A neuro-psychology study by Zhou et al. (1997) suggests that the central subdivision of the bed nucleus of the stria terminalis (BSTc) is the size of the sex transsexual identify with and not the size of their biological sex. Here I explain for lay-persons the psychology and how to interpret results. Marc Breedlove also graciously agreed to have his essay on this study included.

Zhou, Hofman, Gooren and Swaab (1997) A sex difference in the human brain and its relation to transsexuality

The publication of "A sex difference in the human brain and its relation to transsexuality" by Zhou, Hofman, Gooren and Swaab (1997) in the on-line peer-reviewed interdisciplinary academic journal, "International Journal of Transgenderism" is often cited within the transsexuality community. This article was originally published in 1995 in another peer-reviewed academic journal "Nature."

I guess the idea of a clear physical 'cause' of transsexuality brings a sense of legitimacy to some of us. Transsexuals aren't the only ones who seem to feel these findings legitimate transsexual lives. Those who traditionally criticize transsexuals are quick to find flaws (despite their generally poor backgrounds in neuroscience). Personally, I feel the most important aspects of our identities are our interpersonal relationships and our introspective thoughts and our feelings. Causality is of considerable importance to our scientific theories, but distal causes should not really matter when we seek: civil liberties, protection from hate crimes, or acceptance.

Nevertheless, I do have many thoughts that I've felt I should contribute to the debate. But I don't feel comfortable discussing certain points from neuropsychology. Though I have read some journal articles in several different cognitive and developmental psychology classes, I have never taken a class specifically focused on neuropsychology. Fortunately, I came across the follow article written for the layperson by Marc Breedlove, a true expert. Though he may not aware of the political debates concerning transsexuality, his essay addresses many points that we should be aware of. The BSTc finding can not be easily attributed to sexual orientation, hormones, or other seemingly plausible incidental causes. Transsexuality is the most plausible explanation for the difference. However, finding a difference in the brain is not always evidence for a cause. It is possible that transsexuality (or other potentially social causes of transsexuality) causes the brain difference. The brain is not as static as our brain to computer analogies sometimes suggest.

Are the research findings a fluke?

There is only one point I would like to add. Marc Breedlove did not address this point because the intended audience of the article is skilled in statistics. A common argument against the findings is the few number of participants. Many people seem to think that the small numbers mean it's easier to get the findings by a fluke. Though I would agree replicating the results would make the findings more convincing, the small sample size is not a problem.

If you read the results in "A sex difference in the human brain and its relation to transsexuality" you will see things like "p < .05" in parentheses. This is a mathematical way of saying how likely it is that we got the group differences by a fluke (by probabilistic chance). In the field of psychology, we typically say a difference must have a "p" of less than .05 to be considered a real difference; that means there's less than a 5% chance that the differences we see are a fluke. Otherwise we say the groups are the same. We're never completely sure if a difference we find is real; there's always some chance that a finding is a fluke. But lower p values make that less likely. Here are the basic findings in "A sex difference in the human brain and its relation to transsexuality":

In some ways the small sample size illustrates just how blatant the difference really is (the psychology term for this is "effect size"). If a difference is subtle (either the group differences are close together or the variability within the groups is big), it takes a larger sample (number of brains) to see the difference. With only six transsexual brains, the differences in BSTc size must be very pronounced because the group differences were so unlikely to be fluke (p<.005 when p<.05 would be enough for our field).

Are the research finding about all transsexuals or just some?

Some researchers and transsexuals propose there are many different "types" of transsexuals. This raises a questions: Are the neurological findings about all transsexuals or just some 'types'?

One distinction is between transsexual men (Female-to-Male) and transsexual woman (Male-to-Female). The theoretical reasons BSTc was proposed as a possible TS difference imply we would find similar results for transsexual men. However, this study only involved transsexual woman. We should be cautious about making the generalization to transsexual men without the empirical evidence. A nice replication and extension of this finding would be to study the BSTc region of both transsexual men and woman; I hope neuroscientists undertake that study. For the remaining two catgorical distinctions I am limiting my discussion to only transsexual woman.

