Famous 'Female Brain' Study Measured Just Six Trans Women — All on Estrogen, Most Castrated, and Never Replicated

A sex difference in the human brain and its relation to transsexuality

Cohort & registry studies Sex, biology & 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

The study measured the size of a tiny brain area called the BSTc in donated brains after death, using a stain that marks certain nerve fibres.
In comparison brains, this area was about 44% larger in men than in women.
Straight and gay men did not differ in its size, which the authors took to mean the difference is not linked to sexual orientation.
In six trans women it was female-sized, whether their gender feelings began early or later in life.
The authors argued that a few non-trans patients with unusual adult hormone levels showed that adult hormones do not explain the size of this area.
All six trans women had been treated with estrogen and the testosterone-blocking drug cyproterone acetate, and all but one had had their testes removed (Breedlove, Nature 1995).
A later study by the same group found the male-female difference in this area only appears in adulthood (Chung, De Vries & Swaab, J Neurosci 2002), which weakens the idea that it causes gender feelings that begin in childhood.

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.

detrans.ai

Summary

Key findings

Abstract

Conclusion