Tag Archives: Sweden

Review of Gender identity disorder in a girl with autism – a case report

This is a 1997 case of a Swedish teenager who had autism as well as symptoms of gender dysphoria, selective mutism, and obsessive compulsive disorder (OCD).

Treatment with clomipramine decreased her symptoms of OCD and mutism, but not her symptoms of gender dysphoria.

Unlike this earlier case study of two American boys, this patient had clear symptoms of gender dysphoria:

“At the age of 8 years, B had started to claim that she was a boy. She refused to wear girls clothing and jewelery. B corrected persons if she was being addressed as ‘she’ and used her brothers’ shaving machine. At twelve years of age, B refused to visit the girls toilet but was forbidden by the parents to use the boys toilet. She has now been told to use the one and only gender neutral toilet in the school.”

And, at follow up:*

“She refuses to wear women’s clothes or to appear in swimsuit on the beach. Moreover, she claims that she is a boy, although she has discontinued the habit of correcting peers for addressing her ‘her’.”

The authors discuss three possible ways to interpret her symptoms of gender dysphoria and the implications for treatment.

First they suggest that the gender dysphoria could be part of the autism, specifically a ritualized and obsessive-compulsive behavior of a kind which is commonly seen in autistic syndromes.” 

The authors suggest that autism makes social and sexual relationships difficult, although people with autism are attracted to others. The expression of these feeling may be unusual. A minority of people with autism display a variety of paraphilic behaviour, e.g., exhibitionism, voyeurism and fetishism, and the desire for a beloved person may find expression in an obsessive manner.”

Gender dysphoria then might be “a paraphilic consequence of the impairment in social interaction” due to her autism. In that case the proper response would be “similar to the one employed when encountering other sexual manifestations with autistic people: a gradual firm correcting of the behavior in the direction of gender concordant behavior, but without anger or distress.”

The authors do not discuss the possibility that the gender dysphoria could be part of the autism in some other, non-sexual way. They should have.

Second, they suggest that the gender dysphoria might be seen as an obsessive-compulsive disorder and separate from the autism. In that case the proper treatment would be clomipramine.

There have been cases where patients with obsessional gender dysphoria were successfully treated with lithium carbonate, but the symptoms were different from the ones in this case.**

More importantly, in this case, treatment with clomipramine relieved the symptoms of OCD and mutism, but not the gender dysphoria. In fact, her symptoms of gender dysphoria increased, although it may be that they only became more apparent – for one thing she was talking more.

Third, they suggest that the gender dysphoria could be viewed as a disorder on its own and not a symptom of autism or OCD. In that case, the proper approach would be to treat both the autism and the gender dysphoria. When the teenager was of age,*** she would then be eligible for sex reassignment surgery.

They caution that “this patient suffers from a putative risk factor (autism), which has to be seriously considered before any intervention can be performed. “

As with other case studies, this is about one person. We can only draw limited conclusions from it.

It does show, however, that a person with autism can have symptoms of gender dysphoria. Further, in this case, the symptoms were probably not caused by OCD, as treatment for OCD did not relieve her gender dysphoria.

We could use further research to determine the relationship between gender dysphoria and autism and the best way to treat children and teenagers who have both.

Original Source:

Gender identity disorder in a girl with autism – a case report by Landén M., Rasmussen P. in Eur Child Adolesc Psychiatry. 1997 Sep;6(3):170-3.

*It’s not perfectly clear in the case report, but the therapists seem to have seen her initially at age 12 and the follow-up seems to have been at age 14.

**Skoptic syndrome: the treatment of an obsessional gender dysphoria with lithium carbonate and psychotherapy.

***The first reference I can find to using puberty blockers for teenagers with gender dysphoria is a case study of one teenager in 1998, a year after this case study. Thus at the time of this case study, medical transition would not have begun before age 18. (Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent.)

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Sex Dimorphism of the Brain in Male-to-Female Transsexuals – Review

This study found that trans women (born male) had brains like men’s, at least in terms of gray and white matter volumes and hemispheric asymmetry.

In a few areas, trans women’s brains were different from both men’s and women’s brains.

