I have been reading this thread and the more i read it seems me and my sister both was affected by this drug.  We always wondered why my sister would be around my dad more and i was around my mother.  Growing up my sister went hunting with dad, and all boy things with him.  I did some like fishing, but i never liked hunting. I seemed to always be around my mother doing things with her.  Now as i read this it seems me and her fit right in with this.  My mother and father has passed and so has my sister.  So there is no one to ask.  The doctor is long dead. If true it would answer a lot of questions.  My daughter and granddaughter has problems also, i am thinking their problems may come from this.  I am going to pass this along to them so they can ask their doctors if this could be the root or part of their problems. Bad thing with the small town we live in, the doctor that delivered me and my sister also delivered my daughter. 

I'm the fourth child of five, I was born in 1961. My mother went into labor with me at six months and was given something at the hospital to stop it. I was born six weeks later. I was six weeks premature, weighing four pounds even.

Quote from: Joelene9 on August 31, 2015, 03:53:49 PMNo known test is available. By records only.

What a pity there is no test.  I have often wondered if there was something like that in my past.  I never had the confidence nor a close enough relationship with my mother to ask.  And, as she is no longer alive, I have missed my chance.  Unless my older brother (who is gay) had that conversation with her, there is no one who would know.

Ultimately, it makes no difference.  What is, is.  Still it would be nice to understand it.

Quote from: RomeoEcho on August 29, 2015, 01:35:40 PM
I know it's not quite what you're looking for, but as a different data point, my mother was a DES baby, and I'm here. Very little is known about the effects on the next generation, but there do seem to be further effects and mutations.

I have heard that the natal male children of DES daughters (i.e. "DES grandsons") have a considerably higher than normal incidence of the same kinds of problems that were often seen in DES sons, hypospadias and undescended testes being two examples. Since both of those are markers for below normal testosterone during prenatal development, it stands to reason that some of these people would have had below normal male testosterone during the key period for brain development too, and ended up trans as a result.

The main reason I haven't talked about "3rd generation" effects is because I don't have any clear idea what could be causing them (whereas with direct DES exposure, considering the doses used, it's easy to see how it could suppress fetal testosterone production and cause fetal development during that part of the pregnancy to occur as female instead of male). All I know is that there does appear to be an unusually high incidence of DES-like symptoms in DES "grandsons" (who may now be living as granddaughters!). The other thing I've noticed myself from talking to DES daughters, is that a lot more of their kids appear to be autistic than is the case for the general population.

One theory I've heard is that DES exposure changes the epigenetic programming in a DES daughter's eggs. All the eggs a woman has as an adult, actually formed while she was still a fetus, during the first five months of her prenatal development (e.g. see: http://prenatalexposures.blogspot.co.uk/p/fetal-sperm-and-egg-overlooked-tissues.html ).

"Based on a survey of autism parents, we have found severity of neurodevelopmental symptoms to generally be more severe when the mother was exposed than if the father was exposed.  That may be due to the fact that maternal germ cell development remains relatively arrested as compared to the male germ line after birth."

The author of that blog, Jill Escher, was exposed to a cocktail of synthetic hormones during her prenatal development. She doesn't identify as trans, but gave birth to two children with autism. She thinks the hormones she was exposed to damaged her eggs, and that's what ultimately led to her children being born with autism.
http://prenatalexposures.blogspot.co.uk/2013/05/worse-than-thalidomide-consequences-of.html

As Jill's blog entry illustrates, although DES received virtually all of the publicity, doctors were actually handing out colossally high doses of several other manmade hormones at the same time, and the number of people exposed to these hormones could well exceed the numbers exposed to DES (and as I've mentioned previously in this thread, these other hormones could well be a cause of MTF transsexuality too, since  the entire progestin class of hormones are highly effective at suppressing testosterone production in adult men).

Quote from: HughE on September 02, 2015, 02:49:22 PM
I have heard that the natal male children of DES daughters (i.e. "DES grandsons") have a considerably higher than normal incidence of the same kinds of problems that were often seen in DES sons, hypospadias and undescended testes being two examples. Since both of those are markers for below normal testosterone during prenatal development, it stands to reason that some of these people would have had below normal male testosterone during the key period for brain development too, and ended up trans as a result.

The main reason I haven't talked about "3rd generation" effects is because I don't have any clear idea what could be causing them (whereas with direct DES exposure, considering the doses used, it's easy to see how it could suppress fetal testosterone production and cause fetal development during that part of the pregnancy to occur as female instead of male). All I know is that there does appear to be an unusually high incidence of DES-like symptoms in DES "grandsons" (who may now be living as granddaughters!). The other thing I've noticed myself from talking to DES daughters, is that a lot more of their kids appear to be autistic than is the case for the general population.

