Pathological semen and anatomical abnormalities of the genital tract in human male subjects exposed to diethylstilbestrol in utero, The Journal of urology, NCBI PubMed PMID: 850321, 1977 Apr.
The in utero effects of diethylstilbestrol on the human male genital tract are reported in our followup study of male offspring of mothers treated with diethylstilbestrol.
Anatomical and functional abnormalities were significantly greater in male patients exposed to diethylstilbestrol compared to male controls whose mothers were all participants in a prospective, randomized double-blind study on the effects of diethylstilbestrol on pregnancy at our hospital during the early 1950s.
Epididymal cysts, hypotrophic testes and capsular induration of the testes were among the more common genital lesions found in more than 25 per cent of 159 male patients exposed to diethylstilbestrol compared to a 6.8 per cent incidence in 161 male controls.
Spermatozoal analysis revealed severe pathological changes (Eliasson score more than 10) in 32 per cent of 31 patients exposed to diethylstilbestrol and 0 per cent of 20 male controls. Abnormal findings on physical examination combined with severe sperm abnormalities (Eliasson score more than 10) were found in 23 per cent of the male patients exposed to diethylstilbestrol versus none of the male controls.
Cytologic examinations revealed no malignant cells from urine samples before and after prostatic massage or ejaculation, prostatic fluids and aspirates from epididymal cysts.
Reproductive outcomes in men with prenatal exposure to diethylstilbestrol, Fertility and sterility, NCBI PubMed PMID: 16359959, 2005 Dec. Full study: Fertility and sterility, December 2005 Volume 84, Issue 6, Pages 1649–1656, S0015-0282(05)02956-0, 2005 Dec.
OBJECTIVE To examine prenatal diethylstilbestrol (DES) exposure in relation to male reproductive outcomes.
DESIGN Prospective observational study.
SETTING Participants were identified through record review, clinical trial participation, or an obstetrics clinic.
PATIENT(S) A total of 1,085 DES-exposed and 1,047 unexposed men.
INTERVENTION(S) Participants were exposed prenatally to DES through the mother’s obstetrics care or clinical trial participation.
MAIN OUTCOME MEASURE(S) Infertility; never fathering a pregnancy or live birth; number of pregnancies or live births fathered.
RESULT(S) We found little evidence that prenatal DES exposure affects the likelihood of never fathering a pregnancy or live birth, or influences the mean number of fathered pregnancies or live births.
Our data suggest that DES-exposed men are slightly more likely to experience infertility (relative risk [RR] = 1.3, 95% confidence interval [CI] = 1.0-1.6).
The DES dose and gestational timing did not influence infertility or the number of pregnancies or live births fathered, but results were inconsistent for dose effects on the likelihood of never fathering a pregnancy or a live birth.
CONCLUSION(S) Prenatal DES exposure may be associated with a slightly increased risk of having an infertility experience, but does not increase the likelihood of never fathering a pregnancy or a live birth, or the number of pregnancies or live births fathered.
Although speculative, this data may reflect an increased effect of DES on infertility with advancing age.
BACKGROUND Prenatal exposure to diethylstilbestrol causes infertility in male mice and has been associated with malformations of the genital tract in men. However, little is known about the fertility of men who have been exposed prenatally to diethylstilbestrol.
RESULTS Four decades after their birth, we were able to trace 548 of the surviving sons (68 percent). Ninety percent consented to be interviewed (253 who had been exposed to diethylstilbestrol in utero and 241 who had not been exposed).
Congenital malformations of the genitalia were reported three times as often by the diethylstilbestrol-exposed men as by the sons of the women in the placebo group.
Within the exposed group, malformations were reported twice as often among those exposed to diethylstilbestrol before the 11th week of gestation as among those exposed later (P = 0.05).
Men with genital malformations were nonetheless as fertile as other men.
The diethylstilbestrol-exposed men (with or without genital malformations) had no impairment of fertility by any measure, including whether they had ever impregnated a women, age at the birth of their first child, average number of children, medical diagnosis of a fertility problem, or length of time to conception in the most recent pregnancy of the female partner.
Finally, diethylstilbestrol-exposed men had no impairment of sexual function, as indicated, for example, by the frequency of intercourse or reported episodes of decreased libido.
