When an egg and sperm combine to create a new individual, the typical pattern is for the new individual to have 23 chromosomes each from the mother and father. 

Each parent provides one “sex” chromosome. The mother’s is always an X chromosome; the father’s may be either an X or a Y:

• if it is an X, the embryo will have two X chromosomes and will typically follow the female reproductive pathway
• if it is a Y, the embryo will have one X and one Y, and will typically follow the male reproductive pathway.

The process by which a foetus develops is guided by chemicals called enzymes, which are in turn produced according to the instructions encoded in the foetus’s DNA. For each body part and organ – face, heart, bones, muscles, blood and so on – there are standard patterns, with some degree of individual variation. Many of these variations are “bimodal” for males and females. For instance, men are on average several inches taller than women, but some men are short and some women are tall. 

Development of the sex organs is also guided by enzymes, but there is one big difference from other body parts: there are two quite different patterns, one for males and one for females.

In 99.98% of all births, sex differentiation leads to an individual who can easily be classified as one sex or the other (see “What is sex?”). Males have a penis and testicles; females have a vulva, uterus and ovaries. 

Almost all newborn babies can easily be classified as male or female, simply by looking at their external genitals. If there’s a penis, it’s a boy, and if there’s a vulva, it’s a girl. This is one of the most accurate diagnostic tests in all of medicine, even though it requires no special equipment or training. 

Sometimes, however, there is a variation in either the genes or the way they act through enzyme production. This variation is part of what drives evolution. But it can mean that an organ or body part does not develop along standard lines. The result may be a minor difference from normal development, or a major difference that leads to significant malfunction or health problems: examples include cleft palate (when the roof of the mouth does not close fully), thalassemia (a blood defect) and atrial septal defect (“hole in the heart”).

Sometimes, the reproductive organs fail to develop fully, or attempt to develop along the other sex’s pathway. Since there are only two genetic blueprints – male and female – such a variation cannot create an individual who is a third sex, or both sexes. The only possible outcomes are variations on one sex or the other. 

Such a variation may be limited to an individual body part, and be minor enough that it is still easy to tell the baby’s sex. Two examples are cryptorchidism (when one or both of the testicles has not moved down into the scrotum) and hypospadias (when the opening of the penis is along the shaft, rather than at the tip). In both of these cases the baby is clearly male, even though his genitals look a little different from normal.

But very occasionally, in at most 0.02% (2 in 10,000) births, a baby’s sex cannot easily be identified. In these cases, the baby is said to have a “DSD”, a difference of sex development. (The terms disorder of sex development, variations in sex characteristics and diverse sex development are also used; the word “intersex” used to be common, but is now obsolete among medical professionals, because it inaccurately suggests a person who is between the sexes.)

Some DSDs are apparent at birth or shortly after. Others are diagnosed only in adolescence, when puberty does not progress as expected. Accurate diagnosis, and individualised care and support, are essential. This is a specialist area of medicine, since there are dozens of DSDs and some are extremely rare.

What is regarded as best practice has changed a lot over the decades, especially when it comes to surgery on the genitals for purely cosmetic reasons, with no medical purpose.

Further reading

‘What are differences/disorder of sexual development or intersex conditions?’ (CAN-SG, 2022)

FAQ on the DSD Families website

The “Müllerian duct” is a part of the anatomy of a foetus:

• in females, it develops into the Fallopian tubes, uterus, cervix and upper third of the vagina
• in males, a hormone called “anti-Müllerian hormone” (AMH), which is produced by the testes, instructs the Müllerian duct to disappear so that the male reproductive anatomy can develop.

But some male babies have a faulty gene that means they lack either the hormone AMH or the ability to interpret its signals. The Müllerian ducts do not vanish, as they are supposed to. The result is an individual who is male, but has some female reproductive structures, such as uterus or ovaries, that do not work properly and can be harmful to health. Men with this condition are often incapable of producing sperm, meaning that they are infertile.

This condition affects only males: it is named for an enzyme that converts testosterone into dihydrotestosterone (DHT), which in turns triggers the development of a male foetus’s genitalia. Without the genetic instructions to create that enzyme, a baby with XY chromosomes will be born with ambiguous genitalia: female-looking with an enlarged clitoris or male-looking with a micropenis. The testes will be either internal or in the labial folds.

