by M. Italiano

Copyright © 2007, All rights reserved.

     In Dr. Lawrence's recent critique of studies of
brain sex in transsexuals (1), she clearly makes
several errors, which when corrected, would invalidate
her arguments. I will not directly address her least
likely suggestion, that the transsexual brain studies
may be the result of non-representative sampling, as
my discussion will indirectly cover that. Also, I will
not at length, address her more likely assertion that
the BSTc in transsexuals is a marker for
autogynephilia. It is basically a recapitulation of
what she has written around 7 years ago on SexNet, and
what appeared on psychologist J Michael Bailey's web
site, which I have deconstructed here in another

     I should mention, that Lawrence's conclusion that
"Blanchard's theory" of "two distinctly different
subtypes of MtF transsexuals" is "accepted" by "most
knowledgeable clinicians and researchers" (1), is not
one which is found in research which posed this
question directly to clinicans and researchers, let
alone from research which has defined "most
     Thus, I shall direct my attention to the
contention of Lawrence, that the most likely
explanation for the transsexual brain BSTc findings,
are the result of the influence of hormones which the
transsexuals were taking (1).
     Firstly, Lawrence (1) writes "In 1995, Zhou,
Hofman, Gooren, and Swaab reported that a collection
of cells in the hypothalamus, called the central
subdivision of the bed nucleus of the stria terminals
(BSTc), was sexually dimorphic in humans." (1)
However, neither the collection of cells (2), nor the
BSTc which was examined (2,3) are "in the
hypothalamus". Likewise, the suggestion of Hulshoff
Pol, et al. (4) that postnatal hormones would change
these BSTc structures is misguided as well, since they
also mistakenly refer to "the bed nucleus of the stria
terminalis of the hypothalamus." (4) Thus, although
Hulshoff Pol, et al. (4) found (using MRI) that total
brain volume and hypothalamic volume was
"significantly decreased in m to f transsexuals with
hormones", and the converse for f to m transsexuals
"with hormones", the relevancy of this finding for the
BSTc is totally speculative.
     Secondly, Lawrence (1) doesn't address the
evidence, that certain hypothalamic nuclei, such as
the suprachiasmatic nucleus (SCN) VIP subdivision
number, is twice the amount found in young males when
compared to females of the same age, whereas in middle
age, it becomes reversed (females having 1.7 times as
many as middle-aged males), and that in old subjects,
the difference amongst men and women
disappears.(5,6,7) This is certainly important,
because the SCN, which IS a hypothalamic nuclei
(unlike the BSTc), was examined by authors of one of
the transsexual BSTc studies (2) and found not to be
atypical in transsexuals. Surely, if Lawrence (1) and
Hulshoff Pol et al. (4), are going to assert that
hormones which the m to f transsexuals took, had
"shrunk" the BSTc, then by the same assertion, they
are lacking in their explanation as to why hormones
didn't shrink the SCN.
    Thirdly, Lawrence (1) fails to address, that the
sexually dimorphic nucleus (SDN)(of the preo-optic
area) and the paraventricular nucleus (PVN) were not
seen to be altered in size in these transsexuals
either(2). In recognizing the BSTc specific results,
and discussing the unlikihood of its being infuenced
by hormones which the transsexuals were taking, it is
not surprising, that Zhou, et. al. (2), on page 70,
write, "We failed to observe similar changes in three
other hypothalamic nuclei, namely PVN, SDN, or SCN in
the same individuals (unpublished data)." Again, to
reiterate, if the BSTc nuclei were influenced by
hormones which the transsexuals took, it should be
even more likely, especially based upon Hulshoff Pol's
studies of the hypothalamus (4), that other nuclei,
which ARE IN the hypothalamus, would be expected to be
influenced as such as well. However, they weren't (2).
In further support of the likely erroneous claim that
hormones should influence the BSTc in a "peculiar"
way, is the lack of difference in the counterpart of
the BSTc structure of rats, who have androgen
insensitivity syndrome (tfm mutation), when compared
with the BSTc structure of normal male control
rats. (8) The BSTPM (the "animal" equivalent of
the human's BSTc), structure didn't show a sexual
difference, despite the fact, that one group of rats
was not able to utilize androgen at the cellular
level. (8)
    Fourthly, Lawrence (1) also criticizes the lack of
replication of nuclei, such as SDN-POA (1). However,
sexual dimorphism of the SDN-POA actually HAS been
replicated by Braak & Braak. (9) Furthermore,
Lawrence's (1) assertion of a failure of the sexual
dimorphism of SDN-POA to be replicated, is also based
upon a misconception. It is such, because, the failure
to "replicate", is not one which used comparable
methodologies. (10) The differing results are easily
explained as resulting from obvious differences in
variables such as "age selection", "section
thickness", and "sample size". (10) Furthermore, it is
not clear, that the SDN-POA, which has been labeled
INAH-1, by some of the authors who have failed to
replicate its dimorphism (11,12,13), actually is the
counterpart of the same sexually dimorphic nucleus,
described in rats. (10) In fact, Byne, et al. (14)
argue that INAH-3, may more likely to be the human
counterpart of the SDN-POA/INAH-1 in rats. Lawrence
(1) doesn't mention this, or indeed that the sexual
dimorphism of INAH-3, has been confirmed by three
independent groups (11,12,13,14). Finally, using
immunocytochemistry, the SDN-POA/INAH 1, has been
shown to be sexually dimorphic in another study, in
both the intensity and number of neurons stained (15).