CONCLUSIONS High doses of diethylstilbestrol did not lead to impairment of fertility or sexual function in adult men who had been exposed to the drug in utero.
NB: this data focused exclusively on fertility outcomes, it does not address any of DES side-effects and/or health effects of diethylstilbestrol that might emerge at older ages.
2. In 1953, a study of 2000 women at the University of Chicago showed that DES did not prevent miscarriage; on the contrary, it was associated with increases in premature labor and a higher rate of abortions.
3. Despite this study, the drug continued to be used. It wasn’t until 1971 that American drug companies were legally obliged to label DES “unsuitable for pregnant women”. The FDA did not ban the drug but issued a contraindication which means that the drug DES continued to be prescribed to pregnant women even after the link between a rare form of vaginal cancer in young women and prenatal exposure to DES was established.
4. A whole generation of new medical students and doctors don’t know about Diethylstilbestrol, yet a study published in 2011 confirmed lifetime risk of adverse health effect in DES daughters (the youngest are in their mid 30’s early 40’s). DES is one of those cases where the patients often know more about its effects than the doctors.
5. DES is a multi-generational tragedy. Research by the Netherlands Cancer Institute in 2002 suggests that hypospadias a misplaced opening of the penis occurred 20 times more frequently among third-generation sons. In laboratory studies of elderly third-generation DES-exposed mice born to DES daughter mice, an increased risk of uterine cancers, benign ovarian tumors and lymphomas were found. Third-generation male mice were shown to be at risk for certain reproductive tract tumors.
Are we going to ignore these results like we did in 1939?
Third-generation children, the offspring of DES daughters and DES sons, are just beginning to reach the age when relevant health problems can be studied. Funding for more research is critically needed to continue to look for evidence of reproductive abnormalities and cancers among third-generation DES women and men to ensure they receive appropriate follow-up care.
Several published studies in the medical literature on psycho-neuro-endocrinology have examined the hypothesis that prenatal exposure to estrogens (including Diethylstilbestrol) may cause significant developmental impact on sexual differentiation of the brain and on subsequent behavioural and gender identity development in exposed males and females. There is significant evidence linking prenatal hormonal influences on gender identity and transsexual development.
In 1999, Dr. Scott Kerlin (founder of the DES Sons International Network) began researching the effects of Di-Ethyl Stilbestrol® on the health of genetic males who had been exposed prenatally. A substantial amount of research had been done on women who had been exposed but relatively little had been done on men and DES sons. When it became apparent that a significant portion of his research group were either transsexual, transgendered or intersexed, he began to explore the possibility of a connection between prenatal DES exposure and gender variance. Dr. Kerlin is not the first researcher to note a correlation between DES exposure and feminized behaviour in genetic males; studies go back as far as 1973. However, Dr. Kerlin has delved much deeper than those who came before.
Radio Interview: DES Exposure and Gender Variance
Listen to KWMR Radio Interview withDr. Dana Beyer on the side effects of Diethylstilbestrol and its influence on gender identity
Dr. Dana Beyer is the medical advisor and web manager of the DES Sons International Network, on the effects of endocrine disrupting compounds such as Diethylstilbestrol, DDT, phthalates and bisphenol A, on human sexuality and reproduction, as well as providing personal support and mentoring. In 2005 she presented a breakthrough paper, with her colleagues Dr. Scott Kerlin and Dr. Milton Diamond, to the International Behavioural Development Symposium, delineating the impact Di-Ethyl Stilbestrol® has had in causing intersex and gender variations in human beings.
I understand this is a sensitive and controversial matter but I feel it is important to bring this issue to light and break the wall of silence around what is still nowadays considered as “taboo”. I would like to invite all DES exposed individuals who have a knowledge of DES exposure and gender identity either through research or personal experience to share their comments and stories.
The scope of adverse effects in males exposed to diethylstilbestrol (also called DES sons) has been a lot less documented than the effects in females (read post “DES Sons Numbers and Health Concerns“). However, a number of studies have confirmed and identified that DES sons are susceptible to a wide range of medical adverse effects associated with prenatal exposure to diethylstilbestrol.
