the word "Hermaphrodite"
believed that the gonads were the seat of "true sex,"
and thus created a system of nomenclature -- in the absence of any
knowledge of genetics, endocrinology, or embryology -- which categorized
people as "male pseudohermaphrodite," "female pseudohermaphrodite,"
or "true hermaphrodite." It's time to eliminate this quaint
Victorianism from modern medical practice.
word "hermaphrodite" implies that a person is born with
two sets of genitals -- one male and one female -- and this is
actually something that cannot occur.
"male" and "female," because they are based
only upon the gonadal histology, frequently contradict the sex
of assignment, and thus are very misleading and disturbing for
parents and patients.
"pseudo" and "true" are even more harmful,
because they imply a sort of authenticity, or lack of same, that
carry powerful emotional baggage.
As with any
contraversial term there are those that support using it. Some
intersexed people want to reclaim
the word, free of it's Victorian medical misuse.
IS) is a broad class of medical conditions that features "congenital
anomalies of the reproductive and sexual system." A person with
an intersex condition is born with sex chromosomes, external genitalia,
or an internal reproductive system that is not considered "normal"
for either a male or female.
The causes and presentations
of intersex conditions vary greatly. There are environmental factors,
genetic factors, and developmental factors and the effects of them on
a developing child range from "nothing apparent" to "obvious
at birth." Those conditions that are obvious at birth garner the
most attention from the medical community, while there are people who
are intersexed who may be so mildly affected they will never be clinically
Most of the birth
disorders that are classified as "intersex conditions" are
treated as "unusual," and it is not uncommon to find them
listed among "rare diseases." The general public - even many
doctors - have no familiarity with intersex conditions or people. At
best an individual may have heard of the now out of favor term "hermaphrodite"
(taken to mean someone with both male and female genitals). Which is
ironic, because people who used to be called "true hermaphrodites"
are among the rarest of all intersex conditions. For the most part,
though, schools usually omit any mention of intersex conditions in biology,
health, or sex educations classes.
This is unfortunate
because intersex conditions are actually NOT rare! Some intersex conditions
are among the most common birth disorders in the world - collectively
the total number of people whose bodies differ from standard male or
female affects as many as 1 out of every 100 people!
So why haven't you
heard of intersexuality? Good question. It is certainly a major oversight
on the part of society and educators to omit mention of it.
IS and GID
Because the physical
sex of intersexed people is often ambiguous, parents and doctors usually
"choose" whether the child will be identified and reared as
either male or female. As there is no way to know a newborn's gender
identity these decisions are often made somewhat arbitrarily. If the
child doesn't have a penis the bias is toward raising the child as a
girl simply because "assignment surgery" to configure the
child as female is simpler and more advanced than surgical techniques
to construct external male genitals. Conversely, in cases where the
child has a penis the bias is toward raising the child as a male (unless
the doctor judges that it is "too small"). Children born with
what doctors judge to be an enlarged clitoris are also sometimes assigned
A recent study from
Johns Hopkins University led to their recommendation that children born
with a condition called "micropenis" (where the penis fails
to grow for the final two-thirds of the embryo's development) be reared
as males. The report claimed that 20% of those raised as girls were
satisfied with their surgically constructed vaginas, while 50% of those
raised as men were satisfied with their male genitals after testosterone
hormone therapy. However the study found that those raised male considered
themselves masculine and those raised female considered themselves feminine.
Intersex activists like to point out that these studies are often biased
or use very small test groups to determine medical and surgical policy
where intersexed children are concerned. In this particular instance
the test base consisted of just 16 people, now adults, who were diagnosed
with micropenis as babies. 12 were raised as males, 4 as females. [source].
Another study on
the same topic, conducted after the Johns-Hopkins one but by other researcher
using Johns Hopkins former patients, found surprisingly different results
(and also appeared to have much greater success in getting intersex
people to respond, possibly owing to the many negative experiences with
Johns Hopkins that have been reported in the Intersex Community). The
results of that study found:
(76%) were mainly satisfied with their male sex of rearing established
by physicians and parents. Five participants (24%) reported dissatisfaction
with their male sex of rearing, 1 of whom preferred to think of himself
as intersex and 1 reassigned her gender to that of a woman in early
adulthood. Fourteen participants (78%) were mainly satisfied with
their physician/parent-established female sex of rearing. Four participants
(22%) reported dissatisfaction with their female sex of rearing. Among
the dissatisfied women, 1 reported that her female homosexual orientation
was an obstacle and as a result she would have preferred a male sex
of rearing, and 1 subject reassigned his sex to that of an intersexed
man in early adulthood. Satisfaction with physician/parent-established
sex of rearing did not differ between men and women. [
For more information
on the subject of surgical assignments from the intersexed perspective
you may wish to visit the Intersex Society
of North America web site.
