DES Archives - Hormones Matter

Maternal DES Exposure and Intersex Development in Males

Published on October 8, 2024

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In my ongoing research into connections between maternal DES exposure and male sexual development, I recently obtained a copy of the 1953 Physician’s Desk Reference (PDR), a compendium of pharmaceutical products listed together with their manufacturer’s recommended usage.

“Physician’s Desk Reference is published annually by Medical Economics, Inc., through the courtesy of the manufacturers whose major products are described in section 4. It is distributed to over 130,000 active practicing physicians and the pharmacies and libraries of over 4,000 hospitals throughout the United States and its possessions.”

On page 464 is pharmaceutical giant Eli Lilly’s entry for DES, which I’ve scanned and inserted below. Several other manufacturers have their own branded version of DES (for instance, Boyle & Co’s “Hi-Bestrol” DES in 25mg uncoated tablets, for threatened and habitual abortion, supplied in bottles of 100 and 1,000). However, I will concentrate on Lilly’s entry, since they were the major manufacturer and distributor of the drug, and have provided a lot more detailed directions for prescribing the drug than the other manufacturers.

Uses and Dosing for DES According to its Manufacturer

DES Dosing 1953 — Figure 1. DES dosing from 1953 Physician’s Desk Reference.

Lilly specifies a variety of uses for DES: Menopause, “senile vaginitis”, painful engorgement of breasts, functional uterine bleeding, carcinoma of the prostate, and to prevent “accidents of pregnancy” (miscarriages). In addition, they helpfully provided a recommended dosing schedule, based on the one devised by Drs. George and Olive Smith were two of the chief proponents of the use of DES to prevent miscarriages. The dosing schedule involves a progressively increasing exposure to the drug, starting at 5mg per day, and progressively increasing as the pregnancy continues until it reaches 125mg per day in week 35 (I guess because, after week 35, the baby is sufficiently well developed that it doesn’t matter if it is born early).

High Dose DES and the Male Fetus

DES is one of the most powerful estrogens ever developed, and even 5mg represents a high dose. You can tell that by the way most of the other recommended uses involve doses considerably smaller. Treating the symptoms of menopause, for example, involves doses of 0.1 to 1 mg per day. Treatment of prostate cancer (through chemical castration) involves a starting dose of 3mg per day, and a maintenance dose (once testosterone suppression has been achieved) of 1mg per day.

Particularly during the later stages of prenatal development, a male fetus whose mother was given DES according to this schedule was being exposed to many times the dose of DES required to cause complete suppression of testosterone production in an adult man. This is very important, because male development, and masculinization of the brain, are driven by the action of testosterone produced in a male fetus’s testicles. Prevent testosterone from being produced, and a genetically male fetus will develop as female instead of male, despite the Y chromosome. This was easily demonstrated by conditions such as Swyer’s syndrome and Complete Androgen Insensitivity Syndrome, in which a failure to produce testosterone or a failure to respond to the hormone, results in a person who is genetically male but physically female.

The conventional causes of intersex all tend to act throughout prenatal development. What I believe has happened with DES is that it has caused a form of intersex, but one that is different from any of the usual causes of intersex because it allowed relatively normal male development to take place during the first trimester, but from the end of the first trimester onward, DES exposure was high enough for testosterone production to become profoundly suppressed.

As you can see from the table, by the end of the first trimester, the dose had already reached 20mg per day and was still climbing. Presumably, the placenta provided some protection from the drug, or an early-stage fetus is more resistant to chemical castration by DES than an adult man because 20mg is already several times the induction dose for chemical castration of prostate cancer patients.

Male Genital Development

In the figure below, is a chart from an endocrinology textbook showing a timeline of events associated with male physical development. Notice that male external genital differentiation begins in week 7 and has finished by the end of week 12.

During the time genital differentiation is taking place, the main things going on in the brain are very rapid cell division and migration of those cells to their final position in the brain (which is often far distant from where they formed).

fetal brain development — Figure 3. Fetal brain development. Andersen, S.L., 2003. Trajectories of brain development: point of vulnerability or window of opportunity?. Neuroscience & Biobehavioral Reviews, 27(1), pp.3-18.

The first elements of the permanent structure of the brain don’t start to be built until about 16 weeks after conception, by which time some brain cells have reached their final position and can start to form permanent connections with other brain cells (“Axonal/Dendritic outgrowth”). I’m guessing that there are two ways of wiring up brain tissue: a male way and a female way, and if there isn’t testosterone present during the time axonal and dendritic growth are taking place, you get the female version.

A process of programmed cell death starts soon after that, which may also be important for whether you end up with a male or female brain. Perhaps certain cells generate aggressiveness and competitiveness, and they only stay alive when excess brain cells are being removed if there is testosterone present. I look at the way men’s faces light up when they’re watching competitive sports, and it’s pretty obvious that they’re experiencing something that I cannot. It makes me think that there could be cells in their brains that generate that “joy of sport”, which were culled from my brain because there wasn’t any testosterone present when their thumbs up or thumbs down moment arrived.

From these two diagrams, it is evident that the first trimester is the key time for genital development, while brain development with regards to gender comes much later and corresponds with the ever-increasing dosages of DES. With these progressively increasing doses, along with the known effects of synthetic hormones on brain development, a good argument can be made that DES may have produced people who are genetically male and look male but have female brains. From talking to people with a known or suspected history of DES exposure, it certainly looks like that is what happens.

DES was used somewhere in the region of 10 million pregnancies worldwide. The schedule published in the PDR wasn’t used in all of them by any means, but it was the manufacturer’s recommendation, and many doctors must surely have followed that recommendation. This raises the prospect that there could well be several million people alive today who look male but have female brains, as a result of the use of DES.

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This article was published originally on December 12, 2017.

Synthetic Hormones During Pregnancy and Gendered Brain Development

by Hugh Easton

Published on September 12, 2024

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I found a pair of slides illustrating an important scientific discovery made in 1959, which became known as the Organizational-Activational hypothesis. A team of scientists experimenting on guinea pigs, discovered that hormones early in life play a crucial role in determining the sex of the brain, and whether an animal will have male or female behavior in adult life. Similar results have since been found in numerous other animal species, and there is little doubt that the same applies to human beings too. Actually there is no doubt at all, going by my own experiences.

Basically the brain has a sex, which arises during a critical period in prenatal development (or in rats, which are born at an earlier stage of development than humans, during days 1-10 of postnatal life). If there are high levels of androgenic hormones present during this critical time, the brain becomes masculinized, and the adult behavior will be that of a male. If there aren’t androgenic hormones present, the brain develops following the default female pathway instead, and the adult behavior will be that of a female.

Rats are a particularly convenient animal for demonstrating this because their critical period occurs after birth. This makes it relatively straightforward to produce a male rat with a female brain through surgical castration at birth. With most other animals you’d have to do the surgery in utero, which is a much trickier task. It is also relatively straightforward to determine whether a particular rat has a male or female brain, because those with male brains when injected with testosterone will attempt to mate with any females present, whereas those with female brains will not. In addition, rats with female brains will adopt a posture called the lordosis posture when injected with estradiol, whereas those with male brains will not.

Organizational and Activational Effects of Hormones during Pregnancy

organizational and activational effects - males

organizational and activational effects

In the first graphic shown above, we see what happens to the adult behavior of males put through three different treatments:

castrated as an adult
castrated at birth with no supplemental testosterone
castrated at birth, but with supplemental testosterone administered.

