Intersex

Intersex, in humans and other animals, is a variation in sex characteristics including chromosomes, gonads, and/or genitals that do not allow an individual to be distinctly identified as male or female. Such variation may involve genital ambiguity, and combinations of chromosomal genotype and sexual phenotype other than XY-male and XX-female.

Intersex infants with ambiguous outer genitalia may be surgically 'corrected' to more easily fit into a socially accepted sex category. Others may opt, in adulthood, for surgical procedures in order to align their physical sex characteristics with their gender identity or the sex category to which they were assigned at birth. Others will not become aware that they are intersex—unless they receive genetic testing—because it does not manifest in their phenotype. Some individuals may be raised as a certain sex (male or female) but then identify with another later in life, while others may not identify themselves as either exclusively female or exclusively male.Research has shown gender identity of intersex individuals to be independent of sexual orientation, though some intersex conditions also affect an individual's sexual orientation.

Intersexuality as a term was adopted by medicine during the 20th century. Intersex conditions received attention from intersex activists, who criticized traditional medical approaches in sex assignment and sought to be heard in the construction of new approaches.The passports and identification documents of some nationalities have adopted "X" as a valid third category besides "M" (male) and "F" (female).

Research in the late 20th century has led to a growing medical consensus that diverse intersex bodies are normal—if relatively rare—forms of human biology. Milton Diamond, one of the most outspoken experts on matters affecting intersex people, stresses the importance of care in the selection of language related to such people.

In humans, biological sex is determined by five factors present at birth:

- the number and type of sex chromosomes;

- the type of gonads—ovaries or testicles;

- the sex hormones,

- the internal reproductive anatomy (such as the uterus in females), and

- the external genitalia.

People whose five characteristics are not either all typically male or all typically female are intersexed.

Conditions and scope

There are a variety of opinions on what conditions are and are not intersex. For instance, the defunct Intersex Society of North America (ISNA) definition states that the following conditions "sometimes involve intersex anatomy" (note this does not mean they are always intersex conditions):

- 5-alpha reductase deficiency

- androgen insensitivity syndrome

- aphallia

- clitoromegaly

- congenital adrenal hyperplasia

- gonadal dysgenesis (partial & complete)

- hypospadias

- Klinefelter syndrome

- micropenis

- mosaicism involving sex chromosomes

- ovo-testes (formerly called "true hermaphroditism")

- partial androgen insensitivity syndrome

- progestin-induced virilisation

- Swyer syndrome

- Turner syndrome

Cryptorchidism

Prevalence

The prevalence of intersex depends on which definition is used. According to the ISNA definition above, 1 percent of live births exhibit some degree of sexual ambiguity.[9] Between 0.1% and 0.2% of live births are ambiguous enough to become the subject of specialist medical attention, including surgery to assign them to a given sex category (i.e. male or female). According to Fausto-Sterling's definition of intersex, on the other hand, 1.9 percent of human births are intersex. 

According to Leonard Sax the prevalence of intersex "restricted to those conditions in which chromosomal sex is inconsistent with phenotypic sex, or in which the phenotype is not classifiable as either male or female" is about 0.018%.

Signs

There are a range of variations between female and male types of genitalia; the Prader scale demonstrates this and is well illustrated here.

Ambiguous genitalia

Ambiguous genitalia appear as a large clitoris or small penis.

Because there is variation in all of the processes of the development of the sex organs, a child can be born with a sexual anatomy that is typically female, or feminine in appearance with a larger-than-average clitoris (clitoral hypertrophy), or typically male, masculine in appearance with a smaller-than-average penis that is open along the underside. The appearance may be quite ambiguous, describable as female genitals with a very large clitoris and partially fused labia, or as male genitals with a very small penis, completely open along the midline ("hypospadic"), and empty scrotum.

Fertility is variable. According to some, the distinctions "male pseudohermaphrodite", "female pseudohermaphrodite" and especially "true hermaphrodite"[16] are vestiges of outdated 19th century thinking. According to others, the terms "male pseudohermaphrodite", and "female pseudohermaphrodite" are used to define the gender in terms of the histology (microscopic appearance) of the gonads.

"True hermaphroditism"

A "true hermaphrodite" is defined as someone with both testicular and ovarian tissue.

In 2003, researchers at UCLA published their studies of a lateral gynandromorphic hermaphroditic zebra finch, which had a testicle on the right and an ovary on the left. Its entire body was split down the middle between female and male, with hormones from both gonads running through the blood.This is an example of mosaicism or chimerism.

This extreme example of hermaphroditism is quite rare.

Ovotestes

Though naturally occurring true hermaphroditism in humans is unknown, there is, on the other hand, a spectrum of forms of ovotestes. The varieties include having two ovotestes or one ovary and one ovotestis, often in the form of streak gonads. Phenotype is not determinable from the ovotestes; in some cases, the appearance is "fairly typically female"; in others, it is "fairly typically male," and it may also be "fairly in-between in terms of genital development.

Intersex activist Cheryl Chase is an example of someone with ovotestes.

