Title: Transgender people: health at the margins of society

Authors: Sam Winter, Milton Diamond, Jamison Green, Dan Karasic, Terry Reed, Stephen Whittle, Kevan Wylie

Published in: The Lancet (published online June 17, 2016)

This is the first in a series of three papers about the health of transgender people.

---

In this paper we examine the social and legal conditions in which many transgender people (often called trans people) live, and the medical perspectives that frame the provision of health care for transgender people across much of the world. Modern research shows much higher numbers of transgender people than were apparent in earlier clinic-based studies, as well as biological factors associated with gender incongruence. We examine research showing that many transgender people live on the margins of society, facing stigma, discrimination, exclusion, violence, and poor health. They often experience difficulties accessing appropriate health care, whether specific to their gender needs or more general in nature. Some governments are taking steps to address human rights issues and provide better legal protection for transgender people, but this action is by no means universal. The mental illness perspective that currently frames health-care provision for transgender people across much of the world is under scrutiny. The WHO diagnostic manual may soon abandon its current classification of transgender people as mentally disordered. Debate exists as to whether there should be a diagnosis of any sort for transgender children below the age of puberty.

Introduction

Transgender people (often called trans people) experience a degree of gender incongruence;¹ that is, a discordance between their personal sense of their own gender (their gender identity) and the sex assigned to them at birth.² Panel 1 defines some key terms related to gender identity. The terms gender identity and gender incongruence refer to a person’s own experience of who they are, and are not the same as sexual orientation, which is about to whom a person is attracted. A transgender man may be attracted to women (including, perhaps, transgender women), in which case he may identify as a heterosexual transgender man. Alternatively, he may be attracted to men (including, perhaps, transgender men), in which case his sexual identity may be as a homosexual or gay man. Furthermore, being transgender is not the same as being intersex. Intersex people develop atypically in regard to some or all aspects of their biological sex, whereas transgender people identify in a way that does not match their assigned sex (panel 2). In preparing this article we accessed academic papers and documentation published by international agencies, governments and associated institutions, and community-based organisations. We searched various databases, including Google and Google Scholar databases. We also used relevant list serves and journal email alerts to ensure that up-to-date documentation was included. The peer review process, which proceeded by way of several steps, included a consultation meeting in Beijing in November, 2013, attended by, among others, transgender community leaders from several countries.

Gender-affirming health care

Transgender people may seek health-care services for reasons related to their gender incongruence (and accompanying dysphoria). They may seek information and counselling support to help explore identity issues, or to consider difficult decisions about gender transition, and implications for family relationships, employment, and broader social stigma. Children and youth with gender issues, as well as their parents and teachers, may need support and information too.

Young adolescents going through puberty may seek gender-affirming health care involving gonadotropin-releasing hormone analogues (also called hormonal puberty blocking agents or puberty suppressants). Older adolescents and adults may seek masculinising or feminising (“cross-sex”) hormones or surgery, or a range of other services. Such health care is sometimes popularly described as sex or gender reassignment,² or as gender-confirming⁷ or gender-affirming health care.⁸ Outcomes for gender-affirming health care are generally very good, whether the treatment is evaluated as a whole,^9,10 or the effects of hormones alone are considered.^11,12 Outcomes are positive when gender-affirming health care is delivered in adolescence.¹³

Transgender people may seek medical services beyond gender-affirming healthcare. Some will have special sexual and reproductive health-care needs; for example, those associated with gamete storage or care of a surgically constructed vagina. Some may have more general healthcare needs linked to the use of hormones and silicone injections, and diseases associated with birth anatomy (for example, prostate cancer in a transgender woman). Given the probable size of the transgender population, and the range of health-care needs, it is important that primary health-care providers and others be trained in transgender health care, including protocols for referral to specialists where available.

The size of the transgender population

We do not know how many transgender people there are, or how many experience a need for health care, which poses a problem for health-care planners. The first task for the researcher in this area is to decide whom to count, and by what means. Transgender people are a very diverse group. Some live with their gender incongruence, but decide not to transition. Some make a social transition only, without accessing any gender-affirming health care. Some buy hormones from non-medical providers (or on the internet), or visit their local doctors rather than attending specialised clinics. In many parts of the world, stigma discourages transgender people from making their transgender status known to others or accessing health care of any sort. These and other considerations present challenges to the researcher attempting to ascertain the size of the transgender population.

Faced with these difficulties, researchers have tended to focus on the most easily counted subgroup: those who seek gender-affirming health care at specialist clinics (appendix). Clinic-based data are important for the planning of clinic-based services. However, such numbers grossly underestimate the size of the broader population of transgender people who cannot or do not access clinics, and tell us little about the much larger numbers who may benefit from information and counselling services. More direct methods for estimating population sizes, in which samples from the general population are questioned about their identity, generate estimates ranging from 0·5% to 1·3% for birth-assigned males, and from 0·4% to 1·2% for birth-assigned females (table). If one of the lower estimates in the table, the 0.5% reported as an overall mean for birth-assigned males and females,¹⁵ is extrapolated to a global population of 5.1 billion people aged 15 years and older (US Census Bureau, estimates for mid-2011) we arrive at a figure of around 25 million transgender people worldwide. This gives some idea of the potential worldwide (and currently largely unmet) need for transgender health care. The appendix shows more information about the studies cited in the table, as well as specific country population estimates.

