Quote from: spacerace on February 11, 2015, 10:56:47 AM
Thank you for all the information you have posted Hugh. I have more reading to do. It has been really helpful - I appreciate it. One thing I was going to ask you, as I saw it mentioned on of those threads - were you talking about progestins still in use causing both FTM and MTF development in different ways? How does that work in terms of what binds to what receptors, and when?

I'm not sure how much you know about synthetic hormones, but they're manmade compounds that are designed to activate the same receptors that the steroid hormones naturally produced in the human body do.

Steroid hormones control all sorts of different aspects involved in the day to day running of your body, which makes them potentially very useful from a medical point of view. However, the natural hormones suffer from a number of limitations: they're largely or completely destroyed by the liver if taken by mouth, so they generally have to be administered by injection; their biological half life tends to be quite short (particularly with progesterone) so they need to be frequently re-administered; and they often get converted into other hormones with completely different properties (eg testosterone converts to estradiol). Also, they're naturally occurring substances, so can't be patented!

Hence, the pharmaceutical industry developed synthetic hormones to overcome those limitations. Most of them are chemically modified versions of the naturally occurring hormones, although a few (DES is one) have a completely unrelated structure to the hormone they're mimicking. One thing pretty much all synthetic hormones have in common is that they're resistant (or often completely untouched) by all the systems the human body has in place for controlling and limiting what the natural hormones can do, and getting rid of them if they get into the "wrong" place. This is great from a medical point of view, since it means that they're generally more potent and longer acting than the natural hormones (and often orally active too), however it also means that they can cross the placenta and potentially have all kinds of effects on an unborn baby that the natural hormones wouldn't have.

There's 5 different classes of synthetic hormones (corresponding to the 5 different types of hormone receptor): estrogens, progestins, androgens (aka anabolic steroids), glucocorticoids (aka corticosteroids), and mineralocorticoids. The important ones from our point of view are the sex hormone mimics, the two female ones (estrogens and progestins), and the male one (anabolic steroids). Anabolic steroids mimic the action of androgens (testosterone and DHT); estrogens and progestins mimic the action of estradiol and progesterone respectively.

As far as I can gather, the only anabolic steroid that's seen any significant use during pregnancy is danazol, however, due to the fact that an insufficiency of female hormones has long been regarded as one of the main causes of miscarriage, both estrogens and progestins have been used very extensively.

Being female hormone derivatives, one property both estrogens and progestins share is that they're basically completely incompatible with maleness. Quite modest doses of either (well below what are commonly used for medical treatment in women) will completely suppress T production in an adult man. For instance, a dose of between 1 and 3 mg per day of DES is enough to completely suppress T production in prostate cancer patients, whereas the doses being used for miscarriage prevention were much higher than that - greater than 50mg per day throughout the second half of the pregnancy, which appears to be the critical period for gender development in the brain.

A similar situation applies with progestins. They're also highly effective at suppressing T production in adult men (the drug most commonly used to chemically castrate sex offenders in the US is Depo Provera, a progestin that's also used as an injectable contraceptive in women, and (I think) has been used in the past for miscarriage prevention). Apparently the same dose as is used for contraception in women (one 160mg shot every 3 months) is enough to maintain a state of full chemical castration in a man, although I've heard they double up the dose for sex offenders just to make sure!

Provera is the main progestin that's been used in males, however I understand that there's one called hydroxyprogesterone caproate that's sometimes used as part of MTF transgender HRT, and of course plenty of trans women have used birth control pills or contraceptive injections as a stopgap measure when they haven't been able to obtain legitimate access to hormones. Although they often add a small amount of estrogen to increase the effectiveness, progestins are the main hormonal component in womens contraception, and they all seem to work really well when it comes to shutting down T production in a male body. Hence, it's easy to how both estrogens such as DES, and progestins, could cause female brain development in biological males (and MTF transsexuality), by suppressing T production during the second half of the pregnancy.

However, there's a second property of progestins that mean that, under the right circumstances, they might be able to cause the opposite effect too, of causing male brain development in female fetuses.

