The science of transgenderism

[Divine Wind]

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 No studies have been able to demonstrate this, however, and these “findings” are considered outdated and have been highly criticized for their discriminatory implications.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.

For more information:

1. For a previous SITN blog article discussing sex determination systems, see: “I’m XY and I Know It”: Sex Determination Systems 101 - Science in the News
2. For a fairly comprehensive discussion on the genetics of gender, see: WHO | Gender and Genetics
3. For a more complete discussion on queer acronyms, see: https://decahedronofq.wordpress.com/what-is-lgbtqqiaap

While I agree it isn't a "conscious choice", that's a long way from saying it's "natural" meaning "normal".

Speaking of "natural" urges, this thread reminds me of the pickle slicer joke:

Bill has worked in a pickle factory for several years. One day he confesses to his wife that he has a terrible urge to stick his penis into the pickle slicer. His wife suggests that he see a therapist to talk about it, but Bill vows to overcome this rash desire on his own.

A few weeks later, Bill returns home absolutely ashen. His wife asks, "What's wrong, Bill?"

"Do you remember how I told you about my tremendous urge to put my penis into the pickle slicer?"

His wife gasps, "My God, Bill, what happened?"

"I got fired."

"No, Bill -- I mean, what happened with the pickle slicer?"

"Oh, um, she got fired, too."

 

[miketx]

 

[Ringel05]

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 identi...

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 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.

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.

Between the (Gender) Lines: the Science of Transgender Identity - Science in the News

======

RESULTS:

In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal

CONCLUSIONS:

Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.

tract. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. - PubMed - NCBI


It appears to me that the science supporting transgendermism as natural is quite strong.

Not necessarily as we aren't really sure what BSTcs do and cannot be easily attributed to sexual orientation, hormones, or other seemingly plausible incidental causes. Finding differences in the brain is not always evidence of cause, it is just as scientifically plausible that social causes are responsible for the brain differences, unlike a computer our brain is not static. Then we have the research itself and the extremely low sample size, not necessarily a problem but it raises the possibility of the results being a fluke from a statistical standpoint and in a study such as this the sample size needs to be huge to get an accurate overall reading.
Not claiming the study is specifically bad or inherently flawed just indicating that without a much larger sample size and actually peer reviewed studies as well as a determination of the actual causes of neuro-chemical processes and distinct causative relationships we are still only guessing. We have much more work to do in order to make definitive (empirical) claims.

Agreed that more research is needed. There has been a lot of science done proving the differences between the brains of gay and straight men. Example:
Is Homosexuality a Choice?

People don't realize just how little we truly know about the human body and how much less we know about the intricacies of the human brain. The total biochemical and neuro-chemical interactions and causative mechanisms are nearly infinite and can change within each individual numerous times in a day, week, month, year, etc. Right now the best we can do is make correlative guesses in most instances.

 

[miketx]

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 identi...

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 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.

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.

Between the (Gender) Lines: the Science of Transgender Identity - Science in the News

======

RESULTS:

In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal

CONCLUSIONS:

Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.

tract. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. - PubMed - NCBI


It appears to me that the science supporting transgendermism as natural is quite strong.

Can science also show that the tendency to molest children is also natural, so we can be more accepting of theses type humans?

They're not humans, more like animals that need put down

Agree...but that is where liberalism will take us.

The left can't even fathom the damage that is done to a child who has been sexually abused. Trust goes out the window and recovery is a painful process that may last a lifetime.

So long as the leftard has his/its feelings intact, the damage to the child is not important to them. Feelings are all that matter and bogus science created by other freaks of nature.

 

[SassyIrishLass]

Between the (Gender) Lines: the Science of Transgender Identity - Science in the News

======

RESULTS:
CONCLUSIONS:
tract. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. - PubMed - NCBI


It appears to me that the science supporting transgendermism as natural is quite strong.

Can science also show that the tendency to molest children is also natural, so we can be more accepting of theses type humans?

They're not humans, more like animals that need put down

Agree...but that is where liberalism will take us.

The left can't even fathom the damage that is done to a child who has been sexually abused. Trust goes out the window and recovery is a painful process that may last a lifetime.

