Possibly the most important part of the mental model humans construct is their mental model of themselves. This is what we call our identity. It takes all the beliefs we have about ourselves and attempts to put them together into an internally coherent whole. Some of our most cherished political, religious, racial, and gender thoughts about ourselves tells us who we are and how we ought to interact with the world.
Updated 2/29/2024
These beliefs about ourselves are not just thoughts, either. They are deeply held emotional states. They are how we relate to the world. Our identity regulates our preferences and how we react to situations. And our identity determines how we experience the world
We can have multiple sub-identities – my being a metal fan, a hip-hop fan, an atheist, an intellectual, a man, a brother, a son, etc. – but they all come together to form a single identity that we call the I. This is the fabric that holds together our mental model of the world into a single whole. I am a metal fan. I am a hip-hop fan. I am an atheist, and so on.
Our identity is formed in large part through what is called narrative identity. This is the story we tell ourselves about ourselves. As Wikipedia says in its opening:
The theory of narrative identity postulates that individuals form an identity by integrating their life experiences into an internalized, evolving story of the self that provides the individual with a sense of unity and purpose in life. This life narrative integrates one’s reconstructed past, perceived present, and imagined future. Furthermore, this narrative is a story – it has characters, episodes, imagery, a setting, plots, and themes and often follows the traditional model of a story, having a beginning (initiating event), middle (an attempt and a consequence), and an end (denouement).
These emotional states are not purely mental models we even choose to create, either. They can be shaped and formed through our thoughts and self-talk (narrative identity), as is proposed in cognitive behavioral theory, but much of it comes from our biology as well.
For instance, political affiliation has been associated with differential brain structure. An MRI study showed that political conservatives, contrasted with political liberals (in the American sense of the word), had more gray matter in the right amygdala. Another fMRI study of risk-taking behavior showed political conservatives have more activity in the right amygdala. The amygdala is important in processing emotions such as fear and threat. These results seem to suggest that there is a biological component in conservative resistance to change, seeing progress as a threat to the status quo.
Another instance of identity that has become important in our times is gender identity. There is strong evidence of a biological component to this as well. That binary sexes exist is a scientific fact. But even within this binary there is wiggle room. From occurrences of androgen insensitivity syndrome to XY gonadal dysgenesis to Klinefelter syndrome, and other forms of intersexuality, there are plenty of ways to genetically/chromosomally push the limits of the binary. But it’s also the case that genetically/chromosomally typical males and females can have a broad spectrum of masculinity and femininity, often, but certainly not always, connected to sexual orientation.
Going further, some males will identify as female and some females will identify as male in what is known as transgender identity. People with transgender identity experience what is known as gender dysphoria, or the distress a person experiences due to a mismatch between their gender identity—their personal sense of their own gender—and their sex assigned at birth (i.e., natal sex). Indeed, there is research showing that pre-hormone treatment transgender people have brain biochemistry and anatomy more similar to the gender they identify as than they do their natal sex, and that gender affirming treatments (e.g., hormone therapy) increases the quality of life for most people who identify as transgender.
This post will give an overview of some of the literature on the neurobiology and neuroanatomy of transgender identity, the genetics of transgender identity, the affects of gender affirming hormone treatment, detransition, and so-called rapid-onset gender dysphoria (ROGD). I will begin with a few older(ish) studies, primarily from prior to the politicization of gender ideology, before going into newer studies. The newer studies are fine, in my opinion (though I do try to point out when there is dissent to a study’s findings or methodology), but I still want to avoid accusations of bias creeping into science.
Without further adieu, here are the papers.
Older Studies
The 2000 paper by Frank Kruijver et al and the 2008 paper by Garcia-Falgueras and Swaab both show that the number of neurons, as well as the receptor BSTc (bed nucleus of the stria terminalis, which is sexually dimorphic) in the male brain is the same as that in FtM transgender people, and vice versa for MtF transgender people (theirs is the same as cisgender females). This is regardless of whether they had begun hormone replacement therapy.
But don’t just take my word on the above studies looking at the BSTc. The following video is of neuroscientist Robert Sapolsky discussing the study (and also mentioning the studies in my next entry on this post).
A 2007 paper by Ramachandran and McGeoch and a 2008 paper by Ramachandran and Mcgeoch discuss cisgender men who have had their penis amputated for various reasons report the sensation of a “phantom penis” while MtF transgender people who have had sex reassignment surgery report the sensation of a phantom penis significantly less often; FtM transgender people report the sensation of a phantom penis. Phantom limbs are known to occur because the feeling of your body does not happen in your body, but in the brain – the parietal region of the brain has our body “mapped” and all sensations actually occur there. The reduction in phantom penis reports in MtF transgender people, as well as the reporting of a phantom penis in FtM transgender people, suggests that the brains of these individuals has mapped their body in a way that corresponds to their gender identity as opposed to their birth sex.
For more on this notion of phantom limbs, brain-body representation incongruity, and transgender identity, see the following papers:
Gender Dysphoria and Body Integrity Identity Disorder: Similarities and Differences (2014)
Phantom Penis: Extrapolating Neuroscience and Employing Imagination for Trans Male Sexual Embodiment (2020)
The 2009 paper by Luders et al and a 2016 review article by Kreukels and Guillamon both show that, independent of hormone replacement therapy, the neuroanatomy of transgender people matches more closely to the sex with which they identify in some key ways while also displaying morphology similar to the sex to which they were born – in other words, the brain structures of both MtF and FtM transgender people lie somewhere in between male and female, with some regions appearing more like the gender with which they identify and others appear more like the sex to which they were born.
A 2009 study by found significantly enhanced activation for men compared with women was revealed in brain areas involved in erotic processing, i.e., the thalamus, the amygdala, and the orbitofrontal and insular cortex, whereas no specific activation for women was found. When comparing MTF transsexuals with male volunteers, activation patterns similar to female volunteers being compared with male volunteers were revealed. Sexual arousal was assessed using standard rating scales and did not differ significantly for the three groups. In other words, the brains of MtF transgender women responded more like natal women to erotic simuli. Berglund et al (2007) had similar findings.
A 2013 paper by Milton Diamond show that monozygotic (identical) twins show a 33% concordance in transgenderism amongst FtM transgender people and 28% amongst MtF transgender people, as opposed to 4.76% and 0.34% for dizygotic (fraternal) twins respectively. In other words, if one person in a set of twins is transgender, there is a significant chance the other one will be as well, whereas in fraternal twins, the correlation is significantly decreased, indicating a biological cause.
Further Reading
Increased Cortical Thickness in Male-to-Female Transsexualism (2012)
Newer Studies
In the above I have purposefully used older studies. The reason for this is because some may argue that in our recent political climate that science may be compromised. But there are more recent papers that come to the same findings. Here are just a few of them:
A 2022 study by Kurth et al used MRI to examine the brains of 24 cisgender men, 24 cisgender women, and 24 transgender women before gender-affirming hormone therapy using a multivariate classifier that yields a continuous (rather than a binary) estimate for being male or female and found that the brains of transgender women ranged between cisgender men and cisgender women (albeit still closer to cisgender men), and the differences to both cisgender men and to cisgender women were significant (p = 0.016 and p < 0.001, respectively).
