Causes of Intersexuality



“Intersex” is a general term used to describe people who are born with reproductive or sexual anatomy that does not fit the typical definitions of female or male. Some characteristics that are often associated with the development of intersex individuals include hormonal variations during pregnancy, genetic mutations, and environmental toxins. The X and Y chromosomes are the sex chromosomes. Usually, people have two sex chromosomes, either XX or XY. When a person has two X chromosomes, they are genetically female, and when a person has XY chromosomes, they are genetically male. Geneticists determine which chromosomes a person has by looking at their karyotype (a picture of the chromosomes in a cell). The result is usually reported as the number and type of a person’s chromosomes such as 46, XX (the individual has 22 pairs of matched chromosomes and two X chromosomes), or 46, XY (the individual has 22 pairs of matched chromosomes, one X chromosome, and one Y chromosome). Having one or three of these sex chromosomes instead of two can lead to intersexuality.

A 46,XY human male karyotype

Congenital Adrenal Hyperplasia (CAH)

The most common cause of intersexuality in XX (genetically female) embryos is congenital adrenal hyperplasia (CAH). This condition affects the adrenal glands, which are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with CAH, the adrenal glands produce excess androgens, which are male sex hormones.1 This causes male characteristics to appear early on in the development process.2 Females with the classic form of CAH due to 11-beta-hydroxylase deficiency have external genitalia that does not look clearly male or female (ambiguous genitalia).

Ambiguous genitalia in infants with CAH

Oftentimes, these females have enlarged clitorises or labia that resemble a scrotum.3 However, the internal reproductive organs develop normally. This condition only causes ambiguous genitalia in people with XX chromosomes (genetic females). Males and females with the classic form of this condition experience earlier than normal development of their secondary sexual characteristics such as the growth of facial and pubic hair, voice deepening, the appearance of acne, and the onset of a growth spurt. The early growth spurt can prevent further growth later in adolescence and lead to short stature in adulthood.1

High Testosterone Levels

If a pregnant woman is exposed to high levels of testosterone during pregnancy. A genetically female fetus may develop into an intersex individual. In some rare cases, this is caused by a testosterone-producing ovarian tumor in the mother.4

Swyer Syndrome (XY Gonadal Dysgenesis)

A person with Swyer syndrome is born without functional gonads (sex glands) but has a 46,XY karyotype. This means that they are genetically male; however, they will develop as a female and have external female genitalia, as well as a fully formed uterus and fallopian tubes. The gonads present in Swyer syndrome are known as “gonadal streaks.” These are minimally developed gonad tissue present in place of testes or ovaries. The residual gonadal tissue often becomes cancerous and is usually surgically removed early in life.5 People with Swyer syndrome will not develop most secondary sex characteristics without hormone replacement because gonadal streaks are incapable of producing the sex hormones (both estrogen and androgens) that bring about puberty. They will need hormone replacement therapy in order to experience normal puberty.6

Progestin-Induced Virilization

Progestin-induced virilization is caused by prenatal exposure to high levels of progestin, which is the synthetic version of progesterone. Progestin is converted to an androgen (virilizing hormone) by the XX (genetically female) fetus’ metabolism. Depending on when this happens in the pregnancy, the genitals may be virilized with effects ranging from enlarged clitoris to the development of a complete phallus and the fusing of the labia into a scrotum-like structure. In all cases, ovaries and a uterus are present, though in extreme cases of virilization there is no vagina or cervix. Virilization only occurs prenatally because after birth, the child is no longer exposed to these high levels of progestin. After birth, the endocrinological (hormonal) functionality is normal (feminizing puberty occurs due to normally functioning ovaries). In other words, XX people affected in-utero by virilizing hormones can be born into a continuum of external genitalia, which ranges from “female with large clitoris” to “male with no testes.”7 Affected females mature in the same way unaffected females mature, and are usually fertile. There is almost total regression of the genital anomaly in cases of clitoral enlargement (the clitoris becomes smaller). Even the most severe cases, surgical correction of labioscrotal fusion is relatively simple.8