One theory I've heard is that DES exposure changes the epigenetic programming in a DES daughter's eggs. All the eggs a woman has as an adult, actually formed while she was still a fetus, during the first five months of her prenatal development (e.g. see: http://prenatalexposures.blogspot.co.uk/p/fetal-sperm-and-egg-overlooked-tissues.html ).

"Based on a survey of autism parents, we have found severity of neurodevelopmental symptoms to generally be more severe when the mother was exposed than if the father was exposed.  That may be due to the fact that maternal germ cell development remains relatively arrested as compared to the male germ line after birth."

The author of that blog, Jill Escher, was exposed to a cocktail of synthetic hormones during her prenatal development. She doesn't identify as trans, but gave birth to two children with autism. She thinks the hormones she was exposed to damaged her eggs, and that's what ultimately led to her children being born with autism.
http://prenatalexposures.blogspot.co.uk/2013/05/worse-than-thalidomide-consequences-of.html

As Jill's blog entry illustrates, although DES received virtually all of the publicity, doctors were actually handing out colossally high doses of several other manmade hormones at the same time, and the number of people exposed to these hormones could well exceed the numbers exposed to DES (and as I've mentioned previously in this thread, these other hormones could well be a cause of MTF transsexuality too, since  the entire progestin class of hormones are highly effective at suppressing testosterone production in adult men).

Yeah, the third generation problem is much more of a mystery. Partially because there are so many options, and also because research couldn't really start in ernest until recently. I was almost in a study for third generation des, but wasn't able to. I'd heard the explanation of the egg development problem, and also possibly a different hormonal response to pregnancy. My mother seems to solidly identify as a woman, and doesn't really understand gender identity. Though I probably did not experience low testosterone in utero since I identify as male, but if her eggs had some alteration in development, it could have caused any number of things in me. I am very much on the autistic spectrum though. I was unaware of that connection, and am now intrigued.

I know that I questioned what caused this in myself for years. And, a theory needs data points to make it a theory and not just a guess. The largest data point that so many fail to recognize is that there are so many of us. Many of us have felt this way from our earliest memories without external influences that can easily be identified. We are counted, although loosely, at least to the point of being recognized. We have other guesses whether it be DES, the size and nature of our hypothalamus, or hormone levels in our mommys' tummies. But the real data, the fact that we are here and that there are so many of us, can not be simply brushed aside. Ultimately, this is what has helped me understand that I am okay. I AM normal. It doesn't matter how or why, I AM.

Cindi

Hi All,

So I finally got the nerve to ask my mother about taking medication during pregnancy.  She told me she didn't have much morning sickness with me or my younger sisters.  My brother who is a year older apparently gave her much more.  When I asked her about medication, she told me our family doctor at the time didn't believe in giving anything more than gravol for morning sickness.

Anyway, she's a nurse so I guess she would remember.
Paige

Quote from: Paige on September 04, 2015, 11:31:23 PM
So I finally got the nerve to ask my mother about taking medication during pregnancy.  She told me she didn't have much morning sickness with me or my younger sisters.  My brother who is a year older apparently gave her much more.  When I asked her about medication, she told me our family doctor at the time didn't believe in giving anything more than gravol for morning sickness.

Hi Paige, you're getting mixed up with thalidomide! Thalidomide was the drug given for morning sickness.

DES was prescribed in pregnancies where the mother was thought to be at heightened risk of miscarriage (for instance if she was very young or aged over 40; had a prior history of miscarriage; suffered from diabetes; started bleeding or had other signs of going into premature labour). During the 1950s and 60s, they were even adding it to pregnancy vitamins, so it was used in some pregnancies where there were no problems at all.

It was normally dispensed as tablets, but from what I've been told, it looks like they were sometimes injecting mothers with it too.

Quote from: HughE on September 08, 2015, 01:49:26 PM
Hi Paige, you're getting mixed up with thalidomide! Thalidomide was the drug given for morning sickness.

DES was prescribed in pregnancies where the mother was thought to be at heightened risk of miscarriage (for instance if she was very young or aged over 40; had a prior history of miscarriage; suffered from diabetes; started bleeding or had other signs of going into premature labour). During the 1950s and 60s, they were even adding it to pregnancy vitamins, so it was used in some pregnancies where there were no problems at all.

It was normally dispensed as tablets, but from what I've been told, it looks like they were sometimes injecting mothers with it too.

Hi Hugh,  that probably makes it more doubtful my mother was given it.  She had no trouble as far as I know, 4 kids in 5 years.  Maybe I should ask her again, but it sounds unlikely.