Biological correlations in the development of gender dysphoria

A growing body of scientific evidence is now available to inform debate on the extent to which biological factors (especially hormonal and genetic), rather than factors such as parenting or social environment, contribute to the development of gender identity. Putative contributing factors that are not biological are not within the scope of this section. However, gender outcomes are probably influenced by interactions between underlying biology and cultural norms and mores, which generate social pressures on children (including from parents) to conform to behaviours typically associated with the sex assigned at birth. Despite these pressures, gender variant children identify in a way that is incongruent with their birth-assigned sex,¹⁹ and which they may express in behaviours that contravene the norms of their culture. To date, research has established no clear correlations between parenting and gender incongruence.^20,21

In circumstances where infants have been born with ambiguous genitalia, neither genital surgery intended to “correct” the sex anatomy, nor parental upbringing in a social role consistent with that anatomy, guarantees that the child develops a gender identity congruent with the one to which he or she has been surgically and socially assigned. Similarly, when male infants have been surgically assigned to a female anatomy after accidental damage to the penis, it is impossible to guarantee that the children will grow up identifying as girls. These findings indicate that early brain development seems to have an indelible effect on gender identity that is resistant to normative social pressures^22–27 and that may result from prenatal sex hormones,²⁸ direct genetic effects,²⁹ or both.

Biological influences are evident in several other research findings. Two studies have reported the presence in transgender women of repeat polymorphisms in the gene coding for the androgen receptor, suggesting that these individuals have an atypical response to testosterone.^30,31 Other research studies report that some chromosome anomalies in people with a male phenotype (such as XXY, XYY, and mosaicism) are associated with a raised incidence of individuals who identify as women.^32,33 Additionally, in an XY fetus, low androgen levels associated with medication taken by the pregnant mother are associated with a raised incidence of gender dysphoria.³⁴

In another area of research, studies of family co-occurrence of gender dysphoria indicate a genetic link in a subset of transgender individuals.³⁵ Studies of twins in which one of the pair has transitioned show that monozygotic twins have a significantly higher likelihood of concordance for transition than do dizygotic twins. In one study, 33% of male monozygotic twin pairs (where at least one twin had transitioned) were concordant for transition to live as women, including two pairs of twins who were reared apart from birth. Concordance for transition was 23% among female monozygotic twins where one twin had transitioned to live as a man, and this included one pair of twins who were raised apart. By contrast, concordance for transition among male or female dizygotic twins was very low.¹⁹

Studies of cerebral lateralisation of neural pathways associated with listening ability reveal differences between male and female brains in the cisgender population (persons who identify in a way that is consistent with their assigned sex). A study of click-evoked oto-acoustic emissions in untreated children and adolescents experiencing gender incongruence (24 assigned male at birth, identifying as girls), demonstrated responses that were more in agreement with those of 62 cisgender girl controls than with those of 65 cisgender boys.³⁶ The findings did not support the hypothesis that increased prenatal exposure to androgens had an opposite effect, in relation to oto-acoustic emissions, on gender incongruent young people assigned female at birth. However, in the case of the gender incongruent birth-assigned male, the authors postulate a role for atypically low testosterone levels during a crucial period of sex differentiation of the brain.

Similarly, a study of dichotic listening in transgender women showed that their lateralisation resembles that of cisgender women rather than that of cisgender men.³⁷ The cohort of transgender men and women involved in this research also showed a markedly raised prevalence of non-right-handedness compared with the cisgender population; this finding replicates those of previous studies, and reinforces the evidence of correlations between gender incongruence and atypical brain development.^38,39

In addition, drawing on what is known about sex differences in sensitivity to specific odours, research has shown sensitivity patterns in transgender women that reflect their gender identity, rather than their birth-assigned sex, suggesting that they have sex-atypical physiological responses in specific hypothalamic circuits.⁴⁰

Finally, post-mortem studies of small numbers of transgender individuals, two of which focused on the central subdivision of the bed-nucleus of the stria terminalis, and one on the uncinate nucleus, suggest neural differentiation discordant with genital and gonadal characteristics at birth, and similar to that of cisgender individuals of the same gender identity.^41–44 Although not all studies of the brains of transgender people have revealed cross-sex characteristics,⁴⁵ a study based on scans of the white matter in the brains of transgender men who had not yet undergone hormone treatment indicated that their neural patterns were masculinised and closer to those of birth-assigned males than to those of birth-assigned females.⁴⁶ Scans in untreated transgender women showed the patterns to be feminised and substantially different from those of birth-assigned male and female controls.⁴⁷

Taken together, this research provides compelling evidence that the neurobiology of the brain is important in predisposing an individual to an incongruent gender identity. However, people experiencing gender incongruence, including those who are gender dysphoric, might have one, more than one, or none of these markers. Therefore, these indicators cannot be used diagnostically. The only valid route to understanding a person’s gender identity is to listen to them. Whatever our scientific understandings, the needs of transgender people should be met on the basis of universally recognised human rights. It is to those rights, and their relationship to transgender people’s health and wellbeing, that we now turn.