Kurth et al (2022)
A 2021 review article by Frigerio et al examines 39 studies on gender identity and 24 on sexual orientation and found that the neurometabolic features in transgender individuals resemble those of their experienced gender despite the majority resembling those from their natal sex.
A 2022 study by Uribe et al examined the effects of spontaneously occurring local activation (i.e., events) on global integration (Deco et al., 2015) through the intrinsic ignition framework (Deco & Kringelbach, 2017; Deco, Tagliazucchi, et al., 2017) of 29 trans men and 17 trans women with gender incongruence, 22 cis women, and 19 cis men and found that there were significant differences (FWE corrected p < .004) between all gender groups when the intrinsic ignition framework was computed across the whole-brain functional network in both mean-ignition and node-metastability measurements (Figure 2a and Table 1). There was a gradual progression in the mean-ignition, that is, cis men > cis women > trans men > trans women. On the other hand, the average node-metastability was the highest in the cis woman group, and the trans man group showed the lowest average.
A 2020 study by Uribe et al examined the resting state functional connectivity of independent brain component networks, the intra- and inter-network connectivity strengths and global network large-scale characteristics in a homogeneous group of early onset TW [trans women] and TM [trans men]. In line with our predictions, there are three main findings: (i) TM, TW, and CW [cis women] had decreased connectivity in parietal regions compared with CM [cis men] as we predicted based on the cortical developmental hypothesis; (ii) similarly, TW and CW had less small worldness than CM, showing the existence of gender differences (considering the identification with the gender regardless of the assigned sex at birth) in this global network property; and (iii) TM had weaker connectivity in widespread regions mainly located in the frontal cortex and the majority of their significant connection nodes were part of the SN. Some of the regions that presented reduced functional connectivity in TM in comparison with CM were part of the own’s body perception hypothesis.
In summary, similar to TM, TW showed reduced connectivity in the parietal lobe in comparison with CM. In addition, graph-theory measures are able to differentiate CM from TW and CW in both segregation and integration parameters.
Uribe et al (2020)
A 2014 study by Hahn et al found differences on lobar/hemispheric connectivity in transgender people, as well as total intracranial volume for MtF transgender people between those of male and female controls.
In a 2014 study by Burke et al they found that the sex difference in responsiveness to androstadienone was already present in pre-pubertal control children and thus likely developed during early perinatal development instead of during sexual maturation. Adolescent girls and boys with GD both responded remarkably like their experienced gender, thus sex-atypical. In contrast, pre-pubertal girls with GD showed neither a typically male nor female hypothalamic activation pattern and pre-pubertal boys with GD had hypothalamic activations in response to androstadienone that were similar to control boys, thus sex-typical.
A 2020 study by Adnan Majid et al compared brain activation and connectivity in transgender individuals with that in cisgender controls when performing a body self-identification task during functional magnetic resonance imaging. Thirty transgender and 30 cisgender participants viewed images of their own bodies and bodies morphed in sex toward or opposite to birth-assigned sex, rating each image to the degree they identified with it. While controls identified with images of themselves, transgender individuals identified with images morphed “opposite” to their birth-assigned sex. Both groups activated similar self- and body-processing systems when viewing bodies that aligned with their gender identity rather than birth-assigned sex. Additionally, transgender participants had greater limbic involvement when viewing ambiguous, androgynous images of themselves morphed toward their gender identity. These results shed light on underlying self-processing networks specific to gender identity and uncover additional involvement of emotional processing in transgender individuals.
A 2017 study by Clemens et al examined twenty‐eight MtFs (15 hormonally untreated), 21 male and 20 female healthy control participants for resting‐state functional connectivity (rs‐FC) measured by functional magnetic resonance imaging (fMRI) and found that MtFs exhibit patterns of rs‐FC which are different from both their assigned and their aspired gender, indicating an intermediate position between the two sexes. We suggest that the present study constitutes a starting point for future research designed to clarify whether the brains of individuals with GD are more similar to their assigned or their aspired gender.
In a 2019 study, Manzouri and Savic report multimodal magnetic resonance imaging data, including cortical thickness (Cth), subcortical volumes, and resting state functional magnetic resonance imaging, from 27 transgender women (TrW), 40 transgender men (TrM), and 80 heterosexual (40 men) and 60 homosexual cisgender controls (30 men). These data show that whereas homosexuality is linked to cerebral sex dimorphism, gender dysphoria primarily involves cerebral networks mediating self–body perception. Among the homosexual cisgender controls, weaker sex dimorphism was found in white matter connections and a partly reversed sex dimorphism in Cth. Similar patterns were detected in transgender persons compared with heterosexual cisgender controls, but the significant clusters disappeared when adding homosexual controls, and correcting for sexual orientation. Instead, both TrW and TrM displayed singular features, showing greater Cth as well as weaker structural and functional connections in the anterior cingulate-precuneus and right occipito-parietal cortex, regions known to process own body perception in the context of self.
A 2020 study by Flint et al looked to substantiate evidence that the brain structure of TIs [transgender individuals] differs from male and female, we use a combined multivariate and univariate approach. Gray matter segments resulting from voxel-based morphometry preprocessing of N = 1753 cisgender (CG) healthy participants were used to train (N = 1402) and validate (20% holdout N = 351) a support-vector machine classifying the biological sex. As a second validation, we classified N = 1104 patients with depression. A third validation was performed using the matched CG sample of the transgender women (TW) application sample. Subsequently, the classifier was applied to N = 26 TW. Finally, we compared brain volumes of CG-men, women, and TW-pre/post treatment cross-sex hormone treatment (CHT) in a univariate analysis controlling for sexual orientation, age, and total brain volume. The application of our biological sex classifier to the transgender sample resulted in a significantly lower true positive rate (TPR-male = 56.0%). The TPR did not differ between CG-individuals with (TPR-male = 86.9%) and without depression (TPR-male = 88.5%). The univariate analysis of the transgender application-sample revealed that TW-pre/post treatment show brain-structural differences from CG-women and CG-men in the putamen and insula, as well as the whole-brain analysis. Our results support the hypothesis that brain structure in TW differs from brain structure of their biological sex (male) as well as their perceived gender (female). This finding substantiates evidence that TIs show specific brain-structural alterations leading to a different pattern of brain structure than CG-individuals.
A 2013 study by Ku et al found by means of functional magnetic resonance imaging, they found that the TXs [transgenders], as opposed to controls (CONs [cisgenders]), displayed an increased functional connectivity between the ventral tegmental area, which is associated with dimorphic genital representation, and anterior cingulate cortex subregions, which play a key role in social exclusion, conflict monitoring and punishment adjustment. The neural connectivity pattern suggests a brain signature of the psychosocial distress for the gender-sex incongruity of TXs.
A 2021 study by Mueller et al used MRI to examine the neurobiology of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity). They found that transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), they observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. They conclude that rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. They do say that while this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites.