As is illustrated, treatments 1 and 3 result in adults that behave as males, whereas treatment 2 results in adults with female behavior. What this shows is that there is a crucial period early in the postnatal life of a rat during which either the presence of functioning testicles or externally administered testosterone causes male brain development to occur. In the absence of either, the rat ends up with a female brain, and female adult behavior despite being physically and genetically male. The period of development is roughly equivalent to gestational week 20 through birth during human pregnancy.

The second graphic illustrates what happens to females similarly treated. In this case through spaying, or removal of the ovaries, rather than castration. Here, only treatment 3 (spaying at birth + administering supplemental testosterone) results in an adult with male behavior. This is because, ovaries don’t produce much testosterone. So even the females spayed as adults do not have much testosterone present during the critical period for the sex of their brain. Once again, this emphasizes that it is the presence of testosterone during a critical period in brain development that produces a male brain, and the absence of that hormone during the critical period in which the brain ends up female instead. It appears that genetics and the sex of the body have nothing to do with sex based brain development. Instead, the sex of the brain is entirely dependent on whether or not androgenic hormones were present during a critical period in its development.

There are a couple of other things we can take away from this. Firstly, the effects of hormones during that critical period are permanent, and thus, are present for the remainder of the animal’s life. Secondly, anything that results in males being castrated, or females being exposed to testosterone-like hormones, during that critical period is a really bad thing, and likely to result in a male with a female brain or female with a male brain.

DES and Other Hormones Administered During Pregnancy

The miscarriage prevention drug DES given to women from the 1940s through the 1970s is a powerful chemical castration agent, so it is no small wonder that so many of the male-assigned people from DES pregnancies show signs of female brain development. The first generation progestins ethisterone and norethisterone, widely used in the 1950s and 1960s for miscarriage prevention, are both testosterone derivatives that have been shown to masculinize female fetuses (Wilkins 1960). This is why I think there’s likely to be a significant population of female assigned people from that era with male brains, as a result of their use.

DES isn’t the only drug that acts as a chemical castration agent to have been used during pregnancy. Progestins can also act as chemical castration agents, and unlike DES, they were never withdrawn, but remain in use even now. The archetypal progestin, medroxyprogesterone acetate (MPA), is one of the most popular drugs for chemical castration of sex offenders. It is in my 1972 Monthly Index of Medical Specialties (MIMS) and 1981 British National Formulary for treatment of habitual abortion (i.e. miscarriage prevention), so has definitely been used in human pregnancies in the past.

More to the point, hydroxyprogesterone caproate, which seems to be the most popular currently used miscarriage preventative, has similar pharmacological properties to MPA. The primary difference is that it is a pure progestin that doesn’t cross-react with non-target receptor types, whereas MPA, to a small extent, does. Other than that, they are quite similar drugs with similar effects. Therefore, I think there is a big risk of male assigned children from pregnancies in which hydroxyprogesterone caproate is used, being born with female brains. It is certainly something that bears looking at, by people independent of the pharmaceutical industry and the medical establishment.

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More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

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This article was published originally in July 2019.

Save the Pap Smear! A DES Daughter’s Perspective on Cervical Cancer and the HPV Vaccine

by Marian Vickers

Published on January 22, 2024

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DES daughters have unique credentials and knowledge regarding cervical cancer. We have become cervical cancer “experts” based on our own shared experiences and through our knowledge of DES research. We also have the advantage of acquiring this knowledge about cervical cancer before HPV was even detected; and before HPV tests and HPV vaccines were developed.

We know that there are two main types of cervical cancer: the slow-developing squamous-cell cancer (squamous carcinoma); and the much more aggressive glandular-cell cancer (adenocarcinoma). We know because we are at higher risk of both types.

In retrospect the DES story is a result of serendipity, a confluence of very specific and unique circumstances. DES emerged as a public health crisis in 1971 when it was discovered that DES daughters were at risk of an aggressive, glandular cancer of the cervix/vagina because of their in utero exposure to DES.

In a strange way it was actually fortunate that the ‘DES cancer’, clear cell adenocarcinoma of the cervix/vagina, was so unexpected and so shocking that it was noticed by clinicians, i.e. a rare virulent cancer previously only seen in post-menopausal women was suddenly being diagnosed in young women and girls.

It was also fortuitous that these cancer cases were located in a very specific geographical region- a particular hospital, the Vincent Memorial Hospital, in Boston. The original and most influential promoters of DES as a pregnancy maintenance treatment were The Smiths of Boston: Dr George VS Smith, Head of the Gynecology Department at Harvard University Medical School from 1942 to 1967; and his wife Dr Olive Watkins Smith, a biochemist. The ‘DES Cancer’ was originally known as ‘The Boston Cancer’

In retrospect, it was also fortunate that the use of DES during pregnancy was always controversial and that clinical trials were undertaken in the early 1950s. In fact one to the earliest large-scale, prospective, double-blind, randomised clinic trials (RCT) reported in the medical literature was conducted on DES and involved 2,000 women.

As a result of these circumstances – the sentinel finding of the ‘DES Cancer’; and the existence of research cohorts that could be reassembled – there has been follow-up in the USA into the long-term adverse outcomes of DES exposure. The cohorts of these original RCTs were reassembled providing a strong research tool – DES mothers could be compared to mothers in the control group; DES daughters with the control group daughters; DES sons compared to the control group sons.

The DES Cancer: A Decades-Long Side Effect

The ‘DES Cancer’ finding sent shock waves through the medical science community. Up until this time, based on the Thalidomide tragedy, it was believed that any adverse outcomes to a drug would be evident soon after the exposure, as in “birth defects”. With DES and clear cell adenocarcinoma of the cervix/vagina, the adverse outcome was expressed decades after the exposure.

It was found that the timing of the DES exposure was critical; and, using mice, researchers were able to examine more precisely the effect of timing and dose. The mouse is a valid model as the differentiation stages of the reproductive tract is similar and comparable to that of a human. By correlating both dose and time of exposure, researchers were able to replicate in mice the adverse health outcomes found in the human DES population. A 1981 landmark publication, Developmental Effects of DES in Pregnancy edited by Arthur L. Herbst and Howard A. Bern, brought together leading experimental researchers and expert DES clinicians.

DES - Herbst, Berne study

And this collaboration continued. The DES experience was central to the development of the scientific endocrine disruption paradigm. DES is the primary model for environmental endocrine disruptors.

From Lessons learned from perinatal exposure to diethylstilbestrol

“The synthetic estrogen diethylstilbestrol (DES) is well documented to be a perinatal carcinogen in both humans and experimental animals. Exposure to DES during critical periods of differentiation permanently alters the programming of estrogen target tissues resulting in benign and malignant abnormalities in the reproductive tract later in life.
Using the perinatal DES-exposed rodent model, cellular and molecular mechanisms have been identified that play a role in these carcinogenic effects. Although DES is a potent estrogenic chemical, effects of low doses of the compound are being used to predict health risks of weaker environmental estrogens. Therefore, it is of particular interest that developmental exposure to very low doses of DES has been found to adversely affect fertility and to increase tumor incidence in murine reprodu ctive tract tissues. These adverse effects are seen at environmentally relevant estrogen dose levels.
New studies from our lab verify that DES effects are not unique; when numerous environmental chemicals with weak estrogenic activity are tested in the experimental neonatal mouse model, developmental exposure results in an increased incidence of benign and malignant tumors including uterine leiomyomas and adenocarcinomas that are similar to those shown following DES exposure.
Finally, growing evidence in experimental animals suggests that some adverse effects can be passed on to subsequent generations, although the mechanisms involved in these trans-generational events remain unknown.
Although the complete spectrum of risks to DES-exposed humans are uncertain at this time, the scientific community continues to learn more about cellular and molecular mechanisms by which perinatal carcinogenesis occurs.
These advances in knowledge of both genetic and epigenetic mechanisms will be significant in ultimately predicting risks to other environmental estrogens and understanding more about the role of estrogens in normal and abnormal development.”

