Conditions resulting from genetic or hormonal influences
Changes to the usual process of fetal development cause numerous differences in the resulting fetus. When levels of prenatal hormones are altered, phenotypic progression is also altered. The inherent brain bias toward one sex may be discordant with the genetic makeup of a fetus, or even with its external anatomic presentation. Other variations lead to psychologic stressors in later development but have their origin in the prenatal stage. A number of such conditions may ultimately affect a child's gender identity.
Chromosomal alterations
Two very well-described syndromes involving sex and gender, Turner syndrome and Klinefelter syndrome, result from chromosomal abnormalities.
Turner syndrome
In Turner syndrome, one sex chromosome is missing, causing a single X karyotype [a solo Y chromosome is not compatible with life]. Little evidence exists to suggest that hormone levels in utero are markedly lower than in the case of XX fetuses. The resultant XO individual is born with female external genitalia; however, in many such individuals, ovarian development is anomalous. Other characteristics usually include short stature, neck and chest anomalies, and cardiac defects.
A significant percentage of individuals with Turner syndrome have varying levels of mental retardation. This is clearly not true for all XO individuals. Many XO physicians practice in the United States. Female secondary sex characteristics often do not occur, and patients require exogenous estrogen intervention at the time of puberty. The vast majority of individuals with Turner syndrome are infertile.
Although gender identity is usually female, many XO individuals have significant psychologic stress because of their infertility, their appearance, and, in some, the awareness of their genetic profile, which may make them feel inadequate or incomplete as females. This, in turn, may cause some to feel confusion about or to question their gender role.
Klinefelter syndrome
Klinefelter syndrome occurs when the fetus possesses a sex karyotype of XXY. [4] Because of the presence of the Y chromosome and its components, fetal development is that of a normal male. However, as the child grows and approaches puberty, he experiences excessive gynecomastia, with low serum testosterone levels. Infertility is common, and general appearance is tall and thin. Gender identity is affected by these factors. In most cases, the gender role is, in fact, male; activities and rearing typically are also male.
A higher-than-expected percentage of individuals in the XXY cohort have been reported to have emotional disorders. Preliminary data indicate that a higher number of cases of gender identity disorder are specifically associated with Klinefelter syndrome; more research into this phenomenon is required.
Other chromosomal abnormalities
Many other chromosomal findings are described in the literature, including XYY individuals [the extra Y chromosome has been linked to excessively aggressive or antisocial behavior, with no question of confusion about gender identity, which is male]. Mosaicism of sex chromosomes can also be present, including XX/XY persons who may present with the anatomic features of either sex or who may present as intersexed [with characteristics of both sexes]. Another condition is termed gonadal dysgenesis, with partial formation of testicular and ovarian tissue. Each of these very uncommon situations requires a separate assessment of the patient's gender identity.
Hermaphroditism
People with anatomically intersexed conditions are at times referred to as hermaphrodites [or true hermaphrodites]. The word was coined by John Money and has been popularized by him and other workers in the field such as Harry Benjamin. It stems from the Greek god Hermes [Roman Mercury] and goddess Aphrodite [Roman Venus] and parallels the name of their son, Hermaphroditos. [5] The term is now commonly used to describe those with specific gonadal or genital aspects of both sexes.
In the past, almost unequivocally, one sex was chosen for rearing, with all the advantages and disadvantages brought on by that process. Now, increasingly, some suggest allowing hermaphrodites to remain in the intersex state until self-determination can be made to either continue as such or choose a male or female gender role. The brain bias is a matter of conjecture until adequate research studies are completed. The plasticity of gender identity is most apparent in intersexed patients. Some consider themselves both male and female. Others, believing hermaphrodeity, or hermaphroditism, to be a unique third gender, consider themselves to be neither male nor female. Still others begin life comfortably in one gender role with no sense of incongruence, but during puberty begin to find themselves most comfortable with another gender role that is more consistent with a fully developed gender identity.
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia [CAH] is the classic prenatal variation to female fetal development and, in North America, has an incidence of 1:12,000-14,200 population. In patients with CAH, the fetus is exposed to abnormally high levels of cortisol produced by its own adrenal gland. An enzyme defect exists in the pathway by which cortisol is produced; any one of several particular defects can occur. This leads to a greater amount of androgenic adrenal hormone production. For normal XX female fetuses, the prenatal exposure to androgens results in virilization of female genitalia, in what has been called female pseudohermaphroditism.
