Intersexuality: Male, Female, & In-Between

"Is it a boy or girl?" is usually the first question people ask when a baby is born, but sometimes the answer is not so clear-cut. Sometimes a baby is born with ambiguous genitalia that is difficult to classify as male or female. Or the baby's chromosomes may indicate one sex, but its genitalia and reproductive organs indicate the opposite. In such cases, the baby is not exclusively male or female, but intersex.

The precise definition of intersexuality is a matter of debate. A broad definition of an intersex person is someone whose sex chromosomes, internal reproductive organs, genitalia, and/or secondary sex characteristics are a combination of male and female. After surveying medical literature from 1955 to the present, a review published on February 11, 2000 in the American Journal of Human Biology reported that up to 2% of live births may show some deviation from the ideal male or female, and that "corrective" genital surgery was carried out on about 0.1 to 0.2% of newborns. However, an August 2002 review from the Journal of Sex Research limits the definition of intersexuality to "conditions in which chromosomal sex is inconsistent with phenotypic sex, or in which the phenotype is not classifiable as either male or female," and reports that the prevalence of these conditions is about 0.018%.

Some intersex individuals are diagnosed at birth due to ambiguous genitalia. In other cases, babies are born with normal looking genitalia, and the intersex condition is identified at puberty when due to problems with sexual development.

Sexual Differentiation in Fetal Development

During fetal development, a person's sex is determined by a complex series of interactions between the genes, primary sex organs (ovaries and testes), and hormones. In most intersex individuals, the sexual differentiation process was altered by a genetic condition or a hormonal imbalance during pregnancy.

The cues for sexual differentiation are embedded in our genes: Males have XY chromosomes and females have XX chromosomes. Before the seventh week of development, male and female fetuses appear identical. During this stage, the gonads are capable of growing into either testes or ovaries, and both Wolffian and Müllerian ducts are present.

In males, the SRY gene (sex region Y gene) on the Y chromosome triggers the development of the testes. The testes produce testosterone, which causes the Wolffian duct to develop into the vas deferens, epididymis, and seminal vesicles. The testes are also responsible for producing anti-Müllerian hormone (AMH), which destroys the Müllerian duct and prevents the development of female reproductive organs. Externally, testosterone and dihydrotestosterone (DHT) cause the penis and scrotum to develop.

Female sexual differentiation is the default, and occurs if androgens are not present. If the SRY gene is absent, ovaries will develop between month two and six. Without AMH, the Müllerian duct will develop into the uterus, fallopian tubes, and the upper portion of the vagina. The Wolffian duct fails to develop and withers. Externally, undifferentiated fetal tissue develops into the clitoris, vagina, and labia in the absence of androgens.

The following is a list of conditions that can affect fetal development and cause intersexuality:

XX Intersex

Congenital Adrenal Hyperplasia (CAH): CAH refers to several genetic conditions that lead to insufficient production of the hormones cortisol and aldosterone, and the overproduction of androgens (male sex hormones). CAH is the most common cause of intersexuality in females, with an estimated incidence of one in 20,000 to one in 36,000 births. The excess androgens cause the genitalia to "masculinize," and can create an enlarged clitoris that resembles a penis and/or fused labia that resemble a scrotum. Women with CAH have female internal reproductive organs. Later in life, women with CAH may develop facial hair, a deep voice, and other masculine secondary sex characteristics. In women, CAH can also lead to abnormal menstruation or no menstruation, and infertility.

XX Gonadal Dysgenesis: Women with XX gonadal dysgenesis have nonfunctioning streak ovaries and an otherwise normal female body. The cause of the condition is unclear. Since the ovaries cannot produce estrogen and progesterone, puberty is delayed and most female secondary sex characteristics do not develop. XX gonadal dysgenesis is usually treated with estrogen and progesterone hormone therapy.

XX Male (aka de la Chapelle syndrome): XX males carry the SRY gene on one or both of their X chromosomes, which as previously mentioned, causes the fetus to develop testes and determines maleness. XX males have a penis and testes, are unable to produce sperm, and may experience breast development.

XY Intersex

Anorchia (vanishing testes): Anorchia refers to the absence of testes at birth. The cause of the condition is unknown, but genetic factors have been identified in some cases. The effects of anorchia vary depending on when the testes disappeared during fetal development. If the testes do not develop by eight weeks in gestation, the baby will have normal female genitalia. If the testes are lost between eight and 10 weeks, the baby will have ambiguous genitalia. If the testes are lost between 12 and 14 weeks, the baby will have otherwise normal male genitalia and internal reproductive organs.

5-Alpha-Reductase Deficiency: This condition is caused by an inherited mutation in the 5-alpha-reductase type 2 gene, which limits the body's ability to convert testosterone into dihydrotestosterone (DHT). As previously mentioned, DHT is required for the development of external male genitalia in utero. Individuals with 5-alpha-reductase deficiency have low levels of testosterone and DHT throughout life. Individuals with 5-alpha-reductase deficiency often have undescended testes. External genitalia may appear as normal male genitalia, ambiguous genitalia, or normal female genitalia. Most individuals with the condition are raised as girls, and in some cases, those who were raised as female re-identify as male after puberty. In some cases testosterone levels rise during puberty, and cause the testes to descend, a deeper voice, and other masculine characteristics.