From another study looking at the role of endocrine disrupting compounds and developmental timing on female reproductive disorders:

“The ability of synthetic chemicals to alter reproductive function and health in females has been demonstrated clearly by the consequences of diethylstilbestrol (DES) use by pregnant women…. The daughters of women given treatment with DES were shown to have rare cervicovaginal cancers. Since the initial 1971 publication linking treatment of women with DES and genital tract cancers in offspring, other abnormalities have been observed as the daughters have aged, including decreased fertility and increased rates of ectopic pregnancy, increased breast cancer, and early menopause. Many of these disorders have been replicated in laboratory animals treated developmentally with DES. The lessons learned from 40 years of DES research are that the female fetus is susceptible to environmentally induced reproductive abnormalities, that gonadal organogenesis is sensitive to synthetic hormones during a critical fetal exposure window, that reproductive diseases may not appear until decades after exposures, and that many female reproductive disorders may co-occur.
Other synthetic chemicals used in commerce are known to mimic hormones and have been shown previously to contribute to disease onset. These chemicals are called endocrine-disrupting compounds (EDCs). Endocrine-disrupting compounds are either natural or synthetic exogenous compounds that interfere with the physiology of normal endocrine-regulated events such as reproduction and growth. Although there are many hormonal pathways through which EDCs can act (e.g., agonists or antagonists of steroidal and thyroid hormones), many of the reported EDC effects in wildlife and humans are caused through alteration of estrogen (E) signaling. This is because E signaling is evolutionarily conserved among animals and is crucial for proper ontogeny and function of multiple female reproductive organs
The purpose of this article is to establish the state of the science linking EDC exposures to female reproductive health outcomes. After introducing several topics crucial to understanding the etiology of female reproductive disorders, we present an overview of ovarian, uterine, and breast development, as well as how exposure to EDCs may contribute to some of the most prevalent reproductive disorders in these organs and to pubertal timing. Emphasis is placed on the period of development that currently is known to be most susceptible to disruption and harm by exposure to EDCs. To conclude, we present both specific research needs and several general initiatives needed to improve women’s reproductive health.”

DES Mothers and Breast Cancer

Another example of serendipity concerns the discovery that DES mothers have a higher incidence of breast cancer because of their DES exposure. When the ‘DES Cancer’ was discovered, DES Follow-up clinics were established for DES daughters to attend for the recommended special examination. The nurse in charge of one of these clinics, on chatting to the DES daughters before they had their examination, was struck by the number of daughters who were upset that their mothers had been diagnosed and/or died from breast cancer. This anecdotal observation led to research being carried out and the 1984 publication Breast cancer in mothers given diethylstilbestrol in pregnancy.

The findings were that DES mothers were 40 to 50% more likely than the control group to develop breast cancer. The authors noted a trend that the DES mothers developed the cancer at an earlier age; and that they developed a more aggressive form of the disease with a higher mortality rate.

This finding was further confirmed with animal modelling. Of course it has been known for decades that DES caused mammary cancer in experimental animals. As pointed out by Pat Cody in DES Voices: From Anger to Action (2008), animal studies dating from the 1930s showed that oestrogen administered to animals – cats; guinea pigs; monkeys; rabbits; and especially in what came to be the favoured mammals, mice and rats – showed reproductive tract malformations and cancer.

DES was synthesised in 1938 by a team of scientists in England, headed by Sir Charles Dodds. Later in 1938 Dodds reported that orally active oestrogen, including DES, interrupted early pregnancies in rabbits and rats. In 1938, a French researcher reported that male mice treated with DES developed breast cancer.[Lacassagne A (1938) Apparition d’adenocarcinoma mammaires chez des souris males traitees par une substance oestrogene synthetic. Comptes Rendus Biol. (Paris) 129.]

As explained in Barbara Seaman’s highly recommended book The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth (2003), Dodds was aware of what a powerful and potentially carcinogenic drug he had synthesised. In the months following the discovery Dodds became increasingly concerned about the carcinogenicity of the newly synthesised drug. In his laboratory he noticed that men on his staff who handled the stilboestrol powder were growing breasts, suggesting to him stilboestrol might cause breast cancer in men. He suggested that animal studies be carried out looking at the carcinogenicity of stilboestrol in male rodents. In 1940 a paper was published showing that stilboestrol caused mammary cancers in both male and female mice.

DES: Not One but Two Cervical Cancers

That DES daughters also had a higher incidence of squamous-cell abnormalities (when compared to the control group) was recognised quite early on. At the same time it was reported that DES daughters suffered much higher rates of cervical stenosis following minor procedures.

In the early years many of us purchased medical dictionaries and headed off to medical libraries to look at source material. DES Action has always strived to make information contained in medical journal articles accessible to our members. We have a long history of sharing information, reviewing journal articles and explaining terminology, thus empowering members to make informed decisions about their health care. The issue of how to treat dysplasia was featured in our newsletter DESPATCH a number of times. For example, DESPATCH No. 9 November 1982, looked at dysplasia treatment options and cervical stenosis, and explained the terminology.

DESPATCH No.9 p.1

I think our introduction to this edition of DESPATCH is worth repeating:

“The actual changes that DES exposure causes are quite complex. As a result of this, a DES daughter not only has to cope with the actual screening examination, but with an entirely new language.
This issue of DESPATCH is rather dry and technical: We concentrate on defining terms and de-mystifying the jargon. However, it is important that you are not intimidated by the jargon. Remember a true expert will not hide behind jargon but will be able to explain things simply and clearly. So, if you don’t understand what the doctor is saying, say so and ask that it be explained again….and again!”

It was hypothesised that the DES-related structural changes in both the cervix and uterus may be associated with connective tissue alterations that predispose to abnormal healing and increased propensity to cervical stenosis. Therefore the recommended management of DES daughters with these squamous-cell abnormalities was monitoring with minimal intervention. Those of us who knew we were DES exposed, and were attending DES follow-up screening clinics, were in the privileged position of having expert monitoring without intervention. And that is why many DES daughters have personal experience of even high-grade squamous-cell abnormalities resolving over time without any treatment.

That’s not to say it was easy, particularly in the early years. Often we were being called back for 3 monthly checks. But as time passed, and we experienced that the abnormalities ‘matured’ or resolved, we became more relaxed about squamous-cell abnormalities.

We used to joke that discussing cervix status seemed to be almost a defining feature of our group – nowhere else you could comfortably talk about the state of your cervix.

As I said we were in a privileged position of having expert screening with clinicians who explained and discussed issues. Over the years I’ve had three occasions when the clinician noted that “according to the textbook” he should probably do a biopsy but, as he was confident it would resolve, he would leave it. As I knew he was an expert, and that he was referring to squamous-cell abnormalities, I was happy to go along with this suggestion.

Of course lurking in the background was the knowledge that we have a life-long risk of the ‘DES Cancer’, clear cell adenocarcinoma of the cervix/vagina. Initially we were screened every 6 months, but then it went to annual checkups.

DES Daughters and the HPV Vaccine

So when there was news of a ‘cervical cancer vaccine’ being developed, we naturally were very interested and read up on it. However, the more we read, the less sense it made. When we realised it was for squamous-cell cervical cancer, the unanimous opinion was “Why bother?!’ It wasn’t even a cervical cancer vaccine, but a HPV vaccine (or, to be pedantic, a ‘HPV strains 16 and 18’ vaccine).