At times, virilization is complete, with substantial clitoromegaly. In such cases, the genitalia are so masculine that male sex is mistakenly assigned to the newborn at birth. Soon, clinical findings and symptomatology reveal the defect in the adrenal gland and the true female genotype of the child. Serious salt-losing nephropathy may be the presenting problem in certain infants with definable biochemical defects with this disorder. Exogenous adrenocorticoids, as well as mineralocorticoids, in some instances, are used to treat patients once the diagnosis is known.
Both the gender identity and gender role of females with CAH are controversial issues. Exposure to virilizing hormones would seem to cause a male brain bias, and evidence exists that this may be true. Several cases from the mid 20th century, when this diagnosis was more difficult and sometimes was not made until puberty, show that such infants were sometimes mistakenly raised as males, and their later gender identity and role were reportedly male.
Whether these cases truly constitute a diagnosis of gender identity disorder is not clear because of the hormone-induced changes and additional environmental influences involved during rearing. For the most part, gender identity in patients with CAH seems to remain consistent with the genetic profile. Genetic females with this condition have ovaries, so gonadal sex would be congruent with a female gender identity. The gender role can be more stereotypically masculine, with rougher play and a preference for male activities and dress. Further longitudinal studies are needed to assess the real impact of CAH on gender development.
Androgen insensitivity syndrome
When a normal Y chromosome with a fully functional SRY locus is found in a patient with dysfunctional androgen receptors, as is the case in androgen insensitivity syndrome, which has an incidence rate of 1 per 20,000 population, virilization of the fetus does not fully take place. Although testosterone is produced in utero, it cannot change cells that lack normal receptors. In complete androgen insensitivity, the fetus has a total absence of functional androgen receptors. Therefore, progression in the default path toward female genital structure continues uninterrupted. It is growing more common, and such individuals are referred to as XY females. [6, 7]
In such situations, genetically normal XY males have female external genitalia and appear to be normal females at birth. The testes are undescended, although the vagina is blind-ending with no uterus or ovaries. Subsequent gender identity and gender role are typically incongruent with the biologic sex of the patient. The diagnosis is rarely made in early life, and both brain bias and environmental influences in infancy and childhood generally create a female gender identity.
During puberty, the testes produce testosterone, some of which is converted to estradiol. Given that circulating testosterone is unable to exert any virilizing effects, unopposed estradiol allows female secondary sex characteristics to develop. Because of the lack of even the relatively few functional androgen receptors that genetic females possess, body hair and other androgen-induced changes that normally occur in females are absent.
The eventual appearance of these individuals is usually tall, devoid of body and facial hair, with a low percentage of body fat, thin hips, and fully developed breast tissue. The testes may be removed because of the risk for malignant conversion in undescended testicles. Some literature now suggests that surgery may be avoided if consistent and close surveillance of the testes by ultrasonography and serum levels of typical tumor markers [eg, alpha-fetoprotein] are monitored. If the testes are discovered and removed prior to puberty, hormone replacement therapy is required to induce the described changes, since no source exists for the secretion of sex hormones.
Apart from infertility from the female standpoint, this condition has no clinical sequelae. It must be noted that the testes may be a source for spermatozoa, but it is quite unlikely that XY females will ask for this intervention. As mentioned above, despite the incongruity with the genetic profile, almost all such individuals express a female gender identity and assume a normal female gender role. For many, their appearance is perhaps even closer to a media-idealized female form than typical XX females. Thus, the presence of a Y chromosome is frequently accepted as a biologic quirk rather than the source of psychologic distress.
In partial androgen insensitivity, on the other hand, variable degrees of receptor function result in differing degrees of hypoandrogenization, virilization, and phenotypic presentation. In this less common variant of receptor dysfunction, micropenis may be present, as may hypoplastic labia [given an external female appearance]. Because anatomic clues are often used for gender assignment, the degree of masculinization [or lack thereof] often determines recommendations for child-rearing. However, long-term studies appear to support a significant level of gender dysphoria in individuals with partial androgen insensitivity. Unlike the complete androgen insensitivity syndrome, this variant has proven to be difficult to manage in terms of gender congruence.
