by Katherine J. Wu

figures by Brad Wierbowski



Think of your most noticeable feature. Maybe it’s your radiant smile, or your long, piano-playing fingers. Maybe it’s your stellar jump shot, or the way you recite Shakespearean sonnets at the drop of a hat. Or maybe it’s your penchant for scientific knowledge. But whatever it is, for better or worse, it is probably not your most salient feature to the world around you. To others, our most salient feature is one that doesn’t make any of us very salient at all – a feature in which none of us had any say in, which was assigned at, or prior to, birth: are you male or female?

Gender identity haunts every aspect of our lives, dictating the outcomes of our conversations, our workplaces, our relationships – even our bath products. Before most infants are named, they are assigned a sex based on the appearance of their external genitalia by a third party. These decisions are dolled out in a typically binary fashion, with no expectations for ambiguity. This is the norm – but has this simplicity led us astray?

In March of this year, Governor Pat McCrory of North Carolina signed into law the Public Facilities Privacy and Security Act, banning individuals from public restrooms that do not correspond to their assigned biological sex. This controversial legislation was the first of its kind– though certainly not for lack of trying. So called “bathroom bills” have been within political radar since the introduction of public restrooms in the 19th century; dozens of states within the U.S, primarily in the Midwest and South, have attempted, but failed, to bring such bills into law in the past year. The charged political climate of the summer has yielded many tense conversations about gender and LGBT rights – and it’s clear that these discussions are long overdue. But if we are to regulate gender, we must first assess the extent of our knowledge on the topic. What do we know of the “causes” the phenomenon of transgender identity – and what does this mean for the future of transgender politics?

The ABC’s (and LGBTQQIAAP+2S’s) of Gender and Sexuality

First, some (controversial) definitions. It would be remiss to claim to be able to define or categorize all variations in human sexuality and gender (hence the continually lengthening acronyms used, sometimes tongue in cheek, by the community); one of the larger acronyms, LGBTQQIAAP, still humbly accepts that it is not all-inclusive. These lists, while not exhaustive, are exhausting. The labels are useful in some respects, much like any other label denoting origin or role – they help us navigate social situations and can often be signs of respect. It is a natural human inclination to categorize, but broad assumptions can also lead to stereotyping. To limit the scope of this article, we will focus on transgender identity.

Those persons who identify as transgender (the “T” in many queer community acronyms) are those who identify with a gender that differs from their assigned sex (Figure 1). This juxtaposes cisgender, or those who identify with their assigned gender. Though the typical assigned sexes are “male” and “female,” often designated at birth, being transgender does not limit gender identity to these two categories, as many who identify as transgender do not feel they are exclusively masculine or feminine. Importantly, transgender identity is independent of sexual orientation. The subset of transgender individuals who choose to undergo sexual reassignment surgery are often denoted as transsexual.

The transgender identity has long been associated with poor mental health, particularly the diagnoses of “gender identity disorder” and “gender dysphoria.” However, the World Health Organization is actively working towards declassifying transgender identity as a mental disorder, a change partially prompted by a recent study uncoupling the mental and physical health problems experienced by transgender people from their gender identity. Rather, those who had suffered ailments could vastly attribute their afflictions to societal stigma, discrimination, and violence.

“It’s All in Your Head” – Except When It’s Not

Sex determination – the way we are “coded” into a biological sex – is complicated in and of itself. There are far more options than just “male” or “female,” and countless instances of species that can actually transition from one sex to another within a single lifetime. With most mammals, however, the majority of individuals are cisgender male or female; transgender individuals are estimated to comprise about 0.3% of the adult U.S. population.

Little is known about the causes of transsexuality, and many of the studies that have been conducted – particularly psychological studies – have since been widely discredited (more on that later). However, scientists do seem to have some information on the biological basis of several factors.

First and foremost, is gender identity genetic? It seems the answer is yes – though, as with most traits involving identity, there is some environmental influence. One classic way for scientists to test whether a trait (which can be any characteristic from red hair to cancer susceptibility to love of horror movies) is influenced by genetics is twin studies. Identical twins have the exact same genetic background, and are usually raised in the same environment. Fraternal (nonidentical) twins, however, share only half their genes, but tend to also be raised in the same environment. Thus, if identical twins tend to share a trait more than fraternal twins, that trait is probably influenced by genetics. Several studies have shown that identical twins are more often both transgender than fraternal twins, indicating that there is indeed a genetic influence for this identity. So, what genes might be responsible?

Figure 2: Transgender women tend to have brain structures that resemble cisgender women, rather than cisgender men. Two sexually dimorphic (differing between men and women) areas of the brain are often compared between men and women. The bed nucleus of the stria terminalus (BSTc) and sexually dimorphic nucleus of transgender women are more similar to those of cisgender woman than to those of cisgender men, suggesting that the general brain structure of these women is in keeping with their gender identity.

In 1995 and 2000, two independent teams of researchers decided to examine a region of the brain called the bed nucleus of the stria terminalis (BSTc) in trans- and cisgender men and women (Figure 2). The BSTc functions in anxiety, but is, on average, twice as large and twice as densely populated with cells in men compared to women. This sexual dimorphism is pretty robust, and though scientists don’t know why it exists, it appears to be a good marker of a “male” vs. “female” brain. Thus, these two studies sought to examine the brains of transgender individuals to figure out if their brains better resembled their assigned or chosen sex.