One thing that happens when you start tinkering around with the chemical structure of hormones is that they often start to cross-react with non target receptor types. This is particularly a problem with progestins and anabolic steroids. Although they're based on testosterone and meant to target androgen receptors, a lot of anabolic steroids cross-react with progesterone receptors and thus, to varying degrees, act as progestins too. Likewise, most progestins cross-react with androgen receptors and have some anabolic effects. While the pharma industry carefully selected compounds that maximised the progestin effect and minimised the androgenic effects in adults, some of the early progestins turned out to have very strong androgenic effects on female fetuses (I gather this is thought to have been due to hormonally active breakdown products of the parent compound accumulating to an unexpectedly high level in the fetus).

There's yet a further complication to the story: there are two subtypes of androgen receptor, one of which is activated by either testosterone or DHT, the other only responding to DHT. We know from the monkey research that either T or DHT will drive brain masculinization (there's a condition called 5-ARD which confirms the same applies to humans too), which means the (T + DHT) receptor subtype must be the main one in fetal brain tissue. Conversely, genital masculinization only occurs in the presence of DHT, meaning that the DHT-only subtype must be the main one expressed in genital tissue.

What this means is that, if a particular progestin causes genital masculinization, then it's virtually certain that it activates the other, less selective receptor subtype as well, and can masculinize the brain. However, there's no guarantee of the reverse - just because it's not activating the DHT-only receptor subtype and causing genital masculinization, doesn't mean it isn't capable of activating the (T + DHT) receptors and masculinizing the brains of female fetuses exposed to it. In other words, since some progestins have been associated with virilizing effects, IMO that makes the whole lot suspect when it comes to brain masculinization (at least until proven otherwise).

I disagree. And honestly couldn't care less as to how I'm transsexual. I feel that finding a medical answer behind my transsexual biology would only depress me further and make me wish my mother hadn't conceived me even more, and ultimately the biology is unchangeable so it would only indefinitely trigger my dysphoria even more also. Maybe if the biology could be corrected like my presentation can be to a degree, I would care. My mother wasn't given progestins of any kind during her pregnancy with me, so I personally see that theory as illegitimate and a failure in practice, or a partial one in the least, maybe there is a risk but it only effects a percentage of unborn babies. I don't want to be negative or knock anyone but that's just my personal view.

I don't care how I am transsexual, biologically. Not knowing allows me to dissociate from the crap and psychologically negative impact it has on me and my functioning. And knowing would, at best, do nothing for me anyways, and in the worst scenario it would make my life more difficult and hate on myself and my parents even more than I already do, and it would reiterate how much of a freak I feel like and how unchangeable my biology is and will most likely always be. I don't need to be broken further. But each to their own.

-Trez

Quote from: ThatAussieDude on February 13, 2015, 07:07:18 AM
My mother wasn't given progestins of any kind during her pregnancy with me, so I personally see that theory as illegitimate and a failure in practice, or a partial one in the least, maybe there is a risk but it only effects a percentage of unborn babies.

No one's saying that medical hormones are the cause of all cases of transness, just that one at least (DES) does appear to be a significant factor causing both intersex-related abnormalities and MTF transsexuality, and there's good theoretical reasons for thinking that progestins could be a cause of FTM transness (especially since progestins are known to have caused some biologically female people to be born intersexed). Considering the unhappy lives trans folk often have and the high suicide rate, if there's an easy way to prevent people from ending up trans by just restricting the use of certain medicines during pregnancy, then obviously that's what should happen.

Also, if people knew that a lot of trans folk are trans due to a medical accident, I think it'd do a lot to improve public attitudes towards us and acceptance of us (and hopefully improve our prospects when it comes to healthcare, housing and jobs too).

Quote
I don't care how I am transsexual, biologically. Not knowing allows me to dissociate from the crap and psychologically negative impact it has on me and my functioning.

Doesn't it help to know that there's a physical basis to being trans, that it's not a psychological disorder but simply the result of the wrong hormones being present during the time your brain was developing, so you've ended up with a male brain rather than a female one? Once you know that, then it's just a matter of figuring out the best way of dealing with the situation that allows you to be the person you want to be, and live your life the way you want to. If I'd known what I know now when I was younger, I'd have lived my life very differently, and I think it would have been a lot less traumatic and a lot more enjoyable as a result.

I already know it is a physical problem. Doesn't necessarily mean I want or need answers to it. Having gender dysphoria removed from the DSM is far more important to me.

My dad's been trying to come up with a reason for my trans-ness for a long time now. Between ourselves we sort of concluded it probably had something to do with the fact that my mother went off the birth control pill the day before I was conceived, and that her hormones probably weren't quite back to normal yet.