5-Alpha-reductase deficiency
This, too, is an enzyme defect with effects during prenatal development. The incidence in North America is roughly 1:40,000. Lack of 5-alpha-reductase prevents the conversion of testosterone to dihydrotestosterone in normal male [XY] fetuses. Virilization is incomplete; the infant at birth appears female, although the external genitalia may be somewhat abnormal in size, shape, and color. The feminized phallus appears clitorislike, but the internalized gonads are normal and male, and androgen receptors are also fully functional. When the testes produce a surge of testosterone at puberty, bodily changes occur. A full conversion to male appearance is noted, with growth of the phallus. At this point, a female gender assignment quickly comes into question and then becomes clearly inappropriate.
Interestingly, the most striking cases of gender plasticity are observed in this patient population. Some of those who are raised as girls and who seemingly possess a female gender identity turn into males with puberty, converting to a male gender identity. Perhaps the brain bias for a male identity does occur with testosterone exposure prenatally, despite the inadequacy of genital virilization; it remains suppressed until puberty affirms it.
Others have undergone orchiectomy and have been raised as girls, with exogenous estrogen in adolescence to induce female pubertal changes. Some of these patients express and retain a female gender identity. Still others are raised ambivalently and are given the knowledge that, at puberty, they will differentiate into male status. Some do require slight androgen supplementation to fully complete the virilizing process. No consensus yet exists as to which choice is preferable, and many professionals are equivocal about this population, advocating a case-by-case evaluation of circumstances to decide on intervention.
Genital abnormalities and related phenomena of gender variance
Several rare conditions result in anomalous genitalia, either in form or function. Gender identity can be affected in some of these patients for a variety of reasons. One such situation is micropenis, in which a normal male is born with extremely small genitals. A small cohort of patients undergo botched circumcisions, causing phallic mutilation. Many parents in the past have been advised to allow these children to undergo surgery to construct female genitalia and raise them as girls. Case reports indicate that this is not necessarily the best option because most of such patients assigned a female gender develop a gender identity of male and wish to play a male gender role.
A similar situation is observed with cloacal exstrophy, in which intrauterine development of the urogenital structures is incomplete. Cloacal exstrophy has a North American incidence of 1:400,000. Males with this condition are born without a phallus, although testes are present. Reassignment of these children as females [earlier deemed appropriate because of a belief in neonatal neutrality of gender] has not been entirely successful because most demonstrate a desire for a male gender identity. Surgical and medical management, including orchiectomy, construction of a vulva, and exogenous hormone therapy to induce puberty, have classically been recommended for these patients. However, the gender role is frequently more masculinized than in their genetically female counterparts. Notably, this population appears to be very unpredictable in terms of later gender identity; therefore, a consensus recommendation for child-rearing has not yet been reached.
Even the relatively common condition of cryptorchidism may play a part in gender development. Cases exist of patients with undescended testes whose gender identity was questioned and development did not follow the normative path until psychologic intervention in later years. Such instances show that self-perception, personal knowledge about sex and gender, and comparison to societal standards can all be significant in the formation of a person's gender identity.
Subgroups of individuals also exist whose genitals have been deliberately altered. One such group consists of women who undergo female circumcision, a practice that is often termed female genital mutilation. This practice is found in many parts of Africa and sporadically in other areas of the world, as well as in the United States in the past. Severe alterations to the female external genital tract are performed as part of ritual tradition. In many of these individuals, the procedures are performed well after the expression of gender identity. Gender role is only confirmed by the practice, despite the injury to the genitalia.
Another subgroup is the hajra of India, who are eunuchs, males castrated during childhood and reared as neither male nor female. Lacking testes to induce pubertal development and through adherence to custom that effectively equals behavioral modification therapy, their gender role is mostly female. However, because of their prominent and unique status as a separate subgender, they are easily identified as such. This relegates them to a distinct role in society, and they are considered mystical creatures, to be kept apart. Their existence has been recorded for many centuries, with little information as to the origin of this practice. Whether their gender identity remains male is not well known, although most reported practices seem to indicate that their identity is in flux even in later years.
From a societal standpoint, reports also exist of tribes in both Africa and in Papua New Guinea where male individuals are raised for several years in a more typically female gender role, only to switch into a masculine gender role at the time of puberty. These individuals do not experience any alteration of genitalia but purely shift roles, which may or may not correspond to their gender identity. The shaman in North American aboriginal populations was often a gender-neutral or "bi-gendered" individual, and, in the ancient Middle East, there have been numerous reports of "third gender" persons who contributed to society in various specialized roles. Although, in some societies, there has been and remains outright ostracism for any type of gender atypicality or divergence from a strict male-female dichotomy, in many cultures throughout human history, gender variance has been recognized, tolerated, accepted, and even celebrated.