So long as the leftard has his/its feelings intact, the damage to the child is not important to them. Feelings are all that matter and bogus science created by other freaks of nature.

Agreed and a pedophile cannot be cured, if released they will offend again.

Put them down, do it for the children

 

[ScienceRocks]

Even if there is no scientific basis at all and this proves that simply isn't so...Well, people should be free to be such if they choose. Not hurting anyone.

 

[miketx]

Even if there is no scientific basis at all and this proves that simply isn't so...Well, people should be free to be such if they choose. Not hurting anyone.

If it isn't so, then do it anyway? You are insane matthew.

 

[Divine Wind]

Even if there is no scientific basis at all and this proves that simply isn't so...Well, people should be free to be such if they choose. Not hurting anyone.

What happens between consenting adults is their business. Keep the government out of our homes and lives.

 

[ScienceRocks]

Check the Science: Being Trans Is Not a 'Choice'

The Only Sane Opinion Around the Transgender Bathroom Debate
By Leslie P. Henderson

The Daily DoseFEB 25 2017

The author is a professor of physiology and neurobiology at Dartmouth’s Geisel School of Medicine and a former fellow of the OpEd Project.

The countersuits being brought by the federal government and states such as North Carolina over the use of bathrooms by transgender individuals encompass many complex issues on federal versus states’ rights. But they also highlight a critical, common and incredibly damaging misperception: that gender and biology are two separate things. A letter writer to my local paper notes with respect to the Obama administration’s actions dictating bathroom policy, “Strangely enough, it seems to be predicated on the idea that one’s gender is a matter of choice rather than biology.”

The writer is right — it is biology, but not in the way he means. I have spent more than two decades studying sex-specific differences in the brain. I hazard a guess that I know more than most people on this issue, although I also know that we scientists have only a rudimentary understanding of how genetic, epigenetic, hormonal and environmental factors interact during brain development and into adulthood to form the incredibly diverse and complex spectrum that forms gender roles and gender identity.

But, I know for damn sure that biology is a big part of it, and it is not simply what sex gets put on your birth certificate — an assignment that is predominantly based on whether or not one has a penis. There are numerous biological conditions, such as androgen insensitivity syndrome, 5-alpha reductase deficiency or Rokitansky syndrome, in which individuals with either XY and XX chromosomes are born without a normal vagina or uterus but also without a penis, and are nearly always assigned to be “a girl.”

It has to do with the biology of your brain.

What most people don’t know is that our brain is both literally and figuratively our biggest sex organ. The parts of our brain that control behaviors that have to do with sex and things that differ by sex are exquisitely sensitive to hormones and chemicals that can mimic hormones. They also express genes in patterns that differ between males and females.

Tune in Tuesday at 11/10C for PBS’ new late-night series Point Taken to see OZY co-founder Carlos Watson moderate a spirited debate on gender.

What’s more, the factors that regulate these brain regions do so not only during the hormonal rages of puberty but also early on in our development. In humans and other animals, these brain regions are molded to be different from before the time we are born. Once established, many of these changes are permanent. And while we may not fully understand all of these early actions, they are key to sex-specific behaviors, sexual preferences and, just as likely, gender identity.

We don’t know how or if nonhuman animals have a sense of gender, and so can’t study that experimentally. But we do know that male versus female partner preferences in rodents can be changed by altering those brain regions that govern sexual behaviors. We also know that that there are significant differences between cis- and transgender individuals in brain structures and the connections between them; these are correlated with differences in behaviors, such as processing of positive affective and erotic imagery.

Brain differences are biological. We should know then that to be transgender is not a choice.



There is evidence to suggest that increased levels of gender dysphoria (i.e., the variance between gender identity and chromosomal sex) may result from developmental exposure to abnormal hormone environments, especially increased levels of androgens in XX fetuses that can occur in conditions such as congenital adrenal hyperplasia. Anecdotally, my neuroscience colleague Ben Barres has suggested that prenatal exposure to testosterone-like drugs may explain his own transgender identity.

In humans, care must always be taken relating correlation to causation. Differences in brain structures may reflect mutual interactions among innate brain processes, expressed gender roles and society’s response to those actions. But brain differences are biological.

We should know then that to be transgender is not a choice.

