This post is not directly related to the Privacy Matters case, but it does relate to the issue of the diagnosis of gender dysphoria. Consider this entry a work in progress, as new studies come out on this topic fairly often. The reason for looking, however briefly, at some of the studies done so far is that they are rather widely discussed in the press and because the claims made about these studies are put forth to justify policy decisions. The main question for this post is whether any scientific studies give us an adequate basis for such decisions.
Preliminary Conclusion
There is no scientific consensus and no reliable research on brain features or physiological responses that can identify transgender individuals or predict, based on brain scans, who is or will later identify as transgender. In general, sample sizes are too small, alternate hypotheses have not been examined, the definition of who is transgender, controlling for other mental health conditions, and many other factors are not considered. Trans advocates often complain that there are not enough of them to get the sample sizes needed for a reliable scientific conclusion based on good statistical evidence. This is likely true. At the moment, transgender brain science cannot be a meaningful aspect of the conversation and we need to look elsewhere in our attempts to form just policies.
I will look at a few of the studies of male/female brain differences and transgender physiological responses to illustrate the kinds of research that are being done, the difficulties with these studies, and what they would need to overcome in order to produce reliable results. I start with a recent large scale review article.
Research on Overall Differences and Similarities Between Male And Female Brains and Bodies
The paper
Sex Beyond The Genitalia: The Human Brain Mosaic published in 2015 is a meta-analysis of many studies looking at the question of male and female brains. The Abstract reads
Whereas a categorical difference in the genitals has always been
acknowledged, the question of how far these categories extend
into human biology is still not resolved.
Documented sex/gender differences in the brain are often taken as
support of a sexually
dimorphic view of human brains (“female
brain” or “male brain”). However, such a distinction would be possible
only if sex/gender
differences in brain features were highly
dimorphic (i.e., little overlap between the forms of these features in
males and
females) and internally consistent (i.e., a
brain has only “male” or only “female” features). Here, analysis of
MRIs of more
than 1,400 human brains from four datasets
reveals extensive overlap between the distributions of females and
males for all
gray matter, white matter, and connections
assessed. Moreover, analyses of internal consistency reveal that brains
with features
that are consistently at one end of the
“maleness-femaleness” continuum are rare. Rather, most brains are
comprised of unique
“mosaics” of features, some more common in
females compared with males, some more common in males compared with
females, and
some common in both females and males. Our
findings are robust across sample, age, type of MRI, and method of
analysis. These
findings are corroborated by a similar
analysis of personality traits, attitudes, interests, and behaviors of
more than 5,500
individuals, which reveals that internal
consistency is extremely rare. Our study demonstrates that, although
there are sex/gender
differences in the brain, human brains do
not belong to one of two distinct categories: male brain/female brain.
This study comes to similar conclusions as others. There is no such thing as a female brain in a male body or vice versa, because brains are not dimorphic. Moreover, the authors state in the Discussion that "Another noteworthy observation is that the size of the sex/gender
difference in some regions varied considerably between different datasets (
Table S1). This finding is in line with previous reports that the existence and direction of sex/gender differences may depend on
environmental events and developmental stage (
4,
5)".
The paper
The landscape of sex-differential transcriptome and its consequent selection in human adults is being posted in my Facebook feed by various groups. I read the original paper. The authors find that over 6,500 genes are differently expressed in males and females. This points to the physical reality of biological differences between males and females beyond obvious differences in reproduction organs. Since virtually every human cell in a person's body has the exact same genome, it is noteworthy that the genes may be expressed differently in different tissues in males and females. The authors, Moran Gershoni and Shmuel Pietrokovski looked at differential expression in order to better understand human evolution and especially the persistence of genes that can produce negative effects such as infertility. They hypothesize that such gene alleles (alleles are variants of a particular gene that codes for a particular protein) could persist if they were important for one sex, even if deleterious for the other. Most genes they tested were expressed the same in men and women. However, among the ones that had sex differentiated expression (SDE), "the most sex-differentiated tissue, with 6123 SDE protein-coding genes, is the breast mammary glands....This suggests major differences in the physiology and sex genetic
architecture of this tissue. We found 1145 genes to be SDE in
non-mammary gland tissues. The most differentiated of these tissues,
with over 100 SDE genes, are the skeletal muscle, two skin tissues,
subcutaneous adipose, anterior cingulate cortex, and heart left
ventricle...." These differences in gene expression lead to biological differences between males and females. The authors postulate that infertility and various sex-biased human diseases could result from this differential expression, especially when the traits expressed are critical for reproductive or other functions in one sex and not in the other. The mammary glands are a good example of this disparity. Known differences between males and females in musculature, fat deposition, and heart anatomy are supported by these results as well. While this study was not meant to support or refute a biological basis for transgenderism, it does make clear that to practice good medicine and for an understanding of human evolution the distinction between males and females is essential.
