There are many people with 21-hydroxylase deficiency of some kind (1 in 66 in some ethnic groups, about one to ten per thousand overall). And the genetics aren't linked to sex chromosomes, so it should be equally common among XX and XY genotypes.
But there's a lot more information about XX-CAH, probably because it's a more obvious condition. To be honest, I hesitate to say "XY-CAH is an intersex condition." Most of the effects are weak or super-masculinizing.
But... I've been thinking. Here's what we know.
12-OHase is an enzyme that produces corticosteroid hormones. These signal that a person is hungry or thirsty, causing them to conserve water and release stored sugar into the bloodstream. Corticosteroids also rise in response to stress, injury, and waking up.
If the activity of 12OHase is restricted, the brain has to produce more ACTH. This produces more progesterone in the adrenal glands, which turns into androstenedione as a side product.
Here's where things get sex-specific. Androstenedione is, basically, a sex-neutral sex steroid. Testes (Leydig cells, specifically) convert it to testosterone, ovaries (granulosa cells, specifically) convert it to estrogens. However, both pathways are found elsewhere in the body, so everyone produces some T and some E from androstenedione.
And thus, CAH raises both testosterone and estrogen.
So, ovaries can't use all the extra androstenedione. The extra T and backed-up androstenedione can both attach to and stimulate androgen receptors. The overall effect ranges from minor virilization to ambiguous genetalia.
Boys get a blood test for the life-threatening CAH. And that's it.
Here ends the conventional medical knowledge.
Okay, so what can we expect androstenedione to do in boys and men (properly, XY genotype and testes)? Well, the stuff has been tried as a performance-enhancing drug, so there are some answers there. Not much, in terms of sport enhancement, so dopers have stopped using it.
And, I think, the answer is in how the androstenedione interacts with already-high testosterone. Yes, it still activates androgen receptors, but:
- extra estrogen is produced. Since there's little estrogen to start with, this effect is relatively strong.
- estrogen down-regulates testosterone production in the testes
- this increases the androstenedione:testosterone ratio
- and causes a higher fraction of the androstenedione to be converted into estrogen
- some androstenedione knocks testosterone and DHT off the androgen receptors. Androstenedione is much less active.
Thus, the androgenic activity stays about the same, maybe increasing, maybe decreasing. Estrogen is increased. Androgen is steady at at a medium-high level of effect.
If the Leydig cells are turned further down (stress decreasing LH and FSH for example), this shift from androgens to estrogens will be stronger.
Again, this is only theory on my part. I'm not a doctor or biologist, but here's what I predict.
Infant CAH boys are normal, maybe having slightly larger penis than average.
During childhood, CAH boys are mostly normal. They may get cranky, dizzy, nauseous, and shake if they go too long between meals - this is a result of poor corticosteroid production. Salt makes them happy, sugar does not make them hyper. They're average-to-tall, keep baby fat, and start puberty a little to a lot earlier than their peers. The extra estrogen might make them a bit more emotional, but nothing conclusive.
Puberty is crazy. I mean, it's crazy for everyone, but this is the point where estrogen and testosterone start to fight, even more so than is typical for males. When testosterone gets too high, it is converted to estrogen, see, which stimulates bone growth. They become tall, fast.
This takes a lot of energy. If they outpace their digestion, they start to starve. FSH and LH fall. Typically, this would put the brakes on testosterone production. Typically, this would slow estrogen production, because typically male estrogen comes from testosterone.
Typically. But decreased T production makes more E leak in the back path.
CAH boys reach adult height quickly, and then testosterone seals their growth plates. Like girls, actually, who reach adult height by 16 years of age. Likewise, I might expect feminine skeletal characteristics such as large carry angle of the elbows and wide hips.
Once growth plates seal, limbs do not grow longer. However, estrogen can still trigger growth in hands, feet, jaw, and forehead. These are exactly the side effects caused by anabolic steroids. Of course, CAH boys don't get extreme androgenic / anabolic effects because androstenedione cannot go as far as T
CAH men are short, skinny-limbed, and wide in the palms in knuckles - in comparison to their long, almost delicate fingers and limbs. Their jaws and cheeks are square. They have big hip bones, but their fast metabolisms lean them down to muscle and bone. Their arms do not touch their hips when palms face forward. They bald quickly and have acne. They are, emotionally, rather sensitive, even feminine.
In theory. A lot of this might be confirmation bias on my part. I'm very curious to have this tested. (Going to do an adrenal test next week, getting my T and LH results back soon-ish...)