It is not a choice when meta-analysis of suicide rates indicates that lifetime prevalence of attempted suicide in transgender individuals is ~40 percent as opposed to ~4 percent in the overall population. It is not the same as deciding whether you will wear a red tie or a green one.

It is a choice for us to educate those who mistakenly believe that allowing transgender people to use bathrooms appropriate for their identity endangers women and children. Such people either do not know transgender people or, more likely, know them but do not know they are transgender. And those that believe that real sexual predators will be dissuaded by a sign on a bathroom door are truly lost.

It is a choice for those of us who study the complexities of biology and the human brain to inform those who are not neuroscientists so that they can understand why it is not “a choice” for transgender people; it is who they are.

 

[ScienceRocks]

Neuroanatomical Differences. Many of the current hypotheses for the biologic origin of transgender identity are based on atypical sexual differentiation of the brain. The perception of one's own gender is linked to sexual differentiation of the brain, which differs from the body phenotype in transgender individuals.[7] Swaab et al have proposed that this discrepancy could be due to the fact that sexual differentiation of the brain takes place only after sexual differentiation of the gonads in early fetal life.[8] Along these lines, the degree of genital masculinization may not reflect that of the brain.

The notion of transgender-specific cerebral phenotypes is further supported by postmortem brain studies investigating the underlying neuroanatomical correlates of gender identity.[9,10,12] The vast majority of these studies have compared particular regions of interest only in male-to-female (MTF) transgender individuals.[13–15] These studies support the hypothesis that atypical cerebral networks in transgender individuals have a neuroanatomical basis.

Medscape: Medscape Access

 

[Bob Blaylock]

 

[ScienceRocks]

Medscape: Medscape Access

Gray Matter Studies. Studies of cerebral gray matter in transgender individuals have provided the strongest neuroanatomical case for transgender gender identity. Postmortem brain studies suggest that some subcortical structures are feminized in MTF individuals. One of the earliest and most influential studies in this area investigated the bed nucleus of the stria terminalis (BSTc), which was reported to be a sexually dimorphic nucleus in humans with a larger volume in males than in females. In 1995, Zhou et al reported that the size and number of neurons in the BSTc of 6 MTF estrogen-treated transgender individuals was typical for the size and neuron numbers generally found in control females.[9] The authors further reported that these findings could not be explained by differences in adult sex hormone levels.

A similar study by Kruijver et al provided further data supporting the role of the BSTc in transgender identity.[10] They examined tissue from the same 6 MTF estrogen-treated transgender persons studied by Zhou et al and found that the number of neurons in the BSTc was more similar to genetic XX female controls. BSTc neuron number was also in the male range in the 1 FTM androgen-treated transgender individual studied.

Most transgender individuals experience feelings of gender dysphoria that begin in childhood. However, in a study of BSTc volume in postmortem brains of 50 control subjects, Chung et al reported that sexual dimorphism in the BSTc did not develop until adulthood.[11] Yet, the same group remarked that changes in fetal hormone levels could have delayed effects on BSTc volume and neurons in adulthood, thereby suggesting a role for BSTc as a marker for gender identity. Still, delayed development of sexual dimorphism in the BSTc would not explain childhood development of gender dysphoria or gender identity discrepancy.

In 2008, Garcia-Falgueras and Swaab were the first to report a sex reversal in the uncinate nucleus. They examined the third interstitial nucleus of the anterior hypothalamus (INAH 3), which is a sexually dimorphic component of the uncinate nucleus, in relation to the brains of transgender individuals.[12] They reported that the mean INAH3 volume and neuron number in 11 MTF transgender subjects were in the female ranges.


The above studies are limited by the fact that they involved postmortem examinations of a small number of brains from MTF individuals, some of whom had either received hormone treatment or surgery. Therefore, the study findings may represent confounding effects from exogenous hormones in a small group of transgender individuals. Despite their small sample size, these studies provide valuable evidence that gender identity is linked to neuroanatomy.