Rights and health

There remain places (for example, the Caribbean and much of Africa and the Middle East) for which little or no information is available about transgender people, their lived experiences, and their health needs. Nevertheless, across much of the world, transgender people experience stigma on a daily basis, being viewed by others in society as sexually deviant, morally corrupt, unnatural, or mentally disordered.⁴⁸ They often experience what is called “minority stress”, leading to poor health and wellbeing.⁴⁹

Together the available reports indicate discrimination and abuse perpetrated by individuals, groups, organisations, and in broader society (appendix). Young transgender people often face intolerance at home or school, and drop out of education or leave home (or indeed are told to leave). Identity documentation carried by transgender adults is often incongruent with their gender identity and reveals their transgender status. Transgender people encounter workplace discrimination that often results in unemployment or underemployment. They drift towards poverty, especially if they dropped out of education early or left home and are therefore unable to draw on social and financial support. Transgender people can encounter problems accessing housing, basic goods and services, and even spaces that are otherwise public. Living on the margins of society, often excluded from opportunities available to their fellow citizens, and with health and wellbeing compromised, many are drawn into situations and patterns of behaviour involving unsafe sexual practices and substance abuse that leave them at risk of further ill health and wellbeing. Some engage in intentional self-harm.

Excluded from much of the workplace, transgender people (notably transgender women) often enter a narrow range of occupations. Many become involved in sex work,⁵⁰ often in conditions that put the individuals at risk of acquiring sexually transmitted infections.⁵¹ A review of research into HIV prevalence among transgender populations worldwide has shown a prevalence 49 times greater than the background rate (appendix).⁵² Transgender people across much of the world encounter harassment and abuse, often at the hands of law enforcement agencies, and on the basis of laws aimed at enforcing public decency or combating cross-dressing and so-called impersonation of the other sex. When arrested and detained transgender people are often placed in gender-inappropriate facilities that put them at further risk of assault.

Many transgender people live with the constant threat of violence. International research documented a total of 2115 killings of transgender people between January, 2008, and April, 2016.⁵³ Many more killings likely go unreported or are misreported as murders of gay and lesbian people. Non-lethal violence against transgender people is widespread. A national US study indicated that 35% of individuals who expressed their gender identity or gender non-conformity at any time between kindergarten and grade 12 (around ages 5 to 18 years) fell victim to physical violence, and 12% become victims of sexual violence.⁵⁴ In the same study, 7% of transgender adults had been physically assaulted at work, and 6% sexually assaulted.

All these experiences affect the emotional health and wellbeing of transgender people. 41% of the participants in the US study reported attempting suicide, compared with 1·6% of the general population. A national Australian study found that 56% of transgender people had been diagnosed with depression at some point in their lives, four times the rate for the general population. 38% had been diagnosed with anxiety, around 50% higher than the background rate.⁵⁵ Risk factors for suicidal behaviour in the transgender population include discrimination,⁵⁶ verbal and physical abuse,⁵⁷ being recognised as transgender,⁵⁸ internalised transphobia,⁵⁹ poor educational qualifications, unemployment and poverty,⁵⁸ and absence of social support.^49,60,61

Worldwide, the research presents what has been described as a slope leading from stigma to sickness (figure).⁶² Many transgender people experience additional stigma; for example when they are (or are perceived to be) poor, involved in sex work, or HIV positive.⁶² US research shows that race and ethnicity is another source of stigma, with transgender people of colour experiencing the most severe discrimination, poverty, and lack of access to basic health care and social services in that country.54 An Australian study of transgender people from the indigenous community had similar findings.⁶³

Social, hormonal, and surgical transition are associated with improvements in emotional health and wellbeing, and are now widely viewed as effective treatments for gender dysphoria.² However, across much of the world, gender-affirming health care is unavailable, or is difficult to access or afford. Mental health-care services, which are scarce in many countries,⁶⁴ can be especially hard to access. Transgender people can remain at increased risk of death, including death by suicide, even after transition.⁶⁵

Even when transgender people can access gender-affirming health care, they often find that providers lack skills in the area and discriminate against transgender people in a way that mirrors broader society. Providers are often seen as unsupportive or hostile to transgender people’s health-care needs, or as providing inadequate care.^66–69 For these reasons, transgender people often make use of parallel providers (for example, practitioners known as “silicone pumpers”, who often come from the transgender community, are medically unqualified, and use sub-standard equipment and materials) and engage in self-administered (and unmonitored) hormone treatment,^70–72 sometimes as part of social gatherings.⁷³ Those who seek surgery and can afford it often choose to travel to other countries to get it.

Sexual health care for transgender people is often inadequate, with many planners, funders, and providers having failed in the past to address the needs of transgender women as a population distinct from men who have sex with men. Neglect of the needs of transgender women has contributed to the disproportionate risk of HIV in this group, and widespread failure to develop effective interventions to address this global problem.^74,75 Transgender men’s needs for sexual health care have been ignored almost entirely. Finally, many health-care providers remain poorly prepared to address trans-related general health-care needs (for example for a transgender man who is pregnant, or for a transgender woman who has prostate cancer). In summary, transgender people’s daily experience across much of the world is one in which rights are denied. A key human rights document, the Yogyakarta principles, has detailed the ways in which existing human rights law applies to gender identity, as well as to sexual orientation.⁷⁶ The document draws on instruments of international law to which many states are signatories; for example, the International Covenant on Civil and Political Rights, the International Covenant on Economic, Social and Cultural Rights, the Convention on the Rights of the Child, the Convention on the Elimination of all Forms of Discrimination Against Women, and the Convention Against Torture and Cruel, Inhuman and Degrading Treatment or Punishment.

In the context of such documents, it is clear that many transgender people are routinely denied their rights to equality and non-discrimination, to recognition before the law, to security of the person, to privacy, to treatment with humanity while in detention, to work, to an adequate standard of living, to adequate housing, to education, to found a family, to the highest attainable standard of health, to protection from medical abuses, to freedom of expression, to freedom of movement, and to freedom from cruel, inhuman, or degrading treatment or punishment.

