Did you know that males have an undeveloped uterus?

[KayXo]

Aside from the fact that they mimic female hormones, one interesting property both synthetic estrogens (such as DES) and "synthetic progesterone" (progestins such as hydroxyprogesterone caproate) have in common, is that if you give them to an adult man in a high enough dose, they induce a state of "chemical castration" - they shut down testicular hormone production so completely that it effectively ceases altogether, so the testicles might as well no longer be there as far as hormone production is concerned. The effect only continues for as long as the drug continues being administered though, once it's discontinued, the testicles resume producing testosterone.

Bio-identical estradiol and progesterone will also induce a state of chemical castration in an adult man in a high enough dose. During pregnancy, both of these hormones' concentrations are very high in the maternal serum and the umbilical cord.

Perhaps you can see what could happen to a male fetus who is exposed to these drugs in utero. By temporarily shutting down his testicular hormone production, it could result in him ending up in a situation where some parts of his prenatal development occurred as male, and some parts as female. That's what I think has happened with DES, and could be happening with hydroxyprogesterone caproate (and other similar progestin-based treatments).

Then why does this not occur with high levels of estradiol and progesterone, present in the woman and in the embryo, during pregnancy and which work in the same way and shut down testicular production? Your explanation doesn't account for this.

With DES, I know for a fact that, under the standard treatment plan for miscarriage prevention devised by Drs George and Olive Smith, the doses being used were more than 10x higher than that required for total suppression of testosterone in adult men, throughout the second half of the pregnancy.

During pregnancy, levels of estradiol and progesterone are naturally several fold higher than the levels needed for total suppression of testosterone in adult men. Levels of estradiol can go as high as 75,000 pg/ml when less than 1,000 would probably suffice to suppress testicular production. Levels of progesterone can go as high as 300 ng/ml, higher than what is needed to suppress testicular production.

Clin Endocrinol (Oxf). 2003 Apr;58(4):506-12.

"Both progesterone and desogestrel administration resulted in decreases in the concentration of both LH and FSH secretion, as well as testosterone. Analysis of the pulsatile nature of LH secretion indicated that both treatments reduced LH pulse amplitude, and that progesterone reduced LH pulse frequency. Progesterone, but not desogestrel, treatment also reduced the increase in LH secretion in response to GnRH."

With hydroxprogesterone caproate, I couldn't find any examples of where it's been used on its own for testosterone suppression in adult men, however the doses that are being used during pregnancy look enormous, and I'm sure if you were to give the same to an adult man, he'd experience profound testosterone suppression.

There is plateau at which the testicles just shut down completely so that beyond a certain dose, you no longer get any return, any more increased suppression.

Progestins are highly effective as chemical castration agents (in fact, the most commonly used drug in the US for chemical castration of sex offenders is Depo Provera, a progestin).

Bio-identical estradiol and progesterone are just as effective, in high enough doses which produce lower concentrations than that typically found during pregnancy.

[HughE]

Bio-identical estradiol and progesterone will also induce a state of chemical castration in an adult man in a high enough dose. During pregnancy, both of these hormones' concentrations are very high in the maternal serum and the umbilical cord.

I can tell you from my own personal experience that, once your body has adapted to it being there, bioidentical progesterone (in the form of cream) is not T suppressive, even in high, pregnancy level doses. Progestins, on the other hand, are strongly T suppressive, even in doses a lot smaller than those used in maternity treatment. I know this for a fact  because I've experimented on myself with both!

Estradiol is T suppressive in adult men, however the situation for the fetus during pregnancy is complicated by the fact that the fetus and placenta produce very high levels of two estrogens, estriol and estetrol, that act as estradiol blockers. There's probably other stuff going on with hormone degrading enzymes as well, that limits fetal exposure to estradiol. One thing I've found is that no one seems to actually know what blood hormone levels are during late term gestation in human fetuses in situ, and they've probably never been studied. Looking at premature babies doesn't give you an answer, since once the baby has been delivered, it's no longer receiving hormones from either the placenta or the mother.

