Neurobiology of Transgender

Some interesting science links I discovered whilst browsing one of my regular websites (links provided by Disqus commenter Josh Colletta).

The first is 6 minute Youtube video by Robert Sapolsky, an American neuroendocrinologist, professor of biology, neuroscience, and neurosurgery at Stanford University, researcher and author. This video is part of a lecture he gave to one of his classes on the topic of transgender and the fact that gender identity is a biological trait of the brain.

Sapolsky mentions that a specific neurone, bed nucleus of the stria terminalis (BSTc), which is large in males, is half the size in transgender females (being a similar size to cis females).

I was not aware that 60% of males who have their penis removed due to penile cancer have phantom penile sensations (similar to phantom limb sensations experienced by amputees). Transgender females (male to female) who have their penises removed as part of sex reassignment surgery, do not experience this phantom sensation.


Wikipedia: Robert Sapolsky

Peer-reviewed studies:

Abstract

BACKGROUND:
Some gray and white matter regions of the brain are sexually dimorphic. The best MRI technique for identifying subtle differences in white matter is diffusion tensor imaging (DTI). The purpose of this paper is to investigate whether white matter patterns in female to male (FtM) transsexuals before commencing cross-sex hormone treatment are more similar to that of their biological sex or to that of their gender identity.

METHOD:
DTI was performed in 18 FtM transsexuals and 24 male and 19 female heterosexual controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter fibers of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics.

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 tract.

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.

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

Abstract

One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex.

Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND.

These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.

Male-to-Female Transsexuals Show Sex-Atypical Hypothalamus Activation When Smelling Odorous Steroids

Abstract

Transsexuals experience themselves as being of the opposite sex, despite having the biological characteristics of one sex. A crucial question resulting from a previous brain study in male-to-female transsexuals was whether the reported difference according to gender identity in the central part of the bed nucleus of the stria terminalis (BSTc) was based on a neuronal difference in the BSTc itself or just a reflection of a difference in vasoactive intestinal polypeptide innervation from the amygdala, which was used as a marker.

Therefore, we determined in 42 subjects the number of somatostatin-expressing neurons in the BSTc in relation to sex, sexual orientation, gender identity, and past or present hormonal status. Regardless of sexual orientation, men had almost twice as many somatostatin neurons as women (P < 0.006). The number of neurons in the BSTc of male-to-female transsexuals was similar to that of the females (P = 0.83).

In contrast, the neuron number of a female-to-male transsexual was found to be in the male range. Hormone treatment or sex hormone level variations in adulthood did not seem to have influenced BSTc neuron numbers. The present findings of somatostatin neuronal sex differences in the BSTc and its sex reversal in the transsexual brain clearly support the paradigm that in transsexuals sexual differentiation of the brain and genitals may go into opposite directions and point to a neurobiological basis of gender identity disorder.

Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus

Abstract

The fetal brain develops during the intrauterine period in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. In this way, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation are programmed or organized into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in extreme cases in trans-sexuality. This also means that in the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain. There is no indication that social environment after birth has an effect on gender identity or sexual orientation.

Sexual hormones and the brain: an essential alliance for sexual identity and sexual orientation.

Abstract

Transsexuality is an individual's unshakable conviction of belonging to the opposite sex, resulting in a request for sex-reassignment surgery. We have shown previously that the bed nucleus of the stria terminalis (BSTc) is female in size and neuron number in male-to-female transsexual people. In the present study we investigated the hypothalamic uncinate nucleus, which is composed of two subnuclei, namely interstitial nucleus of the anterior hypothalamus (INAH) 3 and 4.

Post-mortem brain material was used from 42 subjects: 14 control males, 11 control females, 11 male-to-female transsexual people, 1 female-to-male transsexual subject and 5 non-transsexual subjects who were castrated because of prostate cancer. To identify and delineate the nuclei and determine their volume and shape we used three different stainings throughout the nuclei in every 15th section, i.e. thionin, neuropeptide Y and synaptophysin, using an image analysis system.

The most pronounced differences were found in the INAH3 subnucleus. Its volume in thionin sections was 1.9 times larger in control males than in females (P < 0.013) and contained 2.3 times as many cells (P < 0.002). We showed for the first time that INAH3 volume and number of neurons of male-to-female transsexual people is similar to that of control females. The female-to-male transsexual subject had an INAH3 volume and number of neurons within the male control range, even though the treatment with testosterone had been stopped three years before deat

A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity.