Studies on DES Sons Health Issues
The most common abnormality in DES sons is epididymal cysts. The likelihood of DES sons having epididymal cysts ranges from 21% to 30%, in comparison with 5% to 8% of unexposed men (Gill, 1988; Gill et al., 1979).The epididymis is a structure on the back of each testicle where sperm are stored. Epididymal cysts are non-cancerous growths that feel like small lumps. They may disappear and recur over time. They do not need to be treated unless they are painful. However, all lumps should be reported to a doctor and testicular self-exams should be performed on a monthly basis.
Testicular problems in some men exposed to Di-Ethyl Stilbestrol® include both small testicles and undescended testicles. Both of these abnormalities are visible at birth. Men with undescended testicles have an increased chance of developing testicular cancer, even if their mothers didn’t take Di-Ethyl Stilbestrol®. The only definitive prospective study to date of the association between in utero exposure to diethylstilbestrol and testicular cancer indicated that levels of testicular cancer were elevated, though not to a statistically significant extent, among DES-exposed men (Strohsnitter et al., 2001). The study found it unlikely that DES exposure is heavily associated with testicular cancer, but concluded that the findings did “lend support to the hypothesis that the prenatal hormonal environment may influence the development of testicular cancer in adults” and suggest follow-up study of DES men for increased risk of testicular cancer.
Some studies have also indicated that testicular varicoceles occur more often in DES sons than in other men. A varicocele is an irregularly swollen or varicose vein on the testicle. This enlarged vein produces a higher temperature than is normal for testicles, and over a period of years can lower the number of normal sperm as a result.
Studies of the psychological effects of DES exposure are limited, but evidence has been found that diethylstilbestrol is linked with increased likelihood of various psychological and neurological impairments. This includes anxiety, major depressive disorder, and other mood disorders (in DES sons and daughters).
Studies of cancer, heart disease, and autoimmune diseases among DES sons are ongoing.
Studies on DES Sons and Infertility
There has been some concerns amongst DES sons that their DES exposure might be linked to infertility. Although one study found a lower sperm count in men exposed to diethylstilbestrol compared with unexposed men (Gill, 1979), a 40-year follow-up study of DES sons found no increased risk of infertility among men exposed to DES before birth (Wilcox, 1995). The men in this study were all born between 1950 and 1953.
The health issues shared by DES sons include but are not limited to the above identified health problems. Prenatal exposure to Di-Ethyl Stilbestrol® is responsible for a wide range of not only medical but personal and social adverse effects. Further study and monitoring of these effects on men is critically needed.
If you suspect or know that you are a DES son, tell your doctor and be sure to learn about the most common symptoms associated with the conditions referenced on this page. The scope of adverse effects in DES sons is less documented than the effects in DES daughters but you are not alone and support is available through the DES Sons International Network. Consider joining the DES community on facebook and twitter.
According to DES Sons International Network, the exact statistics on the number of males exposed to Diethylstilbestrol before birth are difficult to obtain, but the most reliable estimates from within the U.S.A. place the figure at somewhere between 200,000 and 1.5 million males born between 1947 and 1971 (the years that Di-Ethyl Stilbestrol® was used to support pregnancies in the U.S.A.).
DES sons were also born in a number of other nations (Canada, Europe, and Australia) but reliable statistics on global exposure rates are unavailable.
DES Sons or the forgotten piece of the jigsaw
Despite the fact that women who have been prescribed Diethylstilbestrol during pregnancy gave birth to as many sons as daughters (1 to 3 million each, in and beyond the U.S.) far less research and advocacy on behalf of DES sons have occurred. Nearly 90% of the primary research on the human health effects of Diethylstilbestrol has been limited to DES daughters, and most of the public health research, education and advocacy has centered around concerns of DES daughters only.
Although less is known about the consequences of diethylstilbestrol exposure in men than in women, a number of studies have confirmed and identified some important health concerns. It is therefore important for men who know or suspect they are DES sons to be aware of possible problems and know what to do about them.
Health problems experienced by DES sons range from harmless irregularities to problems that may require medical treatment. Many people, including some doctors, do not know that men can be affected by DES exposure. The fact that genital anatomic abnormalities in boys exposed to Di-Ethyl Stilbestrol® in utero are not well known by gynecologists was highlighted in a recent study published in June 2011 by the National French Agency for the Safety of Health Products (AFSSAPS). It has been estimated that as many as half of all DES Sons are currently unaware of their exposure.