Mayer-Rokitansky-Küster-Hauser (MRKH)

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder that occurs in females. Often times, the first noticeable sign of MRKH syndrome is primary amenorrhea, with females having their first menstruation after 16 years of age. In fact, this is the most common cause of primary amenorrhea. MKRH syndrome causes the vagina and uterus to be underdeveloped or absent (vaginal hypoplasia). It can occasionally cause pelvic pain if there is an underdeveloped uterus. This is because blood cannot drain properly and leave the uterus.9 MKRH also often leads to difficulty and pain during penetrative intercourse. Both vaginal hypoplasia and underdevelopment of the uterus can be corrected with surgery, if the patient desires surgery.10 Affected women usually do not have menstrual periods due to the absence of a uterus. Women with MRKH syndrome have a female chromosome pattern (46, XX) and normally functioning ovaries. They also have normal female external genitalia and normal breast and pubic hair development.10 Although women with this condition are usually unable to carry a pregnancy, they may be able to have children through assisted reproduction.11

Androgen Insensitivity Syndrome (AIS)

A group of women with AIS (androgen insensitivity syndrome)

Androgen insensitivity syndrome (AIS) is an inherited genetic condition. It is the most common cause of intersexuality in XY (genetically male) embryos.12 Because their bodies are unable to respond to certain male sex hormones (called androgens), they may have mostly female sex characteristics or signs of both male and female sexual development. Complete androgen insensitivity syndrome occurs when one’s body cannot respond to androgens at all. People with this form of the condition have the external sex characteristics of females, but do not have a uterus and therefore do not menstruate and are unable to conceive (are infertile). Affected individuals have male internal sex organs (testes) that are undescended, which means they are abnormally located in the pelvis or abdomen. People with complete androgen insensitivity syndrome also have sparse or absent hair in the pubic and underarm areas. People with partial androgen insensitivity (also called Reifenstein syndrome) can have normal female sex characteristics, both male and female sex characteristics, or normal male sex characteristics.13 People with mild androgen insensitivity are born with male sex characteristics but are often infertile and tend to experience breast enlargement at puberty because the testes produce testosterone, which is chemically very similar to estrogen. Some of the testosterone converts back to estrogen in the bloodstream, which causes breast growth.12

Klinefelter Syndrome (XXY male)

​Klinefelter syndrome, also called XXY male, is another cause of intersexuality. Most men inherit one X chromosome from their mother and one Y chromosome from their father. People with Klinefelter syndrome inherit an extra X chromosome from either their father or mother; their karyotype is 47, XXY.

Klinefelter syndrome is quite common, occuring in 1 out of every 500 to 1000 male births. The testes and penis are small (about half the average size). Even after puberty, their ejaculate contains no sperm.14 They may not develop much body hair, and they may experience breast development. They may also experience reduced muscle tone, narrow shoulders and wide hips, weak bones, decreased sexual interest, and lower energy levels.15

Underdevelopment of the Testes

Problems with the testes in early life can cause intersexuality later in life with the onset of puberty. The testes normally produce male hormones. If the testes do not form properly, a person will experience undervirilization (when typical male characteristics do not appear at puberty or are underdeveloped). There are a number of possible causes for this.11

True Gonadal Intersexuality (“True Hermaphroditism”)

With true gonadal intersexuality, the person has both ovarian and testicular tissue. These structures may appear in the same gonad (an ovotestis), or the person may have one ovary and one testis. There are no documented cases in which both types of gonadal tissue function; usually, only one does. The person may have XX chromosomes, XY chromosomes, or both (known as mosaic genetics). The external genitals may be ambiguous or may appear to be typically female or male depending on the levels of testosterone produced in the womb.11

5-alpha-reductase Deficiency

People with 5-alpha-reductase deficiency lack the enzyme needed to convert testosterone to dihydrotestosterone (DHT). In the womb, DHT has an essential role in the formation of male external genitalia. During adulthood, DHT acts as the primary androgen in the prostate and in hair follicles. There are at least five different types of 5-alpha-reductase deficiency. Some babies have male external genitalia, some have female genitalia, and many have something in between. However, they do have male gonads (testes). With the onset of puberty, although their DHT levels remain very low, their testosterone levels elevate normally. They then develop some male secondary sex characteristics like deepening of the voice, increased muscle mass, and growth of the penis and scrotum. They do not develop much facial or body hair, and most affected males are infertile. These individuals are often raised as girls due to their lack of conspicuous male genitalia.