Abstract

AIMS:
Despite a range of research on gender identity disorder (GID), at present there is no scientific consensus on whether the etiology of GID is mental or physical. In particular recent advances in the technology of neuroimaging research have led to an increased understanding of the biological basis of various mental disorders. GID also should be evaluated from this perspective. The aim of the present study was therefore to do the first trial to examine the regional cerebral blood flow (rCBF) in GID.
METHODS:

Persons considered biologically male fulfilling the GID criteria are termed male to female (MTF) and, conversely, persons considered biological female are termed female to male (FTM). We compared 11 FTM subjects and nine age- and handedness-matched female control subjects. None of the subjects was regularly taking medication and none had any kind of physical or psychiatric comorbidity. To evaluate rCBF in GID subjects and control subjects, statistical parametric mapping analysis of (99m)Tc-ethyl-cysteinate dimer single-photon emission computed tomography was used.

RESULTS:
GID subjects had a significant decrease in rCBF in the left anterior cingulate cortex (ACC) and a significant increase in the right insula compared to control subjects.

CONCLUSIONS:
The ACC and insula are regions that have been noted as being related to human sexual behavior and consciousness. From these findings, useful insights into the biological basis of GID were suggested.

Regional cerebral blood flow changes in female to male gender identity disorder

I hope some of you may find these links interesting. I did search for BSTc but only found brief mentions a few years ago. I am by no means an expert on this subject.

So are you saying gender dysphoria in men can be cured with testosterone?

a reply to: dashen

I am not actually saying anything. I have presented some scientific links. None of these links suggest this.

originally posted by: Morrad
a reply to: dashen

I am not actually saying anything. I have presented some scientific links. None of these links suggest this.

Sexual hormones and the brain: an essential alliance for sexual identity and sexual orientation.

you sure?
this seems to say something along those lines

a reply to: dashen

None of the links suggest that gender dysphoria can be reversed in MTFs with testosterone.

I have read anecdotal reports of MTF transition regret (for various reasons). These individuals started taking testosterone with a subsequent return/increase in gender dysphoria.

a reply to: Morrad

Great thread. This is what learning about something you don't understand should look like.

I hope this thread can be a place to discuss the medical/science aspects of gender dysphoria instead of the usual stubborn crowd posting ancient and outdated articles. And Hughes... ugh. Politics doesn't need to weigh in on a person's understanding of this and you have done a great job tackling it without bias.

a reply to: Morrad

So are they saying testosterone levels in utero can affect mtf gender dysphoria later in life

Excellent thread! S & F for you and your efforts!

originally posted by: Morrad
Transgender Transsexual females (male to female) who have their penises removed as part of sex reassignment surgery, do not experience this phantom sensation.

I can confirm that at least in my case this is true. Thank goodness! That would be pretty terrible. After 40 years, I even have a difficult time imagining I haven't always been this way. It's not something I'd really want to remember anyhow.

Science is great and there is an overwhelming body of research that does point to neurobiological origins for transsexualism but speaking personally, I've always felt the science was something for other people to look to as I've not felt the need to justify myself or say something like I'm trans because I have a female brain. It is important but I really couldn't care less because I've never known a time in my life when I was not trans so this has been my normal. This is something I never "wanted" to be, it is just something that was/is and indeed, my perception is that this is just the way I was born because I've never known anything different.

We're all aware and in agreement that babies can be born with ambiguous genitalia and a variety of intersex genetic and chromosomal variations so why not other sexually dimorphic anatomical structures such as the brain? I'm sure that once more research comes in we'll come to accept that this is just the way some people are born and not question it or call it a mental illness. I certainly don't have any other explanation for it.

Here's a couple more links:

Is There Something Unique about the Transgender Brain?

Transsexual differences caught on brain scan

originally posted by: dashen
So are you saying gender dysphoria in men can be cured with testosterone?

Absolutely not. Don't you think if it was that simple that this would have been tried? It has been tried over and over in the past only resulting in the distress of having gender dysphoria becoming much, much worse.

originally posted by: dashen
So are they saying testosterone levels in utero can affect mtf gender dysphoria later in life

That's the general consensus or something close to that. It may not necessarily be the levels of testosterone or estrogen in utero but rather the receptivity of the fetus to these chemicals. For example and somewhere only about 60% accurate or predictive of prenatal hormone receptivity is finger length. Males typically have longer ring fingers than index fingers. In females, the two fingers are usually the same length or the ring finger is shorter. This is called the 2D:4D ratio and there's plenty of science discussing it of one chooses to look for it. Another easily observable sexually dimorphic physical trait is carry angle of the elbow. It is larger in women than in men and both these things are attributable hormone influences in the womb. Again, this doesn't mean too much or too little of the right hormones but rather the receptivity to them.

Incidentally, my index finger is 5mm longer than my ring finger and my carry angle is way into the female range. Not that I care but I would imagine my brain structures lean to the female side as well, however, there is no such thing as an all female or all male brain.

a reply to: dashen

Further info from the study you referreed to:

Testosterone, estrogen and progesterone are influential but 50 genes also come into play, even before hormonal activity.

