INTERSEX: MALE PSEUDOHERMAPHRODITISM I GONADAL
The
pseudohermaphrodite is an individual with the gonads of only one sex but with
genitalia (internal and external) and secondary sex characters exhibiting
sexual ambiguity. Such a simple classification of intersex is based purely on
phenotype or morphology, without regard to genetic etiology. Factors that
contribute to such disordered development include (1) gene mutations, (2)
abnormal maternal hormonal influences, and (3) abnormal hormonal influences from the embryonic
gonad, adrenal, or other endocrine organ. The type and degree of disordered
development depend on the intensity and timing of these influences during embryonic
life.
Male
pseudohermaphrodites have varying degrees of female internal or external
genitalia but have gonads that are testes. Although genetically male, they are
often raised as female; the onset of puberty with growth of the penis, hair,
and voice change usually precipitates the medical evaluation for intersex.
Simple penile hypospadias is a very elementary form of male pseudohermaphroditism.
In more severe forms, müllerian structures can develop to various degrees, and
in most instances a bifid scrotum appearing as labial folds co ceals a
rudimentary blind pouch or well-developed vaginal cavity. The testes may lie
intraabdominally, within the canal, or may have descended into a bifid scrotum.
When the sex of the infant is unclear, exploratory surgery and gonadal biopsy
to determine gonadal as well as genetic sex is advisable during infancy. Most
male pseudohermaphrodites develop emotionally as males during puberty, which
has led clinicians to perform gender correction procedures before puberty,
including release of penile chordee, construction of a penile urethra,
orchiopexy and, in some instances, excision of the vagina, uterus, and
fallopian tubes.
Milder
forms of male pseudohermaphroditism include Klinefelter syndrome (47,XXY;
48,XXXY and mosaics), Kallmann syndrome (gonadotropin-releasing hormone
deficiency and anosmia), micropenis, and distal hypospadias. Aphallia is a birth
defect in which the penis or clitoris is congenitally absent. It is a rare
condition, with fewer than 100 cases reported. Its cause is not entirely clear,
but it appears to be due to a failure of the fetal genital tubercle to form
between 3 and 6 weeks after conception. Anatomically, the urethra opens on the
perineum. Although aphallia can occur in both males and females, it is
considered more troublesome in males and engenders controversy about the role
of gender reassignment surgery.
There are
several forms of gonadal dysgenesis that may also result in male
pseudohermaphroditism. The term pure gonadal dysgenesis describes
conditions with normal sex chromosomes (e.g., 46,XX or 46,XY), as opposed to
gonadal dysgenesis in which the genetic constitution involves missing or
truncated sex chromosomes. (e.g., Turner syndrome, 45,X). Mixed gonadal
dysgenesis involves a genetic mixture of sex chromosomes (e.g., 46,XY/45,X). In
this condition, there is a streak gonad that develops on one side, with a
partially developed testis on the opposite side, and it can be associated with
ambiguous genitalia. Importantly, streak gonads with Y chromosome–containing
cells have a high
likelihood of developing cancer, especially gonadoblastoma. In Swyer syndrome,
an example of 46,XY pure gonadal dysgenesis, there is atypical formation of
both gonads early in gestation. In complete gonadal dysgenesis, the gonads do
not function at all, resulting in a female appearance of the external genitalia.
In partial gonadal dysgenesis, the testes function, but not at normal levels,
resulting in a male with ambiguous genitalia. Because the adrenal glands can
make small amounts of
androgens and are unaffected, pubic hair develops in most patients, although it
often remains sparse. In complete forms such as Swyer syndrome, the diagnosis
is often made due to delayed puberty. A karyotype reveals XY, and pelvic
imaging demonstrates a uterus (no müllerian inhibiting substance present) but
no ovaries (streak gonads are not usually seen). The absence of breasts and the
presence of a uterus exclude the possibility of androgen insensitivity.
Another
condition, 5-α-reductase deficiency
(5- ARD), can be observed in phenotypic females with a normal male karyotype.
It is characterized by an absence of the enzyme 5-α-reductase, which converts testosterone to
dihydrotestosterone (DHT). DHT is the primary androgen needed for the normal
development of male external genitalia during development. Without DHT, prenatal
genital development results in a female appearance. Individuals with 5-ARD can
have normal male external genitalia, ambiguous genitalia, or normal female
genitalia. They are born with testicles and wolffian structures but usually have
female sex characteristics.
Because
of the normal action of müllerian-inhibiting substance produced by the testis
in utero, individuals with 5-ARD lack a uterus and fallopian tubes. Consequently,
they are often raised as girls and may develop a female gender identity.
Because male puberty depends more strongly on testosterone than on DHT, puberty
will be virilizing unless the gonads are removed or a blocking medication is
used. As a consequence of virilization at puberty, gender identity issues may
result in adulthood. Phenotypic
girls will also have primary amenorrhea.
Individuals
with 5-ARD are generally capable of producing viable sperm. In individuals with
feminized or ambiguous genitalia, there is a tendency toward a macroclitoris or
microphallus. This structure may be capable of ejaculations as well as
erections; however, assisted reproduction is necessary as intercourse may not be possible.