Here's a few more links that make me think synthetic hormones (progestins in particular) might be a cause of FTM transness.

Firstly, there's this paper, Prenatal Exposure to Synthetic Progestins and Estrogens: Effects on Human Development:
http://www.germlineexposures.org/uploads/6/4/0/9/6409433/reinisch_and_karow_1977.pdf

Which clearly shows that some of the world's top psychologists have known for a long time that estrogens and progestins affect human brain development, and that progestins have masculinizing effects on female behaviour, e.g.:

QuoteEhrhardt and Money (1967) published a study often girls treated prenatally with synthetic progestins in which detailed inquiry was made into IQ and personality development. Analysis of extensive interviews given to both the subjects and their mothers demonstrated an unusually high degree of"tomboyism" in these treated subjects. Tomboyism was defined as "play with boys' toys; athletic energy; outdoor pursuits; and minimal concern for feminine frills, doll play, baby care, and household chores." Unexpectedly, the subjects also evidenced extraordinarily high IQs as measured by the Wechsler Intelligence Scale for Children, The mean IQ of the group was 125, with a standard deviation of 11.8. Sixty percent of the IQs were above 130, when only 2% would be predicted from a random sampling of the normal population.

Then, there's these two papers, which taken together have really got me thinking that progestins (or something else with androgenizing properties) might be an important factor behind FTM transness. The first one is a study of ewes (i.e. female sheep) that were exposed to testosterone in the womb, and ended up developing a pattern of disrupted endocrine function that was very similar to PCOS in human beings:
Prenatal Programming of Reproductive Neuroendocrine Function: Fetal Androgen Exposure Produces Progressive Disruption of Reproductive Cycles in Sheep
http://press.endocrine.org/doi/full/10.1210/en.2002-220965

Right at the end it says this:

QuoteOf interest is the observation that the compromised feedback and multifollicular morphology of ovaries from T60 ewes are remarkably similar to those found in women with disorders of androgen excess, such as polycystic ovary syndrome and congenital adrenal hyperplasia (36, 37, 38). Polycystic ovary syndrome is a disorder associated with abnormal follicle development, hyperandrogenization, and hypersecretion of LH and is probably the most common cause of anovulation in women of reproductive age (36). Many of these characteristics are also displayed by female sheep androgenized in utero (10, 32, 33, 34, 35, 39), raising the possibility that prenatal androgen exposure could be a developmental factor implicated in the etiology of this common disorder.

Put that together with the findings of this paper:
http://www.shb-info.org/sitebuildercontent/sitebuilderfiles/14_saito_et_al.pdf
Association between polycystic ovary syndrome and female-to-male transsexuality

QuoteRESULTS: Of the 69 participating FTM cases, 40 (58.0%) were found to have PCOS...Of 69 for whom androgens were measured, 29 (39.1%) showed hyperandrogenaemia...CONCLUSIONS: FTM transsexual patients have a high prevalence of PCOS and hyperandrogenaemia.

(hyperandrogenemia = above normal female testosterone production)

This is analogous to the way a high percentage of trans women (and in particular, DES-exposed trans women) have signs of hypogonadism (below normal male testosterone) even prior to starting on hormones.

One other thing folks here might find interesting is this paper:
Behavioral and Somatic Disorders in Children Exposed in Utero to Synthetic Hormones: A Testimony-Case Study in a French Family Troop
http://www.intechopen.com/books/state-of-the-art-of-therapeutic-endocrinology/behavioral-and-somatic-disorders-in-children-exposed-in-utero-to-synthetic-hormones-a-testimony-case

Although they don't mention ->-bleeped-<- in that paper, I've a feeling that France has quite a macho culture, and being trans might well have been the underlying cause of most of the suicides and psychiatric problems they're talking about, except nobody wants to admit it.

This discussion is so interesting to me. My 15 year old recently came out to me as FTM. Early in my pregnancy (6 weeks or so) I experienced bleeding during an exam, so the doctor had me take progesterone (maybe synthetic, I don't remember) to prevent miscarriage. If it matters, I was 36, and my baby was born 6 weeks early via C-section. With my second child, pregnancy was normal, and there are no signs of trans-ness yet. The cause makes no difference in my love and support of my child, but it's interesting to me. It may also help the grandparents be more accepting.

I don't know about hormones but I was a twin and my mom miscarried my twin.

Sent from my SM-G870W using Tapatalk

Hmm.