The authors suggest that the differences they found between trans women and cis people’s brains are related to body perception.

They conclude:

“The present data do not support the notion that brains of MtF-TR are feminized. The observed changes in MtF-TR bring attention to the networks inferred in processing of body perception.”

The study only looked at trans women who were attracted to women. This is both a strength and a limitation of the study.

It is a strength because it avoids confusion between gender identity and sexual orientation. Many recent studies have compared trans women attracted to men to men attracted to women; if you find a difference between the two groups, you can’t be sure if it is due to sexual orientation or gender identity.

This study, however, compared trans women attracted to women with men attracted to women and women attracted to men.

This is also a limitation because it is extremely unrepresentative of trans women. About half of trans women are attracted to men, much more than in the general population. If we want to understand how gender dysphoria works, we need to look at both groups of trans women.

A study looking at just trans women attracted to women was necessary, but clearly we need some follow-up research. Is this result true for trans women who are attracted to men? How do these results compare to cis gay men’s brains?

You can stop here if you want. You now know the main result of the study.

On to the specifics of the study. What exactly did they find?

Ways trans women’s brains were like men’s brains

1. Total brain tissue volume was smaller in heterosexual women (HeW) than in heterosexual men (HeM)  and gyenephillic male to female transsexuals (MtF-TR).*

(Gyenephillic=attracted to women.)

2. Total intracranial volume was smaller in HeW than in HeM or MtF-TR. There was no difference between the groups in total white matter volume or total gray matter volume when you took into account the total intracranial volume.

3. HeM had a larger gray matter volume than HeW in the lingual gyrus, the cerebellum, right putamen, and left amygdala and perirhinal cortex. HeW had larger gray matter and white matter volumes in the precentral gyrus.

None of these differences were reproduced when comparing HeM to MtF-TR.

4. HeW had larger hippocampi compared to both HeM and MtF-TR, mostly due to the left hippocampus. There was no difference between HeM and MtF-TR.

5. HeM and MtF-TR had rightward assymetries in the brain; HeW did not. Specifically:

a. the volume of the right hemisphere was larger than the left for HeM and MtF-TR, but not for HeW;

b. the volume of the thalamus was significantly larger in the right hemisphere for HeM and MtF-TR, but not for HeW – however, there was no significant differences in the groups’ assymetry indices (volume of right side/volume of left side).

c. the volume of the hippocampus was significantly larger in the right hemisphere for HeM, but not for HeW. The volume was also larger for MtF-TR, but this was not statistically significant – although the p-value was 0.065, so it was close. However, the differences in assymetry indices between MtF-TR and HeW and between HeM and HeW were significant.

Ways trans women’s brains were different from cis people’s brains

1. MtF-TR had larger gray matter volumes than either HeM or HeW in the “right temporo-parietal junction (around the angular gyrus and in the posterior portion of the superior temporal gyrus)**, and right inferior frontal and insular cortex.”

2. MtF-TR had a smaller gray matter volume than either HeM or HeW in the thalamus.

3. MtF-TR had smaller thalamuses and putamens than either HeM or HeW; this was a measurement of the regional structural volume. There was no difference between HeM or HeW.

Areas where they found no differences between the groups

1. There were no group differences in the caudate volume.

2. There was no assymtery in the caudate or putamen.

What does all this mean?

First, it does look like the authors are right; the trans women’s brains were more like men’s than women’s. It is possible that trans women’s brains are like women’s brains in some other way than the ones the authors looked at. Nevertheless, the similarities to men’s brains found in this study are fairly large.

What is perhaps, more interesting, is the ways that the trans women’s brains were different from cis people’s brains, whether they were male or female.

The authors of the study point out that these are new findings and they need to be confirmed with larger studies. “Any interpretation must, therefore, proceed cautiously and can at this point only be highly speculative.”

The authors go on to suggest that their findings might be related to own body perception. As they point out, one of the main symptoms of gender dysphoria is discomfort with your own body. Some studies suggest that the areas of the brain where trans women were different from cis men and women could be part of a network involved in own body perception.

Of course, as in other studies, the parts of the brain involved in this study have multiple functions. For example, the angular gyrus is also involved in language, math, and memory retrieval. So we can’t be sure exactly what it means that trans women have a larger volume of gray matter in those areas.

On the other hand, people with gender dysphoria don’t have problems with language and math, they have problems with dysphoria about their bodies.

More surprisingly, the authors of this study suggest that people with gender dysphoria may have changed their brains by constantly thinking about their bodies. This is possible, but it seems more likely to me that the problem starts with something in the brain causing people to feel uncomfortable with their bodies.

Here is the author’s argument from their conclusion:

“There is no evidence that this feeling [gender dysphoria] is caused by a general sensory deficit in transsexual persons…Several studies propose that own body perception involves networks in the temporo-parietal, inferior parietal cortex, the inferior frontal, and insular cortex, and their connections with the putamen and thalamus. Thus, theoretically, the experience of dissociation of the self from the body may be a result of failure to integrate complex somatosensory and memory processes executed by these networks.

Such disintegration accords with the present findings and could, perhaps, explain recent observation of poorer parietal cortex activation during a spatial orientation task in MtF-TR compared with male controls.

However, it is difficult to explain how such disintergration can be linked to a dysphoria restricted to the own body’s sex characteristics.

Moreover, even if a link exists, it is uncertain whether the here observed morphometric features in transsexual patients underpin their gender identity or are a consequence of being transsexual.

One highly speculative thought is that the enlargement of the GM volume in the insular and inferior frontal cortex and the superior temporal-angular gyrus could derive from a constant rumination about the own body. Brain tissue enlargement has been detected in response to training, and GM enlargement of the insular cortex has been reported in response to meditation, which involves mental focusing on the own body.”

The authors also point out that it might be that something else is causing both gender dysphoria and changes in neuroanatomy.

They stress that we can’t directly connect changes in gray matter volume to effects on the person.

They point out that they did not look at the hypothalamus, so their findings do not contradict earlier studies of it.

Finally, they call for more research, including research which compares trans women attracted to men to trans women attracted to women, and trans women attracted to men to cis gay men. (Yay!)

“Furthermore, they [the results] were generated exclusively from investigations of nonhomosexual, gynephillic MtF-TR. The issue of possible cerebral difference between gynephillic and androphillic (homosexual) MtF-TR and also between androphillic MtF-TR and homosexual healthy men is of special interest and needs to be addressed separately in future studies. Additional studies of the relationship between brain structure and function in transsexual persons and also extending the material to female to male transsexuals are necessary to more precisely interpret the present observations.”

The bottom line: we need more studies confirming these results. Is there a link between gender dysphoria and the network involved in own body perception? If so, which is the cause and which is the effect? Do these results hold true for trans women who are attracted to men? What about trans men?

There were two results the study did not discuss. It may not mean anything, but I think it is worth mentioning.

1. The volume of the amygdala was larger in HeM than HeF; this fits with other studies of sex differences in the brain. For MtF-TR, their amygdalas seems to have been neither bigger nor smaller than males or females. (Table 3)

2. The subcallosum (BA 24, 32) was larger in HeF than HeM. This fits with a study the authors cite showing that women have larger anterior cingulate gyri – the anterior cingulate cortex includes Brodmann Areas 24 and 32. This area seems to have been neither larger nor smaller in MtF-TR.

According to the authors: “Although sex differences have been described also in the amygdala and cingulate gyrus, these structures were not included in the analysis because the identification of anatomical landmarks in these regions is less reliable, especially when using a 1.5-T scanner.”

In other words, they think there could have been an error in the results. Either there was no sex difference in those areas, or they failed to detect differences between trans and cis women in those areas.

Another possibility is that trans women and cis women were not different in those areas because trans women’s volumes were intermediate between cis men’s and cis women’s.

If this is so, there are many possible explanations. It might have something to do with sex hormones, although it is hard to see why trans women’s brains would have developed like cis men’s in most parts of the brain if they weren’t exposed to sex hormones. You would have to assume that there was something different about how their amygdala and cingulate gyrus responded to sex hormones.