Mosaic Genetics

A person is said to have a “mosaic karyotype” when they have one karyotype in some of their cells and a different karyotype in other cells. For example, when a person is said to have a 45, X/46, XX karyotype, this means they have 46, X in some cells and 46, XX in other cells. Mosaicism occurs when cells divide incorrectly early on in the life of an embryo.  For instance, a woman with Mosaic Turner Syndrome may have some cells that are XO (typical Turner Syndrome karyotype) and some cells that are XX (typical female karyotype). Mosaicism also occurs in milder forms of Klinefelter Syndrome called 46/47, XY/XXY mosaic. In this case, the XY cells have 46 chromosomes (the typical number of chromosomes) and the XXY cells would have 47 chromosomes.16

Turner Syndrome

It is debated whether or not Turner syndrome is an intersex condition because, as previously discussed, the line between intersex, female, and male is an unclear one. Turner syndrome occurs when all or part of one of the X chromosomes is lost before or soon after the time of conception.17 Typically, females have two XX chromosomes, making their karyotype 46,XX. Here, the female’s karyotype is 45, X, with the second X chromosome missing.

A karyotype of a patient with Turner syndrome and a young girls showing symptoms of Tuner syndrome

Symptoms of Turner syndrome include short stature (less than 5 feet tall), a short and webbed neck, low-set ears, and a low hairline. Most individuals with Turner syndrome experience loss of ovarian function early in childhood, and thus, do not begin puberty at a normal age. Some teenagers may undergo some breast development and begin menstruating, but cease further development and menstruation during the later teen years. Typically, girls with Turner syndrome are treated with estrogen to induce puberty if it does not occur spontaneously. Most women with Turner syndrome do not have ovaries capable of producing fertile eggs (oocytes). Current assisted reproductive technologies, however, may allow women to become pregnant with donated oocytes.18


  1. “Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency” Genetics Home Reference. Web. March 2011.
  2. Chad Haldeman-Englert, MD, “Congenital adrenal hyperplasia” MedlinePlus. Web. February 3, 2014.
  3. “Congenital adrenal hyperplasia (CAH)” Intersex Society of North America. Web.
  4. Neil K. Kaneshiro, MD “Intersex” MedlinePlus. Web. August 22, 2013.
  5. “Swyer syndrome” Genetics Home Reference. Web. March 2015.
  6. “Swyer syndrome” Intersex Society of North America. Web.
  7. “Progestin Induced Virilization” Intersex Society of North America. Web.
  8. James L. Schardein “Congenital abnormalities and hormones during pregnancy: A clinical reviewWiley Online Library. Web. May 31, 2005.
  9. “MRKH: General Information for Teens” Center for Young Women’s Health. Web. December 4, 2014.
  10. Andrew J Kirsch, MD, “Mayer-Rokitansky Syndrome” Medscape. Web. April 22, 2014.
  11. “Mayer-Rokitansky-Küster-Hauser syndrome” Genetics Home Reference. Web. March 2015.
  12. “Androgen insensitivity syndrome (AIS)” Intersex Society of North America. Web.
  13. “Androgen insensitivity syndrome” Genetics Home Reference. Web. May 2008.
  14. “Klinefelter syndrome” Intersex Society of North America. Web.
  15. “Klinefelter syndrome” MedlinePlus. Web. December 31, 2013.
  16. “Mosaicism involving “sex” chromosomes” Intersex Society of North America. Web.
  17. “Overview” Turner Syndrome Society of the United States. Web.
  18. “Clinical Features of Turner Syndrome” National Institutes of Health, Turner Syndrome. Web.

Last Updated 24 November 2015.