Other diagnostic signs

In order to help in classification, methods other than a genitalia inspection can be performed:

For instance, a karyotype display of a tissue sample may determine which of the causes of intersex is prevalent in the case.

Management

Clinical management of intersex can be categorized into one of the following two:

Treatments: Restore functionality (or potential functionality)

Enhancements: Give the ability to identify with “mainstream” people, e.g., breast enlargement surgery

However, there are other categorization systems of management of intersex, which falls into neither category.

In any case, the most common procedure is surgery.

Surgery

The exact procedure of the surgery depends on what is the cause of a less common body phenotype in the first place. There is often concern as to whether surgery should be performed at all. A traditional approach to the management of intersexuality has been surgery. However, some such as Alice Dreger say that surgical treatment is socially motivated and, hence, ethically questionable; without evidence, doctors regularly assume that intersex persons cannot have a clear gender identity. This is often taken further with parents of intersex babies advised that without surgery their child will be stigmatized. Further, since almost all such surgeries are undertaken to fashion female genitalia for the child, it is more difficult for the child to present as male if they later find they identify as or are genetically male. 20-50% of surgical cases result in a loss of sexual sensation (Newman 1991, 1992).

Typically, surgery is performed at birth. Intersex advocates such as Anne Fausto-Sterling in her Sexing the Body argue surgery on intersex babies should wait until the child can make an informed decision, and label surgery without consent as genital mutilation.

Causes

Typical sex development

The common pathway of sexual differentiation, where a productive human female has an XX chromosome pair, and a productive male has an XY pair, is relevant to the development of intersex conditions.

During fertilization, the sperm adds either an X (female) or a Y (male) chromosome to the X in the ovum. This determines the genetic sex of the embryo.During the first weeks of development, genetic male and female fetuses are "anatomically indistinguishable," with primitive gonads beginning to develop during approximately the sixth week of gestation. The gonads, in a "bipotential state," may develop into either testes (the male gonads) or ovaries (the female gonads), depending on the consequent events.Through the seventh week, genetically female and genetically male fetuses appear identical.

At around eight weeks of gestation, the gonads of an XY embryo differentiate into functional testes, secreting testosterone. Ovarian differentiation, for XX embryos, does not occur until approximately Week 12 of gestation. In normal female differentiation, the Müllerian duct system develops into the uterus, Fallopian tubes, and inner third of the vagina. In males, the Müllerian duct-inhibiting hormone MIH causes this duct system to regress. Next, androgens cause the development of the Wolffian duct system, which develops into the vas deferens, seminal vesicles, and ejaculatory ducts.By birth, the typical fetus has been completely "sexed" male or female, meaning that the genetic sex (XY-male or XX-female) corresponds with the phenotypical sex; that is to say, genetic sex corresponds with internal and external gonads, and external appearance of the genitals.

Conditions

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The final body appearance does not always correspond with what is dictated by the genes. In other words, there is sometimes an incongruity between genetic (or chromosomal) and phenotypic (or physical appearance) sex. Citing medical research regarding other factors that influence sexual differentiation, the Intersex Society of North America challenges the XY sex-determination system's assumption that chromosomal sex is the determining factor of a person's "true" biological sex.

XX          Congenital adrenal hyperplasia (CAH) The most common cause of sexual ambiguity is congenital adrenal hyperplasia (CAH), an endocrine disorder in which the adrenal glands produce abnormally high levels of virilizing hormones in utero

In XX-females, this can range from partial masculinization that produces a large clitoris, to virilization and male appearance. The latter applies in particular to Congenital adrenal hyperplasia due to 21-hydroxylase deficiency, which is the most common form of CAH.

Individuals born with XX chromosomes affected by 17α-hydroxylase deficiency are born with female internal and external anatomy, but, at puberty, neither the adrenals nor the ovaries can produce sex-hormones, inhibiting breast development and the growth of pubic hair.

XX          Progestin-induced virilisation  In this case, the excess androgen hormones are caused by use of progestin, a drug that was used in the 1950s and 1960s to prevent miscarriage. These individuals normally have internal and external female anatomy, with functional ovaries and will therefore have menstruation. They develop, however, some male secondary sex characteristics and they frequently have unusually large clitorises. In very advanced cases, such children have initially been identified as males.

XX          Freemartinism This condition occurs commonly in all species of cattle and affects most females born as a twin to a male. It is rare or unknown in other mammals, including humans. In cattle, the placentae of fraternal twins usually fuse at some time during the pregnancy, and the twins then share their blood supply. If the twins are of different sexes, male hormones produced in the body of the fetal bull find their way into the body of the fetal heifer (female), and masculinize her. Her sexual organs do not develop fully, and her ovaries may even contain testicular tissue. When adult, such a freemartin is very like a normal female in external appearance, but she is infertile, and behaves more like a castrated male (a steer). The male twin is not significantly affected, although (if he remains entire) his testes may be slightly reduced in size. The degree of masculinization of the freemartin depends on the stage of pregnancy at which the placental fusion occurs – in about ten percent of such births no fusion occurs and both calves develop normally as in other mammals.