Another possibility is that trans women’s amygdalas were as large as men’s amygdalas, but something made them shrink.

Studies have linked a smaller amygdala to obsessive-compulsive disorder (OCD), anxiety, PTSD, sociopathy, and early life stress (abuse, neglect, or poverty). [Click through to see the studies.]

Trans people have higher rates of anxiety than other groups, but this study excluded people with any psychiatric disorders.

Trans people also suffer higher rates of abuse and trauma than most people which might have affected their amygdalas.

A final, hypothetical possibility might be that gender dysphoria is in some way related to OCD.

In the case of the cingulate gyrus, we would have to assume that something happened to trans women’s brains to make the volume of their cingulate gyrus increase to be intermediate between cis women and cis men. This is harder to understand, since OCD, anorexia, and body dysmorphic disorder are all correlated with decreases in the size of the anterior cingulate cortex.

However, there is one study suggesting that a large right anterior cingulate “is related to a temperamental disposition to fear and anticipatory worry.” No doubt the experience of being transgender in our society causes people to worry and feel fear; perhaps this changes the brain. Alternatively, it might be that a tendency to worry is somehow linked to developing gender dysphoria.

Original Study:

Sex Dimorphism of the Brain in Male-to-Female Transsexuals by Savic I, Arver S. in Cereb Cortex. 2011 Nov;21(11):2525-33.

A few fun facts:

You can induce out-of-body experiences by stimulating either the temporo-parietal junction or the angular gyrus. (Read more here and here).

The right temporo-parietal junction is also involved in thinking about thoughts. It, or an area close to it, is involved in directing your attention. (Read more here and here.)

The superior temporal gyrus is involved in recognizing your own face, identifying emotions in other people’s faces, and social cognition.

Information about the self may be processed in the right hemisphere; however, not everyone agrees on this theory. (Read more here.)

Increased volume in the left inferior frontal gyrus and right amygdala are associated with worse symptoms in body dysmorphic disorder. The trans women in this study had increased volumes in the right inferior frontal gyrus only. This does, however, suggest that these areas of the brain are important to perceptions of the body. (Read more here.)

*I am using the language of the study now.

** The original text refers to the superior temporal gurus. A cool idea, but probably a typo.

Genes and Gender Dysphoria

Twin and family studies suggest that there may be a genetic component to gender dysphoria. Researchers have naturally been trying to find genes linked to gender dysphoria.

Most of the research has focused on genes that are known to be related to sex hormones in some way.

I. Researchers may have found genes related to gender dysphoria in trans men (born female).

A large Spanish study found an association between the gene for Estrogen Receptor β and gender dysphoria, but a medium-sized Japanese study did not.

A small Austrian study found an association between gender dysphoria and a different gene related to converting progesterone into androgens. Nobody else has looked at this gene.

A possible flaw with the Austrian study is that the control females were seeking help with perimenopausal issues; it may be that their genes were different from the general public.

Both of these results need to be replicated.

It is also possible that the genes were related to sexual orientation.

In the Spanish study, all of the trans men were attracted to women; it is likely that 95% of the control women were attracted to men.

The Austrian study does not talk about sexual orientation, but typically most trans men are attracted to women and most women are not.

Many control women also had the genetic variations found in trans men. Some other genes or environmental factors must also be involved.

These results need to be replicated. The Austrian study was relatively small and possibly flawed while the Spanish and Japanese studies contradict each other.

II. Researchers thought they had found genes related to gender dysphoria in trans women (born male), but larger studies did not replicate the results. It is possible, however, that the genes related to gender dysphoria are different in different populations.

Four studies looked at genes related to sex hormones, specifically genes for estrogen receptor β, androgen receptor, and CYP19A1. CYP19A1 encodes aromatase, an enzyme involved in turning androgens into estrogens.

None of the studies found a relationship between gender dysphoria and the gene for CYP19A1.

Three studies found no difference in the gene for estrogen receptor β; the study that found a difference was much smaller than the others.

Three studies found no difference in the gene for androgen receptor, including one study of over 400 trans women.