     Other research (16) demonstrates a less clear
effect in general of hormones on brain structure, and
factors, such as (epi)genetics (17) and age (10,18)
known to affect various brain structures in different
ways. The role in which these factors play in the
transsexual studies is not known, but certainly
doesn't lend any credence to Lawrence's position. (1)
     In summary, Lawrence's critique (1) of the
transsexual brain studies, and the BSTc is unfounded.
Likewise, her statement that there "is no longer any
reason to postulate anything more complicated", is
misconstrued, since her "simplicity" is being diluted
by omissions of pertinent reports as well as data.
What actually is subjective "reality" by many
therapists or researchers, need not exclude relevant
laboratory research. Thus, Lawrence's contention that
"Zhou et al. were clearly mistaken" and
"as were Kruijver et al...", in regards to the effect
of hormones the transsexuals took on their BSTc
size(1), as well as the like position of Hulshoff Pol
(4), is a "straw-man" argument.

Prof. Italiano







2) Zhou JN et al. (1995) A sex difference in the human brain and its relation

    to transsexuality. Nature. 328:68-70.


3) Kruijver, FPM et al. (2000) Male-to-Female Transsexuals Have Female

    Neuron Numbers in a Limbic Nucleus. J. Clin. Endoc. Metab. 85:2034-2041.


4) Hulshoff Pol, HE et al. (2006) Changing your sex changes your brain:

    Influences of testosterone and estrogen on adult human brain structure.

    European J. Endoc. 155(Supplement):S107-S114.


5) Hofman, MA et al. (1996) Suprachiasmatic nucleus of the human brain: an

    immunocytochemical and morphometric analysis. Anat. Rec. 244:552-562.


6) Zhou, JN et al. (1995) VIP neurons in the human SCN in relation to sex, age,

    and Alzheimer’s disease. Neurobiol. Aging. 16:571-576.


7) Swaab, DF et al. (1994) Development of vasoactive intestinal polypeptide (VIP)

    neurons in the human suprachiasmatic nucleus (SCN) in relation to birth and sex.

    Dev. Brain Res. 79:249-259.


8) Garcia-Falgueros, A et al. (2005) The role of the androgen receptor in CNS

     masculinization. Brain Res. 1035:13-23.


9) Braak, H & Braak, E (1992) Anatomy of the human hypothalamus (chiasmatic

    and tuberal region). In, Swaab, DF, et al. (eds.), The Human Hypothalamus in

    Health and Disease: Progress in Brain Research, Vol. 93, pp.3-16,

    Elsevier, Amsterdam.


10) Swaab, DF et al. (2001) Structural and Functional Sex Differences in the Human

      Hypothalamus. Horm. Behav. 4:93-98.


11) Allen, L et al. (1989) Two sexually dimorphic cell groups in the human brain.

      J. Neuroscience. 9:497-506.


12) Levay, S (1991) A difference in hypothalamic structure between heterosexual

      and homosexual men. Science. 253:1034-1037.


13) Byne, W et al. (2000) The interstitial nuclei of the human anterior hypothalamus:

      an investigation of sexual variation in volume and cell size, number and density.

      Brain Res. 836:254-258.


14) Byne, W et al. (2001) The Interstitial Nuclei of the Human Anterior Hypothalamus:

      An Investigation of Variation with Sex, Sexual Orientation, and HIV Status.

      Horm. Behav. 40:86-92.


15) Fernandez-Guasti, A et al. (2000) Sex differences in the distribution of androgen

       receptors in the human hypothalamus. J. Comp. Neurol. 350:311-323.


16) Greenberg, DL et al. (2006) Differences in brain volume among males and female

       hormone-therapy users and nonusers. Psychiatry Research Neuroimaging.



17) Vawter, MP, et al. (2004) Gender-Specific Gene Expression in Post-Mortem

       Human Brain: Localization to Sex Chromosomes. Neuropsychopharmacology.



18) Gur, RC et al. (2002) Brain Region and Sex Differences in Age Association

      With Brain Volume. Amer. J. Geriatric Psychiatry. 10:72-80.



See also: Catastrophe and Variations papers!

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