If a female person (one with XX chromosomes) has this mutation, it has no effect, because DHT plays no role in female-pattern development.

People with 5-ARD have male levels of testosterone and the ability to use it. DHT plays no known role in puberty (apart from being part of the process whereby males grow thicker body hair). These individuals therefore grow up along male lines. They do not grow breasts. Their voices break, their muscles strengthen, their shoulders broaden and their hips stay narrow. Sometimes, their genitalia become more clearly male. 

Whether a newborn with 5-ARD is registered male or female depends on the degree of genital ambiguity and local standards of medical care. The child is more likely to be registered female in rural parts of developing countries, where healthcare is rudimentary. Until recently, babies in Europe or North America who were diagnosed young with 5-ARD, and whose genitalia were ambiguous or broadly female in appearance, were often registered female and had their testes removed. 

Recent research has shown, however, that 5-ARD males are usually psychologically more comfortable if registered as their biological sex, no matter how undervirilised their genitalia. A study that looked at nearly 100 children with XY intersex conditions in India found that all those diagnosed with 5-ARD and registered male at birth kept that designation, whereas nearly all those with the condition who were registered female at birth chose to change their legal sex to accurately reflect their biological sex as they grew up.

Male puberty shapes the body in ways that are far more advantageous for sporting purposes than does female puberty. As a result, athletes with 5-ARD are hugely over-represented in female sports. This is the condition that Caster Semenya has, and the male sporting advantage is the reason that the Court for Arbitration in Sport has ruled that 5-ARD athletes can be barred from women’s competitions.

Further reading: Re 5-ARD: Shabir, I., Khuruna, M.L., et al., ‘Phenotype, genotype and gender identity in a large cohort of patients from India with 5α – reductase 2 deficiency’, Andrology, 3:6 (2015), 1132–1139.

These DSDs affect only male (XY) individuals. They involve mutations on the X chromosome that make the body partially or completely unable to respond to the signals sent by testosterone. The result is a body that looks partially or completely female on the outside, with underdeveloped male genitals (PAIS) or normal-looking female genitals (CAIS). But genes on the Y chromosome, and the lack of a second X chromosome, stop the body from developing fully along the female reproductive pathway. The individual will not have a uterus or ovaries, and will be infertile.

If a female person (one with XX chromosomes) has this mutation, it has no effect, because testosterone does not play a part in development along the female reproductive pathway.

CAIS individuals typically are registered as female at birth and retain that classification throughout their lives. They grow up to have a female appearance because their bodies convert the testosterone produced by their internal testes into oestrogen. In puberty they develop female secondary sex characteristics (such as breasts) and do not develop male ones (such as thick facial and body hair and a deep voice).

This is the rarest of all DSDs. People with this condition have both ovarian and testicular tissue, sometimes within the same gonad (this is the joint term for both ovaries and testicles). The condition is caused by a number of genetic variations, and requires individual assessment. 

People with ovotestes usually have XX chromosomes. Their reproductive organs are usually affected, and their genitalia may appear ambiguous. Most are infertile. The very small proportion of people with this condition who are fertile produce either eggs or sperm, but never both.

The word “dysphoria” comes from Greek, and means the opposite of euphoria: a state of misery that is hard to bear. Gender dysphoria is misery caused by a person’s sex, and their sense that it is mismatched with their gender identity. It is an inner sense of unease, distress, or disgust towards oneself, made up of thoughts, emotions and sensations, and can vary from low-level to incapacitating. The quality and conviction of the accompanying thoughts also vary.

The words used by clinicians for this sort of feeling have changed over time. In 1978 the International Classification of Diseases, an authoritative handbook of conditions and diagnoses, included “transsexualism” in a section entitled “Sexual deviations and disorders”. An update in 1992 included a group of “gender-identity disorders” in a section entitled “Adult personality and behaviour disorders”. The most recent update, published early in 2022, has replaced the term “transsexualism” with “gender incongruence”, which has been moved out of the chapter on mental disorders to a new one entitled “Conditions relating to sexual health”. This chapter also includes sexual dysfunctions, which are also no longer classified as mental disorders.

When it comes to relatable symptoms, such as pain, clinicians are expert at unpicking what their patient is experiencing. They ask about the type, location and intensity of the pain, whether it radiates and what makes it better or worse. They learn during training that 80% of diagnoses are made on the basis of a case history, and as they gain expertise, they learn to understand nuances in what is being described.