The result of this
practice of choosing a sex shortly after birth has been that, inevitably,
for some of the children the sex the doctors and/or parents chose was
not in sync with the child's gender identity. If that is the case, the
intersexed person is in the same position as anyone who has a physical
sex that is incongruous with gender identity. In other words, they have
a Gender Identity Disorder.
A person need not
be intersexed to have a Gender Identity Disorder, and not everyone with
GID is intersexed. For some intersexed children the assigned sex happens
to be in sync with their gender identity, in which case they do not
have a gender-related conflict. The same can be said of those who are
not born intersexed, the only difference being that it was Nature that
"assigned" their sex, not a doctor.
I mention these
old medical terms, rooted in Victorian-era medicine, because they are
still pervasive in the definitions used by modern medicine.
traditionally have been divided into the following 5 simplified classifications
based on the differentiation of the gonad:
pseudohermaphrodite - Two ovaries
pseudohermaphrodite - Two testes
hermaphrodite - Ovary and/or testis and/or ovotestis
gonadal dysgenesis - Testis plus streak gonad
gonadal dysgenesis - Bilateral streak gonads
(A streak gonad is dysgenetic and resembles ovarian stromal tissue.
No germ cells are present.)
are based solely on the physical state of the gonads. They do not take
into account the individual's endocrinology, genetic makeup, or embryological
development. And, because many different intersex conditions can produce
a child of similar appearance, these terms do little for the purpose
of diagnosing cause. Furthermore, it is often left to the doctor to
decide if the child with ambiguous genitalia has a small penis or an
enlarged clitoris. Modern medicine obviously needs to go beyond this
trivial visual examination for any meaningful diagnosis.
There are literally
hundreds of specific forms of intersexuality covered under the term.
Sometimes intersex conditions are subcategorized by possible cause or
Intersexed - probably the most common form of intersexuality
involves people who are either missing a sex chromosome or have extra
sex chromosomes. The effects of such a condition vary widely. Some people
show no outward signs of being intersexed while in others it is apparent
Intersexed - technically would encompass "chromosomally
intersexed" people too. However it usually refers to individuals
who have normal chromosomal makeup (XX or XY) but have a faulty gene
on one of those chromosomes resulting in an intersex condition.
Intersexed - the person has physical characteristics of both
male and female. Usually this refers to a person with "ambiguous
genitalia" (genitals that do not appear to be "normally"
male or female). However it is also sometimes used to refer to anyone
with a genetic or chromosomal cause, since those are physical characteristics
as well, albeit at the molecular level. This term also encompasses those
who present with ambiguous genitalia caused by developmental anomolies
in the womb of environmental (termed "Iatrogenic"),
rather than genetic, cause.
OF INTERSEX CONDITIONS
- formerly referred to as "true hermaphroditism." People with
Ovatestis are individuals who have both ovarian and testicular tissue.
Please note that this does not mean the person has
both male and female genitalia! This diagnostic nomenclature is applied
regardless of the peripheral karyotype. Technically, the anachronistic
term "True Hermaphrodite" is still in use to refer to those
withouth gonads that are ovoteste, but have separate organs, with an
ovary on one side and a testis or ovotestis on the other. Additionally,
testicular and ovarian tissue may develop on the same side of the pelvis
as a separate ovary and testis. These gonads are almost always
contained within the abdomen at the positions of ovaries in women, but
ovatestes that descend from that position are not unheard of.
