Quote from: KayXo on November 09, 2016, 08:40:35 PM
Hydroxyprogesterone caproate is a progestogen with similar properties to progesterone that is produced in high quantities during pregnancy. It does not have estrogenic effects, only progestogenic ones. As such, how could it induce feminization of the brain? Is there any evidence supporting your thoughts?
Well, more accurately, it could prevent masculinization of the brain taking place, by suppressing testosterone production.
People often seem to assume that, just because DES is a very powerful estrogen, it caused MTF transsexuality through estrogenic effects on brain development. I think it actually causes female brain development in male fetuses by shutting down testicular hormone production. This is due to the fact that male brain development (as with other aspects of sexual development) is driven by the action of androgenic hormones produced in the testicles (primarily testosterone and DHT), and without those hormones, development occurs as female instead. Although there are species differences, in primates, the sex you develop as appears to be entirely determined by androgen levels, and estrogens don't appear to play any significant role.
It's not actually the Y chromosome that causes a genetically male person to develop as male. All the Y chromosome does is cause the undifferentiated gonads to turn into testicles, it's the hormones produced by the testicles that actually drive male development. If, for whatever reason, the testicles fail to develop and produce their hormones, then a genetically male fetus will develop as female. Here's an example I found on youtube of someone this actually happened to:
The particular condition she has, Frazier's Syndrome, involves a mutation that has nothing to do with the X or Y chromosomes. What it does is to knock out a gene that is required in order for the undifferentiated gonads to turn into testicles or ovaries, and without that gene, they remain forever trapped in their undifferentiated state. Although she is genetically male and her Y chromosome is completely normal and fully functioning, her gonads remained undifferentiated and never turned into testicles. No testicular hormones were produced during her prenatal development, and because of that, she developed as female instead of male. You can see the results in that video. Provided the NHS didn't butcher her, she will have the full set of female internal organs too, including cervix, uterus and fallopian tubes.
In other words, it's the testicles and the hormones they produce that cause a fetus to develop as male, and without those hormones, development occurs as female instead.
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.
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).
It just so happens that, because of the way development occurs in the unborn child and the way these treatments tend to be prescribed, that you tend to get a high exposure during the time the brain is developing and a much smaller (or zero) exposure during the critical period for genital development, so they're tending to produce people with a relatively normal male appearance, and it's the brain that is ending up female instead.
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.
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. 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).