Gender dysphoria, by contrast, can be hard to relate to, since a person’s inner sense of themselves cannot be seen or measured, and many people report not having any gender-identity feelings at all. In a clinical setting, such ambiguity is unusual. It will take time for a clinician to understand what a patient with gender dysphoria is feeling, and to start to understand why. Clinicians should take a careful history as they usually would, and use it to explore what a patient means by “gender”, and how they experience dysphoria. While supporting the patient, they must keep an open-minded and dispassionate approach to diagnosis and treatment.

In seeking to understand how gender dysphoria may arise, whether in childhood or adulthood, it is helpful to consider the related concept of body dysmorphia. In this condition, the miserable feelings are directed at the body, or a part or attribute of it. 

Some people experience body dysmorphia as mild, and can quickly soothe or ignore the accompanying distressing thoughts. Someone who dislikes their chin, for example, may have frequent but fleeting thoughts about it, but find it relatively easy to reassure themselves that the shape of their chin doesn’t really matter, and start thinking about something else.

For someone else, such thoughts may become a major preoccupation. They may ruminate for hours and spend a lot of time in front of a mirror, inspecting their chin from different angles. Their feelings about their chin grow more negative and hostile, and affect their mood. They may try to conceal its supposed flaws with makeup, consider cosmetic surgery and browse websites seeking the “perfect” chin. When they go out they may worry that other people are staring at their chin, and thinking negative thoughts about it. Their thoughts become fixed, and friends and doctors saying their chin looks fine cannot persuade them that it is not deformed.

A person whose life is seriously affected by such feelings, for example by being unable to go out or to work, may be diagnosed with body dysmorphic disorder (BDD). This debilitating condition leads many sufferers to seek cosmetic surgery. But research shows that relief may be short-term, and the condition can return, sometimes shifting to another feature. The result can be a series of expensive, risky and ultimately futile surgeries.

What is generally more helpful is a course of cognitive behavioural therapy (CBT). The sufferer learns to re-evaluate their thoughts and modify their behaviours so they become less concerned about perceived imperfections. SSRIs (a type of antidepressant medication), often in combination with CBT, have also been shown to be useful.

The disorder shows how paying attention to and focusing on a bodily feature or idea about ourselves makes us more aware of it. That in turn magnifies our sensations and makes our thoughts more intense and intrusive, and more time-consuming and harder to ignore. Whether the thing that feels wrong is your chin, weight or thinning hair, attention begets attention.

The same can happen with a person’s ongoing examination of their internal sense of gender. Some people say they do not have any such sense, or if they do, they ascribe no importance to it. (This is not the same as being ignorant of gender roles or unaware of sex differences, which are among the first things that children notice about others and themselves.) People with gender dysphoria, by contrast, are preoccupied with what they feel and how others perceive them with regard to their sexed body or gender role.

All children notice early that boys and girls have different body parts. But the games, clothes and so on associated with the two sexes vary widely from place to place, and are affected by socialisation and environment. In a class of infant schoolchildren, some girls will be drawn to football and running around, and some boys to dressing up and playing shop. From a clinical perspective, all of this is normal. 

A person’s feelings about and experiences of gender will be influenced in part by nature (research suggests that a large part of personality is innate), but also by nurture. Will a two-year-old who refuses to put their shoes on be called naughty or resolute? Will a three-year-old girl playing with a truck be told it is a boy’s toy or encouraged? Will a four-year-old boy who wants to wear a dress be mocked and called a “poofter”, or allowed to wear what he wants? If a child is made to feel ashamed of how they like to play or dress, this can harm the development of their sense of self. 

A child with gender dysphoria experiences a profound and intense distress directed towards their gender (the prescribed social role for their sex), and a wish to be or a belief that they are the opposite sex. The gender dysphoria can be associated with early adverse events, or with other psychological problems, such as depression, anxiety or thoughts of suicide.

As they grow up, people use signals received from family, friends, teachers, colleagues and so on to co-construct their personality and inner sense of self. The former can be understood as related to how others view a person, and the latter to how they view themselves. Personality and sense of self interact with each other, and with societal ideas of gender and a person’s own comfort with engaging in “gendered” behaviours. 