When DES advocate Michael Freilick said to his doctor he was a DES son, his doctor replied: “Forget it. It has nothing to do with your testicular cancer.” Sadly, Michael who was president of DES Action USA passed away in July, 2011 (his death is unrelated to DES). “As a DES Son who had surgery for testicular cancer at age 29 he learned that men, and especially young men, need to pay more attention to their health. He wanted to alert them, and spoke out where ever and whenever he could. Michael used his experiences to show how early detection prolonged his life for decades” comments DES Action USA. Always pushing for continued research for DES sons, his contribution and legacy to the DES cause and DES sons in particular are remarkable.
What to Do if You Are a DES Son?
Tell your doctor and be sure to learn about the most common symptoms associated with the conditions referenced on this page.
Don’t stay alone, join the DES Sons’ Online Discussion Network for support and information on the latest DES research findings.
The DES Sons International Network was founded in 1999 in order to accomplish two major goals:
Provide support for males from around the world who were exposed in utero to Diethylstilbestrol.
Strengthen understanding, awareness, and major research about the range of adverse health effects that DES sons have experienced as a result of their exposure.
I would like to take on the opportunity to thank all the men and DES sons who commented on my facebook page or contacted me since I launched the blog in February 2011. Please break the wall of silence around the DES issues, keep commenting and sharing your DES stories. Together we are stronger!
Diethylstilbestrol (DES) has affected and continues to affect in many different ways the health and lives of those who have been exposed to this drug more than 30, 40, 50 years ago. Cancer, infertility problems, ectopic pregnancies, premature labour, depression, genital abnormalities are just a few of the many delayed side effects of DES exposure; but what most DES victims share in common is that at some point in their lives they all had to face doctors who completely dismissed their DES concerns, doctors who disregarded their medical conditions as being a consequence of diethylstilbestrol.
Despite overwhelming medical evidence, DES continues to be dismissed by doctors
Over 10 million people have been exposed to diethylstilbestrol worldwide between 1938 and the late 70’s, early 80’s in some countries. After more than 40 years of research, there are confirmed health risks and side effects associated with DES exposure.
An entire generation of women have had great problems with infertility and pregnancy. Women and girls as young as nine years old have died from a rare form of vaginal cancer called adenocarcinoma, others have suffered from irreparable genital malformations. Many DES sons have experienced health problems including undescended testicles, epididymal cysts, and testicular cancer. Yet, many doctors dismiss a history of DES exposure as the cause of their patients’ conditions – even for those who were born in the timeframe the drug was prescribed to their mums before a health warning was issued by the U.S. Food and Drug Administration (FDA) in 1971 and even for those who have evidence that they have been exposed before birth to this carcinogen and teratogen.
When Michael Freilick founder of the National DES Sons Network said to his doctor he was a DES son, his doctor replied: “Forget it. It has nothing to do with your testicular cancer.”
When DES daughter Kathy saw her doctor to share her concerns about DES she was told that because she had been conceived a few years after doctors were supposed to stop prescribing DES, she couldn’t have been exposed. Yet her genital abnormality is only seen in DES daughters.
“I hear the struggles, the anger, the depression, the cries of “why me?” echoing from every part of the blogosphere. And these insensitive docs just blithely dismiss it as not a big problem! (…). And then, there are the stories of multiple miscarriages, stillbirths, and so on. Stuff I don’t even want to imagine, but I know is a daily reality to a lot of DES exposed women” writes Kathy in her blog “Women to women childbirth education”.
I recently gave a DES leaflet to my physician hoping it would make her more aware of DES and breast cancer risks for women of my age. She smiled when she read that DES was causing infertility problems. She commented: “Well surely you’ve not been affected by infertility problems with 3 daughters…”.
The lack of recognition of the risks and health issues associated with DES is very distressing for those who have to put up with the consequences of this drug disaster in their everyday lives. This is not only a burden for DES daughters and sons throughout their lives but it poses a health risk in itself due to the consequences of wrong diagnosis, or lack of preventive care which can sometimes lead to disastrous consequences.