Conclusions
The human fetal brain develops in the male direction through a direct action of testosterone and in the female direction through the absence of such an action. During the intrauterine period, gender identity (the conviction of belonging to the male or female gender), sexual orientation, cognition, aggression and other behaviors are programmed in the brain in a sexually differentiated way. Sexual differentiation of the genitals takes place in the first 2 months of pregnancy, whereas sexual differentiation of the brain starts in the second half of pregnancy. This means that in the event of an ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain.

Our observations on reversed sex differences in the brains of transsexual people support the idea that transsexuality is based on an opposite sexual differentiation of

(1) sexual organs during the first couple of months of pregnancy, and (2) the brain in the second half of pregnancy. There is no proof that the social environment after birth has an effect on the development of gender or sexual orientation and hormonal changes during puberty do not seem to be responsible of the adult sexual identity and orientation, while the possible effects on sexual differentiation of the brain by endocrine disrupters in the environment and in medicines given to the pregnant mother
should be investigated.

The differences observed in the INAH3 in relation to sexual orientation and gender identity and this structure’s possible connection with the BSTc suggest that these two nuclei and the two earlier described nuclei that were found to be related to gender and sexual orientation, i.e. the SDN-POA (= intermediate nucleus = INAH1 and 2) and SCN, are all part of a complex network involved in various aspects of
sexual behavior. Neurobiological research on sexual orientation and gender identity in humans is only just gathering momentum, but the evidence shows that humans have a vast array of brain differences. There is a need for further multidisciplinary research on the putative influence of testosterone in development, e.g. in individuals with complete androgen-insensitivity syndrome.

The full study can be downloaded in pdf if you do not have access to PubMed

PDF

Excellent Thread!! I find it interesting to note that in the face of the hard scientific data you have presented there seems to be a lack of the usual haters present. I won't hold my breath though as I'm sure they will be along soon enough.

Thanks for the positive feedback Abysha.

a reply to: Freija

Thanks. Its late here so will take a look at the links you posted tomorrow. Sapolsky used the term transsexuality so I checked on Wikipedia which says transgender is more common. It also says the following so I am guessing you are in the second camp (highlighted in bold).

Relationship of transsexual to transgender

Around the same time as Benjamin's book, in 1965, the term transgender was coined by John Oliven.[2] By the 1990s, transsexual had come to be considered a subset of the umbrella term transgender.[1][2][3] The term transgender is now more common, and many transgender people prefer the designation transgender and reject transsexual.[24][25][26] The term transsexual, however, continues to be used,[27] and some people who pursue medical assistance (for example, sex reassignment surgery) to change their sexual characteristics to match their gender identity prefer the designation transsexual and reject transgender.[24][25][26] One perspective offered by transsexual people who reject a transgender label for that of transsexed is that, for people who have gone through sexual reassignment surgery, their anatomical sex has been altered, whilst their gender remains constant.[28][29][30]

Historically, one reason some people preferred transsexual to transgender is that the medical community in the 1950s through the 1980s encouraged a distinction between the terms that would only allow the former access to medical treatment.[31] Other self-identified transsexual people state that those who do not seek sex reassignment surgery (SRS) are fundamentally different from those who do, and that the two have different concerns,[18] but this view is controversial, and others argue that merely having some medical procedures does not have such far-reaching consequences as to put those who have them and those who have not (e.g. because they cannot afford them) into such distinctive categories. Another reason for objecting to the term transsexual is the concern that it implies something to do with sexuality, when it is actually about gender identity.[32] For example, Christine Jorgensen, the first widely known person to have sex reassignment surgery (in this case, male-to-female), rejected transsexual and instead identified herself in newsprint as trans-gender, on this basis.[33][34]

a reply to: RainbowPhoenix

I didn't put bathrooms in the title so it won't attract the same level of enthusiasm

originally posted by: Morrad
Sapolsky used the term transsexuality so I checked on Wikipedia which says transgender is more common. It also says the following so I am guessing you are in the second camp (highlighted in bold).
One perspective offered by transsexual people who reject a transgender label for that of transsexed is that, for people who have gone through sexual reassignment surgery, their anatomical sex has been altered, whilst their gender remains constant.

Well this is a whole can of worms and there's really no right or wrong. Most medical and scientific research uses transsexual and transsexualism but these have been replaced in popular culture with the word transgender but this delves into areas of political correctness that are likely to cause trouble if I too strongly express my opinion about it.