Why would you bother having a part-HPV vaccine when we knew through experience that even high-grade squamous-cell abnormalities usually resolved spontaneously without any intervention?

The vaccine was designed to prevent the very abnormalities that empirical evidence of the National Cervical Screening Program (NCSP) showed would resolve anyway – crazy. We looked on in bemusement at the HPV hysteria that erupted in 2006. It was an extraordinary example of manipulating the media for commercial gain when the drug manufacturer orchestrated the listing of Gardasil on the Pharmaceutical Benefits Scheme and the National Immunisaton Program.

This battle to list the HPV vaccines, and how commercial pressure and political opportunism threatened the independence of Australia’s healthcare system, is discussed in Healthcare’s Sticking Point.

It was a classic textbook example of disease mongering: Take a common, essentially benign condition (HPV infection) and it suddenly and only becomes “serious” or “life-threatening” when Big Pharma has a product to sell (i.e. HPV vaccine).

It was disgraceful that public health money was diverted into the HPV industry. In terms of women’s health, it would have been more productively spent on education programs and publicity campaigns on the value of Pap smears, in order to raise the participation rate of the NCSP; or on research into a screening test for ovarian cancer.

All we could do was shake our heads in bewilderment: If the government wanted to waste billions of dollars on a school-based vaccine program of unproven value, so be it. At least there was the safety net of the NCSP and women having regular Pap smears.

And now that is under threat. The proposed changes to the NCSP, due to be implemented on 1 December 2017, is that HPV testing has been fast-tracked to become the primary cervical screening tool; that the commencement age be raised to 25 years; and the screening interval be extended to 5-yearly.

This is a public health crisis in the making. There are two type of cervical cancer and the proposed policy is focused on just one. It is modeled exclusively on squamous cancer and ignores empirical evidence from the NCSP that glandular cancer now represents approximately 30% of cervical cancers diagnosed in Australia today.

This will put the lives of women, particularly young women, at risk.

As there appears to be a push worldwide to introduce this screening regimen (HPV testing as the primary cervical screening tool; commencement age 25 years or later; and 5-yearly screening intervals) potentially millions of women are at risk. It could be a medical and public health disaster on a scale never before seen.

If the DES experience teaches us anything, it is to remain vigilant about the efficacy and safety (both short-term and long-term) of pharmaceutical products, and this includes vaccines. It involves understanding the different types of cervical cancer; understanding the various risk factors, including HPV and endocrine disruptors; and being informed about the benefits and limitations of the screening tests, such as the Pap smear and the HPV test.

Stay with us, as we cover each of these topics over the next few weeks.

DES Daughters, Sons, and Grandchildren – Share Your Story

If you are the daughter, son or grandchild of a woman given DES during pregnancy, please share your story with us.

We Need Your Help

More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. We are not funded and accept limited advertising. Unlike many health sites, we don’t force you to purchase a subscription. We believe health information should be open to all. If you read Hormones Matter, like it, please help support it. Contribute now.

Yes, I would like to support Hormones Matter.

This article was published originally on May 1, 2017.

Photo by Ernest Karchmit on Unsplash.

Discovering DES: Opening Pandora’s Box

by Marian Vickers

Published on October 26, 2023

10125 views

Diethylstilbestrol (DES) is a synthetic estrogen. Known as DES in the United States, it is more commonly known as stilboestrol in the UK and Australia. It was the first synthetic estrogen produced, developed by Sir E. Charles Dodds and colleagues in the UK in 1938.

Constructed from a chemical base, it produced the same feminizing effect as estrogens derived from animals (e.g. Premarin) but was more powerful and cheaper to produce. DES cost about two dollars per gram to produce compared to the three hundred dollars to produce natural estrogen.

Never patented, the DES formula was published in the magazine Nature on 15 February 1938, giving the world the first cheap and powerful estrogen. As it was never patented, within months drug companies around the world were working with this formula, vying to market this lucrative new product straight out of the lab.

This has been likened to opening Pandora’s Box, an action that turns out to have detrimental, unintended and far-reaching negative consequences.

Dodds was aware of what a powerful and potentially carcinogenic drug he had synthesised. In the months following the discovery, Dodds became increasingly concerned about the carcinogenicity of the newly synthesized drug. In his laboratory he noticed that men on his staff who handled and inhaled the stilboestrol powder were growing breasts, suggesting to him stilboestrol might cause breast cancer in men. He suggested that animal studies be carried out looking at the carcinogenicity of stilboestrol in male rodents. In 1940 a paper was published showing that stilboestrol caused mammary cancers in both male and female mice.

Many studies of a variety of experimental, agricultural and domestic animals were conducted in the 1940s and showed serious adverse effects of the drug including cancer, fetal death, and sterility of offspring.

Dodds never envisaged that stilboestrol would be given to healthy women and was against the automatic and “promiscuous” prescribing of estrogen: He was aghast when told it was being used to “prevent miscarriage”; particularly as he had conducted research showing the drug could prevent or end pregnancies in rabbits and rats. This made it a potential birth control or emergency contraceptive pill. However, Dodds said that the human female reproductive cycle was too delicate to introduce foreign substances into it, and he denounced the use of DES to prevent or end pregnancies.

The risk of cancer with these drugs was well known and documented. In fact Dodds himself spent many years thereafter warning that these drugs put women at serious risk of endometrial and breast cancer.

However it was all too late – Pandora’s Box was well and truly open.

Despite the controversy and warnings, the Age of estrogen had well and truly begun. Over the following decades, DES and other exogenous estrogens were marketed and prescribed for a bewildering, often contradictory, range of conditions: to slow and prevent aging; to stop hot flushes and as treatment for other menopausal symptoms; to prevent miscarriage, for pregnancy maintenance, as a pregnancy “tonic”; as the oral contraceptive pill; as the ‘morning after’ contraceptive pill; to stunt the growth of tall girls; to suppress lactation; as a hormonal pregnancy test; to treat acne…

What these uses have in common is that they were experimental; they often didn’t work; and they were never proven safe, frequently having serious, often unexpected, long-term health outcomes for those exposed to the drugs.

And, despite Dodds’ concern, it was healthy women who were “automatically and promiscuously” prescribed the drugs.

To quote Barbara Seaman from The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth (2003),

I call the marketing, prescribing, and sale of these drugs an experiment because, for all these years, they have been used, in the main, for what doctors and scientists hope or believe they can do, not for what they know the products can do. Medical policy on estrogens has been to ‘shoot first and apologise later’ – to prescribe the drugs for a certain health problem and then see if there is a positive result.

It wasn’t until 1971 that the magnitude of the adverse effects of stilboestrol use started to emerge. DES emerged as a public health crisis in 1971 with the discovery of the ‘DES Cancer’, an aggressive, clear cell adenocarcinoma of the cervix/vagina, in DES daughters.

The discovery of this “biological time bomb” sent shock waves through the medical science community. Up until that time, based on the Thalidomide experience, it was thought any adverse effects of a drug given during pregnancy would show up immediately as “birth defects”. It was obvious that DES was a whole new ball game.

This lead to a paradigm shift and DES was recognized as an endocrine disruptor. Prenatal exposure to an endocrine disruptor such as DES results in multiple, diverse serious effects that are latent and delayed, being manifest years after the original exposure.

However, it was the Australian study of Tall Girls that moved our understanding of endocrine disruption to a new level. The small study was truly groundbreaking and far-reaching in the implications of its findings. No one had ever researched the long-term effects of exposure to an endocrine disruptor at this critical time of development, i.e. puberty. Another important feature of this study is that while DES was initially used, it was replaced in the mid-1970s (probably as a result of the ‘DES cancer’ being discovered) by ethinyl estradiol. So a very important ‘incidental’ finding of this study is that ethinyl estradiol, the estrogen found in the oral contraceptive pill, is an endocrine disruptor.