People with Ovatestis
usually have ambiguous genitalia at birth, but how ambiguous
is highly individual. The majority of affected individuals have been
reared as males. However, because of functioning normal ovarian tissue,
most people with this problem experience breast development at puberty,
and 40% with a 46,XX karyotype menstruate. Note that some people with
this condition are chromosomally mosaic (see below) but, because karyotyping
tests can be inaccurate in cases of mosaicism, they may "officially"
be delcared to be XX or XY. The author of this site is personally aware
of at least one individual who was tested as being of a male karyotype
(XY) and appeared to have underdeveloped, but complete, male genitals.
Nonetheless, medical imaging uncovered the presence of an ovary and
partially developed uterus. There was also a Urological medical journal
(cited elsewhere on this site) concerning an otherwise "normal
male" who presented with blood in his urine. An ultrasound and
MRI confirmed the presence of a partially developed vagina and uterus;
as well as chromosomal anomolies.
In some of these
cases of of chromosomal mosaicism and the presence in one individual
of organs of both sexes (or combined organs of both sexes) I've read
the cause postulated to have been the absorbtion of an opposite sex
fraternal twin in the womb, but there is no way of verifying if this
theory is correct.
While this birth
condition accounts for less than 10% of all intersex diagnoses it is,
ironically, the most widely known intersex condition among the general
This is a congenital
abnormality in the development of male genitals whereby there is a urethral
opening in the penis, sometimes extending down the shaft so that urine
exits at the base of the penis instead of the tip.
2nd Century A.D. by Galen
- Usually Diagnosed:
at birth, though may appear on prenatal fetal ultrasound scans
1 in 300 births in the United States (and increasing).
- More information:
simply put, is a genetic condition in which a person has either more
or less than 46 chromosomes in at least some of their cells. Most people
are unaware that such a condition is even possible, let alone relatively
different degrees of mosaicism. That is the percentage of cells in
your body that have the extra chromosome. Even when they do a blood
test and tell you that '100% of the cells are XXY,' what they are
saying is '1005 of the cells from your blood that we tested have XXY.'
They may have missed some cells without an X chromosome, and they
do not [know] if the cells in your brain, in your skin, in your gut,
etc., etc. have all XXY. The concept is that there are men with 100%
XXY in all their cells and some others that have a variable percentage."
- Dr. Arturo Rolla, from the KS&A XXY+ADULTS email list, Feb.
It should be noted,
however, that "It seems likely everyone has some small number
of cells in their body which are chromosomally abnormal. However, even
a very minor degree of mosaicism could be important if a crucial tissue
carries the abnormal cells." [source]
In fact, according to a recent article in Nature,
research on nerve cells in the brain has found they appear to naturally
gain and lose chromosomes over time. Why they do so is still a mystery.
The following conditions are all capable of having a "full version"
or a "mosaic variation."
Syndrome (XXY Syndrome)
This is a chromosomal
abnormality affecting males whereby they have sex chromosome makeup
of XXY instead of just XY (referred to as 47,XXY). The extra X chromosome
defines the condition, but there are also physical and hormonal characteristics.
Body shape is usually described as "pear like." Most develop
gynecomastia in puberty (male breasts), have underdeveloped testes of
less than 14ml in volume, and lack development of normal male secondary
sexual characteristics. Developmental delays and learning disabilities
are sometimes present, though more recent studies have found nearly
as many "hyper intelligent" people with Klinefelter Syndrome
so the earlier data was most likely incorrect. 70% of Klinefelters males
are sterile (though it is believed the 30% who are capable of spermatogenesis
may actually be "mosaics" and not Klinefelter males).
In the early 1970's,
researchers around the world sought to identify males having the extra
chromosome by screening large numbers of newborn babies. One of the
largest of these studies, sponsored by the National Institute of Child
Health and Human Development (NICHD), checked the chromosomes of more
than 40,000 babies.
Based on these
studies, the XXY chromosome arrangement appears to be one of the most
common genetic abnormalities known. . . .Although the syndrome's cause,
an extra sex chromosome, is widespread, the syndrome itself - the
set of symptoms and characteristics that may result from having the
extra chromosome - is uncommon. Many men live out their lives without
ever even suspecting they have an additional chromosome. (excerpted
from "Understanding Klinefelter Syndrome: A Guide for XXY
Males and Their Families," by Robert Bock, Office of Research
Reporting NICHD, August 1993 U.S. Department of Health and Human Services.
Pub. No. 93-3202)
First described in1942 by Dr. Harry Klinefelter
47,XXY karyotype confirmed in 1956
- Usually Diagnosed:
1 in 500 to 1000 births
- More information:
Mosacicism: This is a condition is sometimes referred to
as a "Klinefelter Associate" or "Klinefelter Variant"
because it shares with it the common trait of an extra X chromosome.
The difference is that the extra chromosome is not present in every
cell throughout the person's body. About 10% of the cases where
Klinefelters was initially diagnosed turn out to be "Mosaicism."
The most common combination is that some cells will have normal
male makeup of XY and others will be intersexed with XXY, referred
to as 46,XY/47,XXY Mosaicism. Karyotypes of 46,XY/48,XXXY and 47,XXY/48,XXXY
are also found within that ten percent. About 1% of cases are due
to a structurally abnormal X in addition to a normal X and Y. Even
fewer people have the karyotype of 47,XXY/46,XX. One of the problems
with diagnosis is that the intersexed cells are not persistent throughout
the individual's body. When doctors take a blood or tissue sample
it is possible they may not gather any intersexed cells, or that
the ones they do gather might be destroyed in the process of extracting
the DNA to count the chromosomes. Furthermore, diagnosis by blood
sample becomes even less accurate as the person ages because, for
some unknown reason, intersexed blood cells are eliminated over
time by the body. These factors can make a diagnosis elusive, especially
in cases where the Mosaicism is present in only a small percentage
of cells. The expression of Mosaicism is also highly variable. Some
people show no obvious outwards signs of it, while others may present
ambiguous genitalia at birth or developmental abnormalities at puberty.
1956-1960 by various researchers
Diagnosed: depending on intensity diagnosis may be at birth,
puberty, or in adulthood (usually during fertility testing)
1 in 1,666 births
(45, X): This is a chromosomal abnormality affecting females
where they do not have 46 chromosomes, but instead have 45 with only
a single X chromosome. Sometimes it is stated as an XO karyotyope (the
"O" meaning there is no paired chromosome to the existing
X). Turner's girls tend to have broadly spaced nipples and a generally
flatter chest or no breast development (sometimes called a "shield
chest"). Their waist tends to be wide and arms and legs are short
in relation to the torso. Overall stature is usually quite short at
less than 5 feet tall. Turner girls' faces are usually triangular in
shape with a low hairline. There is minimal body hair distribution and
genitals are usually also underdeveloped. Ovarian failure at puberty
and sterility are also common. Approximately 15% of fetuses with Turner
Syndrome spontaneously abort. In some cases the person might have 46
chromosomes, but the second X chromosome has no "short arm"
called "Xp deletion." There is another variation called 45,
X/46, XY Mosaicism where the individual has some cells that are
of the Turner Syndrome karyotype and others that are of a male chromosomal
makeup. In those cases the child may actually have undescended testes
instead of ovaries.
(47, XXX): This is a condition affecting females, sometimes
also called "hypofemale" or "super female." The
physical manifestations of Triplo X are that the woman will usually
have larger than average breasts with wider spaced nipples, a narrow
(wasp) waist, wider hips than average, and a height of usually more
than six feet. Some girls are also born with a "webbed neck"
that is easily surgically corrected. This body type is sometimes describes
as "Vampira" (the 1950's late night horror movie hostess)
or, more recently, like that of the cartoon character Jessica Rabbit
from the movie "Who Framed Roger Rabbit." By most standards
Triplo X females are quite attractive, proving that a genetic/chromosomal
abnormality need not be considered a "deformity." However,
learning disabilities or developmental delays are not uncommon.
(47, XYY): Also sometimes called "Double Y" and "Polysomny
Y." This is a condition affecting males who have an extra Y chromosome.
Physical characteristics are often indistinguishable from an 46, XY
male, though it is not uncommon for those with XYY karyotypes to be
even more masculine than their average XY counterparts. Low, wide waists;
narrow hips; broad, flat chest; wide shoulders; high hairlines; prevalent
facial and body hair; and testes of more than 25ml in volume. It is
also not uncommon for XYY males to have elevated testosterone levels
responsible for the increased virilization they exhibit.
There is a popular
belief that the extra Y chromosome predisposes these men to become criminals
via aggression or sexual predation. There is no scientific
evidence to justify the belief that XYY males are any more prone to
criminal behavior than the general population.
X and Diplo Y sex chromosome disorders are not generally considered
"intersex conditions" since there is no "mixing"
of female and male characteristics, but rather a exaggeration of female
or male characteristics, respectively. They are mostly mentioned here
because "mosaic versions" of them do exist and to illustrate
the diversity of human sex chromosome combinations.
46, XX Male
(Sex Reversal Syndrome): This is a chromosomal variation that
is sometimes mistaken, initially, for Klinefelter Syndrome. People with
this problem have a fragment of a Y chromosome with the "SRY testicular
determining factor" translocated in their system. This causes the
otherwise genetic female to develop physically as a male. 15% of those
with this problem have undescended testes, 10% exhibit hypospadias.
Generally 46, XX Males are shorter than Klinefelter males, but similarly
display a lack of spermatogenisis (frequency unknown). [source: The
Andrology Handbook, American Society of Andrology 1995. full
Figures for occurrence
vary. One study cited that 1 in 5000 births has "full sex reversal,"
with "partial sex reversal" accounting for 1 in 1000 births.
[source: Reaney, Patricia "Gene for human sex reversal syndrome
identified," February 18, 1998 Reuters] Another source claims
incidence is 1 in 20,000 births and that the cause can be attributed
- Mosaicism of
XX and XXY cell lines
- Y;X translocation
(SRY testicular determining factor transposed onto one X chromosome)
- Mutation of a
gene downstream of SRY (testicular determining factor)
Reversal," Clinical Molecular Genetics Society (U.K.), January
2000. full text]
Until about 10 weeks of development in the womb, male and female embryos
appear identical in external anatomy. the same structures then begin
to differentiate as male under the influence of testosterone, or as
female if the influence of testosterone is absent. In the presence of
intermediate amounts of androgens - or partial insensitivity to the
effects - the external genitals may develop in an "in-between"
way. Androgen Insensitivity Syndrome is often abbreviated as AIS and
is caused by a genetic error in the Androgen Recptor (AR) gene on the
X chromosome. People with AIS have a male karyotype of 46, XY but may
not develop a male phenotype.
There are two general
categories for the "complete" and "partial" versions
Androgen Insensitivity Syndrome (CAIS) - the most pronounced
form of the condition where the person's body is almost completely
uninfluenced by androgens. Also sometimes called "Testicular
In CAIS there
will still be no ovaries, fallopian tubes or uterus, and the vagina
will be blind-ending and possibly short or absent. Female pubertal
development occurs but there will be no menstruation and no possibility
of conceiving/bearing children.
testes can result in an inguinal hernia in infancy and this is when
AIS may be diagnosed in an apparently female child (approx. 50% of
cases). Otherwise CAIS may not be discovered until puberty when there
is a failure to menstruate (approx. 50% of cases).
7 - do not develop dark, course hair and often will not
experience acne during puberty due to the complete insensitivity
6 - may develop some dark, coarse hair because its growth
is dependent on the effects of androgens. The nipples usually remain
under-developed and pale in colour. The vagina may need to be lengthened
or constructed before sexual intercourse is possible.
Androgen Insensitivity Syndrome (PAIS)
- a less pronounced form of the condition where the person's body
is immune to androgen influence to varying degrees. Affected individuals
have normal testes with normal production of testosterone and normal
conversion to dihydrotestosterone (DHT), which differentiates this
condition from 5-alpha-reductase Deficiency. Because the testes produce
normal amounts of mullerian-inhibiting factor (MIF), also known as
mullerian-inhibiting substance (MIS) or anti-mullerian hormone/factor
(AMH/AMF) during gestation, affected individuals do not have fallopian
tubes, a uterus, or proximal (upper) vagina. [source]
In PAIS, the external
genitalia can be ambiguous, that is, intermediate in structure between
male and female. Note that the structure of ambiguous external genitalia
can be the same, whether the genetic sex and the sex of the gonads
is male or female. The structure of the external genitals does not
provide a way to determine whether the condition is PAIS of some other
intersex condition. PAIS is also known as "Reifenstein Syndrome."
There are basically five grades of PAIS:
5 - there may be partial fusion of the labia majora (outer
vaginal lips), in which the posterior (back) portion of the labia
form a web of tissue across the back part of the vaginal outlet.
