Over the past few decades, neuroscientists, endocrinologists, geneticists and social scientists have conducted numerous studies involving transgender people, meaning those whose gender identity does not conform to that typically associated with the sex to which they were assigned at birth. Justifications for doing such research have shifted over the years and, today, investigators are increasingly focused on assessments of transgender people’s mental health or the impact of hormone therapies.

But such work raises challenges. Despite researchers’ best intentions, these studies can perpetuate stigmas and make it even harder for transgender people to access appropriate medical care.

Here we focus on neuroscientific approaches to the study of transgender identity to explore how investigators might navigate these concerns.

Brain scanning

In 1995, neuroscientists at the Netherlands Institute for Brain Research in Amsterdam published findings from a post-mortem study, which included six transgender individuals1. They found that the volume of part of the brain’s hypothalamus — called the bed nucleus of the stria terminalis, which tends to be larger in men than in women — corresponded to the gender identity of the transgender individuals, not to their sex assigned at birth. Although the data were only correlative, the researchers suggested that people identify as transgender because of changes in the brain that happen before birth — in other words, that someone can be born with a male-typical body and brain characteristics more typical of a female brain, and vice versa.

Since it was published, the paper has been cited more than 1,000 times, and at least a dozen researchers have probed this theory and related ones using tools such as structural and functional magnetic resonance imaging (MRI).

Although the results of these analyses have been inconsistent, several ideas have nonetheless arisen about a neurobiological basis for gender dysphoria — the distress associated with a person’s gender identity not aligning with the sex they were assigned at birth. These include the ‘own-body perception’ theory2, which proposes that a reduced structural and functional connectivity between certain brain networks is responsible. (Previous work has associated these networks with brain regions thought to be involved in people’s ability to link their own body to their sense of self3.)

As analytical tools and methods advance, brain research is becoming more sophisticated. The number of neuroscientific studies that include transgender participants has increased considerably since 1991 (see ‘On the rise’).

On the rise. Line chart showing the number of neuroimaging studies that include transgender participants has increased from 1 to 83 between 1991 to 2024.

Some neuroscientists are using functional MRI to study the effects of hormone therapy on brain structure4 and to examine cognitive processes such as face perception5. Others are applying machine-learning techniques to establish whether features in brain scans of cis- and transgender people correlate with their gender identity6. Researchers are also trying to assess whether particular features identified in brain scans make it more likely that transgender individuals will benefit from gender-affirming hormone therapy7. And some are conducting ‘mega-analyses’ — pooling the brain scans of hundreds of participants — to identify brain characteristics that are specific to transgender people8.

Help or harm?

One concern arising from such studies is that neuroscientific findings related to transgender identity could make it even harder for some people to access medical treatment that could help them.

In countries or regions where gender-affirming medical treatment is available, individuals often need a diagnosis of ‘gender dysphoria’ or ‘gender incongruence’ to be eligible for hormone therapy or gender-affirming surgery, and to be reimbursed for such treatments. Results from brain scans could be included in the suite of measurements used to assess whether someone is experiencing gender dysphoria or incongruence.

Those in favour of such requirements argue that it is necessary to prevent people taking irreversible steps that they might regret. Hormonal therapy can have adverse effects on fertility, for instance9. However, many transgender people argue that whether someone can receive gender-affirming hormone therapy or other treatment shouldn’t depend on a health-care practitioner deciding that they experience ‘enough’ gender dysphoria to be eligible10. The current approach, combined with a shortage of specialists qualified to make such diagnoses, has been linked to long waiting lists. In the Netherlands, waiting times can be more than two years.

A second possibility is that neuroscientific findings related to transgender identity will fuel transphobic narratives11.

Take the debate on social media and other platforms about gendered public spaces in countries such as the United States, the United Kingdom and Brazil12. Some people argue that allowing transgender women to access infrastructure, such as public toilets or women’s prisons, threatens the safety of “real women”. Neuroscientific research is sometimes misused to bolster flawed claims about what ‘real’ means.

