Structural and functional abnormalities in the sex organs of male offspring of mothers treated with DES

Severe pathological changes and sperm abnormalities found in many DES Sons. Santalum freycinetianum.

Abstract

Structural and functional abnormalities in the sex organs of male offspring of mothers treated with diethylstilbestrol (DES), The Journal of reproductive medicine, NCBI PubMed PMID: 772199, 1976 Apr.

The in utero effects of DES (Diethylstilbestrol) on the human male genital tract are reported in this follow-up study of male offspring of DES-treated mothers.

Both anatomical and functional abnormalities were significantly greater in the DES-exposed males as compared to control males whose mothers were all participants in a prospective, randomized double blind study of the effects of DES on pregnancy at the Chicago Lying-in Hospital during the early 1950s.

Epididymal cysts, hypotrophic testes and capsular induration of the testes were among the more common genital lesions found in 27 per cent of 134 DES-exposed males as compared to a 7 per cent incidence in 119 control males.

Spermatozoa analyses revealed severely pathologic changes (Eliasson score greater than 10) in 29 per cent of 28 DES-exposed males and 0 per cent of 18 control males (with or without genital i.e., physical abnormalities). Abnormal findings on physical examination combined with sperm abnormalities (Eliasson score greater than or equal to 5) were found in 29 per cent of DES-exposed males versus 0 per cent of 18 control males.

Cytologic examinations did not reveal malignant cells from the following materials: urines before and after prostatic massage or ejaculation, prostatic fluids and aspirates from epididymal cysts.

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Abnormal semen analyses in the DES-exposed males

oligospermia
Oligozoospermia, refers to semen with a low concentration of sperm and is a common finding in male infertility.

Abstract

DES Effect on Males, Pediatrics, January 1978, VOLUME 61 / ISSUE 1 61/1/154.3.

We have found defects in the urogenital tract of males exposed to diethylstilbestrol (DES) in utero, but the anomalies are different than those expected from the data of Henderson and co-workers. They reported an increased incidence of suspected urethral stenosis in boys exposed to DES. Their conclusion was drawn from the response of 225 DES-exposed males to a questionnaire.

We have thoroughly examined 163 DES-exposed males and found a significantly increased incidence of

  • oligospermia,
  • hypotrophic testes,
  • low ejaculate volumes,
  • epididymal cysts,
  • and microphallus.
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Spermatozoal analysis in the DES-exposed males

Abstract

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.

More DES DiEthylStilbestrol Resources

Reproductive outcomes in men with prenatal exposure to diethylstilbestrol

This 2005 study suggested that DES-exposed men are more likely than the unexposed to have an experience with infertility ; the effect/risk increasing iwith advancing age.

Abstract

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.

Click to download the full study.

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Fertility in men exposed prenatally to diethylstilbestrol

In this 1995 survey of nearly 500 exposed and unexposed men, researchers say they found no evidence that diethylstilbestrol impairs male fertility.

Abstract

Fertility in men exposed prenatally to diethylstilbestrol, The New England journal of medicine, NCBI PubMed PMID: 7723797, 1995 May 25.
Full study: The NEJM, DOI: 10.1056/NEJM199505253322104, 1995 May 25.

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.

METHODS
In 1950 through 1952, 1646 pregnant women were enrolled in a randomized, placebo-controlled clinical trial of diethylstilbestrol at Chicago Lying-in Hospital. We interviewed men who were born to the women during that study about their fertility.

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.

Click to download the full study.

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DES Sons

What is a DES Son? Who are they?

DES Sons are all the men born between 1938 and 1978 who have been exposed in utero to the anti miscarriage drug and man-made estrogen Diethylstilbestrol (or DES in short) Diethylstilbestrol DES Google+ Page icon.

They live in the U.S.A., Canada, Australia, Europe and all corners of the world where the drug was prescribed decades ago during the pregnancy of their mother (also called DES Mothers).

DES Son image
Image © courtesy of DES activist and CNN iReporter KMFDallas

Five Scary and Shocking Facts about Diethylstilbestrol

1. As early as 1939, researchers had shown that DES Diethylstilbestrol could cause cancer and changes in the reproductive tracts of mice and rats, but drug companies ignored these results ; they also tested DES on pregnant women without consent.

Image from A Healthy Baby Girl, a 1996 documentary in which filmmaker Judith Helfand chronicles the health consequences of her in utero exposure to diethylstilbestrol
DES did not lead to healthier babies, nor did it prevent miscarriages, according to research that began appearing in 1953

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.

Gender Identity and DES Exposure

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.

Gender identity and Diethylstilbestrol DES exposure image
There is a possible connection between DES exposure and gender variance

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 with Dr. 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.

Sources: DES Sons International Network, TransAdvocate.org

MORE DES DIETHYLSTILBESTROL RESOURCES

DES Sons Studies

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.

DES Sons studies on Diethylstilbestrol health issues and infertility for men image
Most DES Sons are unaware of their exposure to Diethylstilbestrol

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.

Read Diethylstilbestrol DES and fertility studies.

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.

DES Sons (Part 2) to be continued – read our next post on DES Exposure and Gender Identity.

Sources: DES Sons International Network, National Cancer Institute, CDC, DES Action USA, TransAdvocate.org

DES Sons Numbers and Health Concerns

How many DES Sons are there?

Des sons versus DES daughters image
Less research has been conducted on men’s Diethylstilbestrol exposure, yet there are as many DES sons as DES daughters…

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:

  1. Provide support for males from around the world who were exposed in utero to Diethylstilbestrol.
  2. 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!

DES Sons (Part 1) to be continued – read our next posts on the DES sons studies and Diethylstilbestrol gender identity.

Sources: DES Sons International Network, CDC, DES Action USA