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!

It doesn't seem to me there is any good reason to exclude women with CAIS or Swyer from female sport.

The possible advantages - being taller, not having periods, could apply to other females and being taller wouldn't be an advantage in all sports anyway.

Our whole case about female sports rests on "excluding male advantage". What's going to happen when a CAIS woman is excluded and the world is told they can't benefit from testosterone? We're going to say "oh well, they're a bit taller than average....."?? How's that going to make us look?

Also, if our case is all about fairness, what fairness would there be in forcing CAIS women to compete in the male category, where they'd clearly be at a big disadvantage?

Emma Hilton, Ross Tucker and others have said what we need is a screening test - everyone without a Y is "passed" automatically, anyone with a Y will have further tests. In reality, if the test was conducted at 18 anyone with CAIS would probably already know it and could just submit medical reports instead of doing the test.

Very interesting.

I don’t know, @HPFA

We group by sex, not height or any other marker.

If people with a specific health condition that impacts which group they join are over represented at elite level sport, should they be competing?

Many people can’t compete at elite levels.

Actually scrap that. It’s all irrelevant, this isn’t about sports, this is a technical question about how DSDs are assigned male or female disorders, not who should do sport.

We group by sex not by other markers because the difference between sexes is so huge.

If there are females competing who have naturally higher testosterone (towards higher end of the normal female range) they probably have a performance advantage too. Are we going to exclude them?

We know what the male advantage is - there are studies measuring it. We have no idea what the CAIS advantage is, or how to measure it. Effectively excluding these women from elite sport can't be justified on that basis

Even if you think it's morally OK, think of the politics. The opponents of sex testing are inevitably going to say its "cruel" to people with DSDs. What's the benefit in proving them right by targeting XY women without a proven advantage?

Hmm, I'm not sure, I guess it's some kind of surpressed SRY!

After posting my message, I then went on my lunchtime dog walk and continued listening to Carole Hooven's audiobook. I've completely neglected to mention any potential issues with the hypothalamus, which releases Gonadotropin-Releasing Hormone (GnRH), which then "tells" the pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) - which "tell" the gonads to produce T, Oestrogen and Progesterone (depending on your genes/biology).

Which adds another layer of complexity to the whole thing 🙃

I've been trying to keep up with this fantastic discussion - thank you all for your thought-provoking contributions! - but @UnderratedGenius I think you've defeated my cognitive powers with this question:

Where does XX male with or without SRY fit in??

I'm stumped by the 'XX male without SRY', what makes them male if they have no SRY? I thought the only XX 'male' was the de la chapelle case, which is XX+SRY. I've either missed or misunderstood any example given on this thread of an XX-SRY who is classified as male.

Sorry for the double post, I should have researched before posting the above. I now see that there are cases of a male phenotype developing in individuals with XX chromosomes and no SRY gene.

Although I'm jiggered if I can work out how that happens.

Emma Hilton, Ross Tucker and others have said what we need is a screening test - everyone without a Y is "passed" automatically, anyone with a Y will have further tests. In reality, if the test was conducted at 18 anyone with CAIS would probably already know it and could just submit medical reports instead of doing the test.

I agreed with this until I read about de la Chapelle syndrome, which cases involve XX chromosomes accompanied with an SRY gene, resulting in male-typical pubertal development and, as far as I understand it, testosterone levels in the male range. I would ordinarily think these cases such an extreme outlier as to not be worth factoring into any standardised screening process, but given the mess we seem to be in with 5ARD, it seems we really do need a bullet proof process.

Because it is not only the SRY gene that matters. The SRY is the main switch to male, but other genes are also important. For example, DHH that I mentioned earlier. Plus, we do not know the entire genome. Our knowledge in this area is relatively poor.

Most people with Swyers have the SRY gene. Their condition comes about because other genes are missing or corrupt.

XX is female and XY is male is simple but fundamentally wrong.

Sry+ is male and Sry- is more complex, closer to being right, but still not the whole picture.

"Maleness" genes (some of which may still need to be discovered) being present and working equals male and vice versa is correct.

But this is way beyond my intellectual ability. I simply do not understand the scientific language.

Think of the SRY as a switch in a fuse box. The light switches are other genes involved in 'maleness'

You flick the switch. Then go around and flick all your light switches. All the lights come on. Excellent - we've got a male.