Thanks for all the info,
Paige

I've recently found a photo that graphically illustrates the power of estrogens to cause female development in biological males:



Here's the article that image came from:

http://www.activistangler.com/journal/2014/8/4/scientists-find-more-mutated-intersex-fish-in-nations-waters.html

I've also tracked down what appears to be the original research that gave rise to the feminized fish:

http://www.researchgate.net/publication/260436624_An_environmental_oestrogen_disrupts_fish_population_dynamics_through_direct_and_transgenerational_effects_on_survival_and_fecundity

The estrogen used in the research was ethinyl estradiol, which is in many ways the sister compound of DES. Both manmade hormones are extremely potent estrogens that were developed in the 1930s, have similar pharmacological properties and similar potency weight for weight, and and have seen extensive use in medicine. DES is considerably cheaper to manufacture though, so became the treatment of choice for miscarriage prevention and other uses involving high doses of estrogen. While DES was eventually pulled off the market due to its link to cancer, ethinyl estradiol remains in use, and is in fact the estrogen most commonly used in birth control pills.

Looking at the research linked above and the photo, it has an astonishing ability to induce female development in male fish. The doses used in the experiments that gave rise to the fish in the photo were tiny, ranging between 5 and 20 nanograms per litre added to the water the fish were raised in. You'd need to drink hundreds of gallons to get the same dose of ethinyl estradiol as is contained in a single contraceptive pill, so the water isn't hazardous to human beings. Although the researchers don't say, presumably the reason the fish are so sensitive to it is because they process several times their own bodyweight in water through their gills every hour, so in a sense they are doing the equivalent of a person drinking hundreds of gallons per day!

Nonetheless, this research shows how even very small doses of a manmade estrogen with similar properties to DES, can alter male development so completely that you end up with a biologically male fish that's virtually indistinguishable from a female. Similar effects have been noted in rats prenatally exposed to DES (see the "Experimental Intersexuality" research I mentioned previously), except I haven't been able to find any photographs of the sex-transformed offspring. It should come as no surprise that biologically male human beings exposed to very high doses of the same drug, undergo female development during the time the exposure is taking place.

Hi Hugh,

I'm just wondering if you might have an answer.  At what stage in a pregnancy back in the late 50s or early 60s would a Dr have normally prescribed DES.  Would it have been right at the start or sometime later?   And at what point would right at the start be?  My guess is that it's probably no earlier than at least four to six weeks after conception.  A delay in administration of DES would answer the question of why so many are transsexed in the brain but exhibit no explicitly visible intersex conditions.


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  My cousin, a water quality chemist for the USGS was involved with this study as well as the other findings of other pharmaceuticals in the streams and rivers. Xenoestrogens are another type made as byproducts of manufacturing are getting in the system as well.

Joelene

  When I changed family doctor at the start of my transition I ended up with a duplicate copy of my medical file with records going back to age 5 in 1982.  My original doctor was a naturopath, which almost entirely ruled out the use of mainstream drugs for me or my mother.  I did however find a record of being prescribed Tofranil by another doctor for the purpose of trying to halt my bed-wetting habit of the time.  My family doctor stated in a letter to my mother that he was concerned about Tofranil because it was also known to be prescribed as an anti-depressant.  Until I just read those pages now I never knew I'd been taking a potentially harmful drug!

  The only reason I mention this is that quite often drugs may not be what they seem.  While my Tofranil ingestion obviously came to late to likely have had any effect on my childhood development, it is illustrative of the need to really dig into every bit of information you can get.  Drugs that a pregnant mother may have taken may have been viewed as completely innocuous because of the prescribed use in her own case.  The mother may not have a clue that something they took could have been involved in generating birth defects.

  I was reading a webpage, http://www.cdc.gov/des/consumers/about/history.html, which has a huge list from 1976 of all the known drugs that were based on DES or related chemical formulations.  It kinda scary to think just how easily women could have taken such a medication without really understanding what they were getting into.

  Although I can't point to an obvious drug-related source for my transgender condition, I get the feeling that erring on the side of statistics and logic points to such a source and that I just don't have enough information to clear up the story.  I'm prepared to accept that my condition is purely a 'fluke' but I'm not placing my bets there just yet.  I really hope that medical science and open study and discussion of the whole trans issue will progress to the point that I can get an answer within my lifetime.  I don't need an answer - I'd just really appreciate one.

When I first started HRT during the primitive days here in New Zealand I was prescribed Stilbestrol.  I did not like it and it did not like me; - could've been due to some kind of left over organic memory I suppose   I was put on Permarin after that which was a whole different story which I won't go into here.