A 2023 study by Torgerson et al examined gender diversity with a continuous felt-gender score and categorized sex based on X and Y allele frequency in a large sample of children ages 9–11 years-old (N=7693). Then, a statistical model-building approach was employed to determine whether gender diversity and sex independently or jointly relate to brain morphology. They found that the magnitude of variance accounted for by sex was small in all cases and felt-gender score was not a significant predictor on its own for any white or gray matter regions examined. Overall, these findings demonstrate that at ages 9–11 years-old, sex accounts for a small proportion of variance in brain structure, while gender diversity is not directly associated with neurostructural diversity.
Further Reading
I highly recommend the following review article (a number of the above studies were discovered here): Neuroimaging Studies in People with Gender Incongruence (2016) by Baudewijntje P.C. Kreukels & Antonio Guillamon
Neural network of body representation differs between transsexuals and cissexuals (2014)
White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging (2014)
Female-to-Male Transsexual Individuals Demonstrate Different Own Body Identification (2016)
A Review of the Status of Brain Structure Research in Transsexualism (2016)
Intrinsic network connectivity and own body perception in gender dysphoria (2017)
Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex (2020)
Cortical Gyrification in Transgender Individuals (2021)
Genetics Studies
The genetic component to transgender identity is still tenuous, but there is some tantalizing evidence that genetics may play a role in transgender identity. Some evidence, such as in Karamanis et al (2022) discussed below, indicates that the intrauterine environment, may play a larger role than genetics. When it comes to genetics and heritability (i.e., how much genetics explains variation in a particular trait) it’s often difficult to tease apart how much variation is due to genetics, how much is due to environment, and how much is due to the interaction of the two (many gene variants are known to increase a propensity for some behavior, but only if the person has grown up in a particular environment or are presented with particular situations). Furthermore, most traits, even something as seemingly straightforward as height, are enormously polygenic, i.e., there are hundreds of genes known to contribute to the trait (and often in ways that aren’t as straightforward as “alleles A, B, and C for genes P, Q, and R cause phenotype X”).
In what follows I will briefly go over a few studies concerning the genetics of transgender identity.
Cortés-Cortés et al (2017) found that XbaI-rs9340799 in ESR1 estrogen receptor gene is involved in FtM gender dysphoria in adults.
Fernández et al (2014) examined sex hormone-related genes ERβ (estrogen receptor β), AR (androgen receptor), and CYP19A1 (aromatase) and found that FtMs differed significantly from control group with respect to the median repeat length polymorphism ERβ (P = 0.002) but not with respect to the length of the other two studied polymorphisms. 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.
Hare et al (2009) found a significant association was identified between transsexualism and the AR [androgen receptor] allele, with transsexuals having longer AR repeat lengths than non-transsexual male control subjects (p=.04).
Bentz et al (2008) examined 102 male-to-female (MtF) and 49 female-to-male (FtM) transsexuals, 756 male controls, and 915 female controls and found that the CYP17 gene to be a candidate gene of FtM transsexualism and indicate that loss of a female-specific CYP17 T -34C allele distribution pattern is associated with FtM transsexualism. Similarly, et al (2015) found that the CYP17 MspA1 polymorphism A2 allele frequency was higher in the FtM (0.45) than the female control (0.38) and male control (0.39) groups, or the MtF group (0.36). This FtM > MtF pattern reached statistical significance (P = 0.041), although allele frequencies were not gender specific in the general population (P = 0.887).
Ramirez et al (2021) found that global CpG methylation is different in transgender people (prior to gender-affirming hormone treatment) compared to cisgender people.
A 2022 twin study by Karamanis et al examined a total of 2592 full siblings from a large register-based population in Sweden over the period 2001–2016 where gender dysphoria (GD) cases were registered, of which 67 were twins; age at first GD diagnosis for the probands ranged from 11.2 to 64.2 years. No same-sex twins that both presented with GD were identified during the study period. The proportion of different-sex twins both presenting with GD (37%) was higher than that in same-sex twins (0%, Fisher’s exact test p-value < 0.001) and in non-twin sibling pairs (0.16%). The present findings suggest that familial factors, mainly confined to shared environmental influences during the intrauterine period, seem to contribute to the development of GD.
A 2019 study by Theisen et al examined rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. They performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Their findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.
Hormone Therapy and Medical Care
Hormone therapy is when someone takes the hormone of the sex they identify as in order to have their body conform to their internal identity (i.e., to develop the secondary sex characteristics of the sex they identify as). FtM transgender people take testosterone (known as masculinizing hormone therapy) while MtF transgender people take estrogen (known as feminizing hormone therapy). These can be administered through injection either intramuscular or subcutaneous. This is not without its health risks. See the following papers:
The effects of oestrogens and their receptors on cardiometabolic health (2017)
Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study (2018)
Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy (2019)
Gender-Affirming Hormone Therapy, Vascular Health and Cardiovascular Disease in Transgender Adults (2019)
Sex and Gender Differences in Clinical Pharmacology: Implications for Transgender Medicine (2021)
There are also what are called puberty blockers, which are meant to halt the onset of puberty. This is primarily done with gonadotropin-releasing hormone (GnRH) agonists. These desensitize the pituitary gland (by causing GnRH receptor downregulation) and thereby reducing the release of the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in less testosterone/estrogen production. The purpose, as Anacker et al (2021) puts it, is:
The clinical purpose of GnRHa administration to transgender youth in early adolescence is: (1) to prevent further development of secondary sex characteristics consistent with sex assigned at birth, which risks increasing or perpetuating anatomic dysphoria and related social stigma; and (2) to gain time for (therapist-assisted) consideration of the transgender identity before starting hormone treatments that lead to irreversible development of secondary sex characteristics consistent with the individual’s gender identity.
Again, this treatment is not without its risks. See the following papers:
Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression (2017)
Now I will give some summaries of studies on the use of hormone therapy and other gender affirming treatments for gender dysphoria:
A 2011 cohort study by Dhejne et al looked at 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973-2003 to estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons using hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]). They found that the overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8-4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8-62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9-8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0-3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls. From this they concluded that persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group.
Davis and Amand (2013) examined the effects of testosterone treatment with or without chest reconstruction surgery (CRS) on mental health in female-to-male transgender people (FTMs). 200 FTMs completed a written survey including quantitative scales to measure symptoms of anxiety and depression, feelings of anger, and body dissatisfaction, as well as qualitative questions assessing shifts in sexuality after the initiation of testosterone. Fifty-seven percent of participants were taking testosterone and 40% had undergone CRS.. Participants who had CRS in addition to testosterone reported less body dissatisfaction than both the testosterone-only or the untreated groups. Furthermore, participants who were injecting testosterone on a weekly basis showed significantly less anger compared with those injecting every other week. In qualitative reports, more than 50% of participants described increased sexual attraction to nontransgender men after taking testosterone. They conclude that testosterone treatment in FTMs is associated with a positive effect on mental health on measures of depression, anxiety, and anger, while CRS appears to be more important for the alleviation of body dissatisfaction.
