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.