DHEA and intracrinology

As we have explained, most of our sex hormones are produced in our gonads: ovaries and testes. That means that in case of surgical removal of the gonads (orchiectomy/vaginoplasty, ovariectomy…), the vast majority (95%) of our sex hormones circulating in the body will be gone. This also means that after such surgery, transfem people on HRT could stop taking anti-androgens.

However, does suppressing our gonad-produced sex hormones really means the end of all masculinizing/feminizing effects of endogenous hormones?

Not exaclty. And this is where intracrinology and DHEA enters into the game.

Intracrinology is a subfield of endocrinology developped in the 1980s. In the framwork of sex hormones, it is mostly based on the activity of DHEA. DHEA is a hormone massively produced in small glands situated right above the kidneys, called adrenal glands. They produced a bunch of other stuff (including small amount of testosterone and estrogens directly).

Intracrinlogy figured out that DHEA (that makes for the most present hormone in the body) travels to target cells (such as skin, hair follicules, prostate cells…) and is converted there, on the spot, by those very cells, into testosterone and DHT. That means that there is a peripheral production of androgens: not in the gonads, but direclty in the target cells. And what matters is that these androgens will actually direclty activate the androgen receptors in the target cells that has just produced them. After that, they will be metabolized and realeased into the bloodstream as something else. Research has shown that surgical or chemical castration (i.e. by GnRHa) in AMAB people leads to an approximately 50% drop of androgens in the target cells of the prostate. That is far from the 95% reduction observed in the bloodstream androgen levels. And this is likely to be true of skin cells, including hair follicule.

This means two things:

• After a gonad-removal surgery, a masculinzing activity is likely to continue, namely in the prostate (which is not much of an issue for transfem people if you don’t have prostate cancer), but also in the skin and facial hair follicule (more anoying for many transfem), since around only 50% of androgens acting on those cells will be gone. However, if you were not taking an androgen blocker of the receptor blocker category (Bicalutamide) before surgery, this will not affect you much. Indeed, if before surgery you had manage to reduce your androgen level either by monotherapy, or by any other blockers than an androgen receptors blocker such as biculutamide, then your target cells were already affected by the local production of androgens from DHEA.
• The bloodtest values after surgery will not reflect the masculinzing activity happening from and in the cells, since, as we said, the androgens localy produced from DHEA do not leave the cell into the bloodstream before being metabolized into something else. This is why bloodtest results ususally show a 95% reduction of androgen after gonadal production suppression. Your bloodtest results will most likely show near 0 androgen (not actual 0 - which you do not want anyway - since the adrenal gland also direclty produces a small amount of androgens that is released into the bloodstream).

I speak here of “masculinizing activity”, and of the consequences of DHEA activity for transfem people, because the conversion of DHEA in the skin cells goes only towards androgens. AFAB people will also sythetise androgen in their skin cells from DHEA. In other words, skin cells are only equipped, in every people, to locally sythetize androgens. The vaginal cells, however, will locally produce estrogens from DHEA (which is why DHEA becomes a central hormone for people postmenopause, as it becames the main source of estrogens for the vaginal tissue.)

It is commonly observed a rise in andrenal activity in the few weeks following gonad-removal surgery. DHEA is increased, which leads to masculinzing effects (acne, facial hair growth…) for AMAB people after orchiectomy/vaginoplasty.

This data leads to reconsider the affirmation that an adrogen blocker is useless after surgery. This is true of most androgen blockers that acts - direclty or not - on the levels of the gonads, that is by stopping the gonadal production of androgens. The gonads gone, there is indeed nothing left to block.

However, it makes the case for continuation of androgen receptor blockers, namely bicalutamide, which will be the only solution to block the masculinzing effects of the locally produced androgens, sythetized from DHEA. This is especially true if you were already taking bicalutamide before, without any problem. You could, however, consider lowering the doses. Bicalutamide could prove particularly useful at least in the first few weeks after MTF/MTX bottom surgery, in order to block the effects of the increased activity of the adrenal glands typically observed after removal of the testes.

This also suggests the superiority of bicalutamide (and receptor blockers in general, but you might want to avoid spironolactone for other reasons) as an androgen blocker before surgery, since it is the only one who’s able to block the masculinizing effects of the adrenal activity.

Sources

Intracrinology

Is dehydroepiandrosterone a hormone?

Intracrinology and The Skin

DHEA, important source of sex steroids in men and even more in women

DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology

Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials