Our culture conceives sex anatomy as a dichotomy: humans come in two sexes, conceived of as so different as to
be nearly different species. However, developmental embryology, as well as the existence of intersexuals, proves
this to be a cultural construction. Anatomic sex differentiation occurs on a male/female continuum, and there are
several dimensions.
Genetic sex, or the organization of the "sex chromosomes," is commonly thought to be isomorphic to some idea
of "true sex." However, something like 1/500 of the population have a karyotype other than XX or XY. Since
genetic testing was instituted for women in the Olympic Games, a number of women have been disqualified as
"not women," after winning. However, none of the disqualified women is a man; all have atypical karyotypes,
and one gave birth to a healthy child after having been disqualified.
The sex chromosomes determine the differentiation of the gonads into ovaries, testes, ovo-testes, or
nonfunctioning streaks. The hormones produced by the fetal gonads determine the differentiation of the external
genitalia into male, female, or intermediate (intersexual) morphology. Genitals develop from a common
precursor, and therefore intermediate morphology is common, but the popular idea of "two sets" of genitals (male
and female) is not possible. Intersexual genitals may look nearly female, with a large clitoris, or with some
degree of posterior labial fusion. They may look nearly male, with a small penis, or with hypospadias. They may
be truly "right in the middle," with a phallus that can be considered either a large clitoris or a small penis, with a
structure that might be a split, empty scrotum, or outer labia, and with a small vagina that opens into the urethra
rather than into the perineum.
What is androgen insensitivity syndrome?
Androgen Insensitivity Syndrome, or AIS, is a genetic condition, inherited (except for occasional spontaneous
mutations), occurring in approximately 1 in 20,000 individuals. In an individual with complete AIS, the body's
cells are unable to respond to androgen, or "male" hormones. ("Male" hormones is an unfortunate term, since
these hormones are ordinarly present and active in both males and females.) Some individuals have partial
androgen insensitivity.
In an individual with complete AIS and karyotype 46 XY, testes develop during gestation. The fetal testes
produce mullerian inhibiting hormone (MIH) and testosterone. As in typical male fetuses, the MIH causes the
fetal mullerian ducts to regress, so the fetus lacks uterus, fallopian tubes, and cervix plus upper part of vagina.
However, because cells fail to respond to testosterone, the genitals differentiate in the female, rather than the
male pattern, and Wolffian structures (epididymis, vas deferens, and seminal vessicles) are absent.
The newborn AIS infant has genitals of normal female appearance, undescended or partially descended testes,
and usually a short vagina with no cervix. Occasionally the vagina is nearly absent. AIS individuals are clearly
women. At puberty, the estrogen produced by the testes produces breast growth, though it may be late. She does
not menstruate, and is not fertile. Most AIS women have no pubic or underarm hair, but some have sparse hair.
When an AIS girl is diagnosed during infancy, physicians often perform surgery to remove her undescended
testes. Although removal of testes is advisable, because of the risk of cancer ISNA advocates that surgery be
offered later, when the girl can choose for herself. Testicular cancer is rare before puberty.
Vaginoplasty surgery is frequently performed on AIS infants or girls to increase the size of the vagina, so that
she can engage in penetrative intercourse with a partner with an average size penis. Vaginoplasty surgery is
problematic, with many failures. ISNA advocates against vaginal surgery on infants. Such surgery should be
offered to, not imposed on, the pubertal girl, and she should have an opportunity to speak with adult AIS women
about their sexual experience and about surgery in order to make a fully informed decision. Not all AIS women
will choose surgery.
Some women have successfully increased the depth of their vagina with a program of regular pressure dilation,
using aids designed for that purpose. Contact the AIS Support Network for more information.
Physicians and parents have been most reluctant to be honest with AIS girls and women about their condition,
and this secrecy and stigma has unnecessarily increased the emotional burden of being different.
Because AIS is a genetic defect located on the X chromosome, it runs in families. Except for spontaneous
mutations, the mother of an AIS individual is a carrier, and her XY children have a 1/2 chance of having AIS.
Her XX children have a 1/2 chance of carrying the AIS gene. Most AIS women should be able to locate other AIS
women among siblings or maternal relatives.
Is there a test for androgen insensitivity syndrome?
The answer depends upon exactly what you are looking for--diagnostic information, or carrier status. If were
born with female genitals and testes, and have very sparse or absent pubic hair, you most likely have complete
AIS. If you were born with ambiguous genitals and testes, there are a number of possible etiologies, including
partial AIS.
Testing for partial AIS is more problematic than the complete form. Hormonal tests in a newborn with 46 XY
karyotype and ambiguous genitals will show normal to elevated testosterone and LH, and a normal ratio of
testosterone to DHT. A family history of ambiguous genitals in maternal relatives suggests partial androgen
insensitivity.
If you are wondering if you are a carrier, or if you know that you are a carrier and are wondering about the status
of your fetus, genetic testing is possible. AIS has been diagnosed as early as 9-12 weeks gestation by chorionic
villus sampling (sampling tissue from the fetal side of the placenta). By the 16th week it can be detected by
ultrasound and amniocentesis. However, prenatal diagnosis is not indicated unless there is a family history of
AIS.
See the following for details of testing.
Hodgins M. B., Duke E. M., Ring D.: Carrier detection in the testicular feminization syndrome: deficient 5 alpha
dihydrotestosterone binding in cultured skin fibroblasts from the mothers of patients with complete androgen
insensitivity. J. Med. Genet. Jun 1984, 21, (3), p178-81.