4 - this fusion extends further forward, covering both
the vaginal opening and the true urethral opening. The cavity formed
by the fused labia, through which urine exits, is called a urogenital
3 - a more "masculinized" version of Grade 4
PAIS where the labia are completely fused, so that the urethral
opening is at the base of the clitoris/penis. The fused labia may
have a rugose, or wrinkled appearance and form a bifid, or double,
scrotum. The fusion is then more properly called 'labio-scrotal
fusion'. The phallus has the appearance of a large clitoris, or
a small, bent, penis, bound down in structures called chordee. The
chordee is formed from the same tissues that form the labia minora
in the female and the frenulum of the penis and the tissues surrounding
the urethra (corpus spongiosum) on the underside of the penis in
the male. It is not true that the presence of chordee makes erections
2 - the genital appearance is that of a male with hypospadias,
that is, with a urethral opening located somewhere on the underside
of the penis. There may be an open gutter running from the urethral
opening to the glans of the penis. Assignment is usually male.
1 - No genital deformity or ambiguity. In almost all of
these cases sex assignment at birth is male. The insensitivity to
androgens is usually only detected at puberty when breast development
(gynecomastia) occurs. The patient may or may not be infertile.
This type of AIS is also known as "Mild AIS" (MAIS) and
"Undervirilized Male Syndrome."
accompanies any AIS greater than Grade 3.
is made by physical examination, internal scans, a chromosomal karyotyping,
hormone testing, and genetic testing for a faulty AR gene on the X chromosome
(called "mutation gene analysis) which is considered 95% accurate
in detecting both CAIS and PAIS from buccal swabs. The genetic testing
is slow (6 weeks or more) and expensive (not covered by most insurances).
unclear. Hereditary pattern identified in 1912. Karyotype identified
in 1937. Genetic cause identified in the 1980s.
- Usually Diagnosed:
at puberty or in adulthood (usually as part of fertility tests)
Note: Doctors have often kept the truth about the diagnosis from their
generally accepted estimate at 1 in 20,000 for all grades of AIS from
other estimates range from 1:2,000 to 1:130,000 depending on grade.
- More information:
Reductase Deficiency (5-ARD)-
also known as "familial incomplete male pseudohermaphroditism type
2" and "pseudovaginal perineoscrotal hypospadias." It
is an recessive genetic error resulting in the inability to convert
testosterone into dihydrotestosterone (DHT). Since DHT is required for
the normal masculinization of the external genitalia in utero, genetic
males with 5-ARD are born with ambiguous genitalia (ie, male pseudohermaphroditism).
In other words, the person may appear to physically be male, female,
underdeveloped as either, or a mixture of both.
Effects range from
infertility with normal male genital anatomy to underdeveloped male
with hypospadias to predominantly female external genitalia. There is
no uterus or fallopian tubes. Testes are intact, as are other male reproductive
structures. Male internal ducts are present but may terminate in a blind
pseudovaginal pouch. An underdeveloped prostate may be present, regardless
of the appearance of the external genitalia.
Two genes coding
for 5-alpha-reductase have been identified, each for a slightly different
isoenzyme. The gene for 5-alpha-reductase type 1 has been determined
to be on chromosome 5. Its product is expressed only in nongenital skin
and liver at low levels from the time the individual is aged 3 years
to puberty, at which time enzyme expression is measurable in sebaceous
glands and scalp. Linkage analysis has demonstrated that the type 1
enzyme is unrelated to the clinical syndrome of 5-ARD. The other isoenzyme,
5-alpha reductase type 2, determined on chromosome 2, correlates with
clinical symptoms. It is expressed in high levels in the prostate and
other androgen-sensitive tissues. Interestingly, partial virilization
of males with 5-ARD occurs at puberty and may be attributable to the
rise in type 1 enzyme activity at that time.
More than 20 different
mutations of this gene have been reported in people with clinical and
biochemical evidence of the enzyme deficiency. The presentation of symptoms
by most people is variable, even within the same family.
Adrenal Hyperplasia (CAH) -
The term congenital adrenal hyperplasia encompasses several autosomal
(single chromosome) recessive disorders that share complete or partial
deficiency of an enzyme involved in cortisol or aldosterone synthesis.