Synthetic estrogens (and synthetic hormones in general) bypass all the body's hormone processing enzymes, hormone binding globulins and other systems for controlling and limiting what the natural hormones do. This means that they can have all sorts of effects, and do all sorts of stuff, that the natural hormones can't. Another factor with DES in particular is that the doses used were insanely high (around 1000x higher than are now used with equivalent synthetic estrogens), meaning that it's more or less inevitable that you'd get full estrogen receptor activation, despite the presence of the antiestrogens estriol and estetrol.

One other thing is that, in adult men, estradiol primarily suppresses T by suppressing LH production. LH is what drives T production in adult men, but in the fetus, up until about week 20, T production is primarily driven by HCG produced in the placenta (HCG acts as an analogue of LH as far as the testicles are concerned). LH produced in the fetal pituitary only take over after about week 20, when placental HCG production falls away, and the fetal hypothalamus and pituitary have matured to the point where they start producing significant amounts of LH. Since the period from week 20 onwards seems to be more important as far as "brain sex" is concerned (whereas the first half of the pregnancy is when all your physical sexual characteristics develop), this could be another factor making the brain more likely to be affected than the genitals when synthetic hormones are used during pregnancy.

I can't talk actual doses on this site, but I've found a paper talking about the use of medroxyprogesterone acetate (MPA) for chemical castration of sex offenders. It shows that a weekly milligram amount of MPA that's almost the same as the weekly milligram amount of hydroxyprogesterone caproate used for preventing miscarriage, will reliably suppress an adult man's T production to female levels or below. They're different drugs, but they have fairly similar pharmacological properties. The main difference between the two is that hydroxyprogesterone caproate is a pure progestin, whereas MPA, in addition to acting as a progestin, cross reacts to a limited extent with androgen receptors and glucocorticoid receptors, which makes it less desirable for use during pregnancy. In my mind that raises a huge warning flag that hydroxyprogesterone caproate treatment could be suppressing T production in late gestation male fetuses, thereby preventing their brains from masculinising, and producing babies that look male but have female brains.

I don't have any figures for the number of pregnancies it's been used in, but hydroxyprogesterone caproate was first introduced in 1956 under the brand name Delalutin, and has remained in use ever since. It's currently marketed as Makena in the US, and Proluton in Europe. It's also sold as Gravibinan, and probably a whole range of other brand names too. My guess is that the total number of people exposed to it is well in excess of the number who were exposed to DES.

[SadieBlake]

Transexual / transgender people have been around as long as humans, I have no idea whether there incidence is higher in the last few decades but clearly the hormonal anomalies that cause the changes in brain structure in-utero can happen without human intervention or modern chemical pollutants.

[KayXo]

I can tell you from my own personal experience that, once your body has adapted to it being there, bioidentical progesterone (in the form of cream) is not T suppressive, even in high, pregnancy level doses. Progestins, on the other hand, are strongly T suppressive, even in doses a lot smaller than those used in maternity treatment. I know this for a fact  because I've experimented on myself with both!

The cream you used resulted in pregnancy serum levels of progesterone? I recall reading somewhere that eventually the area of application gets saturated and that you no longer absorb P to the same extent. Could that have been the reason? Also, studies have shown that creams yield very low levels of P in the blood.

This evidence is also anecdotal so not very convincing to me. The rest is, as far as estrogen is concerned.

In my mind that raises a huge warning flag that hydroxyprogesterone caproate treatment could be suppressing T production in late gestation male fetuses, thereby preventing their brains from masculinising, and producing babies that look male but have female brains.

If progesterone levels are as high as they are during pregnancy, they would also suppress T production and your claim of habituation or desensitization needs more support, as far as I'm concerned. Sample of 1 is not good enough.


In the end, these are all theories and there is no real proof of brain feminization. It will be hard to prove. Our feelings may stem for psychological reasons purely. And who cares? I don't need any of that to justify being female and transitioning. It feels right to me. End of story.

Scientific proof is only needed for those who are prejudiced, for society to finally respect us and provide equal and fair treatment, for those who doubt themselves to finally not doubt themselves. But I say instead, embrace yourself now as you are, trust in yourself and your feelings and those people that love us, embrace us no matter the reason, those are the really good people in this world, pure of heart.

End of rant! 