Smith et al (2014) describe the affects of cross-sex hormone therapy (CSHT) as: Within the first 6 months of CSHT, changes in transsexual females include breast growth, decreased testicular volume, and decreased spontaneous erections, and changes in transsexual males include cessation of menses, breast atrophy, clitoral enlargement, and voice deepening. Both transsexual females and males experience changes in body fat redistribution, muscle mass, and hair growth. Desired effects from CSHT can take between 3 and 5 years; however, effects that occur during puberty, such as voice deepening and skeletal structure changes, cannot be reversed with CSHT. Decreased sexual desire is a greater concern in transsexual females than in transsexual males, with testosterone concentrations linked to sexual desire in both. Regarding CSHT safety, bone mineral density is preserved with adequate hormone supplementation, but long-term fracture risk has not been studied. The transition away from high-dose traditional regimens is tied to a lower risk of venous thromboembolism and cardiovascular disease, but data quality is poor. Breast cancer has been reported in both transsexual males and females, but preliminary data suggest that CSHT does not increase the risk. Cancer screenings for individuals of both natal and transitioned sexes should occur as recommended. More long-term studies are needed to ensure that CSHT regimens with the best outcomes can continue to be prescribed for the transsexual population.
Annelou et al (2014) looked at a total of 55 young transgender adults (22 transwomen and 33 transmen) who had received puberty suppression during adolescence were assessed 3 times: before the start of puberty suppression (mean age, 13.6 years), when cross-sex hormones were introduced (mean age, 16.7 years), and at least 1 year after gender reassignment surgery (mean age, 20.7 years). Psychological functioning (gender dysphoria (GD), body image, global functioning, depression, anxiety, emotional and behavioral problems) and objective (social and educational/professional functioning) and subjective (quality of life, satisfaction with life and happiness) well-being were investigated. They found that after gender reassignment, in young adulthood, the GD was alleviated and psychological functioning had steadily improved. Wellbeing was similar to or better than same-age young adults from the general population. Improvements in psychological functioning were positively correlated with postsurgical subjective well-being.
In 2014 Zubiaurre-Elorza et al found that testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system.
In 2015 Staphorsius et al found no significant effect of GnRHa [gonadotropin releasing hormone analogs] on ToL [Tower of London] performance scores (reaction times and accuracy) when comparing GnRHa treated male-to-females (suppressed MFs, n=8) with untreated MFs (n=10) or when comparing GnRHa treated female-to-males (suppressed FMs, n=12) with untreated FMs (n=10). However, the suppressed MFs had significantly lower accuracy scores than the control groups and the untreated FMs. Region-of-interest (ROI) analyses showed significantly greater activation in control boys (n=21) than control girls (n=24) during high task load ToL items in the bilateral precuneus and a trend (p<0.1) for greater activation in the right DLPFC. In contrast, untreated adolescents with GD did not show significant sex differences in task load-related activation and had intermediate activation levels compared to the two control groups. GnRHa treated adolescents with GD showed sex differences in neural activation similar to their natal sex control groups. Furthermore, activation in the other ROIs (left DLPFC and bilateral RLPFC) was also significantly greater in GnRHa treated MFs compared to GnRHa treated FMs. These findings suggest that (1) GnRHa treatment had no effect on ToL performance in adolescents with GD, and (2) pubertal hormones may induce sex-atypical brain activations during EF in adolescents with GD.
Costa and Colizzi (2016) did a review of the literature and found the following:
More specifically, when treated with hormone therapy, gender dysphoria individuals reported less anxiety,35,37,38 dissociation,45 perceived stress,14 social distress,35 and higher mental health-related quality of life24,36,43,44 and self-esteem.36,38 Also, compared to FtM individuals, MtF individuals seemed to benefit more in terms of body uneasiness,39 emotional functioning,31 and personality-related psychopathology.30,41,42 More mixed results emerged from studies investigating other mental health-related dimensions. In particular, recent studies suggested reduced depressive symptoms in hormone-treated gender dysphoria individuals,35–37 despite previous evidence of no association between cross-sex hormonal treatment and depression among MtF34 and FtM individuals.31 Similarly, global psychopathology appeared to be reduced in two studies,8,37 while a third one did not detect any change.39 Finally, while two studies indicated less functional impairment37 and reduced problems with socialization and interpersonal functioning in gender dysphoria individuals receiving hormone therapy,38 two other studies did not find any effect of hormone therapy on social adjustment34 and psychosocial functioning.36 Negative findings generally came from studies involving a cross-sectional design. On the contrary, the few longitudinal studies identified in this review were consistent in indicating an association between hormonal treatment and better mental health.14,29,31,37,40,45 Conducting observations of the same subjects over a period of time, longitudinal studies can establish sequences of events and better detect changes in the characteristics of the target population, also due to their higher statistical power.
In 2021 Zubiaurre-Elorza et al found that testosterone produces structural changes in the brain [of FtM transsexual people] as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control of astrocyte water trafficking, thereby controlling brain volume.
In 2021 Skewis et al looked at people newly commencing standard full-doses of masculinising (n = 42; 35 = trans masculine, 7 = non-binary) or feminising (n = 35; 33 = trans feminine, 2 = non-binary) GAHT [gender affirming hormone therapy] and cisgender participants (n=53 male, n=50 female) found that in trans people initiating masculinising GAHT, there was a decrease in gender dysphoria with adjusted mean difference -6.80 (-8.68, -4.91), p < 0.001, and a clinically significant improvement in emotional well-being [adjusted mean difference 7.48 (1.32, 13.64), p = 0.018] and social functioning [adjusted mean difference 12.50 (2.84, 22.15), p = 0.011] aspects of QoL [quality of life] over the first 6 months of treatment relative to the cisgender female comparison group. No significant differences were observed in other QoL domains. In trans people initiating feminising GAHT, there was a decrease in gender dysphoria [adjusted mean difference -4.22 (-6.21, -2.24), p < 0.001] but no differences in any aspects of QoL were observed. They conclude that in the short-term, our findings support the benefit of initiating masculinising or feminising GAHT for gender dysphoria. Masculinising GAHT improves emotional well-being and social functioning within 6 months of treatment. Multidisciplinary input with speech pathology and surgery to support trans people seeking feminisation is likely needed. Further longitudinal studies controlled for other confounders (such as the presence of social supports) contributing to QoL are needed.
In 2021 Aldridge et al had participants (n = 178) complete a socio-demographic questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Scale of Perceived Social Support (MSPSS) and the Autism Spectrum Quotient-Short Version (AQ-Short) at pre-assessment (T0) and at 18 months after initiation of GAHT (T1) [gender affirming hormone therapy]. They found that from T0 to T1, symptomatology was significantly decreased for depression (P < .001) and non-significantly reduced for anxiety (P = .37). Scores on the MSPSS predicted reduction in depression, while scores on the AQ-Short predicted reduction in anxiety. GAHT reduces symptoms of depression which are predicted by having higher levels of social support. Although anxiety symptoms also reduce, the changes are not significant and high levels of anxiety still remain post-GAHT. They conclude that the results highlight the important mental health benefits of GAHT. Support services (professional, third sector or peer support) aiming at increasing social support for transgender individuals should be made available.
