A technical question about Swyer Syndrome and CAIS

[QuimReaper]

I have become interested in these syndromes as a result of their getting a lot of discussion on these boards, and although this question has nothing do with FWR, posters here seem exceptionally well-versed in DSDs, so I hope nobody minds me popping a couple of incidental questions here.

First: my understanding is that without hormone treatment, children with Swyer Syndrome never experience puberty due to lack of gonads. I'm just wondering, what actually happens in cases where Swyer Syndrome goes untreated (as must have happened historically and globally)? Or in general when someone doesn't experience puberty for some other medical reason? Do they stay in a pre-pubertal state for their whole lives, and is their life expectancy normal?

Secondly: my understanding is that people with CAIS produce testosterone, but do not at all respond to it; but that all bodies (XX or XY) produce some amount of oestrogen (I think in the pituitary gland?) and it is this that CAIS cases respond to, resulting in an apparently female appearance.

If I'm right about that, why is it that the same isn't true of Swyer Syndrome? And if I'm wrong about that, how is it that people with CAIS do experience female-typical puberty (breast growth etc., although obviously not menarche) and those with Swyer don't?

Thanks in advance to any clever MNers who can answer these!

Fascinating questions! Here's the original paper by Swyer, which suggests they would have been tall,.slightly androgynous infertile women.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1980764/pdf/brmedj03225-0025.pdf

Interestingly, he describes them as male because of their chromosomes, which we would not do today.

Thanks for this, fascinating!

@simmertime This is super interesting, thank you!

The pubic hair growth seems to be the only thing (except height) that really differentiates Swyer patients from pre-pubescence, I wonder why it is that that occurs in isolation.

It will be a gene we have yet to work out. The same thing with height. It was thought that what determined height was the same genes that determine sex, but we now know that is not the case.

Interesting, thanks GCITC.

I suppose it is also probably the case that there are other development hormones swimming around than just testosterone and oestrogen which people may react to in isolation; and that might make people with CAIS more responsive to oestrogen than those with Swyer Syndrome, and therefore go through near-typical growth and puberty. Like how it is the interaction between testosterone and DHT that determines the outcome of sexual development in males, the absence of which leads to 5ARD cases.

(I'm just spitballing here.)

https://www.researchgate.net/publication/257752667_Differentiating_Swyer_Syndrome_and_Complete_Androgen_Insensitivity_Syndrome_A_Diagnostic_Dilemma

This might help.

Those with CAIS are genetically male. Their condition means that their body cannot process testosterone. This means that their body does not masculinize, either in utero or at puberty.

Those with Swyer Syndrome are missing specific genes that determine maleness. In many cases the SRY gene is missing from the Y chromosome. It is this gene that kicks off the masculanization process in utero. In other cases they are missing proteins that cause male development.

Those with CAIS go through puberty because their underdeveloped testes still produce testosterone, which the body turns into oestrogen, leading to female puberty. Those with Swyer's have streak gonads, which don't produce hormones and therefore puberty doesn't occur without medical assistance.

It should be noted that we don't know everything. We still have a long way to go in working out the human genome. We don't know what every gene does and how they interact. We've come a long way from human hermaphrodites but we still have a long way to go to fully understand the wonders of sex.

Can I add a question? I’ve seen ‘penis at 12’ mentioned. Does that mean that some people who are xy but born without clearly male genitalia do in fact ‘grow’ a penis when the go through puberty? There is an old article on the bbc about a whole village in s America where this happens. Is this what caster semenya has (and the Olympic boxers)?
www.bbc.com/news/magazine-34290981.amp

QuimReader I'm no biologist, I have no formal education in this field but I am one of those that was told to 'do my research' and so I've spent many an hour reading studies into DSD's and listening to those with these conditions.

I like the fact it reminds us that in the grand scheme of things we are still quite thick, in that there is a lot we don't know.

I think there is a failure in education, insofar as we told what we are learning is the truth, when in actual fact we are being taught the basics, a lot of which doesn't stand up to scrutiny, and we therefore come out of school thinking we know everything.

With these sorts of questions, even the specialists in the field can only answer with 'what we know right now' because discoveries are always being made.

This specifically refers to 5ARD, the condition that Caster Semenya has and what is thought the two boxers may have)

People with this condition have XY chromosomes with the SRY gene. What they don't have is the enzyme that processes testosterone into dihydrotestosterone (DHT), which in layman's terms is supercharged testosterone.

In utero DHT plays a critical roll in forming external male genitalia. Because those with 5ARD don't produce this they are born with ambiguous genitalia. This could be a combination of large clitoris/small penis, apparent vaginal opening, fused labia, non palpable testes etc.

Those with more typical female genitalia may be denoted female at birth.

At puberty, their testes start to produce hormones like any other male. This results in the growth of the penis (hence penis at 12) alongside other masculanization. As a result of not producing DHT those with 5ARD may grow less body hair and have a smaller prostate than other males, but they are the main differences.

Basically those with severe 5ARD are born with female appearing genitalia and are therefore wrongly assigned female until puberty hits.

Just to add to that, those with 5ARD do produce sperm and can father children with medical help.

I'd add that all bodies also produce testosterone as we know from menopause, declining anounts of testosterone affect women too.

Yes but there is a vast difference between the amount of T produced by Males and Females - there is no overlap between the highest T levels in women and the lowest T levels in men

Sorry, I should have made it clearer, I was responding to OPs statement that 'all bodies produce oestrogen' to add that they also produce testosterone. CAIS individuals presumanly produce much less O than a person with ovaries in the way that people without testes produce much less T?