A second distinction is age of onset, the categories are 'primary' and 'secondary' transsexuals. The defining difference is the age when a transsexual requests a sex change: 'primary' transsexuals usually request a sex change in their early to mid twenties and 'secondary' transsexuals request surgery from forty years old and onward. As groups, they differ in sexual orientation (more 'primary' transsexuals are straight in their target sex) and their gender expression (MtF primary transsexuals tend to be more feminine). However, please be aware that these differences are statistical like sex differences in height. Men are taller than woman but that doesn't mean any particular man is taller than any particular woman. Is the brain difference only a difference for primary or only for secondary transsexuals? No. If you look at the table below, you will see that three transsexuals in the study are primary and two are secondary transsexuals (there is no datat reported for one brain).

transsexual brain number (arbitrarily assigned) 1 2 3 4 5 6
age of onset secondary ts - late onset primary ts - early onset secondary ts - late onset unknown primary ts - early onset primary ts - early onset
sexual orientation attracted to men attracted to women attracted to women attracted to both attracted to women attracted to men

A third distinction is sexual orientation, the categories are "attracted to men", "attracted to woman", "attracted to both", or "attracted to neither." Though this is related to age of onset, it is not the same thing. Earlier we saw that BSTc size does not differ between gay and straight men so there is no particular reason to expect the BSTc findings to apply to transsexuals with a particular sexual orientation. In addition, you can see from the table above that two of the transsexual woman were straight, three were lesbian woman, and one was bisexual. I mention that sexual orientation does not account for these findings because of a dissappointing trend I've noticed among transsexuals. A transsexual medical doctor (not a psychology researcher) has recently promoted one researcher's theory of transsexuality that explains transsexuality through sexual orientation. Since her essay, I have see a growing amount of hostility among transseuxals based on sexual orientation. These findings show there is at least one commonality among transsexuals of different sexual orientations. And I hope these findings can help us focus on our similarities rather than our differences.

In summary, a brain difference has been found between transsexual woman, non-transsexual woman, non-transsexual heterosexual men, and non-transsexual homosexual men. It is unlikely that these differences are a fluke. And these findings are generalizable to all transsexual woman, not just a single 'type'. The following essay by Marc Breedlove discusses the issue of causality. But I hope no person will place his or her legitimacy as a man or woman on the causes of transsexuality.

Marc Breedlove is a professor of Psychology at Berkeley. His areas of research interest are Behavioral Neuroscience and Developmental Psychology. He specializes in the study of behavioral endocrinology, developmental neurobiology, sex differences in the nervous system. The following is an article by Marc Breedlove published in the June, 1996 Psychologue, the newsletter of the Psychology Department of the University of California at Berkeley Marc gave me permission to include the following article on my web site.

The Chicken-and-Egg Argument as It Applies to the Brains of Transsexuals: Does It Matter

