Another Piece of the Puzzle

And a really useful and interesting one this time.

In the past, I've talked about how transsexuality being a "male brain in a female body", or the reverse, while true, is only an approximation. That it would be more accurate to say "masculinised brain in a feminised body", or the reverse.

That's partly because so many "transsexual" people have been shown to be not only neurologically Intersexed, but somatically intersexed in other ways too. But it's also partly because not all of the neurology need be affected to cause transsexuality, only parts. We're still finding out what parts, and to what degree they are cross-gendered.

Professor Italiano (to whom many thanks) has just drawn my attention to a new study. One that gives us more specific information than we've had in the past.

Regional gray matter variation in male-to-female transsexualism by Luders E, Sánchez FJ, Gaser C, Toga AW, Narr KL, Hamilton LS, Vilain E. in Neuroimage. 2009 Mar 30.

We analyzed MRI data of 24 male-to-female (MTF) transsexuals not yet treated with cross-sex hormones in order to determine whether gray matter volumes in MTF transsexuals more closely resemble people who share their biological sex (30 control men), or people who share their gender identity (30 control women). Results revealed that regional gray matter variation in MTF transsexuals is more similar to the pattern found in men than in women. However, MTF transsexuals show a significantly larger volume of regional gray matter in the right putamen compared to men. These findings provide new evidence that transsexualism is associated with distinct cerebral pattern, which supports the assumption that brain anatomy plays a role in gender identity.

So in some ways, the feminised brains of TS women more closely resemble a typical male pattern, but in one specific way, they resemble a typically female pattern.

The mean age (SD) of the MTF transsexuals was 46.73 (13.18) years with an age range between 23 and 72 years. Male and female control subjects were closely age-matched (males 46.57±12.45, 23–69 years; females 46.77±12.88, 23–73 years). Transsexual subjects were 76% dextral, control males were 93% dextral, and control females were 90% dextral, where handedness was determined based on self-reports of hand preference for selected activities. For study inclusion, transsexual subjects needed to self-identify as a MTF transsexual, report no history of hormonal treatment, and declare the intention ofundergoing estrogen replacement therapy. MTF transsexuals were evaluated to be free of psychosis according to a standardized diagnostic interview (Robins et al., 1989) and confirmed to be genetic males as defined by the presence of the SRY gene in their genome (Jordan et al.,2002). All control subjects had to pass a physical and neurological screening examination performed by a neurologist.

A couple of remarks here:

1. Mean age between 45 and 50, so most of the TS women would be "late transitioners".
2. 3/4 were right handed, compared to 9/10 in the control groups. Transsexuality is associated with ambidexterity, and to a lesser extent, left-handedness. That gives us a clue that laterisation of the brain is often affected.
3. Presence or absence of the SrY gene is not definitive as an indication that the TS women weren't Intersexed - either (46xx/46xy) mosaicism or Kleinfelter syndrome (47xxy) would be evaluated as "male".

Back to the paper...

...we detected significant differences between MTF transsexuals, males, and females in a large number of regions across the brain. More specifically, within the frontal lobe, we observed gray matter volume differences bilaterally in the superior frontal gyrus, close to midline and also at the frontal pole, as well as within the right orbital gyrus. Furthermore, we noticed pronounced gray matter volume differences bilaterally across the occipital and posterior temporal lobes, as well as in the parietal lobe, near the intraparietal sulcus, and closer to midline (left). Additional group effects on regional gray matter volume were detected subcallosally in both hemispheres at the brain midline. These regions constitute part of the basal ganglia (i.e., the caudate nucleus and putamen) and limbic system (i.e., the subcallosal gyrus, mammillary body, amygdala, thalamus and hypothalamus). Moreover, we identified two clusters indicating group differences on the basal surface of the right temporal lobe and left frontal lobe.

Ok, so the lymbic system is highly sexually dimorphic, something we already knew. What's interesting is the other parts of the brain, where sexual dimorphism has been inferred by fMRI imaging of blood flow, but relatively little work has been done on the physical structure.

Gosh I love this! It's a detective story, where we're being given clues. Moving right along... now comes the juicy bits.