A Guide to the Design of Pre-Clinical Studies on Sex Differences in Metabolism. in "Cell Metabolism" June 2017.
Examines the importance of sex differences in the study of diseases such
as obesity and diabetes. The authors stress that unless studies are
designed to pick up these differences and use both male and female
subjects, it is likely that results will not be adequate for both
sexes. They stress that every cell in the body is male or female and
that can have quite wide ranging effects. The authors then review
studies with mice as models and go over a lot of important aspects of
such studies that need to be considered when tracking sex differences
and locating the time and location where the differential responses are
determined. The experimental systems and factors to be considered in a
very technical way. There are genetically engineered mouse studies,
surgically altered mouse studies, chemically altered mouse studies. It
turns out that the kind of food or bedding in the mouse cages can affect
the results as can the sex of the researchers. The take home message
is that such differences in response can be very important and go far
beyond reproductive organs.
Research on Disorders of Sexual Development (DSD)
In their review article "
Research Supporting the Biologic Nature of Gender Identity" in
Endocrine Practice (2014)
, Sarawat et al.
set out to find evidence that transgender identity is based in biology. The authors conclude in part "Studies of DSD patients and neuroanatomical studies provide the strongest evidence for an organic basis to transgender identity." Here I examine one of the studies used to support their conclusion, Reiner and Gearhart's "
Discordant Sexual Identity in Some Genetic Males with Cloacal Exstrophy Assigned to Female Sex at Birth." published in 2004. Cloacal Exstrophy is an extreme condition in which the whole pelvic area is abnormal. Organs may be outside the body, the bladder and intestines are not distinct, and in genetic males the penis is severely atrophied or absent, though testes are normal.
This study looked at 16 genetic male patients. All had extensive neo-natal surgeries to repair damage. Fourteen of them were castrated and surgically given facsimiles of female external sexual anatomy. Parents were told to raise them as females and to make sure they never found out that they were genetically male. Two parents refused the sex reassignment surgeries for their sons. These sons identified as males. The authors used a variety of questionnaires and interviews with patients and their parents. The patients varied in age from 5 - 12 when first enrolled in the study and a follow-up was done between 3 to 6 years later. Patients were not told anything about their medical history; they were told that the study was meant to assess psychosocial development.
Unfortunately, not a lot of data is presented. However, of the 14 males who received sex reassignment surgery, 8 had declared themselves male either spontaneously (2) or after being told of their birth status by parents. All patients who knew of their birth status began identifying as males. One would not discuss sexual identity. Five patients continued to identify as female and those who were adolescent were taking estrogen.
The authors rated the patients on questions about toy choice, rough and tumble play, interest in marriage, sex of friends, and wishes to be a boy. The scale ran from 1 - 5, with 1 being a typical female response and 5 being a typical male response. Though these are idiosyncratic criteria, the results showed that most of the patients fell into the male range (I counted this as an average score above 3). The two whose average scores were below 3 identified as female. Both parents and patients were asked to list the child's three favorite activities during age 5 - 8. Most mentioned sports of various sorts. Only one mentioned reading and music. Interesting to me was that in 5 of the cases there was no overlap between the parent and child responses and in 5 more cases there was only one overlap. I mention this because often the parent is used as the authority who declares if the child is content with his sexual identity. The authors could not ask the patients directly because the birth sex was supposed to be a secret. It seems significant that none of the parents of patients identifying as female would allow their
children to participate in follow-up interviews. They answered all
questions themselves.
Patients who ended the study identifying as males were more likely to be sexually active, discuss sex and sexual attraction, and to date. Patients who identified as female did not discuss sex or sexual attraction and none of them dated, even though 4 of them were aged 16 - 19. Though they were not part of this study, girls with cloacal exstrophy known to the authors all identified as female and did express interest in dating and sexual relationships.
This limited study supports a general view that genetic males with normal hormonal response at birth tend to identify as male and engage in what we think of as typical male behaviors, despite being castrated close to birth and being assigned to be raised as females. Lack of a penis and testosterone after infancy did not inhibit these typical patterns. This certainly suggests that male genetics and male typical behaviors have some sort of natural basis. The authors were very concerned that 100% of patients who learned their birth histories switched their identification to male. Would this also happen with the 5 who still identified as female if they knew the truth?
Even though cloacal exstrophy is not an intersex condition, the authors come to the same conclusion that has become common with many of those conditions. It is better to leave the kids alone and not attempt to reassign sex based on the absence of a functional penis. The patients who later identified as male all wished for testosterone and to have penis reconstruction surgery. In conclusion, this paper offers some evidence that male genetics coupled with normal hormone status at birth is associated with male-typical behaviors. It does not offer evidence supportive of the biological reality of a transgender identification. The authors realize that it is very hard to separate cultural, parental, and natural factors. They admit there are many "imponderables".
Research That Aims To Identify Differences Between Transgender Individuals And Others.
The first topic is a series of studies on a brain region known as BSTc. It is interesting to see the progression of the studies.
Zhou et al in 1995 looked at the volume of the central subdivision of the bed nucleus of the stria terminals (BSTc). This research looked at 6 transexual male-to-female brains and found that the volume of the BSTc was in the female range, rather than the male range for this structure. Kruijver et al in 2000 looked at these same brains, but evaluated the BSTc for number of neurons, rather than overall volume. In
Male-to-female transsexuals have female neuron numbers in a limbic nucleus., they show that this difference also shows up in neuron number. In 2002,
Wilson et al published a study in the Journal of Neuroscience that found that the BSTc region did not sexually differentiate significantly until adulthood. Since transsexuality is often claimed to be inborn and to manifest in very young children, it is difficult to see how the BSTc could be used as a reliable marker to identify transexuals.
Anne Lawrence critiqued these studies in a 2007 paper. She emphasizes that neither of the first two papers took into account whether the MtF brains studied were from homosexual or heterosexual transexuals, nor did they adequately consider whether the cross sex hormones taken by these individuals might have caused the differences observed. She also critiques Zhou's study for fishing through the data in order to find a brain region that showed differences, rather than hypothesizing that the particular brain region focused upon should show such differences. Thus, without replicating these results, we cannot accept them as confirmed.
I could not find the full text of this next paper, so I am using several articles that report on it.
Scientific American Mind, January 1, 2016
"Spanish investigators—led by psychobiologist Antonio Guillamon of the National Distance Education University in Madrid and neuropsychologist Carme Junqué Plaja of the University of Barcelona—used MRI to examine the brains of 24 female-to-males and 18 male-to-females—both before and after treatment with cross-sex hormones. Their results, published in 2013, showed that even before treatment the brain structures of the trans people were more similar in some respects to the brains of their experienced gender than those of their natal gender. For example, the female-to-male subjects had relatively thin subcortical areas (these areas tend to be thinner in men than in women). Male-to-female subjects tended to have thinner cortical regions in the right hemisphere, which is characteristic of a female brain. (Such differences became more pronounced after treatment.)"
“Trans people have brains that are different from males and females, a unique kind of brain,” Guillamon says. “It is simplistic to say that a female-to-male transgender person is a female trapped in a male body. It's not because they have a male brain but a transsexual brain.” Of course, behavior and experience shape brain anatomy, so it is impossible to say if these subtle differences are inborn."
Another report on this study in
New Scientists, 2011 comments that "Guillamon isn’t sure whether the four regions are at all associated with notions of gender, but Ivanka Savic-Berglund at the Karolinska Institute in Stockholm, Sweden, thinks they might be. One of the four regions – the superior longitudinal fascicle – is particularly interesting, she says. “It connects the parietal lobe [involved in sensory processing] and frontal lobe [involved in planning movement] and may have implications in body perception.”
The New Scientist article also mentions two other studies that might bear on this question:
"A 2010 study of 121 transgender people found that 38 per cent realised they had gender variance by age 5. White matter differences could provide independent confirmation that such children might benefit from treatment to delay puberty."
"A study by Sean Deoni‘s team at King’s College London suggests it may soon be possible to look for these differences in such children. Deoni’s team adapted an MRI scanner to be as quiet as possible so it could be used to monitor the development of white matter in sleeping infants. Using new image analysis software they could track when and where myelin – the neuron covering that makes white matter white – was laid down (Journal of Neuroscience, vol 31, p 784). Although the sample was too small to identify any gender differences in development, Deoni expects to see differences developing in the brain “by 2 or 3 years of age”."
Guillamon commented about these studies: “Research has shown that white matter matures during the first 20 to 30 years of life,” he says. “People may experience early or late onset of transsexuality and we don’t know what causes this difference.”
Physiological Responses
Berglund et al 2008 looked at the sensitivity to the odor of certain steroid compounds using12 MTF subjects compared with controls using a variety of techniques. They report: "In summary, albeit the present study does not provide conclusions
concerning the possible etiology, it suggests that in transsexuals the
organization of certain sexually dimorphic circuits of the anterior
hypothalamus could be sex atypical. It adds a new dimension to our
previous reports by showing that the observed effects are not
necessarily learned and that a sex-atypical activation by the 2 putative
pheromones may reflect neuronal reorganization."
Burke et al published
Click-evoked otoacoutstic emissions in children and adolescents with gender identity disorder in 2014. These CEOAE emissions are echo-like sounds produced in the inner ear that have different amplitudes of detection in males and females. Based on a test with 47 transgender subjects and 127 control subjects, the authors conclude in part: "Based on the assumption that CEOAE amplitude can be seen as an index of
relative androgen exposure, our results provide some evidence for the
idea that boys with GID may have been exposed to lower amounts of
androgen during early development in comparison to control boys."
The Archives of Sexual Behavior published a
tapping experiment led by Dr. Laura Case on eight transgender men and genderqueer individuals who wanted a double mastectomy. These eight people and eight non-transgender women were tapped with a pencil on their hands and on their upper breasts, while clothed while brain activity was recorded with a neuroimaging machine.
They found that when tapped on their upper breasts, the transgender and male-leaning genderqueer subjects had a reduced response in brain areas that are thought to make “self-other” distinctions. The authors speculate that the low response to breast tapping is a physiological manifestation of gender dysphoria. Case notes that “Scientific reductionism is unlikely to yield a simple explanation for a phenomenon as complex as gender identity.”
These studies give us some preliminary results without giving us strong evidence for a biological basis or biological marker for identifying transgender individuals. Notice that most of the researchers sound notes of caution when communicating about the significance of their studies. They use terms like "suggests", "based on the assumption", "provide some evidence", and "we don't know". However, these studies should serve as a base from which other researchers can try to replicate results, and go back and investigate some of the aspects that were assumed, but not known to be true--such as the association of the BSTc with sexual behavior in humans. Finer grained studies and analyses are needed to distinguish between homosexual and heterosexual transgender men. We may need to control for underlying mental health issues such as depression, autism, and prior sexual trauma--all of which have been associated with female-to-male transitioners. Age of transition and social factors also need consideration.
It is often difficult to get robust statistical and repeatable results when the number of participants is so small, and this is likely to remain a difficulty with transgender studies.
Review and Opinion Articles Frequently Cited
Nature article "Sex Redefined" by Claire Ainsworth
This article has been frequently posted to "prove" that sex is not binary and that Science proves that transgender people are real. The article was published in
Nature 18 February 2015.
This essay focuses on intersex conditions, in which the chromosomes and/or the biology of an individual are not 100% male or female. Intersex biology has a great variety of causes. Depending on how intersex is defined, the occurrence is anywhere between 1% with the broadest definition to .05% with a narrower definition. There are many types of DSD conditions (Disorders of Sexual
Development), many of which do not produce any symptoms and which do not
affect fertility, sexual response, or gender identity. Many people
never know they have these conditions.
The subjects covered in the
Nature essay are fascinating. Since 1990,
scientists have discovered over 25 genes that affect sexual development
in some way and have discovered non-genetic routes to DSDs as well. For
instance, some mothers acquire male cells from being pregnant with a male
fetus and these cells may become part of her body. Scientists have
found that XX vs. XY chromosomes in cells affect more than sex hormones; they can
also create metabolic differences within the body. One woman, pregnant
with her third child, was found to have a mixture of XX and XY cells in
her body thought to be acquired from a conjoined twin that never
developed. In mice, it was found that production of eggs or sperm could
be affected after birth if certain genes were blocked.
The condition that garners the most medical concern is when a child is born with ambiguous genitalia such that a parent or doctor cannot easily identify the baby as male or female. Until recently, parents and doctors would make a decision and surgery would often be used to alter the genitalia to better fit either the male or female sex. The child would then be raised in the sex that had been picked. This produced a variety of problems, particularly when the child later declared a gender identity at odds with the parent or doctor's choice. Intersex adults became active in changing the view that it was necessary to do sex assignment surgery on infants or children. They argue that if there were no health issues, such surgery could wait until children were adults able to give informed consent and could choose for themselves whether to have surgery and what sex they wished to affirm.
This essay addresses intersex
conditions, both genetic and anatomical. Sex researcher John Achermann is quoted "I think there is much
greater diversity within male or female, and there is certainly an area
of overlap where some people cannot easily define themselves within the
binary structure." It is statements of this sort which transgender activists use
to prove that transgenderism has a biological basis. This biological basis is then used to bolster their social and
legal demands.