A 2022 study by Glintborg et al looked at the number of transgender people who go on to receive hormone therapy. They looked at the national register-based cohort study in Danish transgender persons followed from 2000 until 2018. The cohort included 2789 transgender persons (n = 1717, CGI-cohort [received a diagnosis of gender identity disorder] and n = 1072, CPR-cohort [received a legal sex change but without diagnosis of GID]). The median age (interquartile range) at study inclusion was 26.1 (17.7) years for persons assigned male at birth (n = 1447) and 22.5 (10.5) years for persons assigned female at birth (n = 1342). In the CGI-cohort, the event rate for GAHT [gender affirming hormonal treatment] in transgender women increased from 4.0 (95% confidence interval [CI]: [3.1; 5.2]) events per 100 person in year 2000-2005 to 20.6 (17.8; 23.7) between 2014 and 2018. In transgender men, the event rate of GAHT increased from 4.2 (2.8; 6.2) to 18.8 (16.4; 21.6). The rate of discontinuation of GAHT was 0.06 (95% CI 0.049; 0.071) per person year. They conclude that the event rate of GAHT increased during 2000-2018. Our data suggested high adherence to GAHT.
A 2018 review article by Nguyen et al found that although there are some conflicting data, GAHT overwhelmingly seems to have positive psychological effects in both adolescents and adults. Research tends to support that GAHT reduces symptoms of anxiety and depression, lowers perceived and social distress, and improves quality of life and self-esteem in both male-to-female and female-to-male transgender individuals. Clinically, prescribing GAHT can help with gender dysphoria-related mental distress. Thus, timely hormonal intervention represents a crucial tool for improving behavioral wellness in transgender individuals, though effects on cognitive processes fundamental for daily living are unknown. Future research should prioritize better understanding of how GAHT may affect executive functioning.
A 2021 study by Khorashad et al tested the hypothesis that the neurobiology of gender dysphoria (GD) is linked to cerebral networks encompassing self-referential and body ownership regions, primarily with the default mode network (DMN). The authors had recently found that this network is activated during own-body processing among cisgender, as well as transgender individuals, but that the stimuli activating this distributed network differed, aligning with gender identity rather than the at birth-assigned sex. Given that transgender persons feel a strong estrangement from their body, which improves after sex hormone treatment, the authors hypothesized that the DMN could be less integrated among hormone-naïve transgender persons, and become more integrated with cross-sex hormone treatment. Indeed, they found that both trans-men (TrM) and trans-women (TrW) had significantly weaker DMN connections than controls, particularly in the medial prefrontal cortex (mPFC). This observation concurs with previous findings from a more limited study group of TrM, and supports the notion that TrM and TrW share certain characteristics along the cerebral midline. This is also in line with another previous study investigating cross-sex hormone effects on Cth, where we found that testosterone treatment had similar effects in TrM as estrogen in TrW on the cerebral midline structures that showed greater cortical thickness before treatment. Moreover, the own-body perception among TrW and TrM was less accurate (less congruent with body sex-phenotype of the own unmorphed image) than in controls. The ‘self’ ratings to the 0% morph images increased after treatment, whereas the body morph (BM) index turned even more negative (greater correspondence of own body with the desired sex) than before treatment.
Further Reading
Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study (2011)
Young adult psychological outcome after puberty suppression and gender reassignment (2014)
Brain Maturation, Cognition and Voice Pattern in a Gender Dysphoria Case under Pubertal Suppression (2017)
Research gaps in medical treatment of transgender/nonbinary people (2021)
Detransition
The 2015 USTS report
The Report of the 2015 US Transgender Survey is an important starting point, because a lot of people cite it when discussing the number of transgender people and the number of detransitioners. The survey was accessed exclusively through a website created specifically for the promotion and distribution of the survey.3 Data was collected over a 34-day period in the summer of 2015,4 and the final sample included 27,715 respondents from all fifty states, the District of Columbia, American Samoa, Guam, Puerto Rico, and U.S. military bases overseas. The survey contained mainly closed-ended questions, but respondents were also offered the opportunity to provide write-in responses in fifty-three of the survey questions. Over 80,000 write-in responses were provided by respondents.
I also recommend the CDC Behavioral Risk Factor Surveillance System (BRFSS) and the associated paper by Kellan E. Baker (2019), which found that transgender individuals comprised an estimated 0.55% (95% CI, 0.51%-0.59%) of the sample, which is equivalent to 1.27 million transgender adults in the general US population. They also found that transgender adults were more likely to report diminished HRQOL [health related quality of life] in the previous 30 days as measured by greater odds of fair or poor health (adjusted odds ratio [AOR], 1.30; 95% CI, 1.03-1.62; P = .02) or severe mental distress (AOR, 1.66; 95% CI, 1.36-2.01; P < .001) (Table 2). They also reported more days of combined poor physical and mental health (adjusted mean [SE] difference: 1.20 [0.04] days; P < .001) and of activity limitation (1.34 [0.09] days; P < .001).
D’Angelo et al (2020) compare the above two surveys and say:
Table 1, which compares the demographic characteristics of the USTS participants [the 2015 report] to those of transgender participants from a high-quality probability sample collected by the Centers for Disease Control Behavioral Risk Factors Surveillance System (BRFSS) (Baker, 2019; CDC, 2014–2017). As Table 1 illustrates, even after applying weighting to correct for known survey biases, the USTS participants were far more likely to be young (42% vs. 22% were 18–24 years old) and educated (47% vs. 14% had completed post-secondary education) than BRFSS participants. They were far less likely to own a home (16% vs. 55%) or to be married or coupled (18% vs. 46%). They were also much more likely to have a non-binary identity (38% vs. 22%) and a markedly different self-reported sexual orientation: Only 15% of the USTS participants reported a heterosexual orientation, compared to 69% of the BRFSS participants. (It is not clear if sexuality in either case was reported relative to one’s sex or gender identity.)
Other Papers on Detransition
Two studies, one by Call et al (2021) and the other by Tordoff et al (2022) say:
There is increasing evidence that gender-affirming interventions improve mental health outcomes for TGD youth. TGD youth report worse mental health outcomes in invalidating school and family environments and improved outcomes in affirming climates. TGD youth experience significant healthcare disparities, and intersectional clinical approaches are needed to increase access to affirmative care. Providers can best support TGD youth by considering ways they can affirm these youth in their healthcare settings, and helping them access support in schools, family systems, and communities. Understanding the intersection of multiple minority identities can help providers address potential barriers to care to mitigate the health disparities seen in this population. [Call et al (2021)]
And
This study found that gender-affirming medical interventions were associated with lower odds of depression and suicidality over 12 months. These data add to existing evidence suggesting that gender-affirming care may be associated with improved well-being among TNB youths over a short period, which is important given mental health disparities experienced by this population, particularly the high levels of self-harm and suicide. [Tordoff et al (2022)]
Yet there is growing concern about detransition, which is when someone who once identified as transgender stops identifying as transgender and ceases gender affirming therapies. This can occur before any sorts of medical interventions (e.g., puberty blockers, hormone therapy, mastectomy, vaginoplasty, etc.) but can also occur after such measures are taken. The latter case can result in permanent unwanted consequences, making it a touchy subject. This is even more concerning when it comes to children. In what follows I will post links and summaries to papers discussing detransition, and in particular how prevalent it is, since this is what a lot of the current debate is surrounding.