Interestingly, both teams discovered that male-to-female transgender women had a BSTc more closely resembling that of cisgender women than men in both size and cell density, and that female-to-male transgender men had BSTcs resembling cisgender men. These differences remained even after the scientists took into account the fact that many transgender men and women in their study were taking estrogen and testosterone during their transition by including cisgender men and women who were also on hormones not corresponding to their assigned biological sex (for a variety of medical reasons). These findings have since been confirmed and corroborated in other studies and other regions of the brain, including a region of the brain called the sexually dimorphic nucleus (Figure 2) that is believed to affect sexual behavior in animals.

It has been conclusively shown that hormone treatment can vastly affect the structure and composition of the brain; thus, several teams sought to characterize the brains of transgender men and women who had not yet undergone hormone treatment. Several studies confirmed previous findings, showing once more that transgender people appear to be born with brains more similar to gender with which they identify, rather than the one to which they were assigned.

Interestingly, while the hormone treatments may have caused issues in the previous studies, they also gave scientists clues as to how these differences in brain anatomy may have arisen. Brain development is heavily influenced by the prenatal environment – what hormones the fetus is exposed to in its mother’s uterus. Some scientists believe that female-to-male transgender men, for instance, may have been exposed to inadequate levels of estrogen during development (Figure 3). This phenomenon could have two causes: 1) not enough estrogen in the fetus’s immediate environment, or 2) enough estrogen in the environment, but poor sensitivity in the fetus. Think of it like a cell phone tower controlling remote calls – the tower may not be producing enough signal (scenario 1), or the receiving phone may be unable to process the message (scenario 2). In either case, the call doesn’t make it through.

Figure 3: Possible scenarios underlying insufficient feminization. During normal feminization, sufficient estrogen is present in the fetal environment. The estrogen is recognized by fetal cells and triggers the development of a female fetus. In Scenario 1, very little estrogen is present in the fetal environment. Even though the fetal cells are capable of sensing estrogen, very little enters the fetal environment and the fetus is insufficiently feminized. In Scenario 2, there is enough estrogen in the fetal environment, but fetal cells are effectively “deaf” to the estrogen and the fetus is insufficiently feminized.

The amount of estrogen in the fetal environment is a little tough to measure – but there appears to be some evidence for transgender individuals having poor hormonal sensitivity in the womb. A team of researchers found that the receptor for estrogen (that is, the cell phone receiving the signal) seems to be a little worse at receiving signal in female-to-male transgender men – think a 2001 flip phone trying to process photos from Instagram. Thus, the signal doesn’t come through as clearly, and the externally “female” fetus ends up more masculinized.

The psychological studies that have attempted to unravel the causes of transsexuality, on the other hand, have largely failed to gain traction in modern times. For many years, psychologists characterized transgender identity as a psychological disorder. Some, for instance, believed it was a coping mechanism to “rectify” latent feelings of homosexuality, or the result of environmental trauma or “poor” parenting. No studies have been able to demonstrate this, however, and these “findings” are considered outdated and have been highly criticized for their discriminatory implications. Other psychologists have attempted to differentiate groups of transsexuals based on factors such as IQ and ethnicity; similarly, these theories have been overwhelmingly rejected due to poor study design and issues with ethics.

And so, while the list of causes for transgender identity continues to grow, it has become quite clear that it is not a conscious choice – similar to what has been described for the “reasons” behind sexual orientation. Still, at least 63% of transgender individuals experience debilitating acts of discrimination on a regular basis, including incarceration, homelessness, and physical assault. When about 1.7% of the population is in some way affected by cases of ambiguous genitalia at birth, these findings seem staggering.

So, where do we stand on transgender issues? Science tells us that gender is certainly not binary; it may not even be a linear spectrum. Like many other facets of identity, it can operate on a broad range of levels and operate outside of many definitions. And it also appears that gender may not be as static as we assume. At the forefront of this, transgender identity is complex – it’s unlikely we’ll ever be able to attribute it to one neat, contained set of causes, and there is still much to be learned. But we know now that several of those causes are biological. These individuals are not suffering a mental illness, or capriciously “choosing” a different identity. The transgender identity is multi-dimensional – but it deserves no less recognition or respect than any other facet of humankind.

Katherine Wu is a third-year graduate student in the BBS program at Harvard University.

This article is part of our Special Edition: Dear Madam/Mister President.

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For a previous SITN blog article discussing sex determination systems, see: http://sitn.hms.harvard.edu/flash/2016/im-xy-know-sex-determination-systems-101/ For a fairly comprehensive discussion on the genetics of gender, see: http://www.who.int/genomics/gender/en/index1.html For a more complete discussion on queer acronyms, see: https://decahedronofq.wordpress.com/what-is-lgbtqqiaap/

Note (August 10, 2017): We will no longer be accepting some types of comments on this article. We are open to conversations about science whether you agree or disagree with the science presented here. We will not, however, be accepting comments that are personally accusatory or inflammatory towards trans people in general or specific commenters (including, but not limited to, those who have identified themselves as trans). If you have questions about why your comment was not accepted, please e-mail us at sitnbostonblog (at) gmail.

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