Everything You Ever Wanted to Know About Transgender Brains
Research into the brains of transgender people might illuminate some of the deepest mysteries of gender, transness, and sex differences.
by Veronica Esposito
In the years I’ve spent supporting trans people via mental health, I can’t recall a single person who told me that they would consider their transness to be changeable. Most of them also would consider it an inborn trait. This “born this way” narrative accords with prevailing beliefs about transness, and it is backed up by research done into monozygotic twins, who share virtually identical DNA and gestation environments. It is also backed up by the disastrously failed attempts to forcibly convert trans people into cisgender, as well as by the ill-fated efforts by researcher John Money to (nonconsensually) assign a sex to young children with indeterminate or damaged genitalia.
The fact that our transness is likely as inborn and immutable as our eye color would seem to suggest that our brains are somehow different from our cisgender counterparts. Most binary trans people are reported to engage in cross-sex behaviors from a very young age, so it would make sense that even at very young ages our brains are more oriented toward our true sex than that assigned to us by doctors.
To start, let’s review how the born this way hypothesis goes, biologically speaking. It is believed that gender identity develops in the brain at a different gestational point than our largely sexually dimorphic bodies, so it’s entirely possible for them to develop in opposite directions. Brain development is theorized to occur due to hormone washes during the second trimester, whereas bodily development starts in the first and is determined by the presence of the SRY gene on the Y chromosome. Thus, someone with an XX genotype could have a masculinized gender identity and vice versa. Experiments in multiple animals, including rhesus monkeys, have given strong evidence to confirm this hypothesis, although, for obvious reasons, such experiments could never be conducted on human beings. There are also lots of other bodily potentialities—including atypical genotypes like XXY or XXX, hormonal conditions like androgen insensitivity or PCOS, and bodies that develop intermediate genitalia (for a variety of reasons)—that can complicate the picture.
So if a brain can go one way and a body another, what does the research say? In fact, there have been numerous efforts to map and understand the trans brain, and the research—while far from complete—is very suggestive and interesting. Unfortunately, for those hoping for a clean and definitive resolution to the matter, there will be none here (brain science is likely very far away from being able to provide such a thing, if ever). But the information we do have is quite intriguing.
A caveat: this research is still very much in its infancy, and there are those who even say that the data we are deriving from brain scans are more or less meaningless. So, read on if you are interested, but do know that all of this is subject to change.
The first thing to know is that, based on today’s science, the idea that there is a “male brain” and a “female brain” is considered to be nonsense. While certain brain structures are currently believed to be sexually dimorphic (more on that in a moment), for the most part the picture of the gendered brain is extremely complex, with diversity being the rule. A meta-analysis led by researcher Lise Eliot in 2021 found that there was much more overlap than differences between brains belonging to cisgender men and women. In a similar vein, a 2015 study concluded that, although there are certain sex differences ascertainable, a more accurate view of the human brain would be as a “mosaic” rather than an either/or: “Most brains are comprised of unique ‘mosaics’ of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis.”
Notably, none of this research is an examination of the brain for gender identity, and current brain research can neither confirm nor refute the idea that a gender identity might inhere in some brain region or constellation of brain regions. However, a follow-up study co-authored by Eliot very much supports the idea that gender identity trumps bodies: a meta-analysis published by her in 2022 found that there was strong evidence for brain differences that are based on gendered differences—that is level of self-identification with masculinity or femininity, regardless of the sex of a given body. Notably, these measures allowed researchers to see gender more as a spectrum than as a simple binary, and to more finely correlate an individual’s perception of gender with the workings of their brain. This paper concludes with a passionate call to future researchers to “break the binary” and pursue brain research not based on what kinds of gametes you produce or where your gonads hang but rather how you see yourself: “We therefore urge neuroimaging researchers to lead the way and ‘break the binary’ by integrating modern, multifaceted measures of gender into traditional sex-based approaches for understanding brain variation and gender-linked psychopathologies.”
In that study, Eliot did specifically mention that research into trans brains has in fact frequently led the way in researching gendered differences of the mind: “Studies of the brain have barely scratched the surface in exploring the impact of gender attributes on structural and functional measures. An exception is the growing number of studies comparing the brains of transgender and cisgender participants, which we address elsewhere.” So what exactly does this research say about trans brains?
Well, the picture that has emerged is complicated, nuanced, and very much in need of continued examination.
