Beroemde 'vrouwelijke brein'-studie mat zes transvrouwen, allen op oestrogeen, meesten gecastreerd, nooit gerepliceerd

Een sekseverschil in het menselijk brein en de relatie ermee tot transseksualiteit

Cohort- & registerstudies Sekse, biologie & sport

Authors: Jiang-Ning Zhou, Michel A. Hofman, Louis J. G. Gooren, Dick F. Swaab
Journal: Nature
Year: 1995
Source: https://doi.org/10.1038/378068a0

Summary

Dutch scientists led by Dick Swaab measured a tiny area deep in the brain called the BSTc. It was larger in men than in women, and in six trans women who had died it was the size usually seen in women. Published in Nature, the study became the best-known evidence for the idea of a 'female brain in a male body'. The evidence is thin. There were only six trans brains, all from people who had taken estrogen and testosterone-blocking drugs for years, and most had had their testes removed. So hormone treatment, not something present from birth, could explain it. A follow-up by the same group (Chung et al., 2002) found the male-female difference in this area does not develop until adulthood, long after most gender distress begins. No independent team has repeated it. It is an unconfirmed observation, not proof of an inborn gender identity.

Key findings

De studie mat de grootte van een klein hersengebied genaamd de BSTc in na de dood geschonken hersenen, met een kleuring die bepaalde zenuwvezels markeert.
In vergelijkingshersenen was dit gebied bij mannen ongeveer 44% groter dan bij vrouwen.
Hetero- en homomannen verschilden niet in de grootte ervan, wat de auteurs opvatten als teken dat het verschil niet met seksuele oriëntatie samenhangt.
Bij zes transvrouwen had het de vrouwelijke grootte, of hun gendergevoelens nu vroeg of later in het leven begonnen.
De auteurs betoogden dat een paar niet-trans patiënten met ongewone hormoonspiegels als volwassene lieten zien dat hormonen bij volwassenen de grootte van dit gebied niet verklaren.
Alle zes transvrouwen waren behandeld met oestrogeen en het testosteronremmende medicijn cyproteronacetaat, en op één na waren hun testes verwijderd (Breedlove, Nature 1995).
Een latere studie van dezelfde groep vond dat het man-vrouwverschil in dit gebied pas in de volwassenheid verschijnt (Chung, De Vries & Swaab, J Neurosci 2002), wat het idee verzwakt dat het gendergevoelens veroorzaakt die in de kindertijd beginnen.

Abstract

Transsexuals have the strong feeling, often from childhood onwards, of having been born the wrong sex. The possible psychogenic or biological aetiology of transsexuality has been the subject of debate for many years. Here we show that the volume of the central subdivision of the bed nucleus of the stria terminals (BSTc), a brain area that is essential for sexual behaviour, is larger in men than in women. A female-sized BSTc was found in male-to-female transsexuals. The size of the BSTc was not influenced by sex hormones in adulthood and was independent of sexual orientation. Our study is the first to show a female brain structure in genetically male transsexuals and supports the hypothesis that gender identity develops as a result of an interaction between the developing brain and sex hormones.

Conclusion

The authors concluded that the BSTc is sexually dimorphic in humans (larger in men), that male-to-female transsexuals have a female-sized BSTc, and that this difference was not explained by adult sex-hormone levels or by sexual orientation. They presented it as the first evidence of a female brain structure in genetically male transsexuals, supporting the hypothesis that gender identity develops from an interaction between the developing brain and sex hormones.

Methodological limitations

Tiny sample: The key comparison rests on six trans brains, so a single unusual brain could sway the result. The brains also came from one brain bank linked to one gender clinic.
Hormone treatment could explain it: All six had taken estrogen and cyproterone acetate for a long time, and all but one had had their testes removed (Breedlove, Nature 1995). Adult cross-sex hormones are known to change the size of brain areas in trans people (Hulshoff Pol et al., Eur J Endocrinol 2006), so the smaller area may be caused by the treatment.
Weak checks for hormone effects: The claim that adult hormones don't affect the area's size rests on a handful of non-trans patients with short or different hormone exposures (such as a woman with a testosterone-making tumour, or women after menopause). These are not like years of high-dose cross-sex hormones after testes removal.
Timing doesn't fit: Chung, De Vries & Swaab (J Neurosci 2002) found this area doesn't differ between the sexes until adulthood, yet most trans people report gender feelings from childhood. An area that only changes in adulthood is an unlikely cause of gender distress that starts in childhood.
No untreated trans brains: No brains from gender-distressed males who had never taken hormones were studied, so a difference present from birth could not be told apart from a treatment effect.
Possibly picked after looking: Critics note the group looked at several brain areas that differ between the sexes and reported the one where trans women differed. Findings chosen after looking at the data need to be repeated (Lawrence, A critique of the brain-sex theory of transsexualism).
Which trans women: The six were described as mixed in sexual orientation, but most began treatment at older ages typical of trans women not attracted to men (late onset). Lawrence argues the finding may apply only to that subgroup, if at all.
Indirect marker: The area's size was measured by nerve fibres that mostly come from another brain region, not by the area's own nerve cells. The authors' follow-up (Kruijver et al., 2000) was designed to address this.
Never repeated independently: As of the latest critiques, no independent lab has repeated the finding in trans people. Follow-up studies came from the same group and partly reused the same brains.

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Summary

Key findings

Abstract

Conclusion