In general, those who advocate for affirmation only want to downplay the prevalence of detransitioners, or argue that the reasons for detransition have more to do with discrimination (external pressures) than from a person deciding they identify as their natal sex. This is because if detransition is common, and it is because people later on decide they identify as their natal sex (as opposed to detransitioning to avoid psychological or physical stress), then affirmation only would be an undesirable approach because it could cause harmful or unwanted consequences for more people. Those who advise caution against affirmation only, or who are against it altogether, want to emphasize the prevalence of detransitioners for the opposite reason: to show that caution towards (or even abstention of) gender affirmation approaches is warranted in order to reduce or avoid harm.
The following papers attempt to look at the issue of detransitioners, in particular their prevalence in the population.
In 2018 Wiepjes et al published a paper on their study of the medical files of all people who attended their gender identity clinic from 1972 to 2015. They found that 6,793 people (4,432 birth-assigned male, 2,361 birth-assigned female) visited their gender identity clinic from 1972 through 2015. The number of people assessed per year increased 20-fold from 34 in 1980 to 686 in 2015. The estimated prevalence in the Netherlands in 2015 was 1:3,800 for men (transwomen) and 1:5,200 for women (transmen). The percentage of people who started HT within 5 years after the 1st visit decreased over time, with almost 90% in 1980 to 65% in 2010. The percentage of people who underwent gonadectomy within 5 years after starting HT remained stable over time (74.7% of transwomen and 83.8% of transmen). Only 0.6% of transwomen and 0.3% of transmen who underwent gonadectomy were identified as experiencing regret.
In 2020 Turban et al performed a cross-sectional study, to study the affect of gender identity conversion efforts (GICE) [psychological interventions with a predetermined goal to change a person’s gender identity to align with their sex assigned at birth.]. A survey was distributed through community-based outreach to transgender adults residing in the United States, with representation from all 50 states, the District of Columbia, American Samoa, Guam, Puerto Rico, and US military bases overseas. Data collection occurred during 34 days between August 19 and September 21, 2015. Data analysis was performed from June 8, 2018, to January 2, 2019. Of 27 715 transgender survey respondents (mean [SD] age, 31.2 [13.5] years), 11 857 (42.8%) were assigned male sex at birth. Among the 19 741 (71.3%) who had ever spoken to a professional about their gender identity, 3869 (19.6%; 95% CI, 18.7%-20.5%) reported exposure to GICE in their lifetime. Recalled lifetime exposure was associated with severe psychological distress during the previous month (adjusted odds ratio [aOR], 1.56; 95% CI, 1.09-2.24; P < .001) compared with non-GICE therapy. Associations were found between recalled lifetime exposure and higher odds of lifetime suicide attempts (aOR, 2.27; 95% CI, 1.60-3.24; P < .001) and recalled exposure before the age of 10 years and increased odds of lifetime suicide attempts (aOR, 4.15; 95% CI, 2.44-7.69; P < .001). No significant differences were found when comparing exposure to GICE by secular professionals vs religious advisors.
D’Angelo et al (2021) take issue with the above Turban (2020) study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878242/
See also Forsythe et al (2022) for a similar study to that of Turban (2020): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902682/
In 2021 Turban et al issued a cross-sectional nonprobability survey of 27,715 TGD adults in the United States. They found that a total of 17,151 (61.9%) participants reported that they had ever pursued gender affirmation, broadly defined. Of these, 2242 (13.1%) reported a history of detransition. Of those who had detransitioned, 82.5% reported at least one external driving factor. Frequently endorsed external factors included pressure from family and societal stigma. History of detransition was associated with male sex assigned at birth, nonbinary gender identity, bisexual sexual orientation, and having a family unsupportive of one’s gender identity. A total of 15.9% of respondents reported at least one internal driving factor, including fluctuations in or uncertainty regarding gender identity. They conclude that among TGD adults with a reported history of detransition, the vast majority reported that their detransition was driven by external pressures.
In 2021 Lisa Littman obtained information with a link to an anonymous survey that was shared on social media, professional listservs, and via snowball sampling. Sixty-nine percent of the 100 participants were natal female and 31.0% were natal male. Reasons for detransitioning were varied and included: experiencing discrimination (23.0%); becoming more comfortable identifying as their natal sex (60.0%); having concerns about potential medical complications from transitioning (49.0%); and coming to the view that their gender dysphoria was caused by something specific such as trauma, abuse, or a mental health condition (38.0%). Homophobia or difficulty accepting themselves as lesbian, gay, or bisexual was expressed by 23.0% as a reason for transition and subsequent detransition. The majority (55.0%) felt that they did not receive an adequate evaluation from a doctor or mental health professional before starting transition and only 24.0% of respondents informed their clinicians that they had detransitioned.
In 2021 Bustos et al performed a review on several databases (namely, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus). They looked at a total of 27 studies, pooling 7928 transgender patients who underwent any type of GAS, were included. The pooled prevalence of regret after GAS was 1% (95% CI <1%–2%). Overall, 33% underwent transmasculine procedures and 67% transfemenine procedures. The prevalence of regret among patients undergoing transmasculine and transfemenine surgeries was <1% (IC <1%–<1%) and 1% (CI <1%–2%), respectively. A total of 77 patients regretted having had GAS. Twenty-eight had minor and 34 had major regret based on Pfäfflin’s regret classification. The majority had clear regret based on Kuiper and Cohen-Kettenis classification. From this they conclude that there is an extremely low prevalence of regret in transgender patients after GAS. However, they note that there is high subjectivity in the assessment of regret and lack of standardized questionnaires, which highlight the importance of developing validated questionnaires in this population.
In 2022 MacKinnon et al conducted in-depth interviews with 28 people. Among the 28 participants, 18 (64%) were assigned female at birth and 10 (36%) were assigned male at birth; 2 (7%) identified as Jewish and White, 5 (18%) identified as having mixed race and ethnicity (which included Arab, Black, Indigenous, Latinx, and South Asian), and 21 (75%) identified as White. Participants initially sought gender-affirmation at a wide range of ages (15 [56%] were between ages 18 and 24 years). Detransition occurred for various reasons, such as an evolving understanding of gender identity or health concerns. Participants reported divergent perspectives about their past gender-affirming medical or surgical treatments. Some participants felt regrets, but a majority were pleased with the results of gender-affirming medical or surgical treatments. Medical detransition was often experienced as physically and psychologically challenging, yet health care avoidance was common. Participants described experiencing stigma and interacting with clinicians who were unprepared to meet their detransition-related medical needs.