An important paper published from this study showed that tall girls treated with estrogen in early adolescence were nearly twice as likely to experience unexplained infertility as adults when compared to the matched control group of untreated tall girls.

This finding was replicated and extended in a 2011 Dutch study that evaluated fertility and ovarian function. Interestingly the European treatment for tall girls was high doses of synthetic estrogen (ethinyl estradiol) in combination with cyclic progestin. The impact of treatment on impaired fertility was even more pronounced than that observed in the Australian study. In terms of ovarian function, treated women were more likely of being diagnosed with premature ovarian failure.

A 2014 Swedish study found that the tall girl treatment regime was associated with an increased risk of melanoma.

Allied to this was the realization that DES causes epigenetic changes, resulting in the next and subsequent generations potentially being affected. Epigenetics refers to heritable traits in cells and organisms that do not involve changes to the underlying DNA sequence. Scientists believe that DES, as an endocrine disruptor, impairs and changes the normal pattern of gene expression i.e. when genes are turned on and off. It is thought that exposure to DES dysregulates the epigenome, with potential consequences for subsequent developmental disorders and disease manifesting in childhood, over the life course, or transgenerationally.

So DES is not only the first exogenous estrogen to be synthesized; it is the first compound to be recognized as an endocrine disruptor; and it is the primary model for environmental endocrine disrupting chemicals. In addition, it can be seen that DES is the primary model for pharmaceutical endocrine disrupting drugs.

Thus, the DES exposed are the ‘canaries in the coalmine’, the harbingers of the future.

Nearly 80 years ago Sir Charles Dodds inadvertently opened Pandora’s Box and we are still experiencing the unintended effects all these years later.

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This article was published originally on July 24, 2017.

When Being a Tall Girl Was a Medical Condition: DES and the Tall Girls

by Marian Vickers

Published on July 26, 2022

24869 views

To treat young healthy prepubescent girls with a known carcinogen to stunt their adult height sounds like a bizarre science fiction experiment, but it is unfortunately true. From 1959 through the 1970s physicians and researchers from the Royal Children’s Hospital and the University of Melbourne, gave adolescent girls of tall stature a powerful estrogenic hormone with a growing list of known side effects called diethylstilbestrol (stilboestrol) or DES.

DES had been used in obstetrics to prevent miscarriage, in farm animals to bulk up livestock before slaughter, and to caponize (castrate) chickens from the 1940s through 1970s. Early on, the drug was found to be ineffective in preventing miscarriage and serious side effects including cancer were noted. Indeed, cancer in farm hands caring for animals treated with DES and concern about the effect DES-infused meat might have on human health caused the FDA to ban its use in poultry farming in 1958, well before banning its use in human women. Despite the risks associated with this drug, clinicians and researchers in Victoria Australia, funded by governmental agencies and throughout the US, Norway, and elsewhere, thought stunting the growth of tall girls, for purely psychosocial reasons, was a good idea.

The rationale behind treating tall girls was so they could do ballet, buy clothes more easily, and find boyfriends and husbands. DES was used on healthy girls for purely psychosocial reasons. Apparently, being a tall girl was reason enough to consider medical treatment with a powerful, largely untested, synthetic estrogen with mounting evidence of carcinogenicity.

Little consideration was given to the psychosocial effects this drug would have on a young girl including nausea, the immediate onset of menstruation, the sudden development of breasts, and sudden rapid weight gain; and, of course, the long-term health outcomes of this treatment were never a consideration. The only long-term outcome considered was adult height. When meeting the tall women who underwent this treatment, it is reasonable to conclude the treatment did not work. Indeed, most of the research suggests only a 4cm reduction in height.

Discovering the Tall Girls: DES Action Australia

DES Action Australia was established in 1979 as the national support and advocacy group for individuals exposed to DES. In the early 1980s, the DES issue was new to us all and we were devouring information about its history and use. One aspect of interest was its use in veterinary practice. One of the first DES “patients” may have been Tricky Woo of the ‘All Creatures Great and Small’ books and TV series. In the late 1930s, kindly Dr. Herriot prescribed the new “wonder drug” stilboestrol for Tricky Woo’s embarrassing problem with incontinence.

Any drug which was thought to prevent miscarriage and result in bigger, healthier babies was of obvious interest to veterinary science. However, as in the earlier laboratory animal experiments, DES was soon shown to be deleterious to the health of the mother animal, to the DES-exposed offspring, and, interestingly, to subsequent litters. Thus, recommended use of DES in veterinary practice was limited to old animals and animals that were never going to breed.

We first heard of DES being used to inhibit the adult height of tall young girls almost by accident. In the early 1980s a sister of DES Action member, Clare Green, was studying veterinary science at Melbourne University. Through her, we learnt of a Melbourne veterinary scientist, Dr. Anne Jabarah, who had researched DES during the 1960s as part of her Master’s and PhD studies. Clare rang Dr. Jabarah and spoke to her at length about her research findings: that administering DES to cattle led to them subsequently developing mammary cancer. Dr. Jabarah commented that the published articles caused a great deal of interest internationally but not in Australia. Almost as an afterthought, she mentioned the Royal Children’s Hospital (RCH) here in Melbourne had requested details of her research, as they were thinking of using DES to inhibit the growth of young girls. She said she had often wondered whether they went ahead with the treatment.

Clare, on behalf of DES Action, wrote to the RCH seeking clarification on the matter. A letter was received from the medical director of the RCH stating that DES had never been used for such a purpose. In addition, Clare was asked to go into the Victorian Health Department to meet with a department spokesperson. The doctor told Clare that the matter had been looked into and there was no evidence that DES was used for this purpose. We were thus reassured, both in writing and in person, that no such trial had taken place.

So it came quite a shock several years later when I was contacted by a young woman who had been part of this nonexistent trial. She had attended the RCH and had been given DES to stunt her growth. She was in her early 20s and had been diagnosed with advanced invasive cervical cancer. As she was a nurse she knew this was very rare, particularly as she had none of the known risk factors for the disease.

When I asked her how she found out about DES Action and obtained my phone number, she said her treating doctor (a well-known Ob/Gyn) had suggested she ring. He had made the connection between her DES exposure as a young girl and the subsequent cervical cancer.

Another letter was sent to the RCH, again requesting clarification on the matter. We received back a very defensive letter in which the hospital distanced itself from the trials. They said that the clinician involved had been a private consultant and what he did in his clinics was in no way connected to the RCH.

Untangling the Tall Girls Trials after Years of Secrecy and Denials

In subsequent years (the mid-1980s to 1997) we received a handful of further inquiries from “tall girls” requesting information. Unfortunately, these were spaced too far apart for us to put the women in contact with each other. The health concerns of these women had an all-too-familiar ring: dysplasia, endometriosis, ovarian cysts, aggressive cancers (cervix and breast), impaired fertility, and premature menopause (i.e. occurring during their 20s).

I can’t really describe my feeling when I opened The Age newspaper on 27 June 1997 and read on page 1: Hormone tests on teenage girls referred to inquiry. I think the main emotion was a sense of relief – that the truth would finally be known – tall girls were given DES to stunt their growth. It also brought back to me the anger and frustration Clare and I experienced in the early 1980s when our inquiries were fobbed off by the medical establishment and health authorities.