Marc Breedlove

Most of us are perfectly comfortable with the fact that we are male or female. In fact we normally never give it a thought. But there are a very few people who feel they were born with the wrong body - men who feel they should have been born women and vice versa. In many cases these people, referred to as transsexuals, remember feeling this way even in childhood. When the feeling becomes strong enough, the person may seek surgery to remove their testes or ovaries, may have their external genitalia surgically altered and take homones to make them appear like the other sex. These extreme measures are accompanied by discomfort and risk, so no one would entertain them on a whim. Rather, transsexuals take such drastic measures because they feel so strongly and consistently that they should have been born the opposite sex. Because transsexuals are born with bodies that seem perfectly normal to other people, we may suspect that the source of these deep-seated feelings about their bodies arises from their brains. The recent report from Dick Swaab and his colleagues at the Netherlands Institute for Brain Research confirms this notion (Zhou, J. N., Hofman, M. A, Gooren, L. J. G., & Swaab, D. F. A sex difference in the human brain and its relation to transsexuality. Nature, 378, 68-70, 1995). Swaab and colleagues examined the brains of many individuals, including homosexual men, heterosexual men and women and six male-to-female transsexuals. They found that a tiny region with the unwieldy name of the central region of the bed nucleus of the stria terininalis (BSTc) was larger in men than in women. Sexual orientation seemed irrelevant to the size of the BSTc because it was as large in homosexual men as in heterosexual men. But the BSTc of the six transsexuals was as small as that of women - about half the volume of the BSTc in other men. Thus the brains of the transsexuals seem to coincide with their conviction that they are women. Of course such a report seems fantastic for several reasons. We know the brain is the center which controls all our behaviors, so of course differences in our behavior must reflect some differences in our brains. But the brain is a very complex system, and who would suspect that we might discern a difference related to such a rare and complicated condition as transsexuality? On the other hand, perhaps this is no more surprising than the discovery of sex differences in the structure of the human brain, and there have been several such reports over the last decade. If we can discern differences in brain structure between men and women, why not between transsexuls and other genetic males? Is there a simple way to dismiss these findings? Since all the transsexuals had received long-term treatment with estrogen and all but one had been castrated, one concern is whether the brain differences simply reflect the hormone treatments rather than the psychological condition of these people. But among the other men and women are several cases which seem to dispute this view. For example, several of the women were well past menopause and so had seen little estrogen in the years before they died, and two of the heterosexual men had been castrated to treat prostate cancer. Yet the women without estrogen still had a small BsTc and the men without their testes still had a large BSTc. So there does not seem to be any simple relationship between hormone exposure and BSTc size. You can think of other spurious reasons for the correlation, such as body size or brain weight or age, but the scientists have examples that seem to rule out each of those possibilities. So the only variable that seems to explain the small BSTc in the transeexuals is their transsexuality itself.

But there is another aspect of these results that we must consider, and that is the origin of transsexuality and brain differences. When did this difference in the size of the BSTc arise in these individuals - in childhood, in adolescence or in adulthood? We will not know the answer to this soon, because the BsTc is so small that none of the non-invasive imaging techniques provides enough resolution to measure or even detect the BSTc. That means that at present we can measure the BsTc only by removing the brain, which in turn means it can be measured only once in any one individual, after they have died. Thus there remain two alternative explanations for why the BSTc is smaller in traussexuals. Perhaps as babies these individuals were born with a small BsTc (or born with a BSTc that was programmed to grow only a little) and that small feminine BSTc caused them to regard themselves as feminine and to become transsexuals. But on the other hand, it is possible that other factors (such as filily structure, peer interactions, or random variation) caused these boys to regard themselves as feminine and grow up to be traussexuals. And those same "other factors' may have caused their BSTc to develop a small size.

For most laymen the idea that experience can alter the structure of the brain may seem unlikely, but for over 30 years neuroscientists have provided demonstrations that this idea is quite correct. At Berkeley, David Krech, Mark Rosensweig and colleagues found that when rats were raised in enriched environments (with toys and other rats) rather than caged alone, the animals showed many reliable changes in brain structure. Shortly after, David Hubel and Torsten Wiesel of Harvard demonstrated that depriving kittens of visual stimulation to an eye would alter connections between the eye and the brain. Such demonstrations of experience altering brain structure have been extended to monkeys and, in recent years, to humans. For example, a human who had lost his hand as an adult showed clear evidence that the side of the brain controlling that hand was reorganized less than a year after the accident (Yang, T.T., Gallen, 0., Schwartz, B., Bloom, F. E., Ramachandran, V.S., & Cobb, S. Sensory maps in the human brain. Nature, 386, 592-593, 1994 [letter]). As noninvasive imaging techniques are perfected we can expect to see further demonstrations that experience can alter the adult human brain. Why am I so confident that there will be more such demonstrations? I'm well aware of how much humans can learn, how much they can alter their behavior, and how frequently they do so. All of this behavioral plasticity requires that something in the brain remain plastic, too. But there is another important feature of the recent work with transsexuals that we can all ponder. Whether these men were born with a small BSTc which caused them to become transsexuals, or whether these men became transsexuals which then caused them to have a small BSTc, the fact remains that their brains are physically different. And that difference is not trivial, because any difference we can detect with our primitive understanding of neuroanatomy is, by definition, not trivial. Thus we might regard transsexuality as a deep, abiding conviction. Presumably these adults could no more set aside their feelings about which sex they are than you or I could. So perhaps the report of Zhou et al. will make it easier for our society to accept and tolerate transsexuality.