Many of the challenges faced by transgender people are exacerbated by laws and policies that deny them gender recognition. Identity documents undermine privacy when they reveal a transgender person’s birth-assigned sex, and can worsen the risk of discrimination in education, the workplace, housing, health care, and elsewhere. Laws and policies that impose onerous preconditions for gender recognition commonly violate a range of rights. The effect of difficulties related to gender recognition on the lives of transgender people is extensively documented.^77–80 Authoritative voices in the fields of health and rights have highlighted the need to remove unreasonable barriers to gender recognition.^77,78 Preconditions mandating sterilisation or genital reconstruction have been the subject of especially strong criticism,^77,81–83 and in recent years many countries have abandoned surgical and other medical requirements. Some no longer link gender recognition to health care at all, having discarded requirements even for a diagnosis. The World Professional Association for Transgender Health (WPATH) supports such developments and has advocated in recent policy statements for the right to identity recognition without social or medical preconditions of any kind (panel 3).⁸⁹

Transgender people: mentally disordered?

Transgender peoples’ access to health care is complicated by the fact that, at present, their experiences are conceptualised as a mental disorder. The view that transgender people are mentally disordered has long been criticised by transgender people, clinicians, and researchers, with arguments focused on the way that such diagnoses psychopathologise diversity (turn difference into mental disorder), with consequences for health and wellbeing. In response, in 2010, WPATH issued a public statement, in which it “strongly urges the de-psychopathologisation of gender variance worldwide.”⁹⁰

Several arguments (of which only a few can be summarised here) have been made for the removal of transgender diagnoses from the list of mental disorders. First, the view that transgender people are mentally disordered is an accident of history rather than one founded on scientific evidence.⁹¹ Mental health treatments aimed at changing a person’s gender identity and expression to make them more congruent with sex assigned at birth (so-called reparative, reorientation, and conversion therapies) are considered unsuccessful and unethical.² Instead, as discussed in the second paper in this Series,⁹² health care that aims to help transgender people live in their  affirmed gender is widely regarded as the most effective in ensuring their health and wellbeing.

Second, mental disorders are highly stigmatised conditions across much of the world, and perhaps especially in low-income and middle-income countries.⁹³ The psychopathologisation of gender incongruence confers a stigma that is particularly pernicious, since it is the identities of transgender people that are pathologised. The view of transgender people as mentally disordered prompts or reinforces discriminatory behaviour, including in the workplace. It may also undermine the willingness of health-care providers to trust transgender people’s ability to make decisions about their own care, including that related to hormones and surgery.

Third, psychopathologisation can undermine transgender people’s claims for recognition in their  affirmed gender. The view that a transgender woman’s identity is a mentally disordered one implies that she is a mentally disordered man. The transgender man is, by implication, likely to be seen as a mentally disordered woman. The view can therefore encourage (or at least provide a convenient rationale for) the questionable gender reparative therapies mentioned earlier, rather than gender-affirming health care that supports greater wellbeing.

The two key publishers of diagnostic manuals have each responded to these critiques, albeit in different ways. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) contains a diagnosis called “gender dysphoria”.⁹⁴ The diagnosis focuses less on an individual’s gender incongruence, and more on associated distress, than was the case in earlier editions of DSM (for example, “gender identity disorder” in DSM-IV). These changes were largely in line with advice offered by WPATH.⁹⁵ Although these changes are welcomed by many clinicians and researchers (and by transgender people themselves) it remains the case that the distress that prompts the DSM-5 diagnosis of gender dysphoria is distress about gender incongruence, and the diagnosis remains one of mental disorder.

More transformative developments in diagnostic thinking are underway at WHO, which publishes the International Statistical Classification of Diseases and Related Health Problems (ICD). The current revision, ICD-10, is freely available on the web, has been translated into 41 languages, and worldwide is the classification system most often used by psychiatrists working with patients.⁹⁶ The key diagnoses for transgender people in ICD-10 are currently transsexualism (for adolescents and adults) and gender identity disorder of childhood (for children below the age of puberty), both mentioned in chapter 5, entitled “Mental and behavioural disorders”, in a section called “Disorders of adult personality”.⁹⁷ ICD is being revised, with approval of ICD-11 currently expected in 2018. A WHO Working Group on Sexual Disorders and Sexual Health has proposed to reformulate these diagnoses as gender incongruence, with one diagnosis for adolescents and adults, and one for children below the age of puberty. Importantly, the group has proposed that these diagnoses be removed from the chapter on mental and behavioural disorders, and relocated to one called “Conditions related to sexual health”.⁹¹ If these proposals are approved and incorporated into ICD-11, the move will be a truly historic one for transgender people and those involved in their health care (see appendix). However, the group’s proposal for a diagnosis of “gender incongruence of childhood” (GIC), to be used with children under the age of puberty, has generated substantial criticism (panel 4).