However, you could flick the switch in the fuse box. The SRY is working as it should, but when you flick the light switches nothing happens. The light doesn't turn on. Another gene/protein/process is corrupted or missing and so the sequence is incomplete. You end up with a female.

I hope this was more helpful than confusing!

Really great analogy! And shows this is definitely not beyond your intellectual capability in the slightest 😊

So does that bring us back to the easiest way to define male vs female is to use testosterone levels?

We know at no point do the levels over lap, so their should.be no question about reducing testosterone levels to fit female categories.

We know at no point do the levels over lap, so their should.be no question about reducing testosterone levels to fit female categories.

No because reducing T levels doesn't rule out the effects of pelvis angle, vo2 max, lung capacity etc etc.

But let's not derail the thread!

But the simple XX XY isn't as simple as any of us lay people thought a few days ago.

Your saying no to the testosterone level test, even if the levels do not overlap.

Keeping in mind the test or the definition of female needs to be fairly straightforward because it shouldn't only be used at elite level it should be used at every level from about age 12.

How do we keep female sport SRY free?

Do we be very simple XX vs XY and if the very rare XX SRY+ slips thought so be it. And sorry but the very very rare XY-SRY is classed as male?

The boundary for the women’s category should be being female. The sex category exists for the inclusion of females by the exclusion of males. All males, including males with VSDs.

Elite athletes of both sexes may have some sort of physiological natural features that the rest of us don’t have. As long as it’s a feature which has occurred within the right sex category, that’s fine, good luck to them.

In the case of a feature which is a result of being of the ‘wrong’ sex for the category, that’s not fine. Taller and absent menses because of CAIS is a result of being male and therefore appropriate to exclude from the female category.

It’s very simple. We don’t need to measure the advantage. They aren’t female and are therefore excluded. We don’t need to tie ourselves in knots wondering which males could possibly be included if we really really want to be nice. No males. We can have things of our own.

PinkTonic

"It’s very simple. We don’t need to measure the advantage. They aren’t female and are therefore excluded. We don’t need to tie ourselves in knots wondering which males could possibly be included if we really really want to be nice. No males. We can have things of our own."

I agree.

I think that there are several issues here.

Firstly, if this group collectively is found to have advantage and that needs to be proven, then a discussion needs to be had.

Secondly, if this group benefits from advances in medical diagnosis and any treatment that helps their health, this will need to be revisited if it does give advantage.

I agree it is important that they be included while research is happening. But I am also open to this being discussed with facts and honesty and options considered. It is true though that there are groups of people who simply cannot compete because of a medical condition. Equally through no fault of their own.

So the usual thing is that someone with 5-ard is a woman with just a particular genetic advantage in sport (so the Phelps analogy comes out again) but actually they are men with a genetic disadvantage.

Is the key whether someone has gone through male puberty?

It looks like CAIS women couldn't live as anything but women - their inclusion isn't a danger to others and they have the female socialisation and disadvantages that brings

So I've been really mulling this one over the last few days as I feel the same way - socially speaking those with CAIS should be classed as women. To be honest, you wouldn't know who had CAIS or not amongst women so to treat someone with CAIS any differently in a social context would only be possible if you knew their genotype.

However, the study that showed people with CAIS were overrepresented in women's sport troubled me, and I felt that the potential for those with CAIS being taller and also having the advantage of no menstrual cycle weren't really enough of an advantage to set them apart from women with XX chromosomes who also have the potential for being taller (and I guess plenty of women don't have a menstrual cycle?). Anyway, it led me to wonder whether T had an effect elsewhere, and it does!

For one, it aids muscles to take in oxygen more efficiently from red blood cells (if I haven't misinterpreted the findings of this study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796634/ ) It certainly changes the chemical profile of blood.

I don't know the ins and outs of it all yet - it's been over 10 years since I've done any learning on genes and cellular biology, and I've literally just done a quick Google on the topic.

Plus I don't know whether these changes require the same androgen receptors that wouldn't be active in CAIS (thereby making those with CAIS unable to benefit in this way). But T seems to have many more advantages outside of controlling muscle gain and body growth.

Anyway - food for thought!

Isnt the point about CAIS is that there is literally complete androgen insensitivity - there no receptors that 'hear' androgen signals.