Anne-Françoise Lof in her beautifully written book “Saskia or the mourning of a Distilbène baby” tells the sad story of her baby daughter born too early to survive at 22 weeks pregnancy. Anne-Françoise knew her mum had been prescribed Distilbène® during pregnancy, she warned her doctor. Yet, the high risk of premature labor was dismissed. The story of not only Saskia but many other premature babies shows the tragic consequences of some doctors’ misinformation and dismissive attitude towards diethylstilbestrol.
Before the FDA issued a warning that DES was not safe for mums and their unborn babies, many doctors happily prescribed a drug that had not been properly tested and some even continued to prescribe it long after the warning was issued. Others questionned its efficiency and raised their concerns about the possible side effects. Years later, now that many health problems have ruined and continue to ruin the lives of DES exposed individuals very few aware doctors acknowledge the link between diethylstilbestrol exposure and their patients’ conditions.
Many young doctors don’t even know about DES and its consequences. To them it’s something of the past that their predecessors have prescribed in the belief that it would prevent miscarriage, especially if the women had a previous history of miscarriage, bleeding during pregnancy or diabetes. Most DES daughters and sons know more about diethylstilbestrol than their doctors and end up in an awkward situation where they have to educate their doctors in order to get appropriate treatment and preventive care.
DES Aware Doctors List
Most DES Action Groups have compiled a list of doctors aware of the DES history and its devastating consequences. Back in 2001, when I asked DES Action UK if they could provide me with their doctors list they provided me with a list of only four aware doctors, all London based, yet it is estimated that more than 300,000 people have been exposed to diethylstilboestrol in the UK. In the U.S. the doctors list is a compilation of the names of aware doctors given to DES Action USA by its members who were satisfied with their care. These recommended doctors are not considered DES experts, but rather aware doctors who do not dismiss DES concerns. I have no doubt that if DES Action Groups were naming and shaming the doctors who dismiss the DES concerns of their patients the list would be a lot longer.
My DES pregnancy had an happy ending thanks to a fantastic, sensitive and well informed doctor / professor. Without him I wouldn’t be celebrating mother’s day today. So there are aware doctors out there who know how to help DES victims. If you know a sensitive doctor that you would recommend please contact your local DES Action Group and share his / her contact details. It may help others.
If only doctors could understand, be more informed, aware and sensitive to what diethylstilbestrol has done to people’s lives. Di-ethyl stilbestrol is not something of the past. It hasn’t gone away. Years after exposure, the consequences and health risks for DES daughters, sons and their children are still there. The delayed consequences of the drug are felt and will most likely continue to be felt for many years to come as reveal new research carried out to determine the impact on the third generation. DES daughters and sons want answers and recognition. We need, we demand sensitive, aware doctors who acknowledge the danger and continued risks of DES exposure. Is it too much asking? The FDA waited 40 years to acknowledge the DES tragedy. How much longer doctors will need to stop dismissing their patients’ DES concerns?
Sources: Women to women childbirth education, DES Gone but not Forgotten.
Diethylstilbestrol (Distilbène), the synthetic sex hormone prescribed in France up to 1977 (and in many other countries under different names) to pregnant women to prevent miscarriage and premature labour, has caused genital abnormalities, infertility problems, and cancer in children exposed in utero to the drug. A new report reveals that DES may have done even more damage, often associated in cocktail with other estrogens as 17-alpha Ethinyl oestradiol (synthetic EE) or with synthetic Progestin.
A disturbing study conducted since 2004 by Marie-Odile Soyer-Gobillard, former director emeritus at the CNRS (French National Center for Scientific Research) reveals a link between DES and mental illness issues. In January 2011, and next in October 2011, 6 members of the association Hhorages (Halt to Synthetic Hormones for Pregnancies), of which Marie-Odile is the president, were received by the AFFSSAPS (the equivalent of the Food and Drug Administration in the U.S. now named AFSM, French Agency for Medicament Security) to discuss her findings. A working group composed of experts from the agency and the association will now be formed in April.