[Janes Groove]

I guess I'm at the point now where even if I found out I was a DES child it wouldn't really matter that much.
If my mom took it and that's why I'm transgender then I'm fine with it. To borrow from computer language, I actually don't see it as a bug. I see it as a feature.

[HughE]

The cream you used resulted in pregnancy serum levels of progesterone? I recall reading somewhere that eventually the area of application gets saturated and that you no longer absorb P to the same extent. Could that have been the reason? Also, studies have shown that creams yield very low levels of P in the blood.

Who knows what the effect is on serum levels, as I haven't ever had my P levels measured. It's the 10 percent cream though (the strongest one on the market). Like the P creams I've used before, once your body adapts to it, it doesn't have any noticeable effects at all apart from a subtle mood brightening effect. However, it's worth taking, because without it, I get symptoms of estrogen excess (mainly fluid retention, especially in my legs). Also, prior to starting on hormones, I was experiencing some quite alarming neurological symptoms (tinnitus, vertigo, acephalgic migraines), which have stopped since I started taking hormones. I don't know for sure if it't the P that is providing this beneficial effect, but from what I've read about it, it probably is. P has neuroprotective effects and been used experimentally as an antiseizure medication (it's thought to mainly produce these beneficial effects by converting to allopregnanolone, an important neurosteroid).

In the end, these are all theories and there is no real proof of brain feminization.

Actually there is. The link to transgenderism may be contentious, but it's been known for a long time that being prenatally exposed to synthetic estrogens or progestins has permanent, lifelong effects on people's personality and behaviour, that can (and have been) measured in psychological tests.

This is from a 1977 study of male and female children who'd been prenatally exposed to synthetic hormones (estrogens, mainly DES, or progestins). The hormone-exposed children were compared with their unexposed siblings as controls, and as you can see, significant differences in the personality traits measured were noted. The main difference in the estrogen exposed group vs controls is that they're more group oriented and group dependent. With the progestin exposed group, they're more independent, more sensitive, strongly individualistic, strongly self assured, and more self sufficient.

This excerpt from the book "Brain Sex", which seems to mainly have had its origin in that study and other similar ones carried out by Dr Reinisch, has articulated what has been left unsaid in those studies. Basically, estrogens tend to induce feminization of behaviour (particularly in males), whereas progestins tend to masculinize it (particularly in females).

Most of the early progestins were androgenic, so it's an open question as to whether pure progestins such as hydroxyprogesterone caproate would act in the same way, and whether their overall effect is masculinizing or feminizing. Also, if I'm right that both DES and progestins inhibit fetal testicular hormone production, then by lumping boys and girls together, a lot of nuances of what has actually happened have been lost, because both types of hormone will have strongly feminizing effects on males purely by virtue of shutting down their testicular T production (whereas girls won't have comparable feminizing effects because they have no testicles).

It will be hard to prove. Our feelings may stem for psychological reasons purely. And who cares? I don't need any of that to justify being female and transitioning. It feels right to me. End of story.

If it were known that a lot of people have ended up trans as a result of a medical mistake (and that for all trans people, it's basically a form of intersex, except one in which the main effects have been on the brain), I think it would go a long way towards reducing prejudices and increasing acceptance of transgender people. There's also the fact that medical treatment during pregnancy involving synthetic hormones and hormone disrupting drugs is still taking place, and it's highly likely that kids are continuing to be born trans as a result. Don't you think that's something that should be addressed?

[2cherry]

Here is another nice list:

https://en.wikipedia.org/wiki/List_of_related_male_and_female_reproductive_organs

[KayXo]

Who knows what the effect is on serum levels, as I haven't ever had my P levels measured. It's the 10 percent cream though (the strongest one on the market).

But you mentioned pregnancy levels, and talked about personal experience.

"I can tell you from my own personal experience that, once your body has adapted to it being there, bioidentical progesterone (in the form of cream) is not T suppressive, even in high, pregnancy level doses."

How do you know this then? I'm confused.

Like the P creams I've used before, once your body adapts to it, it doesn't have any noticeable effects at all apart from a subtle mood brightening effect.