III. An Italian study that looked at the Y chromosome found no differences between trans women and control males.

IV. An Austrian study that looked at sex chromosomes in trans women and trans men found no significant abnormalities.

V. A Japanese study that looked at genes related to estrogen receptor alpha and progesterone receptor found no differences between the genes of male to female transsexuals and male controls or the genes of female to male transsexuals and female controls. This study also looked at estrogen receptor β, androgen receptor, and CYP19A1 and found no differences for those genes either; this is one of the studies discussed above.

VI. An Austrian study of a gene related to steroid 5-alpha reductase (SRD5A2) found no differences between trans women, trans men, and male and female controls. SRD5A2 is involved in the conversion of testosterone to dihydrotestosterone.

It is important to remember that there may be some other genetic variations that are linked to gender dysphoria in trans women, something that we haven’t studied yet.

At this point, however, we do not seem to have found genes related to gender dysphoria in trans women.

Recommendations for future research:

Look at genes other than the ones related to sex hormones or sex chromosomes. Perhaps the cause of gender dysphoria is different from what we expect.

Control for sexual orientation by including some cis lesbians and gay men in the study.

Study trans people with African ancestry – and other groups that have not yet been studied. Studies so far have looked at people from Spain, Italy, Japan, Austria, America and Australia (Caucasian only), and Sweden.

For more details on the studies, see the links and comments below.

STUDIES OF TRANS MEN (Born female)

2014:

The (CA)n Polymorphism of ERβ Gene is Associated with
FtM Transsexualism – This Spanish study compared the genes of 273 female to male transsexuals and 371 control females. As in the study of trans women below, they focused on three variable regions of genes: estrogen receptor β (ERβ), androgen receptor, and CYP19A1 which encodes aromatase, an enzyme involved in turning androgens into estrogens.

They found no connection between the genes related to androgen receptors or aromatase, but they did find an association between the ERβ gene and gender dysphoria in trans men.

“The repeat numbers in ERβ were significantly higher in FtMs than in control group, and the likelihood of developing transsexualism was higher (odds ratio: 2.001 [1.15-3.46]) in the subjects with the genotype homozygous for long alleles.”

Three caveats:

All the trans men participating in the study had gender dysphoria that began before puberty and were attracted to women (i.e. members of their biological sex). The control females were probably 95% straight. It is possible that the genetic difference they found is related to sexual orientation, not gender identity.

This is not an absolute difference, it is a difference in frequency – 69% of the trans men had the long allele for ERβ, but so did 59% of the control women. Some other genes or environmental factors must also be involved in gender dysphoria (or sexual orientation).

The study below found different results; however, this study was larger.

note: All participants in the study were of Spanish origin.

2009:

Association study of gender identity disorder and sex hormone-related genes.

This Japanese study compared 74 male-to-female transsexuals, 168 female-to-male transsexuals, 106 male controls, and 169 female controls. They looked at genes for androgen receptor, estrogen receptors alpha and beta, aromatase, and progesterone receptor.

They found no differences between the genes of male to female transsexuals and male controls or the genes of female to male transsexuals and female controls. 

“The present findings do not provide any evidence that genetic variants of sex hormone-related genes confer individual susceptibility to MTF or FTM transsexualism.”

The abstract does not provide any information on the demographics of the trans women and trans men.

The results of this study for ERβ contradict the results of the Spanish study. The Spanish study looked at 273 trans men while this study only looked at 74, so it is unlikely that the Spanish study is simply wrong.

It may be, however, that this study is still right, at least in Japan. People in different countries have different genes; they may have different genes for gender dysphoria.

It is possible that cultural differences or medical policies may mean that clinics in different countries are looking at groups of people with different problems.

Finally, gender dysphoria might be caused by different factors or combinations of factors in different cultures. Japanese trans men may be different from Spanish trans men in some important way.

2008:

A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism.

This Austrian study compared 102 male to female transsexuals to 756 male controls and 49 female to male transsexuals to 915 female controls.

A possible flaw in this study is that the females controls were women seeking help with perimenopausal disorders; they may have had genes that were different from the general population. The male controls, on the other hand, were “participating in a health prevention program.”