DES Psychological Side Effects New French Stats
So what does the French study (published in the International Journal “Medicine and Longevity*) reveal? Marie-Odile sent questionnaires to 529 DES mothers and studied a group of 1180 children of which 740 have been exposed to DES in-utero. Of this group, 15 were still born and 684 suffer from psychiatric disorders and / or physical malformations while 41 were not ill. Amongst the studied population, the psychiatric illnesses are essentially depression, anorexia, schizophrenia, …). Today, Hhorages tots up 1223 testimonies representing 1223 mothers with a total amount of 2674 children. Amongst them, 1676 were in utero exposed to synthetic hormones, 1549 exposed children are ill: amongst them: 916 present psychic diseases « only », 448 present somatic and psychic diseases , 183 present somatic diseases « only »; 126 exposed are not ill. Amongst the observed siblings in the same family, only those who have not been exposed to DES in-utero, don’t show signs of psychiatric disorders …. Could this be just a coincidence?
Another shocking statistic: of all the cases reported since 2004, when the study started, Marie-Odile identified 150 suicide attempts series and 48 suicides. In some families, 2 or 3 children have ended their lives leaving their parents with a profound sense of guilt. Amongst the observed siblings in the same family, only those who have not been exposed to DES in-utero, don’t show signs of psychiatric disorders… Could this be just a coincidence?
Herself DES mother, Marie-Odile Soyer-Gobillard has been fighting since 1998 for the recognition of the link between synthetic sex hormones taken during her pregnancy including Distilbène®, and the psychological disorders of her own children, Nicolas and Valerie, who both committed suicide three years apart in 1995 and 1998 at age 28 and 27. She founded the association Hhorages with 3 other mothers in 2000 to raise awareness of the risks synthetic sex hormones prescribed during pregnancy pose on children born from these pregnancies.
According to Fran Howell (Executive Director DES Action USA), American researchers have been having trouble finding a solid link between DES and mental illness issues, except depression. But through the years DES Action USA have heard many reports of DES-exposed individuals suffering with psychological issues.
Pat Cody, co-founder of DES Action USA, wrote in the spring 2005 issue of VOICE (DES Action Newsletter) about why it is difficult for researchers to study these questions and develop definitive answers: “Here, some of the difficulties in getting a valid study are caused by a wide spread in the DES dosages mothers got, in the time in pregnancy when they got it, and for how long they took it (…). Sex hormones are, however, known to have effects on the organization of the brain in experimental animals with consequential behavioural effect”.
A 2005 study carried out by Professor Caston, a neurologist at the University of Rouen (France), has demonstrated that rats born to mothers treated with synthetic sex hormones developed anxiety and depressive behaviour. “These results could be explained by the effect of the molecule on the part of the brain involved in emotional processes, which is under development in foetuses”, the report says.
Could all the known DES side effects which have destroyed the lives of many DES mothers, daughters, and sons, just be the top of the iceberg? Already concerns for the grandchildren of DES mothers arise with a higher risk of hypospadias (misplaced opening of the penis) in sons of DES daughters. If more DES side effects are scientifically validated, DES could well be a real time bomb!
I welcome Marie-Odile’s research study and thank her and Hhorages for their combat and work on behalf of all the DES victims who suffer from the mental side effects of this drug.
More research is critically needed not only to provide DES-exposed individuals with appropriate care and support but for the next generation and all the people who may continue to suffer from the physical or mental consequences of this drug in the future. Please support Hhorages and your local DES Action group, and stay tune for more revelations about DES exposure and its devastating side effects.
DES Action USA Voice newsletter spring 2005
DES Action USA
*Soyer-Gobillard, M.O. 2011. Endocrine disrupters and effects on behavioral disorders: No, we have not as yet learnt all our lessons concerning the DES story. Médecine et Longévité, (Elsevier Masson), 3, 67-74. ** Nicolas Kalfa, M.D., Ph.D,.Francoise Paris, M.D., Marie-Odile Soyer-Gobillard, Ph.D., Jean-Pierre Daures, M.D., Ph.D. and Charles Sultan, M.D., Ph.D. Prevalence of hypospadias in grandsons of women exposed to diethylstilbestrol during pregnancy: a multigenerational national cohort study. Fertil Steril, 2011, 95, 2574-2577(published by American Society for Reproductive Medicine).