Professor M.Italiano of Gendercare Inc. and Organisation Intersex International (to whom many thanks) very kindly sent me an advance copy of a new article, whose abstract is available from Oxford Journals.
From A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity by
A. Garcia-Falgueras A and D.F. Swaab.
In the present study we investigated the hypothalamic uncinate nucleus, which is composed of two subnuclei, namely interstitial nucleus of the anterior hypothalamus (INAH) 3 and 4. Post-mortem brain material was used from 42 subjects: 14 control males, 11 control females, 11 male-to-female transsexual people, 1 female-to-male transsexual subject and 5 non-transsexual subjects who were castrated because of prostate cancer.The key phrase here is "complex network". You can point to one place, the BSTc layer, and say that's a definitive marker, but it can't be causal. The difference appears after symptoms of transsexuality. It's something more subtle, and more complex, involving more than one part of the brain, and in more than one characteristic. There are overlaps, there is fuzziness, there is complexity, and we still have a lot to learn.
We showed for the first time that INAH3 volume and number of neurons of male-to-female transsexual people is similar to that of control females. The female-to-male transsexual subject had an INAH3 volume and number of neurons within the male control range, even though the treatment with testosterone had been stopped three years before death. The castrated men had an INAH3 volume and neuron number that was intermediate between males (volume and number of neurons P > 0.117) and females (volume P > 0.245 and number of neurons P > 0.341). There was no difference in INAH3 between pre-and post-menopausal women, either in the volume (P > 0.84) or in the number of neurons (P < 0.439), indicating that the feminization of the INAH3 of male-to-female transsexuals was not due to estrogen treatment. We propose that the sex reversal of the INAH3 in transsexual people is at least partly a marker of an early atypical sexual differentiation of the brain and that the changes in INAH3 and the BSTc may belong to a complex network that may structurally and functionally be related to gender identity.
The presence or absence of testosterone appears to be important in actively changing neurological structures - how else to explain the "intermediate" figures for castrated males? But it's not the whole picture, as the FtoM subject had male-typical neurology even 3 years after discontinuing hormones for medical reasons. Both hormonal balance and genetic propensity appear to be required, as current theory predicts. There are certainly multiple genetic causes that can potentialise the same effect, but without anomalous hormones, the potential remains just that.
We still don't know enough to draw conclusions about the details, but in my opinion, biological causation is no no longer proven "on the balance of probability", but beyond reasonable doubt. Not beyond all doubt whatsoever, but as they say, "a jury would convict". While no single experiment is definitive, there are now a dozen or more experiments in widely separated areas of knowledge all suggesting the same thing, and sometimes strongly suggesting it. Taken separately, none of the experimental evidence is enough to say anything other than a "definite maybe". Taken together, and with exactly zero evidence to contradict them (a rare thing in Science), there's no "maybe" about it any more.
One thing we don't know for sure is how these neurological anomalies lead to another anomaly, a difference from the expected norm, transsexuality. I won't call it a "disorder", that has far too many negative and unevidenced connotations. It is an anomaly though that, in conjunction with societal attitudes, can lead to significant distress. When it involves the body-image, even if there was a wholly benevolent societal attitude, it will lead to distress so extreme that suicidal ideation, anxiety and acute depression are not just common, but almost universal.
A nose by any other name would smell, and although I have no wish to offend anyone who sees all this as just a "natural variation" like red hair or blue eyes, I can see the reasoning behind calling it a disorder, even if I disagree strongly with that view. Certainly the anxiety and distress in some cases can only be called a medical condition, one caused by biology, and wholly treatable in most cases by aligning body and brain so there is no conflict. The only reason I say most cases is that since the cause is biological, hence messy and fuzzy, there will be some people who will be miserable with either typical male or typical female configurations. Some may be happy as androgynes, but I'm sorry to say that there may well be some for whom there is no good solution, just a "least worst". A significant minority of people with post-operative regret are not merely victims of substandard surgery, they transition back. And more often than not, wish they could go back again after that. I'm not sure I know what can be done to help such people, and I don't think they know what can be done themselves. We should listen to them anyway, because although they may be clueless, we certainly are.
Conversely, there are some Intersexed people perfectly happy with unusual bodies, and highly resentful (as they have every right to be) of those who would force them to conform to majority expectations - expectations often based on pseudo-religious beliefs that actually contradict scripture - and not what would be right for the individual concerned. Some are very unhappy indeed, having been surgically mutilated as infants in order to please others. In extreme cases, they have been butchered and forced into becoming effectively transsexual, with a brain-gender that is exactly the opposite to their somatic-gender. No wonder they feel more than just a teeny bit ticked off by this. Even those proponents of early intervention admit that they get it wrong this way in at least 10% of cases.
From Endocrinology Today :
There are some kinds of medical decisions, such as sterilization and organ donation, that parents alone can’t authorize. In these cases, a court must determine that the decision serves the child’s best interest. The legal rationale for these exceptions to the general rules of parental consent arguably apply to infant genitoplasty as well: the procedures are elective; they are irreversible with dramatic lifelong consequences; and there is a potential for conflict between the interests of parents and child. (Indeed, some providers have recommended genitoplasty in the belief that it is necessary for the parents’ well-being.)And that I find the most jaw-droppingly outrageous thing I've read in a very long time. I knew it happened from talking to the victims, but to have it openly admitted is another matter. I applaud the author for airing this dirty laundry in public, as she wants to make sure that we - society, the medical profession, and parents - do the right thing for these children.
Getting back to Transsexuality... we don't know the mechanism behind the causal relationship. That it is causal has been proven now, though not absolutely. Only correlation has. I've mentioned Diamond's Biased-Transactional theory before in BiGender and the Brain. It says that an anomalously cross-gendered brain (the "Bias") will lead to a cross-gendered identity by the child comparing itself to others (the "Transactions").
I am only an expert in myself, not others. In my case, his theory fits perfectly, though it doesn't involve culturally gendered behaviour as such, only instinct and emotional reactions. I liked toy guns, toy cars, I was stereotypically male when young in what is normally regarded as gendered behaviour. If gender was purely a social construct, I would have been indubitably and unambiguously male, no question of it. But my inner thoughts, my feelings, my emotions, and my hard-wired instincts, they were quite different, and (in hindsight) stereotypically female, more so than even I realised at the time. I did realise it enough to pick the name "Zoe" though, at age 10. I thought I'd have a female puberty, you see. As I did, just delayed 35 years *sigh*.
So we know that the Biased-Transactional theory is true - for one case. Moi. For others, it seems to fit too. For all? I don't know. Perhaps if we could study adults whose gender identity is still crystalising - say those who attempt transition, but temporarily or permanently de-transition for other than economic or family reasons - we could say more.
But in the meantime, this is theory, not hard fact. We have hard facts though, more every month, and this paper is yet another piece of the puzzle.