Not my experience and I take P twice daily orally. The effect can be quite pronounced, still. If I skip a dose, I start to feel groggy, and will even get hot flashes.

However, it's worth taking, because without it, I get symptoms of estrogen excess (mainly fluid retention, especially in my legs).

So, noticeable effects do persist.

Actually there is. The link to transgenderism may be contentious, but it's been known for a long time that being prenatally exposed to synthetic estrogens or progestins has permanent, lifelong effects on people's personality and behaviour, that can (and have been) measured in psychological tests.

Feeling male or female vs having personality traits are that more feminine vs masculine is not the same. Many transgender women and men were not exposed to DES or progestins in the womb.

If it were known that a lot of people have ended up trans as a result of a medical mistake (and that for all trans people, it's basically a form of intersex, except one in which the main effects have been on the brain), I think it would go a long way towards reducing prejudices and increasing acceptance of transgender people.

And that, in my opinion, would be sad. Because if we need to provide this sort of evidence for them to accept us and not be prejudiced, then that says a lot about who they truly are. Accepting us now, just because we say so and feel it, now that is right and pure! Many transgendered women and men have not had anything bad happen to them, no extra hormones in the womb, etc? Are they illegitimate? Less than? Crazy, psychotic? See the problem with this?

There's also the fact that medical treatment during pregnancy involving synthetic hormones and hormone disrupting drugs is still taking place, and it's highly likely that kids are continuing to be born trans as a result. Don't you think that's something that should be addressed?

I don't believe hydroxyprogesterone caproate to be that different from progesterone and consider it safe enough. So, I don't see a problem using it for preventing abortion, maintaining pregnancy and preventing pre-term birth. Only this progestogen, bio-identical progesterone and estradiol are prescribed. I see no problem there. What else?

Like I said, lots of transpeople, the majority, probably didn't even get exposed to extra hormones during pregnancy so that attributing transsexuality to this or that is just too simplistic and there is much evidence lacking.

[HughE]

But you mentioned pregnancy levels, and talked about personal experience.

"I can tell you from my own personal experience that, once your body has adapted to it being there, bioidentical progesterone (in the form of cream) is not T suppressive, even in high, pregnancy level doses."

How do you know this then? I'm confused.

Because I use progesterone cream. You can buy it online without a prescription. It's marketed towards postmenopausal women, but that doesn't stop other people from using it. I used to use the regular strength stuff (which involves significantly less progesterone per dose than Prometrium tablets), but this year I started using a cream that contains 10 percent progesterone, and so the dose I'm now getting per day is similar to what a Prometrium capsule contains. The difference is that it's absorbed through the skin rather than the digestive tract, so it doesn't undergo first pass metabolism through the liver. I also think it must enter the body quite slowly via dermal absorbtion, so you don't get sudden, large changes in P levels from the cream. Those two differences probably explain why the effects are different.

Feeling male or female vs having personality traits are that more feminine vs masculine is not the same. Many transgender women and men were not exposed to DES or progestins in the womb.

DES was used in somewhere in the region of 10 million pregnancies worldwide. I haven't found any statistics for hydroxyprogesterone caproate use, but it is a widely prescribed drug and it's been in use for longer than DES was, so I'd imagine even more people have been exposed to it by now than were exposed to DES. Whether the millions of people who've had these prenatal hormone exposures are the same millions of people who are transgender is an open question to which I don't think anyone knows the answer. Hardly anyone knows what drugs they were exposed to before birth, and as an adult, it's usually impossible to find out. Medical records no longer exist, and the mothers given these drugs were often never told what they were being given. The situation with DES is actually better than it is with other hormones, because there was a big cancer scare associated with it in the 1980s, and many women who'd been given it found out because of that.

I should add that any cause of intersex can also make people trans, because they're caused by the same thing - abnormal hormone levels during your prenatal development The difference is that with intersex, the abnormal hormone situation occurred during (or included) the first trimester, which is the critical time for genital development. Hence the physical appearance of the genitals is affected. With transgender, that person had hormone levels within range for their genetic sex during the first trimester (and so their genitals were unaffected), but then their hormones went out of range later on in their prenatal development. Since the main thing still ongoing after the end of the first trimester as far as development is concerned is brain development, the effects of those abnormal hormone levels are mainly seen in the brain. There's a fair bit of overlap between the two though, for instance many intersex people have a nonbinary gender identity, and many transgender people have endocrine disorders and other symptoms commonly associated with intersex conditions.

