ARTICLES
http://www.time.com/ time/magazine/archive/ 1995/951113/science.html
November 13, 1995 Volume 146, No. 20
Transsexuals often claim they were born the wrong gender. Microscopic studies of a key region of the brain suggest they may be right BY CHRISTINE GORMAN
Most young children like to play dress-up, parading around the house in their dad's wing tips or smearing their mom's lipstick all over their face. But for a few youngsters, usually boys, this childhood rite is more than a game. They are obsessed with their mother's clothes and wear them at every opportunity. It is as if a part of their mind were trying to erase the maleness of their body and allow an inherent femaleness to emerge. As they grow older, their discomfort with their gender often increases, until finally they turn to doctors for help. Some take feminizing hormones to grow breasts. Some even have their sex organs surgically altered so they can live completely--including anatomically--as women.
But are such people, who are known as transsexuals, truly women trapped in men's bodies? For years, scientists searched for but never found any measurable differences between most men and the ones who become transsexuals, whether in the level of hormones, the shape of genitalia or the number of chromosomes. Nor did scientists find any fundamental similarities between transsexuals and women.
Last week, however, investigators from the Netherlands Institute for Brain Research in Amsterdam reported preliminary evidence that transsexuals may be inherently different, after all. Their study of six male-to-female transsexuals showed that a tiny structure deep within a part of the brain that controls sexual function appeared to be more like the type found in women than that found in men. If confirmed, the study seems likely to challenge long-held beliefs about what it takes to make someone a man--or, a woman.
The Dutch research is part of a growing body of evidence suggesting that nature is just as important as nurture in determining how we think and behave as sexual beings. Neurobiologists have cataloged apparent differences in the way men's and women's brains process information and interpret facial expressions. Geneticists have begun sifting through tantalizing clues that sexual orientation--as opposed to sexual identity--may at least be partly inherited (see box). Yet the subject matter is so charged from an emotional, political and even religious perspective that evaluating all the various claims dispassionately can be very difficult.
In many respects, studying transsexuals would seem to be the most difficult undertaking of all. Not to be confused with transvestites or cross dressers, true transsexuals are rare. By some estimates, no more than 1 person in 350,000 believes he or she was born the wrong gender. Moreover, the portion of the brain that seems to be different in transsexuals is smaller than a pinhead. Even advanced imaging techniques, like the pet scan or MRI, cannot detect such tiny variations. To do their research, the Dutch team, led by Dr. Dick Swaab, had to dissect the brains of transsexuals in autopsies and examine them under a microscope. Little wonder, then, that it took Swaab's team 11 years to find transsexual candidates, persuade them to donate their brains and then wait for them to die to make the comparisons.
Despite these constraints, Swaab and his colleagues were able to detect some intriguing patterns. They compared the brains of two dozen "ordinary" men and women. For the most part, the brains appeared to be the same until the researchers examined a section of the hypothalamus called the BSTc. Although no one knows for sure what this tiny patch of neurons does in humans, earlier studies have indicated that, in rats at least, it plays a key role in regulating male sexual behavior. Half the men in the control group were heterosexual and half were homosexual. Yet, regardless of their sexual orientation, they all had a BSTc that was 50% larger than that in the women.
When the researchers examined the BSTc of the transsexuals, they found a marked difference. The transsexuals' BSTc was more like the women's than the men's. In fact, the transsexuals' BSTc was, on average, slightly smaller than the women's. The researchers seemed to have found at least one biological motive for the transsexuals' desire to change sex, although it may not be the only one. Says Swaab: "Our results indicate that other structures in the brain could be involved."
How could the brain and the body become so mismatched? Several explanations are possible. One is rooted in the process by which embyros take on sex differences. All human embryos develop in the very earliest stages of gestation along more or less feminine lines. Those destined to become males differentiate from the master template after a complex series of hormonal secretions starts to masculinize the embryo. Miscues in this process could result in crossed signals in the portions of the brain that are responsible for gender identity. That would help explain why there are more male-to-female transsexuals than female-to-male.
Not everyone is convinced, however. All the transsexuals in the Dutch study took the feminizing hormone estrogen. The smaller BSTc may therefore have been the result rather than the cause of their quest to become women. Swaab concedes this possibility but notes that two women in the study's control group were postmenopausal and presumably no longer manufactured much estrogen. Their BSTc was still the same size as the younger women's, which may mean that estrogen has no effect on the structure's size. There are simpler explanations--stress, for example. "Think about it," says Roger Gorski, a neurobiologist at UCLA who has studied rats' sexual behavior for 30 years. "These people undergo a lot of emotional trauma. To cut everything off to become a woman has got to be awfully stressful, and that has got to affect brain structures."
But for most transsexuals, there is no question that something deeper is going on. From the time she was a boy of six, Bea Jansen, 46, who lives outside Amsterdam, knew her body did not reflect her true gender. "I felt there was something that didn't fit," she says. "And that something was a penis." Jansen, who plans to donate her brain to Swaab's study when she dies, underwent a sex-change operation five years ago. She speaks for many transsexuals when she describes her transformation as a liberation: "I felt as if I could finally take off a mask that I had been wearing for a long time." With Jansen's help, scientists may someday understand how that mask got there in the first place.
Reported by James Geary/Amsterdam and Alice Park/New York Copyright 1995 Time Inc. All rights reserved.