Since the results found that the frequency of a particular mutation was different in female controls from all of the other groups, it matters a great deal if the control females are significantly different in some other way from the other participants.

This study looked at a different gene from the other studies, CYP17. CYP17 encodes cytochrome, an enzyme involved in converting progesterone and pregnenolone into androgens.

The authors found that a particular mutation of this gene, CYP17 −34 T>C, was associated with female to male transsexualism, but not male to female transsexualism.

They also found that, “the CYP17 −34 T>C allele distribution was gender-specific among controls. The MtF transsexuals had an allele distribution equivalent to male controls, whereas the FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls.” 

In other words, trans men and trans women were similar to male controls and not female controls.

They point out, however, that there were women without gender dysphoria who had the mutant allele as well as women with gender dysphoria who did not have it. “Thus, carriage of the mutant CYP17 T−34C SNP C allele is neither necessary nor sufficient for developing transsexualism.”

In other words, there must be other genetic or environmental factors involved.

They do not discuss the sexual orientation of the participants in the study. As discussed above, it is possible that most of the trans men were attracted to women and that this genetic mutation is related to sexual orientation, not gender identity.*

Finally, I keep coming back to the female control group. What if converting progesterone to androgens is related in some way to perimenopausal symptoms? What if the mutant gene protects against problems in menopause somehow and so the female control group includes fewer people with this gene?

2007:

A common polymorphism of the SRD5A2 gene and transsexualism. This Austrian study compared 100 trans women, 47 trans men, 755 control men, and 915 control women. They looked at a mutation of the steroid 5-alpha reductase gene (SRD5A2); this gene produces an enzyme that catalyzes the conversion of testosterone to dihydrotestosterone.

They found no differences between any of the groups. The mutant allele was not associated with transsexualism and its distribution was not gender specific among controls.

This study has the same flaw as the 2008 study listed above; the control females were all seeking help for problems with perimenopause.

2002:

Sex chromosome aberrations and transsexualism. This Austrian study looked at the chromosomes of 30 trans women and 31 trans men. They did not find significant abnormalities, although they suggested further investigation might be worthwhile.

“We could not detect any chromosomal aberrations with the exception of one balanced translocation 46,XY,t(6;17)(p21.3;q23). Importantly, no sex chromosomal aberrations, which would be detectable on the G-banded chromosome level, have been observed.”

They conclude:

“The data described here provide evidence that genetic aberrations detectable on the chromosome level are not significantly associated with transsexualism. In addition, molecular-cytogenetic FISH analyses did not reveal deletions of the androgen receptor gene locus on chromosome Xq12 or of the SRY locus on chromosome Yp11.3. Multiplex PCR analyses demonstrated one AZF deletion in a male-to-female transsexual.”

but:

“However, the detection of one carrier of a Y chromosome microdeletion out of 30 male-to-female transsexuals could argue for further investigations. This is of special interest in light of the recent discussion of gamete banking before hormonal and sex reassignment surgery of transsexuals.”

 

STUDIES OF TRANS WOMEN (Born male)

The Y Chromosome:

2013

Hormone and genetic study in male to female transsexual patients. This Italian study looked at six areas on the Y chromosomes of 30 trans women. They found no abnormalities.

“This gender disorder does not seem to be associated with any molecular mutations of some of the main genes involved in sexual differentiation.”

The trans women were aged 24-39 and had already begun hormone therapy. A little over half of them had already had sex reassignment surgery and the rest were waiting for it.

2002:

Sex chromosome aberrations and transsexualism. This Austrian study looked at the chromosomes of 30 trans women and 31 trans men. They did not find significant abnormalities, although they suggested further investigation might be worthwhile.

For further details, see the description above under trans men.

Genes Related to Sex Hormones:

2007:

A common polymorphism of the SRD5A2 gene and transsexualism. This Austrian study looked at a mutation of the steroid 5-alpha reductase gene (SRD5A2. They found no differences related to gender or gender identity. For more details, see the description above in the section on studies of trans men.

The following studies looked at the same areas of genes related to sex hormones.

Initially, a small Swedish study of trans women (born male) found a difference in the length of the estrogen receptor β repeat polymorphism, but none of the other studies did.