I don't believe hydroxyprogesterone caproate to be that different from progesterone and consider it safe enough. So, I don't see a problem using it for preventing abortion, maintaining pregnancy and preventing pre-term birth. Only this progestogen, bio-identical progesterone and estradiol are prescribed. I see no problem there. What else?

Most steroid esters are "prodrugs": they aren't active as hormones themselves, but instead act as a prodrug for the hormone they're made from, which is released when the ester bond is cleaved. Basically they act as a slow release form of the hormone. However, that's not the case for hydroxyprogesterone caproate. The hydroxyprogesterone caproate molecule itself is capable of activating progesterone receptors, and its ester bond is so stable that most of the molecules in a dose never cleave, but are instead eventually broken down intact in the liver. It's not a slow release form of 17-hydroxyprogesterone, it's a bona fide progestin, with a pharmacology similar to other progestins (except that unlike most other progestins, it doesn't cross react with androgen receptors).

One property of progestins is that they're quite good at suppressing testosterone production in adult men, and therefore it's not unreasonable to think that they could also suppress testosterone production in unborn babies. If they do, then using hydroxyprogesterone caproate (or any other progestin) during pregnancy is a recipe for disaster as far as males are concerned, since it'll cause any development that takes place during the time it's being administered to occur as female instead of male. Considering that this is exactly what appears to have happened with DES, on quite a large scale and over several decades, without any of the medical staff administering the stuff realising what it was doing, this gives me no confidence that they're not continuing to do the same thing with progestin-based treatments.

[KayXo]

Because I use progesterone cream. You can buy it online without a prescription. It's marketed towards postmenopausal women, but that doesn't stop other people from using it. I used to use the regular strength stuff (which involves significantly less progesterone per dose than Prometrium tablets), but this year I started using a cream that contains 10 percent progesterone, and so the dose I'm now getting per day is similar to what a Prometrium capsule contains. The difference is that it's absorbed through the skin rather than the digestive tract, so it doesn't undergo first pass metabolism through the liver. I also think it must enter the body quite slowly via dermal absorbtion, so you don't get sudden, large changes in P levels from the cream. Those two differences probably explain why the effects are different.

But you mentioned pregnancy levels? How would you know if your levels weren't even tested? Progesterone transdermally is poorly transferred to the blood.

Menopause. 2013 Nov;20(11):1169-75.

The serum levels of progesterone were, on average, with cream and gel (doses comparable to oral), 
0.5 ng/ml (Cmax of 0.6 ng/ml) and 0.35 ng/ml (Cmax of 0.4 ng/ml), respectively, during a 24 hour period.

On comparable dose with oral progesterone, in another study, Cmax was found to be 17.3 ng/ml and average levels to be 4.33 ng/ml for the first 10 hours.

CLIMACTERIC 2005;8(Suppl 1):3–63

"The daily administration of a cream containing (...) progesterone on an area of 100 cm2 of the forearm of postmenopausal women resulted in a small rise in the serum progesterone levels. On the first day, the application of either (...) once daily or (...) twice daily caused only a negligible increase, but, on day 42, the progesterone concentrations reached a mean value of about 1 ng/ml(...). The efficacy of transdermally administered progesterone is contested. In a study with postmenopausal women, the daily application of a cream containing (...) progesterone on the skin increased the serum levels of progesterone only slightly to 0.1–0.3 ng/ml."

Levels of progesterone in pregnancy can go as high as 300 ng/ml. My levels are 13-20 ng/ml 12 hours after dose.

Hardly anyone knows what drugs they were exposed to before birth, and as an adult, it's usually impossible to find out.

Ask your mother, if possible. My mom confirmed to taking neither of these during her pregnancy. I'm certainly not alone, there are many like me.

Medical records no longer exist, and the mothers given these drugs were often never told what they were being given. The situation with DES is actually better than it is with other hormones, because there was a big cancer scare associated with it in the 1980s, and many women who'd been given it found out because of that.