Studies by Luders et al provided further evidence that transgender identity is associated with distinct cerebral patterns.[13,14] In 2009, the group analyzed magnetic resonance imaging (MRI) data of 24 MTF transgender individuals who had not yet begun hormone treatment. These subjects were shown to have a pattern that was more similar to control males. However, they also observed a significantly larger, more "feminized" volume of regional gray matter in the right putamen in these subjects. In 2012, the same group observed thicker cortices in 24 MTF transgender individuals who had not yet received exogenous hormones compared with 24 age-matched control males in a number of regions across the lateral and medial cortical surfaces. The data supported a dichotomy between MTF transgender individuals and gender congruent males with regard to brain structure.


The same group investigated 12 living MTF transgender individuals who smelled 2 steroidal compounds: the progesterone derivative 4,16-androstadien3-one (AND) and the estrogen-like compound estra-1,3,5,[10] 16-tetraen-3-ol (EST). These compounds have been reported to activate the hypothalamic networks in a sex-differentiated way. MTF transgender individuals who had not received hormone treatment were found to respond similarly to female controls, with AND activating the anterior hypothalamus.[16] Another study by Gizewski et al showed a similar cerebral activation in MTF transgender individuals relative to female controls while they viewed erotic stimuli.[17] While the above studies only involved MTF transgender individuals, they nonetheless provided evidence of neuroanatomical pathway alteration as an explanation for transgender identity.

The following 2 studies were unique from the aforementioned ones because they included both MTF and FTM transgender individuals who had not received hormone treatment. Zubiaurre et al reported that FTM transgender individuals showed evidence of subcortical gray matter masculinization in the right putamen, while MTF transgender individuals had feminized cortical thickness.[18] In 2013, Simon et al reported differences in gray matter in 17 living transgender subjects compared with controls.[19] Differences were seen in transgender patients in the cerebellum, angular gyrus, and parietal lobe compared with controls, independent of their biologic gender.

White Matter Studies. Although an early study by Emory et al[20] found no difference in the whole corpus callosum or splenium region between MTF and FTM transgender individuals, the following MRI studies of white matter brain characteristics of transgender individuals suggested a strong neuroanatomical explanation for transgender identity. Yokota et al reported that the pattern of corpus callosum shape in both FTM and MTF transgender individuals was closer to subjects with shared gender identities than to subjects who shared the same natal sex.[21] Among FTM transgender individuals who had not received hormone treatment, certain white matter fasciculi involved in higher cognitive functions were closer to the pattern of control males than to control females.[22] Among MTF transgender individuals who had not received treatment, diffusion tensor imaging revealed an intermediate white matter pattern that was between those of male and female controls.[23]

 

[ScienceRocks]

Evidence supporting the biologic nature of gender identity.
Saraswat A1, Weinand JD2, Safer JD3.
Author information
Abstract
OBJECTIVE:
To review current literature that supports a biologic basis of gender identity.

METHODS:
A traditional literature review.

RESULTS:
Evidence that there is a biologic basis for gender identity primarily involves (1) data on gender identity in patients with disorders of sex development (DSDs, also known as differences of sex development) along with (2) neuroanatomical differences associated with gender identity.

CONCLUSIONS:
Although the mechanisms remain to be determined, there is strong support in the literature for a biologic basis of gender identity.
An Error Occurred Setting Your User Cookie

 

[SixFoot]

 

[Bob Blaylock]

 

[ScienceRocks]

View attachment 135535

This is the response a very screwed up 5 year old would give that doesn't give a shit about science...Of course, that is too be expected from a idiot like you as everything is a joke to you and you don't wish to be educated on anything....Go play with your ball and let the adults talk science.

 

[Bob Blaylock]

This is the response a very screwed up 5 year old would give that doesn't give a s••• about science...Of course, that is too be expected from a idiot like you as everything is a joke to you and you don't wish to be educated on anything....Go play with your ball and let the adults talk science.

One who denies the difference between men and women is in no position to lecture anyone else about “science”.

 

[ScienceRocks]

I am laying real science down and I ask for people to consider it.

 

[Bob Blaylock]

I am laying real science down and I ask for people to consider it.

Madness is not science.

 

[TNHarley]

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 identi...

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 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.

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.

Between the (Gender) Lines: the Science of Transgender Identity - Science in the News

======

RESULTS:

In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal

CONCLUSIONS:

Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.

tract. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. - PubMed - NCBI


It appears to me that the science supporting transgendermism as natural is quite strong.

Has some said mental illness isn't natural?