And then my phone started ringing. As DES was mentioned in the article, the newspaper must have had me as a contact and referred any inquiries to me. Remembering how previously we were unable to put the women in contact with each other, I made a contact list of every phone call received. I explained to every caller the importance of organizing, of forming a group to share experiences, and offered to give them the list to follow up. From memory, I think Janet Cregan-Wood was about the fifth caller. She rang back the next day and “volunteered” to take on the role. And so the Tall Girls group formed and their DES story emerged.

More about DES and Tall Girls Story

Normal at Any Cost: Tall Girls Short Boys, and the Medical Industry’s Quest to Manipulate Height
Participation, Empowerment, and Effectiveness: The Tall Girls Inc. Experience.
Tall Girls, Inc. Australia
DES and the Meat Industry: My Year of Meats, by Ruth Ozeki

About the author: Marian Vickers is a DES daughter and, in 1979, was a founding member of DES Action Australia. As the DES story has evolved over the years so her focus has broadened – from issues around DES exposure to the wider issue of safety of pharmaceuticals; and finally to an understanding of endocrine disruptors and the implications for public health, particularly in terms of inadequate drug safety surveillance and reporting systems. In 2008 Marian became a ‘Gardasil mother’ when her elder daughter’s health was severely impacted by the HPV vaccine. Not only did she gain an appreciation of what DES mothers went through, she sees disturbing parallels between the DES and Gardasil stories.

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This article was published originally on Hormones Matter on April 21, 2014.

Is Prenatal Dexamethasone Safe: The Baby Makers’ Hubris

by Chandler Marrs, PhD

Published on January 20, 2022

19886 views

For some reason, maybe hubris, medical science seems doomed to repeat the sins of their fathers. The lessons of thalidomide and diethylstilbestrol (DES) of generations past (present and future because of transgenerational effects) have not been learned. Reproductive endocrinologist, obstetricians and others tasked with protecting maternal and fetal health are at it again; happily and blindly dosing pregnant women with synthetic steroids with neither the evidence to support their efficacy nor the research to prove safety.

Prenatal Dexamethasone and Congenital Adrenal Hyperplasia

Dexamethasone or DEX is a synthetic corticosteroid that mimics the anti-inflammatory and immunosuppressant effects of endogenous cortisol. DEX is used in the treatment of variety of conditions from arthritis to cancer. Since DEX easily crosses the placental barrier and can have detrimental effects to the developing fetus, it is considered unsafe for pregnant women. Per the FDA:

Dexamethasone is listed as a pregnancy Category C drug. Corticosteroids have been shown to be teratogenic (causes birth defects) in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women.

Despite the risk, dexamethasone has been given to pregnant women who are at risk of delivering a child with the congenital adrenal hyperplasia (CAH) for almost 30 years. CAH is a genetic disorder that involves the inability to appropriately metabolize certain hormones.

Female children with CAH are often more masculinized than their non-CAH counterparts, both in behavior and physiology. Sometimes the virilization extends to the genitalia with atypical clitorises and labia. High dose dexamethasone is given prenatally, as soon as the woman becomes pregnant, to ‘feminize’ the female genitalia of CAH babies. Prenatal DEX serves no other purpose but to change the appearance of the female genitalia. It neither prevents CAH nor does it promote the health of the developing fetus relative to CAH. It merely de-masculinizes female fetuses, feminizes her genitalia. Conversely, it also feminizes male genitalia.

The effective dose of DEX given from early pregnancy onward and elicits 60-100 times the normal physiological levels of cortisol. Because female sexual development happens very early in gestation, DEX is given to all women who might be carrying a female CAH child. With a previous history of delivering a CAH child, there is a 1 in 8 chance that a woman will have a second CAH child, who is female. So 7 of the 8 non-CAH babies are also exposed.

Previously, we reported animal research showing that DEX combined with common environmental endocrine exposures in early pregnancy is linked to significant reproductive abnormalities in male offspring. Moreover, the adrenal system is a critical component of our stress-response and regulates a variety of physiological functions from heart rate and blood pressure to insulin response and fat storage. Research on animals shows prenatal dexamethasone has significant adverse effects on each of these systems, many of which are likley to be transgenerational – affecting the offspring and the offspring’s ‘children’ in ways that have yet to be investigated.

The Hubris of the Baby Makers

As if dosing pregnant women with dexamethasone to somehow prevent the potential masculinization of female CAH babies without evidence or safety data isn’t bad enough, physicians who specialize in in vitro fertilization (IVF) are now also using DEX, again without sufficient evidence. One small and recent study suggests that DEX may augment ovarian response and increase follicle production for egg retrieval. There was no statistically significant improvement in fertilization, implantation or pregnancy rates. Miscarriage was not an outcome variable. There are no data about the long term safety of DEX for IVF or even any efficacy studies to support the use of DEX to prevent miscarriage. And yet, DEX is used to prevent miscarriage with IVF.

The physicians using dexamethasone have no idea if it works and appear to be operating on hunch versus hard evidence. Of course, they contend, using DEX in early pregnancy (pre-implantation through 10 weeks) couldn’t hurt and therein lay the hubris – that their talents, education and years of medical practice suffice. For these experts, no confirmatory analysis or evidence is needed to verify that their treatment protocols work. Trust us, they say.

As reported in the Atlantic, a prominent IVF specialist explains:

We tell our IVF patients that in our opinion it is by and large safe to take as prescribed, that there are no proven developmental risks to the baby [and] that side effects to the woman are infrequent, temporary in nature and reversible on proper withdrawal.” He went on, “We do not go into detail describing everything in the literature on what we consider to be safe treatments. That would be overly time consuming, impossible to accomplish thoroughly and comprehensively[,] and in my opinion [would] create unnecessary patient consternation.”

Well, of course there are no ‘proven’ risks, no one has ever done the appropriate research either for the DEX in CAH or the use of DEX in IVF. After 30 years of being used off-label for CAH and potentially thousands, if not tens of thousands of babies exposed worldwide, there are no controlled studies showing either its efficacy or its safety – no robust analyses of adverse events. This may be worse than either DES or thalidomide. A recent meta-analysis on the risks of prenatal DEX use for CAH found only four studies with marginally useful data. Most done by the same research team with a highly questionable history. Except the one study cited above, there are no studies, none, not even in animals, on the use of DEX to prevent miscarriage. Its use with IVF remains highly speculative and experimental.

Perhaps, one of the only studies on prenatal DEX worth examining was conducted in Sweden. The researchers reviewed 43 pregnancies from 1985 -1995 where prenatal DEX was used to treat CAH. What they found was troubling; an excessively high rate of severe adverse events in the DEX pregnancies versus the control group. In the prenatal dexamethasone group, researchers identified eight severe adverse events compared to only one in the control group. These included:

3 children failed to thrive during the first year
1 child with developmental delay and hypospadias (malformed male urinary tract opening)
1 child had hydrocephalus
2 girls were born small for gestational age; one was later diagnosed with mental retardation
1 child had severe mood fluctuations resulting in hospitalizations

As a result of this study, researchers in Sweden petitioned their Regional Ethics Committee to put on hold a prospective study using DEX for CAH, citing the high risk of adverse events for what is essentially an elective treatment for reproductive cosmetics. In the US, despite petitions to the Office of Human Research Protection (OPRH – the oversight body tasked with approving human subjects research and protecting research subjects) and the FDA, there has been little oversight of the use of DEX in either CAH or IVF.

In both cases, these treatments are considered experimental and their use must be fully consented to and presumably monitored by OPRH and the FDA. Neither is happening with any rigor. Indeed, the fertility specialist’s claim – that there are no proven developmental risks to the baby [and] that side effects to the woman are infrequent, temporary in nature and reversible on proper withdrawal – mirrors the unsubstantiated and dubious claims of the one research group funded continuously by NIH for the last dozen years who have failed to produce any robust or rigorous data on the topic but nevertheless continue to market the benefits of DEX, their practice and ‘research’.