Any sense of gender an individual experiences will interact with other aspects of their personality and the ideas about gender they are exposed to in their social environment. As with other aspects of their identity, this sense will evolve throughout their lifetime, as they react and adapt to their environment and gain life experience, and as their values and beliefs develop. The idea that a person can have a single, “authentic self” is therefore a strange one. It might be more accurate to say that every person has “true selves”, which will change as they mature from infant to child to adolescent and young adult, and pass through middle and old age.

People commonly feel discontented or uncomfortable with some aspect of themselves, or misunderstood by others, and these feelings can be fleeting or long-held. Adolescence, in particular, can be turbulent, consumed by the psychological task of separating and individuating. As we learn more about ourselves and how others perceive us, we discover how complicated others are, and how easy it is to misread and misunderstand them. Splitting the idea of gender from strands of identity and conceptualising it as a standalone, innate and permanent aspect of a person, especially when young, is unlikely to be helpful, either to a person’s self-understanding or to a clinician’s investigations.

Gender dysphoria can arise when confusing and complicated developmental processes get stuck, and a person’s attention becomes fixated on an inner self that is difficult to define and therefore to describe. The idea that people should have an instinctive understanding of this one aspect of themselves, understood as entirely separate from every other part of their personality or self-concept, is very new. Many professionals think this presents their patients with a pretty much impossible task. This may help explain the proliferation of labels used to define this essence.

What clinicians do know is that people develop in diverse ways. No one should feel put in a box, especially during youth, when opportunities should be opening up rather than becoming more restrictive. Adolescence is a time for exploring and expressing different aspects of selfhood. Pushing back against societal expectations of women and men may be part of that. 

The diagnostic criteria for gender dysphoria (previously known as gender-identity disorder) can be found in the Diagnostic and Statistical Manual of Mental Disorders (DSM), an American psychiatric guide widely used in the UK. This book is regularly updated, and diagnostic descriptions reflect societal and cultural change. 

The latest edition, DSM-5, defines gender dysphoria in adolescents and adults as a marked incongruence between experienced/expressed gender and assigned gender, lasting at least six months, as manifested by at least two of:

• a marked incongruence between one’s experienced/expressed gender and primary and/or secondary sex characteristics (or in young adolescents, the anticipated secondary sex characteristics)
• a strong desire to be rid of one’s primary and/or secondary sex characteristics because of a marked incongruence with one’s experienced/expressed gender (or in young adolescents, a desire to prevent the development of the anticipated secondary sex characteristics)
• a strong desire for the primary and/or secondary sex characteristics of the other gender
• a strong desire to be of the other gender (or some alternative gender different from one’s assigned gender)
• a strong desire to be treated as the other gender (or some alternative gender different from one’s assigned gender)
• a strong conviction that one has the typical feelings and reactions of the other gender (or some alternative gender different from one’s assigned gender).

In order to meet criteria for the diagnosis, the condition must also be associated with clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Gender dysphoria in children is defined as a marked incongruence between experienced or expressed gender and assigned gender, lasting at least six months, as manifested by the first of these criteria, plus at least five of the others: 

• a strong desire to be of the other gender or an insistence that one is the other gender (or some alternative gender different from one’s assigned gender)
• in boys (assigned gender), a strong preference for cross-dressing or simulating female attire; or in girls (assigned gender), a strong preference for wearing only typical masculine clothing and a strong resistance to the wearing of typical feminine clothing
• a strong preference for cross-gender roles in make-believe play or fantasy play
• a strong preference for the toys, games or activities stereotypically used or engaged in by the other gender
• a strong preference for playmates of the other gender
• in boys (assigned gender), a strong rejection of typically masculine toys, games, and activities and a strong avoidance of rough-and-tumble play; or in girls (assigned gender), a strong rejection of typically feminine toys, games, and activities
• a strong dislike of one’s sexual anatomy
• a strong desire for the physical sex characteristics that match one’s experienced gender.

As with the diagnostic criteria for adolescents and adults, the condition must also be associated with clinically significant distress or impairment in social, occupational, or other important areas of functioning.

As clinicians assess a child against these criteria, they must consider what is known about child development, and how the sense of incongruence might have arisen. They should also consider the reactions of the family and others around the child to the gender incongruence, any adverse events in the child’s life, the child’s personality and any neurodevelopmental or psychiatric conditions.