Conclusions

We have noted that transgender people have a gender identity that is not congruent with their assigned sex, and that they may experience discomfort or distress where opportunities to express that identity are denied them or where that identity is not respected. Some transgender people seek gender-affirming healthcare aimed at bodily changes to match their gender identity. Gender incongruence is more common than clinic-based studies suggest, and may be linked to biological factors. We have seen that transgender people often encounter stigma, discrimination, and abuse in their lives. They are edged towards the margins of society, where they get involved in risky situations and risky behaviours. Globally they bear a heavy burden of violence, as well as of HIV risk. Some governments are taking steps to address human rights violations against transgender people. Across much of the world, transgender people have difficulty accessing or affording good quality health care, whether specific to their gender needs or more general in nature. The view of transgender people as mentally disordered has potentially negative impact on transgender people’s health and wellbeing. WHO proposals to abandon the psychopathological model are welcomed by many researchers, clinicians, and transgender communities. These reforms promise empowerment for transgender people, enabling them to exercise greater autonomy in their lives. The question as to whether there should be a diagnosis for children below the age of puberty is currently the subject of debate.

Contributors

S Winter took the lead in writing and revising the manuscript, with all authors contributing to the literature search and writing.

Declaration of interests

We declare no competing interests. S Winter, JG, DK, S Whittle, and KW are or have been members of the WPATH board of directors. JG is, and S Whittle has been, president of WPATH. S Winter, JG, DK, S Whittle and KW were among the co-authors for the WPATH standards of care (version 7). S Winter was a member of the WHO Working Group on Sexual Disorders and Sexual Health, as well as of the GATE Civil Society Experts Group.

Acknowledgments

The United Nations Development Programme funded a developmental review meeting for this Series.

 

REFERENCES

1 Drescher J, Cohen-Kettenis P, Winter S. Minding the body: situating gender identity diagnoses in the ICD-11. Int Rev Psychiatry 2012; 24: 568–77.

2 World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people (7th edn). Minneapolis: WPATH, 2012.

3 Diamond M. Human intersexuality: difference or disorder? Arch Sex Behav 2009; 38: 172.

4 Greenfield C. Should we “fix” intersex children? The Atlantic (Washington, DC), July 8, 2014. http://www.theatlantic.com/health/archive/2014/07/should-we-fix-intersex-children/373536.

5 Liao LM, Audi L, Magritte E, Meyer-Bahlburg HF, Quigley CA. Determinant factors of gender identity: a commentary. J Pediatr Urol 2012; 8: 597–601.

6 Government of Malta. Gender identity, gender expression and sex characteristics act. 2015. http://justiceservices.gov.mt/DownloadDocument.aspx?app=lom&itemid=12312&l=1 (accessed Nov 18, 2015).

7 Jim Collins Foundation. Gender-confirming surgery grants awarded by Jim Collins Foundation. http://jimcollinsfoundation.org/gender-confirming-surgery-grants-awarded-by-jim-collins-foundation (accessed Oct 1, 2013).

8 Global Action for Trans* Equality. (2011). It’s time for reform: trans* health issues in the International Classifications of Diseases. A report on the GATE Experts Meeting, the Hague November 16–18 2011. https://globaltransaction.files.wordpress.com/2012/05/its-time-for-reform.pdf (accessed Oct 19, 2013).

9 Murad M, Elamin M, Garcia M, et al. Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes. Clin Endocrinol 2010; 72: 214–31.

10 Dhejne C, Oberg K, Arver S, Landen M. An analysis of all applications for sex reassignment surgery in Sweden, 1960–2010: prevalence, incidence, and regrets. Arch Sex Behav 2014; 43: 1535–45.

11 Keo-Meier C, Herman L, Reisner S, Pardo S, Sharp C, Babcock J. Testosterone treatment and MMPI–2 improvement in transgender men: a prospective controlled study. J Consult Clin Psychol 2015; 83: 143–56.

12 Gorin-Lazard A, Baumstarck K, Boyer L, et al. Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study. J Sex Med 2012; 9: 531–41.

13 De Vries A, McGuire J, Steensma T, Wagenaar E, Doreleijers T, Cohen-Kettenis P. Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics 2014; published online Sept 8. doi:10.1542/peds.2013-2958.

14 Conron KJ, Scott G, Stowell GS, Landers SJ. Transgender health in Massachusetts: Results from a household probability sample of adults. Am J Public Health 2012; 102: 118–22.

15 Glen F, Hurrell K. Technical note: measuring gender identity. Manchester: Equality and Human Rights Commission, 2012.

16 Clark T, Lucassen M, Bullen M, et al. The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth’12). J Adolesc Health 2014; 55: 93–99.

17 Kuyper L, Wijsen C. Gender identities and gender dysphoria in the Netherlands. Arch Sex Behav 2014; 43: 377–85.

18 Van Caenegem E, Wierckx K, Elaut E, et al. Prevalence of gender nonconformity in Flanders, Belgium. Arch Sex Behav 2015; 44: 1281–87.

19 Diamond M. Transsexuality among twins. Int J Transgend 2013; 14: 24–38.

20 Stevens M, Golombok S, Beveridge M. Does father absence influence children’s gender development? Findings from a general population study of pre-school children. Parent Sci Pract 2002; 2: 47–60.

21 Zucker KJ, Bradley SJ. Gender identity disorder and psychosexual problems in children and adolescents. New York: Guilford Press, 1995.

22 Diamond M, Sigmundson HK. Sex reassignment at birth. Long term review and clinical implications. Arch Pediatr Adolesc Med 1997; 151: 298–304.

23 Kipnis K, Diamond M. Pediatric ethics and the surgical assignment of sex. J Clin Ethics 1998; 9: 398–410.

24 Ochoa B. Trauma of the external genitalia in children: amputation of the penis and emasculation. J Urol 1996; 160: 1116–19.