Androgen Insensitivity Syndrome: Androgen insensitivity syndrome is a group of disorders caused by mutations in the androgen receptor, which interferes with the body's ability to respond to testosterone and other male sex hormones. Individuals with complete or partial androgen insensitivity have XY chromosomes, but are female in appearance. They have normal female genitalia, sometimes shorter than usual vaginas, and testes in the abdominal cavity. Those with androgen insensitivity syndrome have no uterus or ovaries, and therefore cannot menstruate or conceive children. According to the Intersex Society of North America, the estimated frequency of androgen insensitivity syndrome is one in 13,000 births, and the estimated frequency of partial androgen insensitivity syndrome and one in 130,000 births.

Frasier Syndrome: Individuals with Frasier syndrome have XY sex chromosomes and ambiguous or normal looking female genitalia. The condition is also associated with kidney disease and gonadal tumors. Frasier syndrome is caused by a mutation in the WT1 gene.

Persistent Müllerian Duct Syndrome (PMDS): The condition is caused by a genetic mutation that interferes with the body's ability to produce or use anti-Müllerian hormone (AMH). Men with PMDS typically have a small and underdeveloped uterus, undescended testes, and normal male external genitalia. Treatment usually involves surgically retrieving the testes and repositioning them in the scrotum. Infertility can occur if the Müllerian ducts interfere with the functioning of vas deferens and epididymis, and surgery may be used to improve the chances of fertility.

Swyer Syndrome (aka XY gonadal dysgenesis, XY Female): Individuals with Swyer syndrome have normal female external genitalia and internal organs (uterus, fallopian tubes, cervix, and vagina), and nonfunctional gonads instead of ovaries or testes. Most cases of Swyer syndrome are caused by a defect in the SRY gene. Swyer syndrome is usually diagnosed at puberty, when the girl fails to menstruate or develop secondary sex characteristics. The condition is usually treated with estrogen and progesterone therapy, and the nonfunctional gonads are usually removed since they are at high risk of developing cancer.

True Gonadal Intersex

Individuals with this condition have both ovarian and testicular tissue, and were previously referred to as true hermaphrodites. The person may have one ovary and one testis, or ovotestes which contain both ovarian and testicular tissue. According to the Intersex Society of North America, ovotestes occur in one in 83,000 births. Genetically, the person may have XX chromosomes, XY chromosomes, or XX chromosomes in some cells and XY chromosomes in other cells. The external genitalia can be ambiguous, or appear male or female. Most people who are true gonadal intersex are raised as male. However, since they have functioning ovarian tissue, most people with the condition experience breast development, and 40% of those with XX chromosomes menstruate.

Unusual Chromosomal Combinations

Some people have a missing sex chromosome or more than two sex chromosomes. These individuals have unambiguous male or female genitalia and reproductive organs, and it is debatable whether or not their conditions fall under the category of intersexuality. Unusual chromosomal combinations can be caused by a mistake during gamete production, which creates a sperm or egg with more than one sex chromosome. Unusual chromosomal combinations can also occur during early embryo development, when a mistake in cell division creates a cell with three or more sex chromosomes. This can result in different cells in the body containing different combinations of sex chromosomes, which is known as mosaicism. For example, women who are 46,XX/47,XXX mosaics have two X chromosomes in some cells and three X chromosomes in others. Some of these chromosomal conditions, such as Turner syndrome and Klinefelter syndrome, can have significant impacts on physical and sexual development. Other conditions, such as XXXX syndrome and XXYY syndrome, cause few or no medical problems.

Women with Turner syndrome have one X chromosome that is missing or incomplete, causing infertility, lack of sexual development at puberty, and other health problems. Women can also have three (XXX syndrome), four (XXXX syndrome), or five X chromosomes (XXXXX syndrome).

Men with Klinefelter syndrome have the chromosomes XXY, which leads to small testes, low sperm production, and infertility. Men may also have an extra Y chromosome (XYY syndrome), or double the usual number of chromosomes (XXYY syndrome).

Earlier Approaches to Intersexuality

Beginning in the 1950s, doctors typically assigned a gender to newborns with ambiguous genitalia, and subsequent medical treatments were aimed at making the intersex individual to conform to the assigned gender. The gender assignment was usually based on the appearance of the external genitalia, rather than chromosomal status or the presence/absence of ovaries and/or testes. Genital surgery was usually performed to give the infant the appearance of standard male or female genitalia. Since it was easier to surgically construct female genitalia, most intersex infants were assigned as girls. Some doctors withheld medical information from parents and intersex children, and some people never learned of their intersex status. This approach often generated serious problems for intersex individuals and their families. Early genital surgery resulted in unnecessary trauma and loss of sensation. Most intersex children and teens were aware that their bodies were different, and not knowing the cause of their difference led to psychological distress. Some intersex individuals grew up and rebelled against the gender that they were assigned at birth, and found it impossible to reverse the effects of early surgery.

Today's Views of Intersexuality

Some of the practices described above are still carried out today. However, intersex rights advocates and healthcare professionals recommend a different approach that involves delaying any medically unnecessary surgery and providing full disclosure to intersex individuals and their families. All medical decisions that are not crucial for the health of the intersex individuals should be based on free choice and informed consent. The Organisation Intersex International advocate that intersex children should be free to choose their gender identity, even if it's different from the one assigned at birth, and have access to medical treatments (e.g., hormone therapy in adolescence) that will help them live as their chosen gender. Intersex children should be free to decide whether or not to undergo genital surgery when they are older, and not have the process forced on them during infancy. Counseling and intersex support groups are recommended for the intersex children and their parents.

Some intersex rights advocates believe that the traditional definitions of male and female are too narrow. Instead, they argue that biological sex is a spectrum, and that intersex individuals represent the natural variations which exist in the human race.

Visit the following websites for more information: • Intersex Society of North America • Organisation Intersex International

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