[only the CYP21, CYP17, and StAR forms of CAH are discussed below]
All disorders of this group share the common feature of a deficiency
or relative defect in cortisol or aldosterone synthesis resulting in
some degree of cortisol or aldosterone deficiency, or both.
The phenotype (whether
the person looks male or female) depends on which particular protein
is affected and the severity of the mutation or degree of deletion of
the particular gene encoding for the protein involved in steroidogenesis.
The appearance of people with CAH can vary from no apparent effect (clinically
referred to as occult or cryptic adrenal hyperplasia) to a mild form
that becomes obvious during adolescence or adulthood (nonclassic adrenal
hyperplasia), to severe forms diagnosed in infancy, with or without
virilization and salt wasting (classic adrenal hyperplasia). CAH activity
is generally divided clinically into a simple virilizing (masculinizing)
form and a salt-wasting form.
Females with some
forms of CAH have ambiguous genitalia at birth (classic virilizing adrenal
hyperplasia) or become virilized in later childhood (simple virilizing
adrenal hyperplasia) or in adolescence and adulthood (nonclassic virilizing
Males with the "CYP21"
form of CAH are not generally identified as infants because their genitalia
appear normal. If the chromosomal defect is severe, resulting in salt
wasting, these male infants are seen at 1-4 weeks of age because of
failure to thrive, recurrent vomiting, dehydration, and shock. Some
male infants are initially misdiagnosed with gastroenteritis or pyloric
stenosis. If not diagnosed in infancy, they are often diagnosed in later
childhood because of early pubic hair and/or phallic enlargement accompanied
by accelerated linear growth and advancement of skeletal maturation.
Males with "CYP17"
deficiency generally have ambiguous genitalia or female genitalia because
of inadequate testosterone production in the first trimester of fetal
A female with "CYP17"
deficiency appears female at birth, but does not develop breasts or
menstruate in adolescence because of inadequate estradiol production.
Males with StAR deficiency (lipoid adrenal hyperplasia) have female
or ambiguous genitalia. Females have normal female genitalia. Genetic
females who survive infancy do develop breasts and menstruate at puberty.
then, varies along the full continuum from "normal male" to
"normal female," with the possible added complication of metabolic
problems which upset serum sodium balance. The metabolic effects of
CAH can be counteracted with cortisone.
1865 Luigi DeCrecchio. Treatment devised in 1950.
- Usually Diagnosed:
birth or early childhood
Cryptic: 1 per 60 in the general population*
Non-Classic: 1 in 27 to 1 in 100
Classic: 1 per 13,000 to 1 per 16,000
CYP21 accounts for 90% of all cases
CYP11 accounts for 5-8% of all cases*
* CYP21 errors are present in as many as 1 out of 3 people of
Ashkenazi Jewish heritage. CYP11 are more often observed in people
of Moroccan, Iranian, or Jewish descent.
- More information:
Induced Virilization (PIV)
- Progestin is a drug which was administered to pregnant women in the
1950's and 1960's and is converted to an androgen by the prenatal XX
fetuses' metabolism. Sometimes the genitals of fetuses affected by progestin
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 feminizing puberty occurs due to normally functioning
- DES is a synthetic estrogen that was given to millions of pregnant
women between 1937 and 1971 because the medical profession believed
it would help prevent miscarriage and insure a healthy full term pregnancy.
A 1957 advertisement claimed desPLEX® would "prevent ABORTION,
MISCARRIAGE and PREMATURE LABOR…recommended for routine prophylaxis
in ALL pregnancies…" This was only one of numerous brand
names that DES (diethystilbestrol) was sold under.
DES did not work.
In fact, the unfortunate use of this drug has resulted in severe risks
and consequences to the health of many of the women who took the drug,
as well, the daughters and sons whom they bore.
(46, XY DES) - DES sons are those who's mothers took DES
during pregnancy. Although, most DES sons will not experience adverse
health effects from this exposure there are certain signs that should
be watched for by a medical professional.
The effects faced
by DES sons include:
- Meatal stenosis-
a narrowing of the opening of the penis.
cysts- the most common abnormality, non-cancerous cysts located
on the back of the testicles.
problems- undescended or small testicles, which are visible at,
birth. Men with this condition are at increased risk of testicular
(also called Micropenis)
varicoceles- an irregularly swollen or varicose vein on the testicle.
do not show a correlation between DES and fertility problems in men.