Transgenderism is not
specifically addressed here. However, some transgender activists believe that showing biological ambiguities between males and females can also account for the feeling that you are born in the wrong body. This claim would have to
be substantiated by screening people who identify as transgender or non-binary
and seeing if this identification reliably correlates with any of the 25
genes or other anatomical intersex conditions. Would those that
identify as transgender have these gene mutations at a significantly higher rate from those that identify as male or female?
Is biological determinism a valuable argument for establishing the legitimacy of transgenderism? If we look at arguments about gay genes, which have been going on since the 1980s, we see that there is still no agreement. Yet, articles pro and con keep appearing, such as
this recent one from Newsweek. One of the reasons for the continued disagreement is that it is very rare for one gene to "determine" anything. There are multiple genes for most traits and these genes interact with many others to affect whether and how they are expressed. Also, environmental factors such as upbringing, peer groups, and social situation affect expression of traits in many different ways. Homosexual identity can take many different paths and manifest at different times of life as can a transgender identity. All these factors make it hard to "prove" anything about transgenderism from the kind of research reported in this article.
Even if such research produced positive conclusions, we still need to further ask what social and legal consequences should follow. For instance, if a certain gene correlated with gender dysphoria in males with male anatomy, does that mean that these men are "really" and completely women? It would seem that they are biologically ambiguous and choose to identify with and practice certain culturally female activities. Does it follow that such men should be able to join all women's sports teams? Does it mean that the typical anatomy, genetics, and physiological functions of over 99% of females should be disregarded and the definition of female changed so that the functions of giving birth or nursing are not considered female? Does it follow that all men should now be able to access formerly female spaces such as showers and changing rooms? These are typical demands of transgender activists and they use articles like "Sex Redefined" to support their case, though here as elsewhere more research is needed on both the biological and the sociological aspects of these questions.
These are not simple questions with obvious answers. Doctors warn that there is much we do not know. "They think that changing medical practice by legal ruling is not ideal, and would like to see more data collected on outcomes such as quality of life and sexual function to help decide the best course of action for people with DSDs...."
One important achievement of the intersex activists has been to forego medical interventions until patients were old enough to give truly informed consent. Experience with child genital surgeries had shown that very often sexual function and response were compromised and the possibility that these surgeries might not be necessary at all was another reason to delay. In contrast, transgender activists and their doctors are pushing for earlier and earlier drug and surgical intervention, ignoring what would seem to be relevant experience from doctors and patients from the intersex community.
Here are some more resources from Fair Play For Women
Differences between male and female part 1:
Bones and Muscles
Better Science With Sex And Gender: Facilitating The Use Of A Sex And Gender-based Analysis in Health Research.
December 2017: Gender or Sex Stereotypes: Part 1 by Paul Cockshott. The author sets out to see how researchers into gender differences in a great variety of fields actually identify the sex/gender differences. He finds that only sex is and can be used operationally as there is no way to code for gender without referring to sex. He analyzes at some length Judith Butler's arguments that sex is a social construct and finds them, rightly I believe, to be rhetorically and logically flawed as well as offering to actual evidence to support her claims or suggesting ways that her claims could be tested. He cites some studies that refute her specific claim that identification of gender is only through language. Gender or Sex Stereotypes: Part 2 is an extended critique of Judith Butler's position.
Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study.
Abstract
OBJECTIVE:
To
examine the factors associated with the persistence of childhood gender
dysphoria (GD), and to assess the feelings of GD, body image, and
sexual orientation in adolescence.
METHOD:
The
sample consisted of 127 adolescents (79 boys, 48 girls), who were
referred for GD in childhood (<12 years of age) and followed up in
adolescence. We examined childhood differences among persisters and
desisters in demographics, psychological functioning, quality of peer
relations and childhood GD, and adolescent reports of GD, body image,
and sexual orientation. We examined contributions of childhood factors
on the probability of persistence of GD into adolescence.
RESULTS:
We
found a link between the intensity of GD in childhood and persistence
of GD, as well as a higher probability of persistence among natal girls.
Psychological functioning and the quality of peer relations did not
predict the persistence of childhood GD. Formerly nonsignificant (age at
childhood assessment) and unstudied factors (a cognitive and/or
affective cross-gender identification and a social role transition) were
associated with the persistence of childhood GD, and varied among natal
boys and girls.
CONCLUSION:
Intensity
of early GD appears to be an important predictor of persistence of GD.
Clinical recommendations for the support of children with GD may need to
be developed independently for natal boys and for girls, as the
presentation of boys and girls with GD is different, and different
factors are predictive for the persistence of GD.
Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
