Introduction

Transsexual, transgender, and gender nonconforming individuals have been a part of all cultures historically, yet the emergence of, and advocacy for, transgender individuals in the Western world have become prominent only in recent decades.

The majority of clinical experience related to transgender care is derived from higher-income settings. Therefore local adaptation of clinical care protocols is required, in view of varying cultures and social norms across low- and middle-income countries. Gender roles are culturally stereotyped in most societies where men and women are supposed to participate in masculine and feminine roles specific to their assigned sex at birth.

Deviation from normative gender roles often results in devaluation of social status and experiences of stigma. Although transgender people exist across cultures throughout the world, transgenderism and transsexualism are considered abnormal in most societies, because they transgress the normative sex-gender binary system. Perceptions of transgender people are affected by the profound differences in culture, religion, and history that exist between countries, and presentation and acceptance of gender diversity can vary widely even within regions of the world. For example, the variation in acceptance of gender diversity across Asia is independent of religion, economic level, and even subregion, with some countries having broader acceptance (such as Thailand, Laos, and Indonesia) and other countries (including Malaysia) having less acceptance. Although many transgender people struggle to establish a separate gender category beyond the male-female binary system, only a few countries have acknowledged transgender as a “third” gender. In December of 2007, the Supreme Court of Nepal issued a groundbreaking verdict in favor of gender minorities and recognition of a third gender. In November 2013, two remarkable developments took place in the gender debate and legal and human rights framework: Germany became the first European country to officially recognize a third gender for babies born with ambiguous genitalia, through a new legislation by the country’s constitutional court ; and the Government of Bangladesh officially approved a proposal by the social welfare ministry to identify transgender women (also known as hijra ) within a separate gender category. In April 2014, India’s Supreme Court recognized transgender people as members of a third gender in a landmark ruling. In 2015, the Nepalese authorities decided to issue passports to gender minorities, adding a third gender category.

Although transgender people across cultures are known by various indigenous terms, the increased visibility in many settings of transgender women, compared with transgender men, has resulted in increased social awareness of these women. Transgender women across many settings share some commonalities, such as preferences for feminine attire and body gestures, a sense of community, and, because of their gender incongruence, a status that has traditionally not been socioculturally, religiously, politically, and legally acknowledged. Because of such pervasive nonacceptance, many transgender women seek social or medical transition. Nevertheless, scientific information about transition-related issues is scarce. Access to transition-related health services is often limited, especially in many low- and middle-income countries. Many transgender women seek clinical or surgical procedures, or both, by taking hormones, removal of genitals, or other gender-affirming surgery. For example, hijras in south Asian countries often seek social and psychological fulfillment by partial or complete removal of the male genital organs (castration) by modern or traditional caregivers, and some even seek modern gender affirmation surgery that is unavailable in their home countries. The limited numbers of clinically skilled providers and high costs of medical interventions in most Asian countries have encouraged access to providers who are unskilled in performing medical interventions, causing untoward physical and psychological effects.

Castration for transgender women involves removal of the penis and scrotum without the construction of female genitals. The underlying reasons for seeking castration and gender affirming surgery can go further than relief from physical dysphoria and perceived needs for compatible and socially acceptable sex-gender aligned lifestyles. The meaning of castration can vary—for example, for some hijra, it represents sociocultural restructuring through which they ensure their economic survival by their engagement with the hijra community. Members of this community can earn their living through traditional hijra occupations (known as badhai ), such as collecting money from the market places ( bazar tola ) and blessing newborn babies ( bachcha nachano ). Castration can also enhance their self-esteem, power, and status within and outside of the hijra community; through castration they become “real” hijras who can earn more than noncastrated hijras through badhai and by selling sex.

Not all transgender women go through castration or gender-affirming surgery. Instead, many adopt feminine gestures, clothing, voices, and roles. This type of sociocultural adaptation enables the individual to have the experience of being transgender without any medical or surgical intervention. Those who have undergone castration often report substantial physical side effects, such as urethral strictures, severe infections, and loss of libido. Moreover, social and legal dilemmas exist. For example, some noncastrated hijra believe that medical intervention may reemphasize the dominant binary gender construction that ignores transgender as a separate gender. This is seen as a violation of their basic rights to life and survival.

People whose gender identity does not align with a rigid male/female dichotomy have been ostracized, leading to pervasive stigma and discrimination in all areas of life for transgender people. Normative notions often marginalize transgender people and place them in an abusive sociolegal environment, in which they are sociopolitically, religiously, and economically excluded from the mainstream, which in turn may enhance their risk-taking behaviors. Pathologization of gender and sexual minorities in the Western medical model has often resulted in transgender people being labeled as deviant individuals requiring medical and legal attention. As cross-cultural diversity and fluidity of gender and sexuality have received attention, it is expected that standard care and services for transgender people will become available in most countries within the framework of human rights.

