, the final analysis showed no increased risk of hypospadias among boys born to DES Sons over the nonexposed controls, even though an increase has been seen in sons born to DES Daughters. To see the statistical analysis and explanation of what this preliminary study means, read about it in the VOICE Spring 2018.

Research shows that undescended testicles predispose men to testicular cancer. All men should practice testicular self-exams regularly. DES Grandsons who may have been born with undescended testicles should be especially vigilant about testicular self-exams.

Hypospadias (indicated but not confirmed)

Hypospadias is a congenital condition in which the urethral opening on the penis is in the wrong place, emerging somewhere down the shaft instead of at the tip. In many cases, hypospadias can be corrected with surgery.

Several studies from France and the Netherlands identified a higher risk of hypospadias in DES Grandsons. However, a larger US study evaluating the male children of 3916 exposed women during the same time period showed no significant increase. And the previously mentioned 2018 French study looking at birth defects in the children of DES Sons found no association for DES Grandsons.

A review article on the topic was published in the journal Current Environmental Health Reports in 2021. The researchers analyzed 37 earlier studies that met their criteria for exploring how endocrine-disrupting chemicals such as DES might contribute to an increase in hypospadias. The window of exposure for defects is on or before weeks 8–16 of gestation, when male genital development occurs.

Among the pharmaceutical agents studied, sex steroids, DES, and progestin fertility treatments have all been associated with hypospadias risk, the researchers concluded. But most of the studies included small groups of participants, making it difficult to understand risks at the population level.

Thus, there is not enough evidence currently to establish a strong link between DES and hypospadias in DES Grandsons.

Birth Defects in DES Grandchildren (indicated but not confirmed)

A French study published in the journal Therapie in September 2016, led by Michel Tournaire, MD, an obstetrician-gynecologist with the Hospital of Paris and the DES France Association Network, revealed six types of birth defects that occurred more frequently among DES Grandchildren. These were listed in order of decreasing risk: esophageal defects, other digestive defects, male genital tract anomalies, cleft lip/palate, musculoskeletal anomalies, and congenital heart defects. The evidence did not show any increased risk for defects of the female genital tract in DES Granddaughters.

The researchers did find a greater likelihood of cerebral palsy among DES Grandchildren that corresponded with a higher rate of preterm birth in the DES-exposed group. Cerebral palsy is a neurological disorder resulting from injury to a child’s brain during early development.

The data analyzed in this study were collected from questionnaires given to DES Daughters throughout France, who self-reported the conditions in their children. These DES Daughters either had their mother’s medical records or consistent details about their mothers’ being prescribed DES during pregnancy. Read the article covering this study and any bias to the results in the VOICE Summer 2017.

Overall Cancer Risk

Human studies of DES Grandchildren, at this time, have found no increased overall cancer risk for DES Grandchildren.

Partial Androgen Deficiency Syndrome (a potential connection but not proven)

This rare condition is caused by a genetic mutation that prevents the body from responding to the hormones that produce male characteristics. The condition, also known as PAIS or androgen insensitivity, results in a range of effects in genetic males, depending on how much the individual’s tissues respond to androgens.

Only one study, published in 2021, has examined a potential association between PAIS and DES exposure. It documented 11 DES Grandchildren in France with PAIS, but its small scale prevented the researchers from establishing a clear relationship.

ADHD Risk (indicated but not confirmed)

A 2018 study published in JAMA Pediatrics, titled Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits, found a 7.7% increased risk of attention-deficit/hyperactivity disorder (ADHD) in DES Grandchildren, compared to 5.2% in those without a history of DES exposure. After accounting for several other factors, the study suggests that DES Grandchildren whose grandmothers were exposed in the first trimester of pregnancy have a higher risk for ADHD than the general population.

The research was observational, using data that had already been collected from the Nurses’ Health Study II for different purposes unrelated to DES. Therefore, it cannot show definitively that DES exposure is what caused ADHD in the third generation. There is a chance that other factors, including statistical oddities, might account for the observed increased risk.

The study’s findings emphasize the need for further research into ways the DES third generation might differ from the general population. As more studies identify these differences, it will become easier to identify which effects directly result from DES exposure in the parents of the third-generation offspring.

In this most recent study, the strongest finding suggesting possible causation is the increased risk among those whose mothers’ DES exposure was in the first trimester. Read about this in more detail in the VOICE Summer 2018.

TELL YOUR DOCTOR

Findings from studies involving DES Grandchildren are relatively new and ongoing as this generation ages, so many doctors may have yet to hear of them. Tell your doctor of your known or suspected DES exposure and that you would like to discuss its implications further in subsequent visits. Note your history of exposure or potential exposure on the intake form, or request that your doctor add this to your chart.

Currently, no special health screenings have been recommended for DES Grandchildren.

It is best to stay aware, not overly concerned but rather informed, as researchers continue to study the effects of DES on DES Grandchildren.

References

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