Altogether, females had the largest gray matter volumes in all but two significant clusters, which were located in the left and right putamen. Here, MTF transsexuals had the largest gray matter volumes

More "typically feminine" than the usual factory model... or should we say that most women are less "typically female" than TS women? Less "strongly gendered" on average? You'd expect TS women to be more "strongly gendered" than average, as many would otherwise be able to cope with transsexuality without seeking treatment. But what about the rest of the brain? Many TS women show more typically male abilities in instinctive ballistics calculations for example.

For the remaining clusters, MTF transsexuals had the smallest gray matter volumes, but their data spectrum largely overlapped with that of males.

Fascinating! Not just more female than female in some areas, but slightly more male than male in others! I wonder, is this environmental? Would the same thing be shown in younger, "primary" transwomen? Or could it be that the anomalous hormonal wash in the womb bollixes things up in an even more complex manner than we thought? We're in the realm of conjecture here, so we can't say without a lot more study. One thing - there's a correlation between Transexuality and what has been described as "ultra male syndrome" - Asperger's. Might this "ultra-male" grey matter pattern be the cause? And could a change to a female hormone regime cause changes to it? I'd love to see this repeated not just for younger transitioners, but for those on various HRT regimes, and FtoMs too of course. There's so much we don't know, but now we may be able to find out!

Overall, our study provides evidence that MTF transsexuals possess regional gray matter volumes mostly consistent with control males. However, the putamen was found to be “feminized” in MTF transsexuals. That is, the gray matter volume of this particular structure in the MTF transsexual group was both larger than in males and within the average range of females. Interestingly, in a positron emission tomography (PET) study, it was demonstrated that the left putamen in a sample of MTF transsexuals (n=12), who had no history of estrogen treatment, activated differently to odorous steroids when compared to control males (Berglund et al., 2008). Taken together, these findings lend support to the hypothesis that specific neuroanatomical features are associated with transsexual identity, where the particular role of the putamen requires investigation in future studies.

All good science discusses the implications of the work, and what pitfalls might arise in drawing definite conclusions from it. And this work is good science.

Further research needs to resolve whether the observed distinct features in the brains of transsexuals influence their gender identity or possibly are a consequence of being transsexual.
Alternatively, other variables may be independently affecting both the expression of a transsexual identity and the neuroanatomy in transsexuals that led to the observed association between both. Some possible candidates include genetic predisposition, psychosocial and environmental influences, hormonal exposures, or most likely an interplay between these variables. In support of the influence of genetics and environment, multiple cases of variations in MTF transsexuals (Hare et al., 2009; Henningsson et al., 2005). Furthermore, both transsexualism occurring within families have been reported (Green, 2000) as well as studies on heritability in twins (Coolidge et al., 2002) and preliminary findings on specific genetic SC variations in MTF transsexuals (Hare et al., 2009; Henningsson et al., 2005). Furthermore, both genes and environmental demands have been demonstrated to determine brain anatomy (e.g., regional gray matter) (Draganski et al., 2004; Thompson et al., 2001). Finally, hormones have been shown to affect brain development (Arnold and Gorski, 1984), and neuroanatomical alterations in MTF transsexuals (Kruijver et al., 2000; Zhou et al., 1995) have been detected in cerebral structures shown to significantly change in response to hormonal exposure (Del et al.,1987; Guillamon et al., 1988).

No-one said it would be easy. And there may be many distinct etiologies leading to the same result. Perhaps sometimes the brain is cross-gendered ab initio, and sometimes it changes.

From my own experience, I can give the following data points. n=1 I know, but what can you do?

1. My sense of smell changed, and early, within weeks
2. I became able to read body language over a month. Many of my Asperger's symptoms disappeared.
3. My co-workers remarked about how, well, less dominant I became at meetings. Shy, even. Maidenly modesty, if you like.
4. Other aspects of my personality changed too, but over a longer period.

I recorded this at the time, before any of these study results came out. And published them on my blog... That would seem to indicate that hormones post-birth may activate an atypical predisposition. Certainly my brain got re-wired, something I found most disturbing! Now I might have a clue as to what changed neurologically, and to what extent.

And yet, despite all the changes, in many ways I'm still that 10 year old girl who picked the name Zoe, back in 1968. Just as thrilled at solving puzzles and finding things new.