OP had said that it was this (non-ovarian) oestrogen that CAIS individuals were responding to when they developed)... individuals with Swyer don't have any functional gametes so will only be exposed and potentially respond to, the lower levels of O & T that are produced by non-gamete tissues and which may be too low, or counter each other enough to prevent any puberty like changes...

I've just been sent a graph which says otherwise - there is overlap. BUT one axis was "gender". so did it include XY as "women"? therefore meaningless
and very ill women?

their underdeveloped testes still produce testosterone, which the body turns into oestrogen

I didn't know this was possible!

Thank you all so much for contributing to my understanding here.

OP had said that it was this (non-ovarian) oestrogen that CAIS individuals were responding to when they developed)... individuals with Swyer don't have any functional gametes so will only be exposed and potentially respond to, the lower levels of O & T that are produced by non-gamete tissues

This is an interesting point. Presumably both CAIS and Swyer individuals are exposed to similar levels of (non-ovarian) oestrogen, but Swyer individuals, unlike CAIS, would be sensitive to any (non-testicular) androgens, which would explain their differing presentations.

One thing I am still puzzled about is the suggestion (from Emma Hilton) that CAIS cases appear to be over-represented in elite sports. I'd have thought a complete insensitivity to testosterone would actually put that person at a disadvantage to natal women. Although she did concede that her CAIS figures might include PAIS, so I suppose the jury's still out on that one.

It's posited that their height and lack of menstrual cycle may give them the edge over other women.

Simply it's something we don't really understand yet.

One thing I am still puzzled about is the suggestion (from Emma Hilton) that CAIS cases appear to be over-represented in elite sports. I'd have thought a complete insensitivity to testosterone would actually put that person at a disadvantage to natal women. Although she did concede that her CAIS figures might include PAIS, so I suppose the jury's still out on that one.

This puzzled me too, I was thinking it must be PAIS, not CAIS!

I've been listening to Testosterone by Carole Hooven on Audible. I'm nowhere near finished, but it's been a good introduction to the topic of DSDs. It's certainly changed my more basic stance on "XY should always be excluded from female spaces" since I think those with CAIS are the exception - many don't find out until puberty and display female typical behaviours, have female appearance and feminized genitalia.

I don't feel I know enough about CAIS to say whether I feel it's fair for them to compete in female sports or not; I see they have a potential advantage based on height and lack of menstrual cycle, but in those cases there are plenty of women who might have those advantages. CAIS cannot by definition benefit from testosterone which seems to be the leading cause of sex differences in sporting ability.

Conversely, having binge watched "I am Jazz", Jazz is reported to have had exceptional sporting ability (for a "girl") in spite of having his puberty blocked, so I do think there's more to it - although this is obviously one person!

It's such an interesting topic, but the more I learn, the more angry I get that the trans movement use those with DSDs to further their cause, when it really is a completely separate issue.

One thing I am still puzzled about is the suggestion (from Emma Hilton) that CAIS cases appear to be over-represented in elite sports

Over represented in FEMALE sports though, so clearly they do have increased T, suggesting either there is no such thing as COMPLETE AIS, or these individuals have PAIS, albeit with low amounts of T. Plus of course lack of menstrual cycle which affects female athletes.

I would expect CAIS individuals to be exposed to more estrogen than Swyer, as with Swyer the gonads don't produce either estrogen or testosterone, so they will have low levels of both.

With CAIS there is a high circulating level of testosterone, some of which will be considered to estrogen via the enzyme aromatase.

So it just could be that CAIS has more estrogen than Swyer. Or it could be the balance between the two, as CAIS has no response to testosterone, so is only responding to the estrogen?

It’s very interesting, and I’m relieved to hear Swyer thought it was a male DSD, as it makes more sense than otherwise.

It makes no sense to assign M/F based on appearance! Perhaps it seemed kinder back when we didn’t have our current issues!

As far as I know, it's never been established whether males with CAIS or Swyer syndrome develop male-pattern skeletal and muscular structure. Men have proportionally longer legs, straighter hip-leg placement, straighter arms and more fast-twitch muscle (more oxygen, greater explosive power). Any one of these would be an advantage in sport.

If it hasn't been a topic of much importance until now, it's certainly becoming one!

Thinking about it, those males could also have the larger hearts & lungs enjoyed by men, as their torsos don't need the extra room for reproductive organs. No idea whether that's the case.

I agree with this, although I think we have two scenarios at play. Scientific and social - scientifically both are male. But socially those with CAIS have everything female about them (according to the Carole Hooven book). I've also listened to a Gender: A wider lens podcast episode where they interviewed a person with CAIS. Socially it would genuinely not be "kind" to refer to them as women, although unless you knew a person had CAIS, you genuinely would have no clue and refer to her as a woman.

This is why it's different from the trans debate. A person who has "womanly feelz" should not be given access to spaces for women, no matter how well they pass, and no matter how "unkind" it might be to not let them in.

A person with CAIS is SO feminized and socialised as female, and has female associated behaviours (to the point those with CAIS have female-typical jobs, don't tend to be attracted to other women; again from Carole Hooven's book) that it just feels pretty cruel to say "you can't get changed in my changing room". When it comes to sports though, I haven't a clue. I don't know anything about Swyers so have no opinion (yet!).

With 5-ARD, the "Caster Semenya" DSD, many are socialised as a girl if they have feminised genitalia when they are born, but it seems they're often "tom boys" due to the effects of testosterone, even if the lack of DHT is causing them to lack fully masculinisation. I once saw an interview with Caster Semenya where he was talking disparagingly about girls and women, and said he grew up playing with the boys.