As most should know by now, transgender has become an umbrella term that in my opinion has become too broad and too vague to have any sort of consistent meaning. It seems now that any element of gender variance is now considered transgender and I personally think this is crap. Non-binary, genderqueer, genderfluid and 76 Tumblr and Facebook genders and in some cases even cross-dressers all supposedly fall under the transgender umbrella which is very confusing because when you say transgender, there are just too many interpretations. Although coming into use now as a pejorative that hopefully changes, the word transtrender is a better definition for those that are mid-spectrum and don't transition from one gender to the other. I have no problem with that other than their co-opting of the trans label for legitimacy. There are also a variety of opinions on the etiology of the word transgender and when it came into popular use.

The word transsexual has also fallen from disfavor because it has the word sex in it and has been associated with the porn industry. Remember though that I'm old school, have lived my life buried in the woodwork of the cisgender world, am not associated with the trans community other than through reading, know absolutely nothing about the porn industry and wasn't even sure what transgender was supposed to mean until a few years ago when I started posting on the subject here and looked it up. Supposedly, all transsexual people are transgender but not all transgender people are transsexual.

I use the word transgender to refer to those that do transition or are in the process thereof of moving from one gender to the other. I also use transgender to refer to children because children don't change sex.

Some prefer to apply the word transsexual to anyone undergoing medical procedures but I feel this is a misnomer because FFS, hormones and a breast augmentation facilitate changing/transing gender but do not actually change one's sex. Depending on what statistics you believe 70% of 90% of transgender people that transition do not have sex reassignment surgery. Because we are politically correct these days, making a distinction between transgender and transsexual is uncool as is making a distinction to those with early onset gender dysphoria (trans kids) and adults of late onset. There are differences but these are things of which we do not speak.

I prefer to use the term transsexual to refer to those that have had sex reassignment surgery. I also find it better describes my experience because I changed/transed my sex, not my gender which has been consistent throughout my lifetime, at least from an internal perspective. For those that say "you can't really change your sex", please save that argument for another thread.

Furthermore, I am not A transsexual and do not refer to myself as such. Changing sex is something I did, not something I am. I have never referred to myself as transgender and don't really care for the association with the umbrella. According to some, this makes me a stuck up elitist bitch separatist but I don't think anyone that actually has undergone SRS feels this way.

When called for, I might refer to myself as trans but much prefer a euphemism such as a woman of transsexual experience/history because technically I do not feel a disconnect between my gender and my sex and the active experience of being trans* was decades and decades in the past. I began to outwardly transition at 14/15, earlier if you consider I'd been growing my hair out since the 3rd grade, I completed social transition right out of high school at 18 and had SRS at 22 in 1977 which was forty years ago. I also didn't go through all this to be trans anything. For some, being trans is the end goal and there's absolutely nothing wrong with that. My genuine preference is to just use woman without any modifying adjectives and what I use in daily life in the real world. I am not out except here.

Other self-identified transsexual people state that those who do not seek sex reassignment surgery (SRS) are fundamentally different from those who do, and that the two have different concerns,[18] but this view is controversial

Controversial? I'll say it is! I will also say that people that are transgender and don't have SRS don't realize how fundamentally different things really are with female genitalia and what a huge change this is. It genuinely does make you something different in ways I probably can't even describe but for me it was liberating, made me whole and maybe we're not supposed to talk about sexual motivations but it allowed me to be the sexual being I never was but knew I should be.

None of what I said here was meant to be offensive, just the probably old-fashioned thoughts of some dumb old blonde chick that's been around all this longer than most. I am no authority on what words to use but have shared how I like to use them. If you change sex (SRS) you are transsexual. If you don't, you are transgender. This doesn't make one better than the other which is something I want to make perfectly clear. People are free to call themselves whatever they want.

It is a shame this thread doesn't look like it is going to get the same traction as bathrooms, Obama/Trump transgender student guidelines or transgender boys wrestling girls. Too bad because it is probably one of the best around as far as factual information and science goes but unfortunately, nobody wants to learn when they can't throw out their own baseless opinions and outrage.

So this seems to say that it is all in someone's head.

originally posted by: 3daysgone
So this seems to say that it is all in someone's head.

Is it a gland that is small or something? A tiny brain dick?

a reply to: 3daysgone

Yes but with a biological cause rather than a psycho-social cause.

a reply to: Freija

I thought about this issue some more and having read your post this morning I agree with making a differentiation. I remember in the 80s and 90s the term was pre-op transsexual or transsexual.

a reply to: Morrad



One of my favorite neuroscientists discussing phantom limb syndrome and how it relates to, of all things, synesthesia (which I have).

genuine question here: is there a consensus in the LGBTQ community of whether or not their gender identity and or sexual attractions are based in biology or not?

a reply to: tribal

See here.