For those who like to do their own research, this 2021 systematic review synthesizes the findings of dozens of studies attempting to understand similarities and differences between cisgender and transgender brains. I won’t cover the conclusions in detail—as they are voluminous, technical, and challenging to interpret—but suffice to say that the current information is conflicting and very much incomplete. The study did find some resemblances between the brains of trans people and cisgender members of their birth-assigned sex, while it found other resemblances to the sex indicated by their gender identity. This study, like others, seemed to say that possibly trans brains are just different from cisgender brains, or that brains in particular are such a “mosaic” of traits that it’s hard to generalize, and that specifics may come down to person-to-person differences. More than anything, these studies seem to say, “we really need a better basic understanding of human brains.”
What about the impacts of hormones on the brain, particularly when trans individuals make use of hormone replacement therapy to transition? A 2018 systematic review concluded that the experience of puberty causes meaningful changes to the brains of cisgender boys and girls, as well as to the neurotransmitters circulating in said brains. In its review of studies that focused on the brains of trans people undergoing HRT, it found that medication tended to act quickly (producing noticeable changes within a matter of months) and that it tended to make transgender brains more like those of their cisgender counterparts.
The study emphasized the need for longer-term longitudinal studies to better understand the brains and bodies of trans individuals—for instance, the study posed the question of if a trans man’s brain on testosterone mimics that of a cisgender woman with naturally elevated testosterone, or if his brain is somehow different and would use the testosterone in a different way: “While cisgender males aromatize testosterone to estradiol in the [central nervous system], it is not known whether FTM transgender individuals also aromatize testosterone to estradiol sufficiently to estrogenize the brain.” The answers to questions like this could have important implications for the long-term cognitive health of trans men.
The study also raised the point that the brain impacts of intense childhood adversity (of the kind experienced by most trans people) are still poorly understood—this adversity may impact the brain in meaningful ways that could complicate the administration of hormones. Lastly, it cautioned against extrapolating research on individuals who transitioned as adults to the growing numbers of those who are doing so as minors—research into the latter is very much in its infancy still, and the authors stated that it should be carried out to attain a fuller picture of the evolving transgender brain. Answers to questions like these are crucial to ensure the long-term health and functioning of trans individuals on HRT for prolonged periods.
Now for a dose of the weird. Here are studies regarding transgender brains that are quite suggestive and intriguing, but that are certainly too small to be taken as authoritative—and are also as of now not reproduced.
It is an open question as to just what are the impacts of estrogen in trans woman following the removal of their gonads. This study used post-surgical volunteers who went off of their estrogen for 30 days to see what would happen. It found that even going off of estrogen for as little as 30 days seemed to produce noticeable brain differences in trans women without any means of producing their own hormones, and that when they resumed estrogen their brains returned to baseline. It seemed to show very clear brain changes due to estrogen, although exactly what those changes mean is difficult to interpret.
This 2021 study attempted to predict which individuals would respond best to HRT (measured as body congruence) via a combination of brain scans and various surveys.The researchers claimed to be able to predict who would do well on HRT to a level of statistical significance. This study attempted to investigate the biological bases for gender dysphoria—it found that, after the application of HRT, participants’ brains showed increased indications of own-body perception and “reversal of cerebral patterns associated with gender dysphoria to the baseline of cisgender controls.”
Lastly, let’s talk a little about the (here comes a mouthful) central subdivision of the bed nucleus of the stria terminalis (BSTc). This is an important brain structure—it is well-known for being very sexually dimorphic, and some researchers have proposed it as a kind of smoking gun for gender dysphoria. A 1995 study published in Nature found that trans women showed a female-sized BSTc, even before any cross-sex hormones. A follow-up study seemed to confirm these findings; it also extended the research to transmasculine individuals and found that the BSTc followed the established patterns of individuals with varying levels of hormones due to various disorders. Subsequently, an interesting piece of research complicated the picture by showing that the BSTc only reaches its fully dimorphic status in adulthood—this led researchers to wonder how it could be a driver of gender dysphoria in children if it does not significantly differentiate until adulthood. Possibly, there are differences not detectable by current brain scans, but we just don’t know.
I think it may be fairly said that, while there is still much that we don’t know, the available evidence seems to very much indicate that there is something biologically different about trans brains, and that HRT and other interventions further impact our brains in ways that meaningfully bring us into bodily congruence. Undoubtedly, research will continue in this area, but, given the complexity of brains overall and the relative simplicity of our tools for studying them, it’s hard to say if we will make meaningful progress toward understanding our neuroanatomy. For the time being, I find the available research provocative and meaningful in my own personal way, even though the science shows a lot of open questions and not a lot of clear answers.
Veronica Esposito (she/her) is a writer and therapist based in the Bay Area. She writes regularly for The Guardian, Xtra Magazine, and KQED, the NPR member station for Northern California, on the arts, mental health, and LGBTQ+ issues.