Quote from: Deborah on October 24, 2015, 08:50:41 AM
I'm just wondering if you might have an answer.  At what stage in a pregnancy back in the late 50s or early 60s would a Dr have normally prescribed DES.  Would it have been right at the start or sometime later?   And at what point would right at the start be?  My guess is that it's probably no earlier than at least four to six weeks after conception.  A delay in administration of DES would answer the question of why so many are transsexed in the brain but exhibit no explicitly visible intersex conditions.

There's a table of doses taken from the 1953 Physician's Desk Reference here:
http://ireport.cnn.com/docs/DOC-1071366

(the PDR is the industry "bible" that tells doctors how to prescribe a particular medication)

Apparently, that same table was published in the PDR every year until 1962, when it was replaced by a less specific recommendation to use doses of 25 - 100mg per day (even after that, most doctors probably stuck to what was in that table, since it was what they were already familiar with).

I put that table into Excel to see what the cumulative dose over the course of a pregnancy would be, and here's the results:

So, a total of 11,718 mg of DES over the course of a pregnancy if the dosing schedule was followed to the letter (which it probably was in a lot of cases, since it was the manufacturer's recommendation, and the patient would potentially have grounds to sue any doctor varying from it).

When you consider that a dose of between 1 and 3 mg per day will achieve suppression of testosterone production to castrate levels in an adult man being treated for prostate cancer, you can see how large these doses were, and how it's virtually inevitable that a male fetus exposed to this treatment would no longer be producing any testosterone during the second half of the pregnancy (which appears to be when all the important differences between male and female brains arise).

Note that the starting point was 7 weeks after the final day of the last period, which doesn't necessarily correspond to when conception actually occurred (it could be anywhere from that day up to a month later). For that reason alone, there'd be a fair bit of variability over how heavy exposure actually was during the critical period for genital development (between 7 and 12 weeks after conception), which probably explains the wide range of variability in effects on the genitals (anything from relatively normal looking male genitals to something that looks like high grade AIS). There wasn't nearly as much variability during the critical period for brain development though; it was uniformly high. It makes me think there must still be quite a lot of people who are trans as a result of DES but have yet to come out, either because they're in denial about it or are remaining closeted for personal reasons.

Interesting that I just read that DES was used in the 1940s for the purpose of, "The first reported attempt of hormonal manipulation to reduce pathological sexual behavior occurred in 1944, when diethylstilbestrol was prescribed to lower testosterone levels.".  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565125/#!po=1.61290

Where does the testosterone come from to masculinize a fetus?  Is it produced by the mother or the baby?


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just got into reading this thread (from the beginning) the other day and so much of it seems to apply - two years ago (at 61) I was really hitting bottom depression-wise and eating myself to death - since I was a kid I had gender and crossdressing issues but trans was not a "thing" so parents and society forced me along the straight path - marriage and family kept me there but I never felt right and when I finally started therapy for my depression my therapist thought I might be trans and recommended an endo to check me out - first blood test hormone results were so whacked out he did a series of tests to make sure there wasn't some form of cancer causing them - like others the T and E were both floating in limbo land at the time - with guidance and input from my therapist when the endo finally asked which hormone I want to supplement I chose the E - so E it was along with spiro - T levels refused to budge any lower so upped the dosages - 3 months later same thing and upped them again - now after a year plus on HRT I am hyperkalemic from the spiro and about to start on Lupron to try and knock out the T - now the endo is thinking that DES might be involved but with mom and dad both gone there is no way to prove it so just have to trudge along and see what happens

be well
jenifer

Quote from: Deborah on October 27, 2015, 10:48:42 AM
Where does the testosterone come from to masculinize a fetus?  Is it produced by the mother or the baby?

It is produced by the baby.  According to Wikipedia ("sexual differentiation"):

QuoteSpecific genes induce gonadal differences, which produce hormonal differences, which cause anatomic differences, leading to psychological and behavioral differences, some of which are innate and some induced by the social environment.

So during the time a baby is supposed to produce testosterone to do various things including brain differentiation it is receiving from 1 to 25 times the anti androgen dosage required to chemically castrate an adult male sex offender.  Normalize that to body weight and it's probably a dosage between 90 to 2250 times higher.

And who said the pharmaceutical indistry  didn't have our best interests in mind.  (Sarcasm Intended).


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Quote from: HughE on September 08, 2015, 01:49:26 PM

DES was prescribed in pregnancies where the mother was thought to be at heightened risk of miscarriage (for instance if she was very young or aged over 40;

My mom was 19 when she had me, which is probably why they gave it to her.