Researchers in the Netherlands have discovered that a region of the hypothalamus, located at the floor of the brain, is about 50 percent larger in men than in women, and almost 60 percent larger in men than in male-to-female transsexuals. If smallness of this brain structure is at all correlated with the feeling of being a woman, the results raise tantalizing possibilities that transsexuals may in a sense be more female than females.
The discovery is the first detection of a difference in transsexual brains and could at least partly explain why such individuals describe themselves as "women trapped in men's bodies."
The finding may also cast light on the larger issue of sexual identity, of what makes a person feel comfortable--or tormented--in the skin of a man or a woman.
Significantly, the region of the hypothalamus does not differ in size between gay and straight men, and so it cannot be said to play a role in male sexual orientation. Other recent studies have focused on identifying minor brain discrepancies between homosexual and heterosexual men, in general reporting that gay brains appeared comparatively feminine. Such findings, which remain deeply contested, have troubled many people for the simple reason that gay men overwhelmingly think of themselves as men, not as abnormal women. But genetic men who undergo sex reassignment often claim that they felt like girls from early childhood on.
Dr. Dick F. Swaab of the Netherlands Institute for Brain Research in Amsterdam, who with his colleagues is reporting the work in today's issue of the journal Nature, emphasized that this section of the hypothalamus is by no means the entire source of sexual identity.
"I'm convinced this is only one structure of many that are involved in such a complex behavior," he said. "This is just the tip of the iceberg."
In addition, the study remains to be replicated by other researchers, which will not be easy. It was performed by dissecting the autopsied brains of transsexuals, homosexual men, heterosexual men and heterosexual women. Because transsexuality is rare, it took the scientists 11 years to collect six transsexual brains.
But while the number of transsexual brains examined is small, Dr. Swaab said the results has scientific power because the discrepancies in size of the hypothalamic structure were quite large.
Others in the field concur. "These are astonishing data," said Dr. Geert de Vries, a neurobiologist at the University of Massachusetts at Amherst. The specific region under study is called the central subdivision of the bed nucleus of the stria terminalis. Research in rats and other laboratory animals indicates that this part of the hypothalamus helps coordinate sexual behavior and the release of essential reproductive hormones.
But Dr. S. Marc Breedlove of the University of California at Berkeley, who wrote an editorial that accompanies the new report, said that the function of the bed nucleus in human behavior, sexual or otherwise, remained "a complete black box."
In heterosexual and homosexual men, the bed nucleus measures about 2.6 cubic millimeters, about the size of the colorful, spherical head of a pushpin. In women, it averages 1.73 millimeters, and in transsexuals the average figure is 1.3.
Some scientists cautioned that the estrogen treatment the transsexuals took as part of their sex-change therapy might have affected the size of their hypothalamus; but the Dutch researchers tried to rule out that factor by including brains of transsexuals who had stopped estrogen years earlier, as well as brains of men and women with varying hormonal conditions. In no case did the size of the bed nucleus appear to be influenced by adult hormone levels.
The researchers are now trying to collect autopsied brains from women who were surgically changed to men--a considerably less common type of transsexuality than male-to-female--to see if their hypothalamic regions are of masculine dimensions.
Some scientists remain guarded about the meaning of the latest work, as do people in the increasingly activist "transgendered" community, which includes transsexuals and those born with conditions like hermaphroditism, in which both male and female sexual organs are present. "I think that these studies have a very poor history of reproducibility, and that they're undertaken with a particular social agenda," said Cheryl Chase, editor of Hermaphrodites With Attitude, the newsletter of the Intersex Society of North America.
But Dr. Joy Diane Shaffer, director of the Seahorse Medical Clinic in San Jose, Calif., and herself a transsexual, said the results jibed with those that she and her colleagues were gathering, using a very different approach to brain analysis. They are using magnetic resonance imaging technology to scan the brains of hundreds of living people, including heterosexuals of both sexes and transsexuals of both directions. Their method would not pick up differences in the tiny bed nucleus, but it may observe differences in other, larger structures, like the corpus callosum, which connects the two hemispheres of the brain.
Dr. Swaab proposes that the sexual variances in the size of the bed nucleus arise during fetal development, and thus are essentially built in. But Dr. Roger Gorski, a neurobiologist at the University of California at Los Angeles, said the possibility could not be ruled out that the changes in the hypothalamus occurred after birth, perhaps as a result of one's behavior while growing up, or even during early adolescence when a surge in sex hormones flooded the brain.
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