XY          Androgen insensitivity syndrome (AIS)               People with AIS have a Y chromosome, (typically XY), but are unable to metabolize androgens in varying degrees.

Cases with typically female appearance and genitalia are said to have complete androgen insensitivity syndrome (CAIS). People with CAIS have a vagina and no uterus, cervix, or ovaries, and are infertile. The vagina may be shorter than usual, and, in some cases, is nearly absent. Instead of female internal reproductive organs, a person with CAIS has undescended or partially descended testes, of which the person may not even be aware.

In mild and partial androgen insensitivity syndrome (MAIS and PAIS), the body is partially receptive to androgens, so there is virilization to varying degrees. PAIS can result in genital ambiguity, due to limited metabolization of the androgens produced by the testes. Ambiguous genitalia may present as a large clitoris, known as clitoromegaly, or a small penis, which is called micropenis or microphallus; hypospadias and cryptorchidism may also be present, with one or both testes undescended, and hypospadias appearing just below the glans on an otherwise typical male penis, or at the base of the shaft, or at the perineum and including a bifid (or cleft) scrotum.

XY          5-alpha-reductase deficiency (5-ARD)  The condition affects individuals with a Y chromosome, making their bodies unable to convert testosterone to dihydrotestosterone (DHT). DHT is necessary for the development of male genitalia in utero, and plays no role in female development, so its absence tends to result in ambiguous genitalia at birth; the effects can range from infertility with male genitalia to male underdevelopment with hypospadias to female genitalia with mild clitoromegaly. 

The frequency is unknown, and children are sometimes misdiagnosed as having AIS. Individuals can have testes, as well as vagina and labia, and a small penis capable of ejaculation that looks like a clitoris at birth. Such individuals are usually raised as girls. The lack of DHT also limits the development of facial hair.

XY          Congenital adrenal hyperplasia (CAH) In individuals with a Y chromosome (typically XY) who have Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency, CAH inhibits virilization, unlike cases without a Y chromosome.

XY          Persistent Müllerian duct syndrome (PMDS)   The child has XY chromosomes typical of a male. The child has a male body and an internal uterus and fallopian tubes because his body did not produce Müllerian inhibiting factor during fetal development.

XY          Anorchia             Individuals with XY chromosomes whose gonads were lost after 14 weeks of fetal development. People with Anorchia have no ability to produce the hormones responsible for developing male secondary sex characteristics nor the means to produce gametes necessary for reproduction due to the lack of gonads. 

They may develop typically feminine secondary sex characteristics without or despite the administration of androgens to artificially initiate physical sex differentiation (typically planned around the age of puberty). Psychological and neurological gender identity may solidify before the administration of androgens, leading to gender dysphoria, as anorchic individuals are typically assigned male at birth.

XY          Gonadal Dysgenesis      It has various causes and are not all genetic; a catch-all category.

It refers to individuals (mostly XY) whos gonads don't develop properly. 

Clinical features are heterogeneous.

XY          Hypospadias     It is caused by various causes,including alterations in testosterone metabolism.

The urethra does not run to the tip of the penis. In mild forms, the opening is just shy of the tip; in moderate forms, it is along the shaft; and in severe forms, it may open at the base of the penis.

Other:Unusual chromosomal sex         

In addition to the most common XX and XY chromosomal sexes, there are several other possible combinations, for example Turner syndrome (XO), Triple X syndrome (XXX), Klinefelter's Syndrome, (XXY/XXXY), XYY syndrome (XYY), de la Chapelle syndrome (XX male), Swyer syndrome (XY female), and there are many other individuals who do not follow the typical patterns (such as individuals with four or even more sex chromosomes).

Klinefelter's Syndrome

Other: Mosaicism and chimerism           

A mix can occur, where some of the cells of the body have the common XX or XY, while some have one of the less usual chromosomal contents above. Such a mixture is caused by either mosaicism or chimerism. In mosaicism, the mixture is caused by a mutation in one of the cells of the embryo after fertilization, whereas chimerism is a fusion of two embryos.

Mosaicism

In alternative fashion, it is simply a mixture between XX and XY, and does not have to involve any less-common genotypes in individual cells. This, too, can occur both as chimerism and as a result of one sex chromosome having mutated into the other.

However, not all cases of mosaicism and chimerism involve intersex.

Complications

In the cases where nonfunctional testes are present, there is a risk that these develop cancer. Therefore, doctors either remove them by orchidectomy or monitor them carefully. This is the case for instance in androgen insensitivity syndrome.

Identification documents

Nepal, the United Kingdom, Australia, Portugal, Uruguay, and New Zealand are states that took steps to allow for transgender and intersex people to list their gender as other than male or female.[30] Australian and New Zealand authorities allow passports to have a third gender option which is marked "X" meaning "indeterminate/unspecified/intersex" instead of "F" for female or "M" for male. The move was seen as removing discrimination against transgender and intersex people so they will no longer have to choose between "M" (male) or "F" (female).