Most recently, a prominent physician and researcher from UCSF has come out to state that risks do not outweigh the benefits and that “prenatal treatment of congenital adrenal hyperplasia with dexamethasone should only be done in prospective clinical research settings with institutional review board approval, and therefore is not appropriate for routine community practice.” No such review or research exists for prenatal dexamethasone and IVF.

Is Prenatal Dexamethasone Safe?

Probably not. Administering synthetic steroids during critical periods of fetal development- when physiological systems are organizing and developing – will impact system and organ functioning. Some of those effects will be seen early on and may be visible, like malformed reproductive tracts, but others will be more subtle and present as the child ages – cognitive deficits, heart disease, or cancer. Many effects will be epigenetic or transgenerational with the grandchildren suffering the consequences. We saw that with DES, we’re seeing that in animal studies with BPA and other endocrine disruptors. One has to assume, we will see the same effects with DEX given from pre-conception or early pregnancy onward. It’s just a matter of time.

Unfortunately, it may be years before the research catches up. Therefore, it is incumbent upon pregnant women educate themselves and make informed decisions.

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This article was published originally on April 15, 2013.

More recent research (2018), reiterates much of the same.

DES, Nazis, and American Industrialists

by Chandler Marrs, PhD

Published on December 14, 2021

14992 views

DES is a synthetic estrogen-like compound developed in 1938 by English chemist Charles Dodd. German chemists under the employ of the Nazis were able to synthesize DES cheaply and easily from coal tar and used it to fatten livestock. There was a problem, however. The young boys who cared for the livestock, and thus were exposed to the chemical, developed swollen and painful breasts, a condition now called gynecomastia. This would be one of many indications that perhaps the drug was not as safe as proclaimed. The German solution to avoid this side effect was to have women care for the animals because they had breasts already, after all. An American scientist in the employ of several American industrial interests and with ties to German researchers during and after the war, concurred:

“A drug effect of interest in relation to industrial hygiene is that of DES, the manufacture of which only female workers are employed, because untoward effects induced in males by the absorption of this material in the course of a day’s work. Boys develop a mammary swelling with such severe pain and pressure of a shirt cannot be endured. On the discontinuance of exposure the condition subsides spontaneously within a week or two. No sequelae have been reported and no abnormalities of the testes have been seen. On the other hand, older males develop some atrophy of the testes and some apparently temporary loss of sexual potency. This condition is said to have been cured by the administration of androsterone. Exposed women had no nausea or menstrual abnormalities.” The Secret History of the War on Cancer, pp 90.

Despite the early indicator that DES might not be safe, and without any other testing beyond the basic toxicology to determine lethality, it was approved by the FDA in 1941 for vaginitis and as an early hormone replacement therapy for menopausal women. It was later approved a variety of low estrogen indications. In 1947, the FDA approved its use in pregnant women with a history of miscarriage. DES had been used off-label for miscarriage prevention since the early 1940s, despite the fact that little evidence supported its use and animal studies indicated clear carcinogenic and congenital reproductive abnormalities in the offspring. Indeed, years before the development of DES, the relationship between synthetic hormones and several forms of cancer, were recognized. Nevertheless, the promise of pharmaceutical industry profit overrode any potential long term consequences of the drug.

After 10 years of widespread use and marketing, a double-blind, placebo-controlled study on the efficacy of DES was finally conducted. As one might expect, it was found ineffective in preventing miscarriage. In fact, women on DES had a higher risk of miscarriage. Later studies in the 1960s began detailing the adverse effects this drug. Nevertheless, despite mounting evidence of the dangers of diethylstilbestrol, it remained on the market and widely used through the early 1970s in the US and into the 1980s in some European countries. In the US alone, it is estimated that some 5-10 million women and their children were exposed to DES. Because the compound was never patented, 287 drug companies sold DES under a multitude of brands and for an array of low-estrogen conditions.

Two decades after both the Germans and the English recognized that DES caused gynecomastia in the male farm hands, US reports of gynecomastia and sterility in US poultry workers were evident. As a result, the FDA banned it for use in poultry under the newly enacted Delaney Clause to the FDA 1958. It would be another 13 years before DES was banned during pregnancy and 20 years before DES was banned in cattle. That means that neither the evidence that DES was ineffective in the prevention of miscarriage but may actually increase risk, nor the evidence of congenital abnormalities and cross-generation cancer risks were sufficiently troubling to initiate its ban. DES was finally banned for use in cattle until 1979. It would be years after before it was removed from the food chain (if it even is now). “In 1980, half a million cattle from one hundred and fifty-six feedlots in eighteen states were found with illegal DES implants.” Even upon FDA’s decision to withdraw its approval of DES in cattle and feed, it did so on grounds of the procedural non-compliance of the manufacturers, while simultaneously maintaining the safety of DES, “because there is no evidence of a public health hazard.” Even now, despite its clear carcinogenic and teratogenic risks, it is still used in veterinary care.

DES represents just one of many pharmaceuticals marketed as safe upon the flimsiest of measures. It was a known carcinogen before its approval. By 1939, 40 papers had been published detailing its carcinogenic activity. Unfortunately, they were countered heavily by industrial interests with some 257 papers published within the proceeding two years touting its benefits. As is the case today, the influence of advertising to skew public opinion, whether the medical public or lay public, was intense and ultimately successful. Even though the evidence suggesting DES prevented miscarriage was highly controvertible, it was approved by the FDA and adopted wholeheartedly by the medical industry. Even when it was proven ineffective at preventing miscarriage in 1953, it was still prescribed regularly.

“…doctors continued to widely prescribe DES in normal pregnancies like ‘vitamins’ or ‘a little extra insurance.’ They continued because of the highly aggressive sales tactics of pharmaceutical representatives and because it was widely advertised in medical journals and the popular press. Influenced by the advertisements, and in their desperate desire to avoid miscarriages, women demanded DES.”

It was not until 1971, that the FDA finally recognized the risks. DES, like thalidomide, DDT, and other chemicals developed during this period, are often viewed through the lens of history as representative of a bygone era, when science and technology were yet nascent endeavors. I would argue that is incorrect. While it is true that science and technology have advanced significantly in recent decades, what remains steadfast are the cultural and monetary conflicts that motivate and define what is accepted as true in this field; and sadly, what is accepted as true is whatever industry tells us.

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This article was published originally on October 23, 2019.

Maternal DES and Male Sexual Development

by Hugh Easton

Published on November 30, 2021

14380 views

In the course of trying to figure out why I have certain symptoms normally associated with intersex conditions, but do not fit the criteria for any of the conventional genetic causes of intersex, I have stumbled across what appears to be a gigantic medical and pharmaceutical industry disaster that has been quietly unfolding ever since WWII. This post is my latest attempt to bring the problem to wider public attention.

DES: A Hormone for Every Ailment

In the years during and immediately after WWII, rapid advances in chemistry suddenly made it possible to produce man-made versions of many of the hormones that occur naturally in the human body. Hormones control a wide range of biological processes involved in the day to day running of the human body, and are also key drivers of the development and maintenance of masculine and feminine attributes.

Doctors and the pharmaceutical industry quickly realised that hormones had tremendous potential as medicines, and they were rushed to market with comparatively little safety testing, and even in spite of clear evidence of harm during what animal experiments were performed.

