New Report:

In Humans, the Central Subdivision of the Bed Nucleus of the Stria Terminalis Does Not Become Sexually Dimorphic Until Adulthood

By Anne A. Lawrence, M.D., Ph.D.

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Two reports from the Netherlands Institute for Brain Research, published in 1995 and 2000, have been widely interpreted as demonstrating a possible neuroanatomic marker for male-to-female (MtF) transsexuality. In 1995, Zhou et al. reported that the central subdivision of the bed nucleus of the stria terminalis (BSTc), a collection of cells in the hypothalamus, was sexually dimorphic in humans. BSTc volume was significantly greater in male brains than in female brains. However, the brains of six MtF transsexuals Zhou et al. studied were found to have BSTc volumes within the typical female range. A follow-up paper by Kruijver et al. (2000) looked at the same six transsexual brains and two additional ones, including one from a female-to-male transsexual. Kruijver et al. reported that the sexual dimorphism in BSTc volume found by Zhou et al. reflected a genuine difference in neuron number, and was not simply an artifact of the measurement technique Zhou et al. used.

These two reports have spawned some truly fantastic extrapolations, including the assertion by some MtF transsexuals that they have the "brain-sex" of females (example: "[I] was born and raised as a boy. It was a terrible mistake, because [I] had the brain-sex . . . of a girl."). Unqualified assertions like this have been made even by persons trained as scientists. Never mind that the papers cited above studied only eight transsexual brains, and have never been replicated in another laboratory. Never mind that, of the dozens of other sexually dimorphic structures in the human brain, not one has been shown to be sex-atypical in transsexuals. Never mind that we have no idea exactly what functions the BSTc might subserve in humans. The true believers in transsexual "brain-sex" had found their biologic marker, and no amount of ordinary scientific skepticism could dissuade them.

Until, perhaps, now. A recent paper by Chung et al. (2002) has demonstrated a most unexpected finding: In humans, unlike the rat and perhaps other species, BSTc volume does not become sexually dimorphic until well into adulthood. However, most MtF transsexuals report that they experienced gender dysphoria beginning in childhood, often from the time of their earliest memories. It is hard to imagine how BSTc volume could be a marker for gender identity if BSTc volume has not yet become sexually dimorphic at a time when gender identity has already been firmly established. As Chung et al. wrote:

"Late sexual differentiation of the human BSTc volume also affects our perception about the relationship between BSTs [sic] volume and transsexuality. Interestingly, transsexuals receive their first consultation between the ages of 20 and 45 years, which coincides with the period of sex-dependent divergence of BSTc volume found in the present study (Van Kesteren et al., 1996). However, epidemiological studies show that the awareness of gender problems is generally present much earlier. Indeed, [about] 67-78% of transsexuals in adulthood report having strong feelings of being born in the wrong body from childhood onward (Van Kesteren et al., 1996)."

Of course, it is still possible to construct explanations of these findings that are consistent with the hypothesis that BSTc volume in adulthood could be a marker for gender identity in MtF transsexuals. Chung et al. conjectured that fetal or neonatal hormone levels could affect gender identity, and could perhaps simultaneously produce changes in BSTc "synaptic density, neuronal activity, or neurochemical content" that might not immediately affect BSTc volume, but that might somehow do so much later, during adulthood. Naturally, they did not propose any specific mechanisms by which such delayed effects might occur. Alternatively, they conjectured, failure to develop a male gender identity might itself somehow affect adult BSTc volume, again by an unspecified mechanism.

These possibilities notwithstanding, it should be apparent that the Chung et al. paper has dealt a serious blow to the hypothesis that BSTc volume is a biologic marker for gender identity in MtF transsexuals. Whether this will diminish the fanciful claims of "female brain-sex" by MtF transsexuals themselves remains to be seen.

Here is the complete citation and abstract for the Chung et al. paper:

ABSTRACT: Gonadal steroids have remarkable developmental effects on sex-dependent brain organization and behavior in animals. Presumably, fetal or neonatal gonadal steroids are also responsible for sexual differentiation of the human brain. A limbic structure of special interest in this regard is the sexually dimorphic central subdivision of the bed nucleus of the stria terminalis (BSTc), because its size has been related to the gender identity disorder transsexuality. To determine at what age the BSTc becomes sexually dimorphic, the BSTc volume in males and females was studied from midgestation into adulthood. Using vasoactive intestinal polypeptide and somatostatin immunocytochemical staining as markers, we found that the BSTc was larger and contains more neurons in men than in women. However, this difference became significant only in adulthood, showing that sexual differentiation of the human brain may extend into the adulthood. The unexpectedly late sexual differentiation of the BSTc is discussed in relation to sex differences in developmental, adolescent, and adult gonadal steroid levels.

References:

Chung WC, De Vries GJ, Swaab DF (2002) Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood. J Neurosci 22(3): 1027-1033.

Kruijver FP, Zhou JN, Pool CW, Hofman MA, Gooren LJ, Swaab DF (2000) Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab 85(5): 2034-2041.

Van Kesteren PJ, Gooren LJ, Megens JA (1996) An epidemiological and demographic study of transsexuals in the Netherlands. Arch Sex Behav 25(6): 589-600.

Zhou JN, Hofman MA, Gooren LJ, Swaab DF (1995) A sex difference in the human brain and its relation to transsexuality. Nature 378(6552): 68-70.

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© 2002 by Anne A. Lawrence, M.D., Ph.D. All rights reserved.
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