Quote from: anjaq on September 16, 2014, 08:05:00 AM
Yes, you are right, the injections contain Hydrogyprogesterone caproate.
So one would have to check its properties, not MPAs
As far as I can tell, hydroxyprogesterone caproate is a progestin with similar properties to MPA, except that it's a pure progestin and doesn't cross react with other receptor types to any significant degree (whereas MPA cross reacts with androgen and glucocorticoid receptors I think).
Most long chain steroid esters (eg estradiol valerate) are regarded as "prodrugs". Once they get into the bloodstream, the ester bond usually breaks fairly easily and releases the active steroid molecule, and all having it in the ester form does is make it more fat soluble, so (when it's dissolved in oil and given by IM injection) you get a gradual release of the hormone into the bloodstream and so you only need to give injections once a week or even less frequently. That appears to not be the case with hydroxyprogesterone caproate though, from what I was reading, the ester bond never breaks and the molecule remains intact until it's broken down in the liver. In other words, the hydroxyprogesterone caproate molecule itself is the active compound, meaning that it's a bona fide progestin and not a slow release form of 17-hydroxyprogesterone. I get the impression that fact might not have been realised until after it had already gone into production and was being used as a medicine.
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(Whether the effects of testosterone are interrupted for part or all of the pregnancy) That is so , for sure, although I guess usually the medication is given all over the time of the pregnancy. I am not aware though of any significant reports about an influence on the body - significant feminization - in children who had a possible exposure in early fetal stages - this would have to be the case, would it not?
With DES, treatment was often started in the first trimester. With hydroxyprogesterone caproate, treatment normally starts between 16 and 21 weeks into the pregnancy. That makes a big difference as far as genital abnormalities are concerned, and explains why there were (going on what I've seen) high rates of often quite severe genital abnormalities associated with DES, whereas you'd expect far fewer physical abnormalities with hydroxyprogesterone caproate, purely because it's started too late in the pregnancy to have much effect on genital development. It could still be suppressing testosterone and driving female brain development though, for both drugs the treatment period covers more or less the entire second half of the pregnancy, the time when the brain development responsible for gender identity later in life seems to take place.
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Hormone control? Thats interesting since we were thinking on whether or not the hypothalamus of different individuals with different types of transsexuality can react differently to hormones. in some, estradiol alone lets the internal testosterone drop, in others you need progesterone as well and in others nothing works and they need antiandrogens. Is there more work done on that subject?
In my early days of trying to find out what hasd happened to me, I discovered that there'd been quite a bt of research conducted on sheep, in which they used testosterone injections or implants at various stages of the pregnancy to create female sheep - ewes - that had had parts of their prenatal development pushed down the male pathway instead of the female one. One thing they discovered was that there's a fairly narrow developmental window in which the hypothalamus gets patterned as either female or male. In some of the experiments, they produced ewes with a male hypothalamus. Those sheep were unable to produce the "LH surge" that triggers ovulation, and the result is that they developed ovarian cysts and higher than normal androgen levels (symptoms that sound very similar to PCOS in women!).
Here's one where they were more looking at behavioural effects, however most of their sheep no longer had oestrous cycles, something which is under hypothalamic control:
"The sexual behaviour of prenatally androgenized ewes observed in the field"
http://www.reproduction-online.org/content/49/2/311.longThat paper shows quite well how exposure to external hormones can affect genital development, hypothalamic hormone control and several different kinds of behaviour more or less independently of each other, depending on when exposure starts and ends. It also shows how hormone exposure can produce sheep that have some aspects of their behaviour male and other aspects female, which was quite an important insight for me, since it explains how I could have ended up with some parts of my identity female and other parts male!
Here's another one, that was looking specifically at the effects of testosterone exposure on hypothalamic hormone control:
"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.2002-220965That one was quite insightful for me too, because in that experiment, their sheep were fertile and able to breed while still young, but their "reproductive axis" became progressively more disrupted with age, rendering them completely infertile by their second breeding season. In my case, I've had symptoms of hypogonadism all my life, however it didn't adversely affect my health while I was young, and I successfully fathered two children. However, the whole thing went pear shaped in my early 40s, when my testosterone production appears to have collapsed more or less overnight, and I started to develop a lot of health problems as a result.
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What do you mean "part of you" - another part of you wants a male body with all that goes with it physically?