25 Bradley SJ, Oliver GD, Chernick AB, Zucker KJ. Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months, and a psychosexual follow-up in young adulthood. Paediatrics 1998; 102: e9.

26 Hines M. Brain gender. New York: Oxford University Press, 2004.

27 Dessens AB, Froukje ME, Slijper FME, Stenver LS, Drop SLS. Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav 2005; 34: 389397.

28 Bao A-M, Swaab DF. Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders. Front Neuroendocrinol 2011; 32: 214–26.

29 Dewing P, Shi T, Horvath S, Vilain E. Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Mol Brain Res 2003; 118: 82–90.

30 Hare L, Bernard P, Sanchez FJ, et al. Androgen receptor repeat length polymorphism associated with male to female transsexualism. Biol Psychiatry 2008; 65: 93–96.

31 Henningsson S, Westberg L, Nilsson S, et al. Sex steroid related genes and male to female transsexualism. Psychoneuroendocrinol 2005; 30: 657–64.

32 Snaith RP, Penhale S, Horsfield P. Male-to-female transsexual with XYY karyotype. Lancet 1991; 337: 557–58.

33 Diamond M, Watson LA. Androgen insensitivity syndrome and Klinefelter’s syndrome: sex and gender considerations. Child Adolesc Psychiatr Clin N Am 2004; 13: 623–40.

34 Dessens AB, Cohen-Kettenis PT, Mellenbergh GJ, van der Poll NE, Koppe JG, Boer K. Prenatal exposure to anticonvulsants and psychosexual development. Arch Sex Behav 1999; 28: 31–44.

35 Green R. Family co-occurrence of gender dysphoria: ten sibling or parent-child pairs. Arch Sex Behav 2000; 29: 499–507.

36 Burke S, Menks W, Cohen-Kettenis P, Klink D, Bakker J. Click-evoked otoacoustic emissions in children and adolescents with gender identity disorder. Arch Sex Behav 2014; 43: 1515–23.

37 Govier E, Diamond M, Wolowiec T, Slade C. Dichotic listening, handedness, brain organisation and transsexuality. Int J Transgender 2010; 12: 144–54.

38 Green R, Young R. Hand preference, sexual preference, and transsexualism. Arch Sex Behav 2001; 30: 565–74.

39 Zucker KJ, Beaulieu N, Bradley SJ, Grimshaw GM, Wilcox A. Handedness in boys with gender identity disorder. J Clin Child Psychol Psychiatr 2001; 42: 767–76.

40 Burglund H, Lindstrom P, Dhejne-Helmy C, Savic I. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex 2008; 18: 1900–08.

41 Luders E, Sánchez FJ, Gaser CW, et al. Regional gray matter variation in male-to-female transsexualism. Neuroimage 2009; 46: 904–07.

42 Zhou J-N, Swaab DF, Gooren LJ, Hofman MA. A sex difference in the human brain and its relation to transsexuality. Nature 1995; 378: 68–70.

43 Kruijver FPM, Zhou J-N, Pool CW, Hofman MA, Gooren LJ, Swaab DF. Male to female transsexuals have female neuron numbers in a limbic nucleus. J Endocrinol Metabol 2000; 85: 2034–41.

44 Garcia-Falgueras A, Swaab DF. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain 2008; 131: 3132–46.

45 Savic I, Arver S. Sex dimorphism of the brain in male-to-female transsexuals. Cereb Cortex 2011; 21: 2525–33.

46 Rametti G, Carrillo B, Gómez-Gil E, et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J Psychiatr Res 2011; 45: 199–204.

47 Rametti G, Carrillo B, Gómez-Gil E, et al. The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. J Psychiatr Res 2011; 45: 949–54.

48 Winter S, Chalungsooth P, Teh YK, et al. Transpeople, transprejudice and pathologization: a seven-country factor analytic study. Int J Sex Health 2009; 21: 96–118.

49 Bockting WO, Miner MH, Swinburne Romine RE, Hamilton A, Coleman E. Stigma, mental health, and resilience in an online sample of the US transgender population. Am J Public Health 2013; 103: 943–51.

50 Nadal K, Davidoff K, Fujie-Doe W. Transgender women and the sex work industry: roots in systemic, institutional, and interpersonal discrimination. J Trauma Dissociation 2015; 15: 169–83.

51 Poteat T, Wirtz A, Radix A, et al. HIV risk and preventive interventions in transgender women sex workers. Lancet 2015; 385: 274–86.

52 Baral S, Poteat T, Strömdahl S, Wirtz A, Guadamuz T, Beyrer C. Worldwide burden of HIV in transgender women: a systematic review and meta-analysis. Lancet Infect Dis 2012; 13: 214–22.

53 Transgender Europe. IDAHOT 2016: Trans Murder Monitoring update. 2016. http://transrespect.org/en/idahot-2016-tmm-update (accessed May 24, 2016).

54 Grant J, Mottet L, Tanis J, Harrison J, Herman J, Keisling M. Injustice at every turn: a report of the National Transgender Discrimination Survey. Washington DC: National Centre for Transgender Equality and National Gay and Lesbian Task Force, 2011: 3.

55 Hyde Z, Doherty M, Tilley PJM, McCaul KA, Rooney R, Jancey J. The First Australian National Trans Mental Health Study: summary of results. Perth: School of Public Health, Curtin University, 2014.