Similarly, an American-Australian study found that trans women had longer repeat lengths for the androgen receptor allele, but none of the other studies did.

It looks like these genes do not affect gender dysphoria in trans women, although it is possible that different genes affect people in different countries.

2014:

Association Study of ERβ, AR, and CYP19A1 Genes and MtF Transsexualism – This Spanish study compared the genes of 442 trans women and 473 control males. They focused on three variable regions of genes: estrogen receptor β, androgen receptor, and CYP19A1 which encodes aromatase, an enzyme involved in turning androgens into estrogens.

They found no connection between these genes and gender dysphoria.

Interestingly, 98% of the trans women had chromosomes that were 46,XY, i.e. normal, but 2% of the group showed aneuploidy, or abnormal chromosomal numbers. This is slightly higher than usual.

The abstract does not go into detail, but presumably the aneuploidies were cases of Klinefelter syndrome; a condition where a person typically has one Y chromosome and two X chromosomes. Most people with Klinefelter’s syndrome identify as male, but there may be a higher than usual occurrence of gender dysphoria among people with Klinefelter’s.

There are no details on the trans women in the abstract; however, the same researchers did a very similar study of trans men (see above). It may be that the participants in the two studies were screened in the same way.

2009:

Association study of gender identity disorder and sex hormone-related genes.

This Japanese study compared 74 male-to-female transsexuals, 168 female-to-male transsexuals, 106 male controls, and 169 female controls. They looked at genes for androgen receptor, estrogen receptors alpha and beta, aromatase, and progesterone receptor.

They found no differences between the genes of male to female transsexuals and male controls or the genes of female to male transsexuals and female controls. 

“The present findings do not provide any evidence that genetic variants of sex hormone-related genes confer individual susceptibility to MTF or FTM transsexualism.”

The abstract does not provide any information on the demographics of the trans women and trans men.

Androgen receptor repeat length polymorphism associated with male-to-female transsexualism.

This Australian and American study compared 112 male to female transsexuals to 258 control males. They looked at genes for androgen receptor, estrogen receptor beta, and aromatase. No differences were found for the estrogen receptor or aromatase, but transsexuals had longer repeat lengths for the androgen receptor allele.

“This study provides evidence that male gender identity might be partly mediated through the androgen receptor.”

This result was not found in the Spanish study or the Japanese study above. The Spanish study was larger than this one. Thus, this result has not been replicated.

However, it is possible that this genetic variation is connected to gender dysphoria for Caucasian trans women in America and Australia, but not in Spain or Sweden and not for Japanese trans women.

It is also possible that the genetic difference found here is related to sexual orientation, not gender identity. The researchers in this study only knew the sexual orientation for about 40% of the participants in the study, but people with gender dysphoria are much more likely to be attracted to people of the same biological sex than people without gender dysphoria.

As in the Spanish, study above, this is not an absolute difference, it is a relative one. There were also cis men who had long AR repeat lengths (Figure 1). Again, some other genes or environmental factors must also be involved in gender dysphoria (or sexual orientation).

The trans women in this study were all Caucasian; 76 of them were from an Australian clinic and 36 of them were from UCLA in America. Almost all of them were on hormones. Some of them had gender dysphoria in childhood. “The sexuality is only known for approximately 40% of patients, because some patients did not wish to discuss or disclose this information or the patient’s sexuality was flexible and not easily classified.”

2005:

Sex steroid-related genes and male-to-female transsexualism.

This Swedish study compared the genes of 24 male to female transsexuals and 229 male controls. They looked at specific areas in the androgen receptor gene, the aromatase gene, and the estrogen receptor β gene.

They did not find a difference between male-to-female transsexuals and men for the first two genes, but they did find a difference related to the gene for estrogen receptor β. “Transsexuals differed from controls with respect to the mean length of the ERβ repeat polymorphism.”

In addition, “binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism.” 

The study was very small, however, and as the authors said, “results should be interpreted with the utmost caution.”

The three more recent studies above did not replicate the findings of this study. The other studies were much larger than this one, so it is possible that these results were a fluke.