Testicular self-exam and yearly check-ups are important for all men,
but particularly for DES sons.
(46, XX DES) - Contrary to prior belief, women who were exposed
to DES before birth also experience problem. They require special
care during pregnancy because of an increased risk of problems such
as ectopic pregnancy and premature labor and delivery. However, with
proper care most women can achieve and maintain healthy full term
pregnancies. Some DES exposed women may have an increased risk of
fertility problems, however getting pregnant is not difficult for
most women, and routine infertility evaluation is not usually necessary.
The greatest risk to DES daughters is an increased risk for a rare
form of cervical or vaginal cancer called clear cell carcinoma. Abnormal
cell changes on the cervix may occur more frequently among this group
of women and they should be treated in most cases. DES daughters need
regular pelvic exams at all ages. The pelvic exam for DES daughters
is slightly different from the normal pelvic exam because it includes
a separate Pap smear of the upper vagina. If DES-related changes are
detected during a pelvic exam, it may be necessary to have pelvic
exams more than once a year.
- Usually Diagnosed:
at any stage of life problems may be discovered that can be linked
to DES exposure before birth or as children.
- More information:
- Although DES is no longer given to pregnant women, a new problem has
been identified. There are a number of industrial chemicals and pesticides
like DDT and PCBs that mimic estrogenic activity (called pseudo-estrogens).
Many of these chemicals, although either discontinued or restricted
in use, have found their way into the ecosystem. There is a growing
body of evidence concerning how these "environmental estrogens"
feminize the male reproductive systems across almost all species exposed
to them - including human beings. Obviously those exposed to these chemicals
in utero or after birth are at risk, though the effects are far more
pronounced on a developing fetus than on an adult.
Allen, E. and E.A. Doisy. 1923. DDT's estrogenic effect identified
- Usually Diagnosed:
at any stage of life problems may be discovered that can be linked
to Environmental Estrogen exposure before birth or later in life.
- More information:
LIST - This list of Intersex Conditions is far from comprehensive.
There are simply too many variations, causes, and presentations to create
a complete catalog of them on this site. For more detailed information
click on the "More information" links following each condition.
It should be pretty
obvious that anyone who taught you that men have a penis and testicles
and XY chromosomes and women have a vagina and ovaries and XX chromosomes,
at best, oversimplified the diversity of biological sex.
FREQUENCIES - The
prevalence of each condition listed may not reflect the true frequency
of it in the general population. Estimated frequencies are based on
diagnosed, recorded cases identified in a clinical setting. It is likely,
especially for milder forms of each condition, that there is a significant
portion of cases that are misdiangosed or go undiagnosed altogether.
Frequencies are also affected by the databases and recording methodologies
used, which vary widely from one locale to another. For example, the
estimate for Androgen Insensitivity Syndrome at 1 in 20,000 comes from
a Danish database of genetic anomolies. Denmark has a national healthcare
system with standardized reporting to a government maintained database.
And the number refers to all incidence of AIS without distinction of
grade. The American prevalence of 1 in 60,000 is based on girls identified
as having Complete Androgen Insensitivity Syndrome (grades 7 or 8) who
were discovered during routine hernia operations. Until that point those
girls were assumed to be genetic females. Partial Androgen Insensitivity
Syndrome may be mild enough to go undiagnosed, or may be misdiagnosed
as another problem. The Intersex Society of North America quotes a frequency
of 1 in 130,000 for PAIS cases. However, that only represents those
cases that were clinically identified. It is likely mild PAIS forms
(especially grade 1) are quite common but are never clinically identified.
The most comprehensive
study of chromosomal anomolies, the National Institute of Child Health
and Human Development (NICHD) multi-year study in the early 1970's of
some 40,000 infants, found an incidence of 1 in 500 to 1 in 1000 for
XXY karyotypes. Follow up studies of reported clinical identification
of XXY conditions indicated that only about 2% of such people were ever
formally diagnosed. This either indicates that, while XXY karyotypes
are quite common adverse effects are relatively rare, or doctors are
overlooking or misdiagnosing the conditions, or the bulk of people with
XXY karyotypes never present themselves to a doctor.