Well, for me, I have two older (straight) brothers, both had difficult births if that helps, so there had to be a c-section procedure performed upon both of them. My birth would have been natural, but since my brothers had c-section births, they decided it'd be best for my mother's health if I had a c-section, too.

I was born in 2001. My mother never smoked or drank, but she did eat unhealthily during her pregnancy with me. I'm also exclusively attracted to other men. I wonder how this would all work for me.

I find the science of how we become trans to be fascinating and I hope that some more research comes out soon on sex differentiation and the myriad ways it goes kablooey.

Hugh, what you said about T+DHT receptors vs. T-only receptors is interesting to me. I looked totally female at birth but my brain was masculinized. So your hypothesis would fit my case quite well. I have always wondered how I could have a male brain but no sign of maleness on my body. 

I find interesting as well, being that my mother who was sixteen when she got pregnant and was having tons of risky sex (no protection) and it took her 13 months to get pregnant with me. Though she had one questionable six months before me.  Adding in she has a very masculine build (more like a trans woman then cis), and questionable health issues (that she has PCOS).

For me while I don't have proof I have always assumed it was due to her have messed up hormones her own self (though my grandmother is the same way with the same issues). Same reason why my aunt and uncle who are twins are both bi. 

Quote from: momofftm on May 23, 2016, 03:41:43 PM
This discussion is so interesting to me. My 15 year old recently came out to me as FTM. Early in my pregnancy (6 weeks or so) I experienced bleeding during an exam, so the doctor had me take progesterone (maybe synthetic, I don't remember) to prevent miscarriage. If it matters, I was 36, and my baby was born 6 weeks early via C-section. With my second child, pregnancy was normal, and there are no signs of trans-ness yet. The cause makes no difference in my love and support of my child, but it's interesting to me. It may also help the grandparents be more accepting.

Sorry to side track the thread for a moment. I wanted to take a  moment to welcome momofftm to our site. So glad you found some helpful information. I hope we are able to provide you with much.

I also wanted to mention that there is an area here called SO(Significant Others). It is also for support of the family of a trans person. There is an area here your son might find helpful  called  Youth Talk. He could potentially share common stories (or differences)with others his age.

Lastly, I wanted to share some links with you. They are mostly welcome info and the rules of the site. If you have not taken a moment to read through them, please do so:

Site Terms of Service & Rules to Live By	Standard Terms & Definitions	Post Ranks (including when you can upload an avatar)
Reputation rules	News posting & quoting guidelines	Photo, avatars, & signature images policy

It is so amazing to see parents come on to the site looking for information. It shows the depth of love and commitment we all would want. It is inspirational.

Once again, welcome to Susan's. I hope we can help you find what you are looking for. On behalf of the members, thanks for being the kind of parent you are.

With warmth,

Joanna

PS Now back to your regularly scheduled thread.

Progestins (synthetic hormones that mimic the action of progesterone) are known to be capable of physically masculinizing a female fetus if exposure to them occurs during the first trimester, so it's only commonsense that they would also be capable of masculinizing the brain.

This is an interview I did recently with Transition Radio:
http://www.transitionradio.net/hugh_easton.html

which is co-hosted by Mark Cummings, a trans man whose mother was given miscarriage treatment with what we think were progestins (I was hoping he'd talk about his experiences a bit more during the interview, but unfortunately he remained quite cagey). The interview is mainly about DES, but there's a segment he included 57 minutes into the interview taken from a video, "Hermaphrodites Speak", of Mani Mitchell, another victim of progestin-induced virilization, who is presenting as female in that segment, but if you see some of the other videos she's done more recently is clearly nonbinary. I had another person who was progestin exposed comment recently on a post on my facebook wall, and from what they said, their gender identity has clearly been affected too. Considering that hardly anyone who's been exposed to these hormone treatments knows anything about it, it makes me think that progestin exposure could be an important cause of FTM transsexuality.

Quote from: Charles96 on May 23, 2016, 10:09:45 PM
For me while I don't have proof I have always assumed it was due to her have messed up hormones her own self (though my grandmother is the same way with the same issues). Same reason why my aunt and uncle who are twins are both bi.