56 Clements-Nolle K, Marx R, Katz M. Attempted suicide among transgender persons. J Homosex 2006; 51: 53–69.

57 Nuttbrock L, Hwahng S, Bockting W, et al. Psychiatric impact of gender-related abuse across the life course of male-to-female transgender persons. J Sex Res 2010; 47: 12–23.

58 Haas A, Rodgers P, Herman J. Suicide attempts among transgender and gender non-conforming adults: findings of the National Transgender Discrimination Survey. Los Angeles: UCLA, Williams Institute and American Foundation for Suicide Prevention, 2014.

59 Perez-Brumer A, Hatzenbuehler M, Oldenburg C, Bockting W. Individual-and structural-level risk factors for suicide attempts among transgender adults. Behav Med 2015; 41: 164–71.

60 Yadegarfard M, Meinhold-Bergmann M, Ho R. Family rejection, social isolation, and loneliness as predictors of negative health outcomes (depression, suicidal ideation, and sexual risk behavior) among Thai male-to-female transgender adolescents. J LGBT Youth 2014; 11: 347–63.

61 Bauer G, Scheim A, Pyne J, Travers R, Hammond R. Intervenable factors associated with suicide risk in transgender persons: a respondent driven sampling study in Ontario, Canada. BMC Public Health 2015; 15: 525.

62 Winter S. Lost in transition: transgender people, rights and HIV vulnerability in the Asia-Pacific region. Bangkok: United Nations Development Programme, 2012.

63 Kerry S. Sistergirls/brotherboys: the status of indigenous transgender Australians. Int J Transgend 2014; 15: 173–86.

64 Kakuma R, Minas H, van Ginneken N, et al. Human resources for mental health care: current situation and strategies for action. Lancet 2011; 378: 1654–63.

65 Dhejne C, Lichtenstein P, Boman M, Johansson AL, Långström N, Landén M. Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PLoS One 2011; 6: e16885.

66 Riggs D, Due C. Gender identity Australia: the healthcare experiences of people whose gender identity differs from that expected of their natally assigned sex. Adelaide: Flinders University, 2013.

67 Whittle S, Turner L, Combs R, Rhodes S. EuroStudy: legal survey and focus on the transgender experience of health care. Brussels: International Lesbian and Gay Association Europe and Transgender Europe, 2008.

68 McNeil J, Bailey L, Ellis S, Regan M. Speaking from the margins: trans mental health and well-being in Ireland. Dublin: Transgender Equality Network Ireland, 2014.

69 WHO Western Pacific Region. Regional assessment of HIV, STI and other health needs of transgender people in Asia and the Pacific. Manila: WHO Western Pacific Regional Office, 2013.

70 Winter S, Doussantousse S. Transpeople, hormones, and health risks in Southeast Asia: a Lao study. Int J Sex Health 2009, 21: 35–48.

71 Gooren L, Sungkaew T, Giltay E. Exploration of functional health, mental well-being and cross-sex hormone use in a sample of Thai male-to-female transgendered persons (kathoeys). Asian J Androl 2013; 15: 280–85.

72 Xavier J, Honnold J, Bradford J. The health, health-related needs, and lifecourse experiences of transgender Virginians. Richmond: Virginia Department of Health, 2007.

73 Poompruek P, Boonmongkon P, Guadamuz T. “For me…it’s a miracle”: injecting beauty among kathoeis in a provincial Thai city. Int J Drug Policy 2014, 25: 798–803.

74 Baral S, Poteat T, Strömdahl S, Wirtz A, Guadamuz T, Beyrer C. Worldwide burden of HIV in transgender women: a systematic review and meta-analysis. Lancet Infect Dis 2012; 13: 214–22.

75 AmFAR. Trans populations and HIV: time to end the neglect. New York: Foundation for AIDS Research, 2014. http://www.amfar.org/issue-brief-trans-populations-and-hiv-time-to-end-the-neglect (accessed Nov 17, 2015).

76 Alston P, Anmeghichean M, Cabral M, et al. Yogyakarta principles: the application of international human rights law in relation to sexual orientation and gender identity. 2007. http://www.yogyakartaprinciples.org (accessed Feb 24, 2014).

77 Amnesty International. The state decides who I am: lack of legal gender recognition for transgender people in Europe. London: Amnesty International, 2014.

78 Balzer C, Hutta JS, Adrian T, Hyndal P. Transrespect versus transphobia worldwide: a comparative review of the human-rights situation of gender-variant/trans people. Berlin: Transgender Europe, 2012

79 Byrne J. Discussion paper: transgender health and human rights. New York: United Nations Development Program, 2013.

80 Byrne J. License to be yourself: laws and advocacy for legal gender recognition of trans people. New York: Open Society Foundations, 2014.

81 UNCHR, UN Women, UNAIDS, UNDP, UNFPA, UNICEF, WHO. Eliminating forced, coercive and otherwise involuntary sterilization: an interagency statement. Geneva: World Health Organisation, 2014.

82 American Medical Association. AMA calls for modernizing birth certificate policies. 2014. http://www.ama-assn.org/ama/pub/news/news/2014/2014-06-09-modernizing-birth-certificatepolicies. page (accessed May 31, 2016).

83 World Medical Assocation. Statement on forced and coerced sterilisation. http://www.wma.net/en/30publications/10policies/s21 (accessed Nov 18, 2015).

84 ILGA-EUROPE. Rainbow map (index). 2015. http://www.ilga-europe.org/sites/default/files/Attachments/side_b-rainbow_eurpe_index_may_2015_no_crops.pdf (accessed May 31, 2016).