People who believe in gender-identity ideology generally describe sex as “assigned at birth” – a doctor’s best guess at how the person may later feel, to be set aside if desired by the person themselves when they are old enough to declare their own identity. Insisting on recognising an individual’s sex then becomes, in the words of some influential British gender clinicians, “reductionist” and acting to “privilege biology over lived and felt identity”. 

This belief system grew out of the claim, first made by some scientists who studied sexual behaviour in the 1960s, that everyone has a “gender identity”: an inner, gender-related awareness of who they are that is separate from their knowledge of their biological sex. Those scientists believed that this awareness usually aligns with bodily sex, but occasionally differs from it. It might be described as a preference for being read by others as more masculine or feminine, or as androgynous – neither masculine nor feminine – or as a specific mixture of the two. No one can know someone’s gender identity without being told: it is invisible and subjective.

Among those who find the idea of gender identity meaningful, some think that it is fluid. This idea originates in postmodern philosophy, in particular the work of two French philosophers, Michel Foucault and Jacques Derrida, and in later interpretations of their work by the American philosopher and gender theorist Judith Butler. 

Postmodern philosophy is very hard to write about for non-specialists. The ideas are unintuitive and often self-contradictory, in part because the language is confusing. But roughly, postmodernists regard language as playing a decisive role in shaping what we experience as being reality. They regard subjective experience as more important than objective statements, and emotional responses as more authentic than rational ones. And they think that conventional understandings of the world need to be “deconstructed” in order to reveal how traditional knowledge structures, including science and medicine, are supposedly inherently oppressive.

According to Butler, gender is “performative”, by which she means that it is not an objective fact about a person, but is created by their actions. For example, she argues that a person becomes feminine by acting in a feminine way, which means that other people see that person as feminine. A woman, then, is “someone who does womanly things”. In this sense Butler sees gender as socially constructed rather than innate. 

One piece of evidence in favour of the idea that gender identity is fluid is that some people experience themselves as having a gender identity that is not stable. They may describe themselves as  “gender-fluid” or say that their gender identity has changed over time (for example, that they used to feel very masculine and now feel more androgynous). 

Some believers in gender identity – confusingly, including some who quote Butler frequently – think it is innate. These people usually think it is fixed at a young age, perhaps even at or before birth. 

These people often posit the existence of a biological marker of gender identity (a “brain sex” that usually aligns with the body’s sex but occasionally does not). For evidence, they point to a handful of studies that have attempted to show differences between the brains of people who identify as transgender and those who do not, which they think help explain why a small minority of people say they have always experienced a deep-seated feeling of having a gender identity different from their sex. 

But studies that purport to show brain differences in trans people are generally very weak in at least one way: 

• the differences they find are small and inconsistent with each other
• they do not take account of sexual orientation (that is, they may be picking up differences between the brains of straight and gay people, for which there is a fair bit of evidence, rather than those of “cis” and trans people)
• they do not control for the use of cross-sex hormones (exactly how these affect the brain is not known, but it is very likely that they do).

Moreover, even if there were brain differences this would not necessarily mean they cause the transgender identification. They could be as a result of that identification. Or they could indicate something else that causes gender dysphoria and hence a trans identification, such as a tendency to dissociate from one’s body.

The claim that gender identity is innate sits oddly with the postmodern approach out of which it grew. The reworking of ideas of gender from fluid to fixed seems to have happened during the early 21st century, as postmodern ideology evolved online and went mainstream. 

The key to understanding it is postmodernism’s emphasis on subjective experience and opposition to fixed, objectively delineated categories. If bodies cannot be classified according to clearly defined characteristics, and if beliefs trump observations, then anyone can say “I am a man” or “I am a woman”, and no one else has authority to overrule that statement, or supply criteria against which it can be assessed. 

This reasoning has political, legal and clinical consequences. For doctors, the biggest is when patients seek life-changing medical and surgical interventions because they feel that their bodies do not represent who they feel themselves to be. This is not a situation that healthcare professionals are trained to handle. 

The whole aim of modern medicine is to use objective symptoms and research evidence to diagnose and treat diseases and disorders. But now the body is supposed to take second place to a sense of identity, and what is wanted is help in manipulating it with hormones and surgery to make it conform to an inner sense of what is “real”. This may be called “medical treatment”, but there is no evidence-based link between cause and consequence, and no expectation of the usual sorts of health benefits.