It is also possible, that the genes linked to gender dysphoria in Sweden are different from the genes linked to it in other countries.

The authors of the American-Australian study described above say, “Our sample size was approximately four times larger than that of the Swedish study, so it is possible that the former study was underpowered to detect a false positive. Alternatively, there might be differences between Swedish and non-Swedish populations in this polymorphism. In the Swedish study, the long repeat occurred in 51.8% of control subjects and 67.1% of transsexuals, whereas in the present study the long repeat occurred in 36.5% of control subjects and 44.1% of transsexuals. Thus, although there was a trend in the same direction in both studies, there are major differences in prevalence of these long repeats between the two populations.”

The only data we have on the participants in the study are that the trans women were Caucasian and the vast majority of the controls were also Caucasian. Again, it is likely that there was a higher percentage of people attracted to male in the group of trans women than the general population; this might have affected the results.

As the authors point out, “the gene variants investigated in this study are relatively common, none of the studied variants could hence be assumed to be the primary cause of this condition.” Rather, genes might increase or decrease the chance of developing gender dysphoria.

So, if the results of this study are not a fluke, we are still left with the questions of what other factors contribute to developing gender dysphoria and is this a gene related to gender dysphoria or sexual orientation in Sweden?

The end result of all this:

We have a couple of possible candidates for genetic variations related to gender dysphoria in trans men, but we need further studies. We need to replicate the results and to control for sexual orientation. In the case of the CYP 17 gene, we need to compare trans men to healthy control females instead of women with perimenopausal issues.

We don’t have any strong candidates for genetic variations related to gender dysphoria in trans women. Future studies might do well to look for genes that are not related to sex hormones. As always, they should control for sexual identity. (This should be done by adding lesbians and gay men without gender dysphoria, not by excluding trans women who are attracted to women from the studies. See my rants in articles on brain sex.)

 

*A group of trans women would include many more people attracted to men than a group of control males, but typically about half of trans women are attracted to women while most trans men are attracted to women. Thus this could be a comparison of two groups (control males and trans men) where a large majority of the people are sexually attracted to women, one group where half the people are attracted to women (trans women), and a group where about 5% of the people are attracted to women (control females).

PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects – Brief Review and a cautionary note

This is the abstract of a study which shows that the brains of gay men are similar to the brains of straight women in certain ways while the brains of lesbians are similar to the brains of straight men.

The study looked at hemispheric asymmetry and functional connectivity, two areas where scientists have found differences between men and women.

They scanned the brains of 25 straight men (HeM), 25 straight women (HeW), 20 gay men (HoM), and 20 lesbians (HoW). Fifty of the subjects also participated in a test of blood flow that is used to analyze connections between the right and left amygdalae.

Results (from the abstract):

“HeM and HoW showed a rightward cerebral asymmetry, whereas volumes of the cerebral hemispheres were symmetrical in HoM and HeW. No cerebellar asymmetries were found. Homosexual subjects also showed sex-atypical amygdala connections. In HoM, as in HeW, the connections were more widespread from the left amygdala; in HoW and HeM, on the other hand, from the right amygdala. Furthermore, in HoM and HeW the connections were primarily displayed with the contralateral amygdala and the anterior cingulate, in HeM and HoW with the caudate, putamen, and the prefrontal cortex.”

They conclude:

“The present study shows sex-atypical cerebral asymmetry and functional connections in homosexual subjects.”

This study shows the critical importance of controlling for sexual orientation when studying the question of gender identity and the brain.

An extremely high proportion of people with gender dysphoria are primarily attracted to people of their birth sex. In the general population, only about 5% of people are primarily gay or lesbian.

Studies of gender identity and the brain should include both gay and straight control groups.

There is also a need for studies comparing the brains of transgender people who are attracted to people of their birth sex to gay men and lesbian women who are cis. This might be the most fruitful avenue of research into what causes gender dysphoria.

Original Abstract:

PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects by Ivanka Savic and Per Lindström in Proceedings of the National Academy of Sciences of the United States of America, July 8, 2008, vol. 105 no. 27.