Moreover, such studies could exacerbate tensions between scientific and transgender communities.

A person is helped into an MRI machine

Scientists are aiming to identify brain characteristics that are specific to transgender people.Credit: Alain Jocard/AFP/Getty

Although cis- and transgender researchers have taken steps to improve people’s understanding, there is a history of tension between the scientific and transgender communities13. In the late 1980s, for instance, a sexologist argued that trans women who are mainly attracted to women experience sexual arousal from their own expression of femininity. He described their feelings of gender dysphoria as resulting from paraphilia — a sexual interest in objects, situations or individuals that are atypical14. This theory has not held up under broader scientific scrutiny15, but it has become notorious in the transgender community and, from our discussions with transgender people and discussions by other groups16, it is clear that such studies have reduced transgender people’s trust in science.

In 2021, for example, a neuroimaging study with transgender participants was suspended in the United States after backlash from the transgender community. The study would have involved showing participants images of themselves wearing tight clothes, with the intention of triggering gender dysphoria — an experience that is associated with depression, anxiety, social isolation and an increased risk of suicide. The study’s researchers had acquired ethical approval from their research institute and obtained informed consent from the participants. Yet they had failed to anticipate how the transgender community would perceive their experimental procedure.

In 2022, to learn more about how transgender people view current neuroscientific approaches to the study of transgender identity, we conducted focus-group interviews that lasted for three hours with eight transgender participants — all of whom had differing levels of knowledge about the topic.

The group expressed concern that studies that look for a neurological basis to transgender identities could have a pathologizing effect. “I think questions of aetiology are just inherently wrong,” one participant said. “We don’t ask ‘Why is someone’s favourite colour blue?’. These are questions that come from wanting to pathologize.” Participants also agreed that a biological-determinist approach does not do justice to the complex and layered experience of identifying as transgender.

Four steps

Decades of work aimed at establishing how science can benefit minority groups17 suggest that neuroscientists and other scholars could take several steps to ensure they help rather than harm transgender, non-binary and intersex individuals and other people who don’t conform to narrow definitions around sex and gender. Indeed, the four actions that we lay out here are broadly applicable to any studies involving marginalized groups.

Establish an advisory board. Researchers who work with transgender participants should collaborate with an advisory board that ideally consists of transgender people and members of other groups with relevant perspectives, including those who have some understanding of the science in question. Funding agencies should support such initiatives, to help prevent further distrust being sown because of how studies are designed.

Set up multidisciplinary teams. Researchers trained in neuroscience will view phenomena such as transgender identity through a different lens from, say, those trained in psychology. To prevent the outcomes of neuroscientific and other studies being described and published in an overly deterministic and simplistic way18, research teams should include social scientists. Ideally, such collaborations would also include transgender researchers or others with diverse gender identities, because their input would help to prevent a cis-normative bias in study design and in the interpretation of results. Indeed, our own group has benefited from this diversity (one of us is transgender).

Prioritize research that is likely to improve people’s lives. Neuroscientists and others engaged in research involving transgender participants, non-binary people or individuals with diverse gender identities should prioritize research questions that are likely to enhance the health of these groups. Although the applications of basic research can be hard to predict, investigations into the neurobiological impacts of hormone treatment on the brain, for instance, could be more directly informative to health-care practitioners and transgender individuals than might investigations into the underlying bases of transgender identity.

Rethink how ethical approval is obtained. Ethical boards at universities typically consist of scientists with diverse backgrounds. But it is unrealistic to expect them to be educated on the sensitivities of every minority group, whether in relation to gender, religion, ethnicity or anything else. One way to address this problem is for ethical boards to require researchers to state what feedback and other information they have gathered through community engagement. A university’s ethical review committee could then evaluate whether the researchers have done enough to understand and address people’s concerns and sensitivities.

In context

Our aim is not to halt scientific enquiry. But when it comes to transgender identity, knowledge cannot be pursued in isolation from the many societal factors that shape how that knowledge is received and acted on.