The earliest of these substances was an artificial estrogen called diethylstilbestrol (or DES). DES was developed by a team of chemists in the UK in 1938. It is a completely man-made substance that has a chemical structure unrelated to naturally occurring estrogens. Nonetheless, the DES molecule has a similar shape to natural estrogen molecules, binds really well to estrogen receptors and acts as an extremely potent estrogen (one of the most powerful ever developed). Furthermore, it is active when taken by mouth, and it is comparatively easy to synthesize, so can be manufactured in bulk very cheaply. DES had all the right characteristics to become a blockbuster drug.

Because it was developed using public funds, DES was never patented. The people who developed it hoped that, by making the secret of its manufacture freely available, it would make a low cost source of estrogen available to women who needed it. However, US pharmaceutical giant Eli Lilly spotted a moneymaking opportunity, and quickly made DES their own, becoming the main manufacturer and distributor of the drug worldwide throughout the time it was used as a medicine

With this new drug in their armory, Lilly needed to find uses for it. One of the first uses they came up with was in pregnancy, as a treatment for preventing miscarriages and premature births. Their theory was that one main cause of miscarriage was inadequate hormone production, and that by supplementing a woman’s own hormones with DES, she would be less likely to miscarry. Never mind that the animal research showed no reduction in miscarriages,

“Dodds was always against the automatic prescribing of estrogen for any reason. He was sickened when he first heard about the work of Dr Karl John Karnaky in Houston, the first to use DES widely to “prevent miscarriages”. Dodds sent Karnaky a study that he himself had performed, showing that in rabbits and rats, the drug caused miscarriages.” (p37 of Barbara Seaman’s “The Greatest Experiment”)

More importantly, there was a whole series of experiments carried out between 1938 and 1941 at Chicago’s Northwestern University (here, here, here) showing that DES causes female development in male rat fetuses!

Consequences of Maternal DES

Undeterred, Eli Lilly pressed ahead, and through an aggressive marketing campaign and with a bit of arm twisting at the FDA, soon had DES licensed as a wonder drug for preventing miscarriages. Between 1940 and about 1980 (by which time it had largely been withdrawn from use as a miscarriage preventative), DES was used in somewhere in the region of 10 million pregnancies worldwide . In the US, it is estimated that 4.8 million children were exposed prior to 1971 when the FDA withdrew its approval, although doctors continued to use it off-label for several years after (p14 “DES Voices”, Pat Cody).

“It is estimated that DES was prescribed to between 2 and 10 million pregnant women world-wide as pills, injections, suppositories, and creams to prevent miscarriage between 1947–1971 … The exact number of women/fetuses prenatally-exposed to DES world-wide is unknown (IARC 2012). The majority of reports of DES use are from the U.S. where it is believed that between the 1940s and 1970s, 5 to 10 million people either consumed DES during pregnancy or experienced in utero exposures (IARC 2012). DES use was also popular in Europe and Australia, and like the U.S., many women did not know that they were taking DES. Therefore, estimated numbers of people reporting exposure during pregnancy or in utero are around 300,000 in the United Kingdom and 200,000 in France (Harris and Waring 2012).”

DES Daughters

The “DES daughters” from those pregnancies have since been acknowledged to have suffered all kinds of problems as a result of their exposure, including: very high rates of several kinds of cancer; infertility; abnormalities of their internal reproductive organs; several times greater risk of miscarriage and ectopic pregnancies; and various other health problems, including autoimmune disorders, osteopenia, degenerative disc disease, endometriosis, premature menopause, the list goes on and on. Everyone I have talked to who was prenatally exposed to DES seems to have health problems of one kind or another attributable to their exposure.

DES Sons

In contrast with the daughters, the official line has always been that the “DES sons” suffered virtually no ill effects as a result of their exposure. Based on what I’ve seen since first finding out about DES in 2011, that is not true at all, and in fact what it has done to us is exactly the same thing it did to the rats at Chicago’s Northwestern University: it caused us to develop as female instead of male during the time it was being administered.

Under the standard dosing schedule, increasing doses of DES was given to women with doses of across pregnancy reaching a 125mg in the last month of pregnancy (Physician’s Desk Reference, 1953). As a result of this graduated hormone exposure, we might expect relatively normal male development during the first trimester, but predominantly female development during the second and third trimesters. The first trimester is when genital takes place and physical sexual attributes develop. During the second and third trimesters, the main things still ongoing as far as development is concerned, is brain development. With this graduated dose of synthetic estrogens, we would expect relatively normal genital development although there is emerging evidence of alterations here too, but feminized brain development. In other words, with DES sons, we see a person who looks male but whose brain has predominantly or overwhelmingly, in a fair number of cases it seems, developed as female. The way this tends to manifest itself later in life is as a person who everyone regards as male, but who has a strong inner sense of being a woman.

Other common effects associated with DES exposure in males include subfertility or infertility, and hypogonadism (chronic below normal male testosterone production). I suspect this may also be a big risk factor for testicular cancer, however, this is unproven. All the genuine research into DES effects on males appears to have been discontinued by about 1980, and the total number of people studied is too small to assess cancer risk.

In Utero Synthetic Progestins

DES isn’t the only man-made hormone with gender bending properties to have seen widespread use during pregnancy. There is a class of hormones called progestins (which are all man-made versions of the hormone progesterone), that have also seen extensive use for miscarriage prevention. The first progestins were actually derivatives of testosterone. Although they act more like progesterone in adult women, in female fetuses they turned out to act more like testosterone. Female babies who had partially developed as male were being born throughout the 1950s as a result of progestin exposure. I have found a number of papers all published around 1960 reporting on cases of “progestin induced virilization”, so that appears to be when the medical community first realized there was a problem with these drugs. How long these androgenic progestins continued beyond this point I don’t know, nor do I know how many pregnancies they were used in in total. However, in her book “DES: The Complete Story”, the author, Cynthia Laitman, describes how she was given an androgenizing progestin alongside DES during her pregnancy in 1969, so it appears these gender bending drugs were being used throughout the 1960s too.

Unlike DES, progestins were never withdrawn. They are the main ingredient in birth control pills and other forms of hormonal contraception, and taken by several hundred million women every day for contraception. In fact some progestin formulations are still used for miscarriage prevention (allegedly these are non-androgenizing types of progestin, however, I think there’s a big risk they could be inducing female brain development in male babies).

In the course of trying to find out about the effects of DES on the unborn child, I came across a group of people whose babies were harmed by another hormone-based medicine, a drug called Primodos (marketed as Duogynon in Germany). A similar drug, called Gestest, was marketed in the United States. Here, the exposure occurred very early in the pregnancy, during the time organogenesis and limb development is taking place in the fetus, and before the process of sexual development is underway. As a result, the main effects have been severe, thalidomide like disabilities rather than abnormalities of sexual development (although, at least one member of their Facebook group had a Primodos exposed brother who was trans identified).

As with DES and the androgenizing progestins debacles, the pharmaceutical industry has been given a free pass by the governments of the countries involved, and the whole thing swept under the rug. An important fact about Primodos is that it contains exactly the same hormones as are used in birth control pills, the only difference being that the dose is higher.

A third group of people I’ve come across whose lives have been blighted by prenatal exposure to synthetic hormones, are in Hhorages France . The main issue this group is trying to highlight is that many of their hormone exposed children later committed suicide or developed serious psychiatric illnesses (although reading some of their published research, it appears that many of the children have intersex related abnormalities too).

My hope is that by alerting people to the harm so many have suffered as a result of being exposed in the womb to medically prescribed hormones, I can help to prevent such exposures from taking place in the future. I am also hoping this post and my Facebook page, Protect the unborn child from synthetic hormones, will help gain greater public acceptance for the transgender community; a much maligned group of people who, through no fault of their own, were born with brains that do not properly match their biological sex.

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This article was published originally on December 5, 2017.

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