There's already data showing such issues are intergenerational between XX people. No reason to assume that introducing artificial hormones is the only pathway. My maternal grandmother and great grandmother were both tough women with an arm's length attitude towards men. It is in fact possible that grandma got prescribed hormones b/c of a history of miscarriage but the youngest, which she nearly lost (was on bedrest for months), turned out normal fwiw. (He is a jerk. But het cis male and a HS star athlete.) But you wouldn't need drugs to explain my mom, butch and bisexual, or me, on the lesbian/ftm spectrum. (I had no endocrine "abnormalities" on my labs on starting T.)

Let's throw another theory onto the pile. I have noticeable (to me) facial asymmetry. That's a sign of a high number of genetic copy errors (over 300). I've noticed a lot of other FTMs who post videos online also have visible facial asymmetry. (This is also associated with autism spectrum, and ASD ppl are more likely to be trans. Confounder!) Obviously we can all agree the FTM thing happens during fetal development. Maybe some of us have genetic quirks that initiate it?

As far as I am aware, my mother took no hormones during her pregnancy with me. I was her first, and unexpected. I have no idea what her natural hormone levels were like, however. Like me, she has severe PCOS - runs in the family.

Quote from: WorkingOnThomas on May 25, 2016, 03:06:45 AM
As far as I am aware, my mother took no hormones during her pregnancy with me. I was her first, and unexpected. I have no idea what her natural hormone levels were like, however. Like me, she has severe PCOS - runs in the family.

PCOS can be experimentally induced in animals by prenatally exposing them to testosterone, the same hormone that masculinizes the brain, e.g. see:

http://press.endocrine.org/doi/full/10.1210/jc.2005-2757

QuoteStudies have shown that female rhesus monkeys exposed in utero to levels of testosterone equivalent to those found in fetal males develop clinical and biochemical features in adult life resembling those observed in women with PCOS.

Since you have both PCOS and a male gender identity, that's a good indication that you had some kind of androgen exposure during your prenatal development, which has both given you a male brain and led to you developing PCOS. Since you say no hormones were used and PCOS appears to run in your family, maybe your family have some kind of genetic predisposition to producing high androgen levels. Who knows. I'm not saying that pharmaceutical hormones are the only cause of transsexuality, just that administering external hormones during pregnancy is one of the things that can do it, and this isn't being taken into account in current medical practice.

Interesting! I don't really care about the WHY of my own trans-ness but this thread has been an interesting read.
As for me: I was born in 1970 and was was my mother's first (as far as I know) pregnancy.

Yes, my mother had miscarriages before, and after, me. To my knowledge though she was not "trying" for a child. I was an accident, as my father so nicely put it - but she also claimed she was on birth control pills, and insists she hadn't forgotten to take any in the schedule, which also makes me a bit of a "miracle", apparently. She says she was on no other medication. So essentially she didn't want to be pregnant and wasn't feeling particularly broody at the time. My father's accident comment is consistent with this.

Female hormones should not though - far as I know lead to masculinization of a female fetus in the same was as certain substances are know to in a male fetus.

What I do know though, is that just prior to, and during her pregnancy with me, she was experiencing a turbulent life. She was only 20 years old, a big party goer and drinker, and had just been turned out of her family's house for some reason and was occasionally sleeping in a car before her older brother stepped in to help. She and my father had a very brief marriage, marked by some savage fights and disagreements. Various family members mentioned how she was "very stressed" at this time, in different conversations. As a person she is quite petite and feminine-looking, but had a raging bull personality, was a violent and aggressive person when drunk, particularly in the younger years. I would not be surprised if this "stress" caused or was caused by hormonal imbalances because she certainly has a more masculine than feminine personality. Hormonal imbalances that could well have led to my digits having the typical "straight male" ratio length, and my current trans condition. 

It's definitely not nurture or some kind of imitation, as I've had a lifelong loathing for her aggressive behavior and never considered it acceptable.

I'm always torn between wanting to know what causes us to be transgender, and afraid that if we knew it would invite some kind of eugenics, and that people who truly felt trans would be rejected because they fail a medical test for whatever cause is found...

I've been thinking about this for a while. If being intersex and transgender are both caused by hormone imbalances during development of the fetus, that makes them pretty similar, right? In the case where someone's gender is binary, an intersex person will have sort of mixed genitals (from what I gather), while a trans person completely has the body of the opposite sex. This would imply that there's a scale, with cis being at one end, trans (with binary gender) at the other end, and intersex in between. Not only does this mean that the cause of being trans is biological, it also implies that it's just a more extreme version, or the next step, after intersex. What do you guys think of this?