Batch J. A., Davies H. R., Evans B. A. J., Hughes I. A., Patterson M. N.: Phenotypic variation and detection of
carrier status in the partial androgen insensitivity syndrome. Arch. Dis. Childh. 1993; 68: 453-457.
What is partial androgen insensitivity syndrome?
The extent of androgen insensitivity in 46 XY individuals is quite variable, even in a single family. Partial
androgen insensitivity typically results in "ambiguous genitalia." The clitoris is large or, alternatively, the penis
is small and hypospadic (these are two ways of labeling the same anatomical structure). Partial androgen insensitivity may be quite common, and has been suggested as the cause of infertility in many men whose
genitals are of typically male appearance.
Individuals with ambiguous genitals have typically been subjected to "corrective" surgery during infancy. Based
on our own painful experiences, ISNA believes that such cosmetic surgery of the genitals is harmful and
unethical. Surgery is justified only when it is necessary for the health and well-being of the child. Surgery which
is intended to make the genitals appear more male or more female should be offered, but not imposed, only when
the child is old enough to make an informed decision for her/himself.
What is Progestin Induced Virilization?
Caused by prenatal exposure to exogenous androgens, most commonly progestin. Progestin is a drug which was
administered to prevent miscarriage in the 50's and 60's and it is converted to an androgen (virilizing hormone)by the prenatal XX persons metabolism. If the timing is right, the genitals are virilized with effects
ranging from enlarged clitoris to the development of a complete phallus and the fusing of the labia. In all cases
ovaries and uterus or uterine tract are present, though in extreme cases of virilization there is no vagina or
cervix, the uterine tract being connected to the upper portion of the urethra internally. The virilization only
occurs prenatally and the endocrinological functionality is unchanged, ie. 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 sex
phenotype which ranges from "female with larger clitoris" to "male with no testes". It is noteworthy that the use
of progestin is not effective in the prevention of miscarriage.
Progestin androgenized children are subjected to the same surgically enforced standards of cosmetic genital
normalcy as other intersexed children... meaning that clitoridectomy and possibly more extensive procedures are
often performed early in life, most often with the effect of loss of erotic sensation and ensueing psychological
trauma. ISNA believes that this surgery is unneccessary, cosmetic and primarily "cultural" in its significance. It
is of no benefit to the child, who suffers even more from the stigma and shame of having been surgically altered
than she would have had her non-standard genitals been allowed to remain intact.
Occasionally a female neonate will be so genitally virilized that she is given a male identity at birth and raised as
a boy. It is important not to hide the circumstances of her biology from such a child, in order to the avoid shame,
stigma and confusion which results from secrecy. After the onset of puberty the child may want to explore the
option, hopefully with the aid of loving parents and peer counseling, of having surgery to allow expression of
either female or male sexuality. This is not a choice that should be forced prematurely, it is a personal choice to
be made by a teenager about his/her body and about her/his choice of sexual identity and sexuality.
What is Adrenal Hyperplasia?
Adrenal Hyperplasia is the most prevalent cause of intersexuality amongst XX people with a frequency of about 1
in 20000 births. It is caused when an anomoly of adrenal function (usually 21-hydroxylase or 11-hydroxylase
deficiency) causes the synthesis and excretion an androgen precursor, initiating virilization of a XX person in
utero. Because the virilization originates metabolically, masculinizing effects continue after birth.
As in progestin induced virilization, sex phenotype varies along the same continuum, with the possible added
complication of metabolic problems which upset serum sodium balance. The metabolic effects of CAH can be
counteracted with cortisone. The scenario for medical intervention for intersex is similar... but CAH people have
an increased likelihood of early detection due to metabolic imbalances (Salt Losing Form). The long term use of
cortisone itself produces significant dependance and other side effects, all of which need to be explained honestly
and openly.
What is klinefelter syndrome?
Most men inherit a single X chromosome from their mother, and a single Y chromosome from their father. Men
with klinefelter syndrome inherit an extra X chromosomes from either father or mother; their karyotype is 47
XXY. Klinefelter is quite common, occuring in 1/500 to 1/1,000 male births.
The effects of klinefelter are quite variable, and many men with klinefelter are never diagnosed. The only
characteristic that seems certain to be present is small, very firm testes, and an absence of sperm in the ejaculate,
causing infertility. Except for small testes, men with klinefelter are born with normal male genitals. But their
testes often produce lower than average quantities of testosterone, so they don't virilize (develop facial and body
hair, muscles, deep voice, larger penis and testes) as strongly as other boys at puberty. Many also experience
some gynecomastia (breast growth) at puberty.
Physicians recommend that boys with klinefelter be given testosterone at puberty, so that they will virilize in the
same way as their peers, and that men with klinefelter continue to take testosterone thoughout their lives, in
order to maintain a more masculine appearance and high libido. Many ISNA members, however, report that they
do not like the effects of testosterone, and prefer to reduce their dosage, or not to take it at all.
What is hypospadias?
Hypospadias refers to a urethral meatus ("pee-hole") which is located along the underside, rather than at the tip
of the penis. In minor, or distal hypospadias, the meatus may be located on the underside of the penis, in the
glans. In more pronounced hypospadias, the urethra may be open from mid-shaft out to the glans, or the urethra
may even be entirely absent, with the urine exiting the bladder behind the penis.
The preceeding article was written and produced by ISNA and appears here with permission.