Legislative Changes and Trends

Many countries do not offer legal or administrative measures enabling gender recognition for transgender people. Even in Europe, which is often seen as progressive on these matters, 8 out of 49 states fail to offer any such measures. Worryingly, among the 33 states where measures are available, 17 impose sterilization requirements on those who seek recognition, despite opposition from authoritative voices in health and human rights, who view such requirements as a form of coercive medicine. Some states are moving towards less intrusive legal arrangements for gender recognition. In Europe, 10 states (Austria, Belarus, Denmark, Germany, Ireland, Malta, Moldova, the Netherlands, Portugal, and the United Kingdom) have dispensed with requirements for any type of medical intervention. Steps towards less onerous legal requirements have also taken place in parts of Canada, the United States, Australia, New Zealand, Nepal, India, and Pakistan.

Three European countries—Denmark, Malta, and Ireland—have stopped their medical requirements altogether (even a requirement for a diagnosis), following the lead of Argentina in adopting a so-called declaration model, in which transgender people are able to determine their gender through a simple administrative procedure.

The Argentinian and Maltese laws are particularly progressive. First, they extend legal gender change rights to children and young people. At least two children in Argentina, one of whom was aged 6 years, have availed themselves of this right. Second, these laws explicitly affirm the right of transgender people to appropriate health care. The Maltese law arguably goes the furthest. It contains antidiscrimination provisions offering protection on the grounds of not only gender identity but also gender expression.

There are also provisions that are of particular importance for intersex infants and young children, as they prohibit any medical procedures on the sex characteristics of a minor until that minor can provide informed consent. Several countries are also providing opportunities for transgender people to be recognized outside the gender binary. New Zealand, Australia, Nepal, Pakistan, and India have moved, or are moving, towards such changes.

Community-based organizations continue to fight for gender recognition rights and for removal of onerous requirements for approval. Research on the effect of legislative changes on gender recognition is sparse. Available findings suggest that such changes can positively affect transgender people’s quality of life.

Terminology: Spectrum of Gender Identity and Expression

Epidemiology and Population Trends

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 nonmedical providers (or on the internet), or visit their local doctors rather than attending specialized 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. 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 counseling 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 1.1 ). If one of the lower estimates in the table 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 approximately 25 million transgender people worldwide. This gives some idea of the potential worldwide (and currently largely unmet) need for transgender health care.

Etiology

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, which generate social pressures on children (including those from parents) to conform to behaviors 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, which they may express in behaviors that contravene the norms of their culture. To date, research has established no clear correlations between parenting and gender incongruence. 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 a male infant has been surgically assigned to female anatomy after accidental damage to the penis, it is impossible to guarantee that the child will grow up identifying as a girl. These findings indicate that early brain development seems to have an indelible effect on gender identity that is resistant to normative social pressures and that may result from prenatal sex hormones, direct genetic effects, or both.

Biological influences are evident in several other research findings. Two studies have reported the presence of repeat polymorphisms in the gene coding for the androgen receptor in transgender women, suggesting that these individuals have an atypical response to testosterone. Other research has shown that some chromosome anomalies in individuals with a male phenotype (such as XXY, XYY, and mosaicism) are associated with a raised incidence of individuals who identify as women. There is also evidence that low androgen levels associated with medication use in pregnancy may be associated with a higher incidence of gender dysphoria in an XY fetus.

Additional studies of family cooccurrence of gender dysphoria indicate that there may be a genetic link in a subset of transgender individuals. Studies of twins have shown that monozygotic twins have a significantly higher likelihood of concordance for transgenderism than dizygotic twins. In one study, 33% of male monozygotic twin pairs (where at least one twin had transitioned) were concordant for transition, 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 reported to be low.

Studies of cerebral lateralization of neural pathways associated with listening ability reveal differences between male and female brains in cisgender individuals (persons who identify in a way that is consistent with their assigned sex at birth). A study of click-evoked otoacoustic 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. The findings did not support the hypothesis that increased prenatal exposure to androgens had an opposite effect, in relation to otoacoustic emissions, on gender incongruent young people assigned female at birth. However, in cases of gender incongruent birth-assigned males, the authors postulate that atypically low in utero testosterone levels may affect the crucial period of sex differentiation in the brain. Similarly, a study of dichotic listening in transgender women showed that their lateralization resembled that of cisgender women rather than that of cisgender men. The cohort of transgender men and women involved in this study also showed a markedly raised prevalence of non–right-handedness compared with the cisgender population. This finding augments those of previous studies, and it is highly likely that there is an association between gender incongruence and atypical brain development.

Other studies have also shown that sensitivity to odors may be different in transgender individuals compared with those who are cisgender. Transgender women have demonstrated certain odor sensitivity patterns that reflect their gender identity, rather than their assigned birth sex, suggesting that there may be sex-atypical physiologic responses in specific hypothalamic circuits.

Not all cadaveric or in vivo studies of transgender individuals have revealed cross-sex characteristics, but there are many studies that have. For example, 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 that is discordant with genital and gonadal characteristics at birth but similar to that of cisgender individuals of the same gender identity. A study based on scans of the white matter in the brains of transgender men who had not yet undergone hormone treatment showed that their neural patterns were masculinized and closer to those of birth-assigned males than to those of birth-assigned females. Scans in untreated transgender women showed that their patterns were feminized and were substantially different than those of birth-assigned male and female controls.

In summary, the aforementioned research provides compelling evidence that the neurobiology of the brain is important in predisposing an individual to incongruence between his or her gender identity and his or her assigned sex at birth. 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 and only serve to help us better understand the etiology of transgenderism.