85 Transgender Europe. Trans rights Europe 2016 map and index 2016. http://tgeu.org/trans-rights_europe_map_2016 (accessed May 23, 2016).

86 Global Action for Trans* Equality. English translation of Argentina’s gender identity law as approved by the Senate of Argentina on May 8, 2012. 2013. http://globaltransaction.files.wordpress.com/2012/05/argentina-gender-identity-law.pdf (accessed Feb 23, 2014).

87 Kohler R, Recher A, Ehrt J. Legal gender recognition in Europe Toolkit. Berlin: Transgender Europe, 2013.

88 Aristegui I, Romero M, Zalazar V, et al. Transgender people perceptions of the impact of the gender identity law in Argentina. 20th International AIDS Conference, Melbourne, 2014. http://pag.aids2014.org/Abstracts.aspx?SID=1112&AID=7341 (accessed May 23, 2016).

89 World Professional Association for Transgender, Health. Statement on legal recognition of gender identity. 2015. http://www.wpath.org/uploaded_files/140/files/WPATH%20Statement%20on%20Legal%20Recognition%20of %20Gender%20Identity%201-19-15.pdf (accessed March 15, 2015).

90 World Professional Association for Transgender Health. Identity recognition statement. 2010. http://www.wpath.org/uploaded_files/140/files/de-psychopathologisation%205-26-10%20on%20letterhead.pdf (accessed May 25, 2015).

91 Drescher J, Cohen-Kettenis P, Winter S. Minding the body: situating gender identity diagnoses in the ICD-11. Int Rev Psychiatry 2012; 24: 568–77.

92 Wylie K, Knudson G, Khan SI, Baral S, Bonierbale M, Watanyusakul S. Serving transgender people: clinical care considerations and service delivery models in transgender health. Lancet 2016; published online June 17. http://dx.doi.org/10.1016/S0140-6736(16)00682-6.

93 Drew N, Funk M, Tang S, et al. Human rights violations of people with mental and psychosocial disabilities: an unresolved global crisis. Lancet 2011; 378: 1664–75.

94 American Psychiatric Association. Diagnostic and statistical manual of mental disorders: fifth edition. Washington DC: American Psychiatric Association, 2013.

95 Fraser L, Karasic DH, Meyer WJ, Wylie K. Recommendations for revision of the DSM diagnosis of gender identity disorder in adults. Int J Transgender 2010; 12: 80–85.

96 Reed G, Correa JM, Esparza J, Saxena S, Maj M. The WPA-WHO global survey of psychiatrists’ attitudes towards mental disorders classification. World Psychiatry 2011; 10: 118–31.

97 WHO. International statistical classification of diseases and related health problems, 10th revision. Geneva: World Health Organization, 1992.

98 Drescher J, Cohen-Kettenis P, Reed G. Gender incongruence of childhood in the ICD-11: controversies, proposal, and rationale. Lancet Psychiatry 2016; 3: 297–304.

99 American Psychological Association. Guidelines for psychological practice with lesbian, gay, and bisexual clients. Am Psychol 2012; 67: 10–42.

100 Winter S, Riley E, Pickstone-Taylor S, et al. The “Gender Incongruence of Childhood” diagnosis revisited: a statement from clinicians and researchers. 2016. https://docs.google.com/forms/d/1aSlSKqyZi6zC3-gWm320dFRYawDEwlkM8KerkyN3pg4/viewform (accessed 23rd May 2016).

101 Cochran S, Drescher J, Kismodi E, et al. Proposed declassification of disease categories related to sexual orientation in the International Statistical Classification of Diseases and Related Health Problems (ICD-11). Bull World Health Organ 2014; 92: 672–79.

102 Global Action for Trans* Equality Civil Society Expert Working Group. Critique and alternative proposal to the “gender incongruence of childhood” category in ICD-11. Report of working group meeting; Buenos Aires; April 4–6, 2013. http://globaltransaction.files.wordpress.com/2012/03/critique-and-alternative-proposal-to-the-_gender-incongruence-of-childhood_-category-in-icd-11.pdf (accessed Feb 24, 2014).

103 World Professional Association for Transgender Health. Report of the WPATH ICD-11 Consensus Meeting. WPATH, 2013. http:// www.wpath.org/uploaded_files/140/files/ICD%20Meeting%20 Packet-Report-Final-sm.pdf (accessed Feb 23, 2014).

104 World Professional Association for Transgender Health. Results of member survey on gender incongruence of childhood (GIC) diagnosis for ICD-11. 2015. http://www.wpath.org/site_page. cfm?pk_association_webpage_menu=1635&pk_association_webpage=6638 (accessed May 23, 2016).

105 Second Trans* Health, Advocacy and Research Conference. Statement on gender incongruence in childhood. Cape Town, 2014. http://genderdynamix.org.za/%E2%80%8Bcape-town-declaration (accessed Jan 19, 2016).

106 ILGA-Asia Trans* Pre-conference. Statement on gender incongruence in childhood. Taipei, 2015. http://ilga.org/the-ilgaasia-trans-pre-conference-statement-on-gender-incongruence-inchildhood (accessed Jan 19, 2016).

107 European Parliament Committee on Civil Liberties, Justice and Home Affairs. Report on the situation of fundamental rights in the European Union (2013–2104). Rapporteur: Laura Ferrara. http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+REPORT+A8-2015-0230+0+DOC+XML+V0//EN (accessed Nov 18, 2015).