In general, mothers are quite aware.

With transgender, that person had hormone levels within range for their genetic sex during the first trimester (and so their genitals were unaffected), but then their hormones went out of range later on in their prenatal development. Since the main thing still ongoing after the end of the first trimester as far as development is concerned is brain development, the effects of those abnormal hormone levels are mainly seen in the brain.

As far as brain being feminized due to abnormal levels of hormones, this is only a theory. Not proven with certainty.

One property of progestins is that they're quite good at suppressing testosterone production in adult men, and therefore it's not unreasonable to think that they could also suppress testosterone production in unborn babies. If they do, then using hydroxyprogesterone caproate (or any other progestin) during pregnancy is a recipe for disaster as far as males are concerned, since it'll cause any development that takes place during the time it's being administered to occur as female instead of male. Considering that this is exactly what appears to have happened with DES, on quite a large scale and over several decades, without any of the medical staff administering the stuff realising what it was doing, this gives me no confidence that they're not continuing to do the same thing with progestin-based treatments.

Are there actual studies showing an association between the use of hydroxyprogesterone caproate and transsexualism and/or intersex conditions? If not, this is pure speculation. Time will tell.

[HughE]

But you mentioned pregnancy levels? How would you know if your levels weren't even tested? Progesterone transdermally is poorly transferred to the blood.

Synthetics were quickly abandoned for men's HRT, but until very recently they were the mainstay of women's HRT (I guess because women didn't complain as much about the horrible side effects they were experiencing). You'd think it'd be common sense that, if you're going to replace someone's hormones, you'd use hormones that are chemically as close as possible to the ones that occur naturally in the human body. However, common sense often doesn't feature very prominently in medicine, and other considerations such as pharmaceutical industry profit margins and the convenience of pills versus injections seem to be far more important. The result is that doctors have needlessly maimed and killed loads of women over the last several decades with non bioidentical hormones such as Premarin, Provera, DES and ethinylestradiol. They're not going to admit that of course!

The use of bioidentical hormones for women's HRT actually started with the alternative medicine movement, and because of that, mainstream medicine seems to be very hostile to it even now. At least, that's the impression I've gained. For instance, if you read this Wikipedia article, it has a very deprecating tone towards bioidentical hormones.

https://en.wikipedia.org/wiki/Bioidentical_hormone_replacement_therapy

In other words, the whole thing of using bioidentical hormones for women's HRT is highly politicized, and whenever that happens, science goes straight out the window and you get all sorts of studies that have been slanted to produce results that tie in with whichever side the author's ideology happens to lie on. Since progesterone cream is probably the single most widely used form of bioidentical HRT, naturally there are going to be a lot of negative studies about it coming from the medical establishment. 

What I can tell you from my own experience is that it does have an effect, although the effects are a lot more subtle than the effects you get from estrogen containing creams (estriol/estradiol).

Ask your mother, if possible. My mom confirmed to taking neither of these during her pregnancy. I'm certainly not alone, there are many like me.

In general, mothers are quite aware.

Not possible in my case unfortunately. However, you're wrong about mothers being aware of what medicines they were given during pregnancy. Their recollection of it is so bad that you can't do science based on what the mother remembers, you have to have access to the medical records. This is something Dr June Reinisch mentions in her research, and in this interview:

http://www.germlineexposures.org/reinisch-qa.html

When I interviewed these women after the pregnancy, they didn't know what they took—sometimes they didn't remember that they took anything. But I had read their records and I knew what the doctor gave them. I would say, for example, "Don't you remember taking little red pills every day?" "No." They were so focused on being pregnant, maintaining their pregnancy, having the baby, that they had forgotten all about it, including even when they received regular hormone injections. My studies included women who had been taking injections twice a week all the way through their pregnancy. Often they too had no remembrance of it whatsoever.

You should read that interview, and Dr Reinisch's 1977 paper that's linked within it. It isn't just theory that synthetic estrogens and progestins can disrupt both physical sexual development and sexual development of the brain in human babies, it's well established science that has been known about for a long time, but doesn't get talked about very much.