Do you have a clear male gender identity or what is it that causes you to say you are definitely not a woman?
It's kind of difficult to explain, but I experience life a bit like I'm made up of two separate identities, a male one and a female one. I think there's an actual physical basis to it, and it's due to there being no testosterone present during the early stages of my brain's sexually dimorphic development, but normal male levels during the later stages. It's given me a brain where some parts are male and other parts are female, and a personality and behaviour to match.
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Well I guess it is more random than that. For me, if those injections caused anything, they were there from the start. Sadly the lack of T did not feminize my body though. So I am not sure there was an effect of it at all or if it was just pure chance. Do you have data on your exposure to something that can pinpoint the times a bit?
Unfortunately, my mother passed away in 2010, so I'm unlikely to ever know for sure what happened. Whatever it was must have taken place very early during the process of building the permanent structure of my brain though, which apparently starts about 17 weeks after conception. Although I went through a lot of the same social difficulties during my teens that DES sons seem to commonly experience, and I've got the feminine body structure and hormonal problems that seem to be a common feature of DES exposure too, there was no medical reason for my mother to be prescribed DES. Also, I seem to have undergone a lot less female brain development than is typically the case with DES. I think that's because the period when my testosterone was disrupted was limited to the second trimester only, whereas with DES (and with hydroxyprogesterone caproate), the exposure nearly always covers more or less the entire third trimester as well.
My thought was that it does look a lot like what might happen as a result of a failed attempt to end the pregnancy by talking an overdose of birth control pills. My mother suffered from quite severe depression when I was younger, and I have confirmed that they were using birth control pills for conrtraception - the high dosage first generation ones. There's also something that happened during my childhood that makes me think she could have been hiding a guilty secret along those lines. I'm unlikely to ever know for sure if that's what happened though. It's impossible to completely rule out DES as the cause, because they were adding it to pregnancy vitamins and using it as a growth promoter in cattle. There have apparently been instances where the DES implants weren't removed from the slaughtered cattle, and high doses of DES ended up in peoples food as a result.
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(Regarding the almost universal female gender identity in CAIS women) Well, I disagree on the latter part - maybe on youtube it is so, but in reality it is more diverse and some have a rather male expression of behaviour even. Part of it certaily is that body leads to role and both lead to a certain behaviour that is expected. But yes - in most cases it seems to be so, I do not know if CAIS would also limit the expression of enzymes converting T to E2 int he brain - those would probably only be produced if there is T and that is sensed by Androgen receptors which are broken...
Nope, one striking feature of CAIS is that it seems to produce people who are invariably highly feminine and identify as female. If you look at this paper:
"Male gender identity in Complete Androgen Insensitivity Syndrome"
http://link.springer.com/article/10.1007%2Fs10508-010-9624-1#page-1The first thing they say is that CAIS women invariably have a female gender identity, and their patient is the first reported instance of a CAIS women with a male gender identity. As rare DSD's go, CAIS is actually quite common, due to the fact that genetic females are carriers, so it can be passed from generation to generation. There are thousands of CAIS women alive today, and just that one reported instance of one with a male gender identity. Maybe that person has a mutation that means their gene for male brain development is always switched on even in the absence of testosterone, who knows.
CAIS more or less proves that brain masculinisation in humans must occur entirely through androgenic hormones and androgen receptors, because everything else in CAIS is exactly the same as it is in normal males. Their aromatase enzyme, estradiol production and estrogen receptors are all fully functional, in fact CAIS women are able to produce enough estradiol so that they go through a normal female puberty (except they don't menstruate, due to having no uterus). The only thing that's different is that their androgen receptors are nonfunctional, so all their development takes place as if there were no testosterone present.
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Do you happen to have a paper that describes virilization in the brain in humans to be different than in rodents?
Not off the top of my head. The first 3 sections of this paper:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654067/give quite a good summary of the importance of testosterone in driving male brain development, however later on they start quoting research conducted on rats, and how externally administered estradiol masculinises the rat brain (with the implied assumption that the same happens in people). That can't be true in humans though, because if it was, CAIS women would predominantly have male gender identities, and DES daughters would identify as male rather than DES "sons" identifying as female.
This one mentions that both testosterone and DHT masculinise the brain of Rhesus monkeys:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458140/However, even that one starts saying that estradiol plays a role too, and quoting rat research to support that claim.