In 2022 Olson et al examined the rate of retransition and current gender identities of 317 initially transgender youth (208 transgender girls, 109 transgender boys; M 5 8.1 years at start of study) participating in a longitudinal study, the Trans Youth Project. Data were reported by youth and their parents through in-person or online visits or via e-mail or phone correspondence. They found that an average of 5 years after their initial social transition, 7.3% of youth had retransitioned at least once. At the end of this period, most youth identified as binary transgender youth (94%), including 1.3% who retransitioned to another identity before returning to their binary transgender identity. A total of 2.5% of youth identified as cisgender and 3.5% as nonbinary. Later cisgender identities were more common among youth whose initial social transition occurred before age 6 years; their retransitions often occurred before age 10 years. They conclude that retransitions are infrequent, find that more commonly, transgender youth who socially transitioned at early ages continued to identify that way.
A paper in 2023 by Jedrzejewski et al report on meeting with 1989 individuals who underwent gender-affirming surgery at the authors’ program (which they describe as “[a] care environment that welcomes and normalizes authentic expression of gender identity, affirms surgical goals without judgment, and destigmatizes the role of mental health in the surgical process”) between 2016 and 2021 and found that only six (0.3%) either requested reversal surgery or transitioned back to their sex assigned at birth.
For the 2023 article “The Detransition Rate is Unknown” by Jay Cohn I am going to quote it at length since he brings up some important questions and issues on the topic of detransition as a subject of scientific study (if you are interested in the topic, which I assume you are since you are reading this post, I would also recommend checking out the full article and the references linked to in the quote below).
Regret and sometimes detransition are negative outcomes. Loss to follow-up, premature outcome measurement, flawed instruments, and irrelevant samples all contribute to produce unreliable regret, detransition, or discontinuation rates. The proposed follow-up of NHS GIDS Tavistock outcomes (Crawford, 2022) shows promise, as do the proposed requirements for research contexts for new minor patients in Sweden (Swedish National Board of Health & Welfare, 2022). Research settings have also been proposed for puberty blockers for new minor patients by NHS England (2022), with similar proposals in preparation regarding hormones. There is also a two year follow-up time for a US-funded, four-center study underway (Chen et al., 2023; Olson-Kennedy et al., 2019); however, this appears too short to reliably measure long-term outcomes given the average observed regret and detransition times, albeit for older populations, as shown in Table 1. Better follow-up studies can help better constrain regret, detransition, and discontinuation rates, and other significant unknowns as well, such as the rates and time scales for detransition followed by retransition (Turban et al., 2021) and the rates of positive long-term outcomes. Although there are many anecdotal reports of positive long-term outcomes, inadequate long-term follow-up limits understanding how common these are as well.
These outcome rates alone cannot illuminate how well medical intervention itself helps gender dysphoria, as the “no treatment” alternative, the natural history of gender dysphoria, is not well understood, especially for those with adolescent onset (Kaltiala-Heino et al., 2018). In particular, it is unknown how to reliably determine when any given individual’s gender dysphoria might be temporary (Levine et al., 2022). Some temporary cases of gender dysphoria have been associated with the presence of comorbidities, including autism spectrum disorders, obsessive compulsive disorders, separation anxiety, depression, anorexia, homophobia, or trauma (Bockting et al., 2006; Churcher-Clarke & Spiliadis, 2019; Evans & Evans, 2021; Parkinson, 2014; Withers, 2020), conditions frequently present in the current large adolescent cohort (Kaltiala-Heino et al., 2018). Exploratory psychotherapy (Ayad et al., 2022; Evans & Evans, 2021), group therapy (Withers, 2020), and other supportive mental health interventions sometimes resolve gender dysphoria without medical intervention. These alternatives to medical intervention are also currently backed by low-quality evidence (Levine et al., 2022). Evidence would benefit from “randomized controlled trials, well-conducted comparative observational studies or very large case series (which include a large sample of consecutive patients who are representative of the whole population)” (Brignardello-Petersen & Wiercioch, 2022, p. 5).
…
…when someone regrets, detransitions, or discontinues medical intervention for gender dysphoria, serious consequences from medical intervention frequently remain, often for life. These can include sterility (Cheng et al., 2019), loss of breasts, irreversibly harmed genitals and/or sexual function, and lifetime dependence upon medication due to gonad removal, as well as loss or growth of hair, voice changes, and breast growth. Detransition can also incur detrimental social consequences: many in the Vandenbussche (2022) study “expressed a feeling of rejection and loss of support in relation to their decision to detransition, which lead (sic) them to step away from LGBT + groups and communities” (p. 1611). That is, not only might their gender dysphoria not be resolved, but the medical harm they incurred in order to try to resolve it and the consequences of detransition or feeling regret may create additional, sometimes devastating, challenges. In one convenience sample of detransitioners who identified as such, 60% reported needing help in learning to cope with feelings of regret (Vandenbussche, 2022). In another convenience sample, comprised of those who medically detransitioned, almost two-thirds “indicated that if they knew then what they know now, they would not have chosen to transition” (Littman, 2021, p. 3364). Negative outcomes can be extremely painful, and cause long-term suffering: “Some of us will now never be able to have children and many of us live with great distress and regret every day” (Fox, 2021). Knowing the number of those who discontinue, detransition, and/or regret is clinically crucial, but currently unavailable information.
Given the long-known and well-known limitations of outcome studies, one might question why these issues have not been addressed sooner. Medical interventions for gender dysphoria are already widespread: in the USA alone, over 17,000 children aged 6–17 started puberty blockers or hormones from 2017 to 2021, with at least 56 genital surgeries and 776 double mastectomies in the 13–17 age range from 2019 to 2021 (Respaut & Terhune, 2022). In response to the lack of systematic outcome studies, the irreversible nature of many of the hormonal and surgical interventions, and the serious consequences of poor outcomes, it has recently been asked (Clayton, 2022, p. 695): “Why are these experimental interventions, with inherent risks and scarce, low-quality evidence for benefits, being implemented outside HREC regulated clinical trial settings?”.
It is important for those considering medical intervention to know that the likelihood of regret, detransition, and discontinuation is unknown, that regret and detransition can be traumatic, and that the extremely small numbers quoted by some (Bustos et al., 2021; McNamara et al., 2022; Rosenthal, 2021; Turban, 2022) are not reliable or representative. With patient preferences for treatment pathways paramount in the common affirmative model, it is crucial that risks and benefits of medical intervention, and those of the alternatives, be clearly communicated, including accurate information about detransition and regret rates. Until more is known, young people considering these interventions and their families should be made aware of this significant uncertainty as part of informed consent, following the recommendations of Levine et al. (2022).
Further Reading
A Typology of Gender Detransition and Its Implications for Healthcare Providers (2021)
Rapid Onset Gender Dysphoria (ROGD)
This is a controversial notion, primarily put forward by Lisa Littman, that says that children, particularly girls, will take on a transgender identity due to social pressures and undiagnosed mental disorders (e.g., depression, anxiety, autism, personality disorders). There is now even a website for parents of children with ROGD. I will link to Lisa Littman’s papers, as well as countering papers, here.
Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria (Littman, 2018)
– Correction: Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria (Littman, 2018)
Formal comment on: Parent reports of adolescents and young adults perceived to show signs of a rapid onset of gender dysphoria (Costa, 2019)
In Support of Research Into Rapid-Onset Gender Dysphoria (Hutchinson, Midgen, and Spiliadis, 2020)
Methodological Critique of Littman’s (2018) Parental-Respondents Accounts of “Rapid-Onset Gender Dysphoria” (Arjee Javellana Restar, 2019)
Do Clinical Data from Transgender Adolescents Support the Phenomenon of “Rapid Onset Gender Dysphoria”? (Bauer, Lawson, and Metzger, 2022)
(June, 2022) Lisa Littman and Joanne Sinai respond to the above Bauer, Lawson, and Metzger (2022) paper: https://www.jpeds.com/article/S0022-3476(22)00183-4/pdf
(June, 2022) Bauer, Lawson, and Metzger respond to Lisa Littman and Joanne Sinai: https://www.jpeds.com/article/S0022-3476(22)00184-6/pdf
Alison Clayton (2022) brings up the issue of possible placebo effect in gender-affirming treatment in children experiencing gender dysphoria. She says:
In the field of GD youth medicine, there is a combination of features that seems to create a perfect storm setting for placebo effect. Thus, we have a population of vulnerable youth presenting with a condition, which has no objective diagnostic tests, and that is currently undergoing an unexplained rapid increase in prevalence and marked change in patient demographics. The treatment response is mainly based on patient-reported outcomes (yes, this can be the case for other conditions but remember we are considering the combination of features, not just a feature in isolation). Some clinicians, who may be affiliated with prestigious institutions, enthusiastically promote GAT, including on the media, social media, and alongside celebrity patients. Some make overstated claims about the strength of evidence and the certainty of benefits of GAT, including an emphasis on their “life-saving” qualities, and under-acknowledge the risks. Alternative psychosocial treatment approaches are sometimes denigrated as harmful and unethical conversion practices or as “doing nothing.” This combination of features increases the likelihood that there will be a complex interplay of heightened placebo and nocebo effects in this area of medicine, with significant implications for research and clinical practice.
In Turban et al (2022) wanted to look at whether being “transgender or gender diverse” (TGD) was due to social contagion. In particular, they wanted to look at whether, as the ROGD hypothesis claims, this affected young female-to-male transgender people (“assigned female at birth” or AFAB) more than young male-to-female transgender people (“assigned male at birth” or AMAB). To do this they looked at the AMAB:AFAB ratio among United States TGD adolescents using the 91,937 adolescents in 2017 and 105,437 adolescents in 2019 through the Youth Risk Behavior Survey across 16 states. They found that in 2017, 2161 (2.4%) participants identified as TGD, with an AMAB:AFAB ratio of 1.5:1. In 2019, 1640 (1.6%) participants identified as TGD, with an AMAB:AFAB ratio of 1.2:1. Rates of bullying victimization and suicidality were higher among TGD youth when compared with their cisgender peers. They concluded that the sex assigned at birth ratio of TGD adolescents in the United States does not appear to favor AFAB adolescents and should not be used to argue against the provision of gender-affirming medical care for TGD adolescents.
Bauer et al (2021) looked at another postulate of ROGD, which is that identifying as transgender is comorbid, or even caused by, other psychological issues, or by social pressures (online or among friend groups) to identify as transgender. They found that, controlling for age and sex assigned at birth, recent gender knowledge (how long ago the person became aware that they are transgender) was not significantly associated with depressive symptoms, psychological distress, past diagnoses with mental health issues or neurodevelopmental disorders, gender dysphoria symptoms, self-harm, past-year suicide attempt, having gender-supportive online friends, general support from online friends or transgender friends, or gender support from parents. Recent gender knowledge was associated with lower scores on anxiety severity/impairment (b = 3.272; 95% CI 5.172, 1.373), and lower prevalence of marijuana use (prevalence ratio = 0.11; 95% CI 0.02, 0.82), counter to hypothesized directions of effect.
Standards of Care
Regardless of where you stand as far as what treatment should be used for gender dysphoria, you should definitely check out the following for what is considered the standard of care for transgender people (as of 2022)
Standards of Care for the Health of Transgender and Gender Diverse People, Version 8 (2022)
Transgender and Queer People in Science
The following are articles that popped up in my literature search for this post. They are here for your consideration.
Rajkovic et al (2022) sought to understand the perspectives of TGD (transgender and genderdiverse) individuals about trans-associated genetic research (TAGR). Eighteen semi-structured interviews were conducted with members of the TGD community to explore how TGD individuals view TAGR. Through inductive content analysis, five major themes were emergent: (1) TAGR could affect self-perception of identity; (2) TAGR could affect external views of TGD people; (3) TAGR could affect access to gender-affirming services; (4) TAGR could contribute to the pathologization and elimination of TGD identities; and (5) researchers should consult TGD community members and consider ethical concerns before conducting research. Participants highlighted concerns about TAGR being used as a tool for discrimination. Those who identified potential advantages of TAGR gave warning that TAGR would be unlikely to solely have positive effects. It is important for genetic researchers to prioritize the perspectives and concerns of TGD people highlighted in this study. Research about the TGD community needs to include TGD individuals as core members of the research team. Moreover, due to the serious ethical issues outlined in this study, TAGR should be reconsidered altogether.
Casper et al (2022) interviewed students with queer genders to understand the messages about sex, gender, and orientation they encountered in biology and the impact of these messages on them. They found five overarching themes in these interviews. Students described two narratives about sex, gender, and orientation in their biology classes that made biology implicitly exclusionary. These narratives harmed students by impacting their sense of belonging, career preparation, and interest in biology content. However, students employed a range of resilience strategies to resist these harms. Finally, students described the currently unrealized potential for biology and biology courses to validate queer identities by representing the diversity in sex and orientation in biology. We provide teaching suggestions derived from student interviews for making biology more queer-inclusive.
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Concluding Remarks
What is sex besides biochemistry? Besides chromosomes? Biology is dictated by chemicals and those chemicals can be administered exogenously. Anatomy can be surgically altered. With gene editing systems like CRISPR/Cas9, it is even theoretically possible to alter someone at the genetic level. Do these people still contain some essence of their former sex? None of this is to say how gender dysphoria ought to be treated medically/therapeutically, but there is compelling evidence that it is a real phenomenon and that it may have a significant biological/neurological component.
The logical next step for this post would be to discuss probably the two most controversial issues surrounding transgender people: (1) whether or not children can reliably identify as transgender and what parents, doctors, therapists, and lawmakers ought to do about this; and (2) whether transgender athletes, primarily MtF transgender athletes, have an advantage over their opponents in sports and whether they should be allowed to compete in leagues that align with their gender identity as opposed to their natal sex. Both of these are hot-button issues, so in this post I am going to punt on those topics. Perhaps I will make separate posts for them in the future, but suffice to say that for (1) I understand the arguments on both sides, though I lean more towards a policy of caution than affirmation only; but for (2) I think it’s fairly clear that MtF transgender women have a distinct advantage over cisgender women in most sports, on account of having developed with high levels of testosterone (essentially having steroids for a significant portion of their life), and any discussion about whether or not they should be permitted in women’s leagues needs to begin from there.
Edit from 4/29/2023: the following video is a great discussion on the topics covered in this post