Male and Female Gonadal Abnormalities 

    In males, a number of gonadal abnormalities
may exist. One of these is known as the vanishing testis syndrome: an XY fetus
develops tests that then undergo atrophy. The reason for this remains
speculative, although torsion, thrombosis and viral infections have been
suggested. However, the failure of the development of the tests leads to a
female default state, as above (similar).

    In Leyding Cell hypoplasia the Leyding cells
responsibility for the production of testosterone either completely fail to
produce this or produce it in only small quantities. A range of abnormalities
may result, dependent on the level of androgen produced, and therefore the
phenotype may range from female through to the hypospadiac male.

    In XY gonadal dysgenesis, a genetic abnormality
leads to an abnormal testicular development. The testis fails to secrete
androgen or Mullerian inhibitor, resulting in an XY female. If the genetic
abnormality leads to an enzyme deficiency in the biosynthetic pathway to
androgen, testosterone will fail to be secreted by the testis. 

    However, some
androgen may be produced, depending on which enzyme is absent in the pathway.
Therefore some effect on the external genitalia may be possible and a varying
degree of virilism will occur. If the biosynthetic production of Müllerian
inhibitor is deficient, its absence will, of course, mean the persistence of
the Müllerian duct. This is an extremely rare syndrome.

    In the female, gonadal dysgenesis may occur,
and in this situation (similar to Turner’s syndrome) the gonad is present only
as a streak. These individuals have been found to have small fragments of a Y
chromosome and. as a result of this, the gonad may undergo mitotic change,
which leads to ne development of a gonadal tumor, eg a gonadoblastoma. 

    The
Mullerian structures remain and the Wolffian structures regress, because of the
absence of tests. At puberty, the failure of development of the ovary will mean
that there is no possibility for the production of oestradiol, and a failure of
secondary sexual characteristic growth will occur,

    In the rare condition known as mixed gonadal
dysgenesis, there is a testis and a streak gonad in the same individual. The
chromosome complement is typically 46 XX or a mosaic with a Y component. Here,
strangely, the Wolffian structures develop only on the side of the testis, but
all Müllerian structures regress. The external genitalia in this rare condition
may be ambiguous, depending on the functional capacity of the testis.

    In true hermaphrodites, the gonad may develop
into either a testis or an ovary, or a combination of the two known as an
ovotestis. Here, a number of permutations may occur, with either a testis and
an ovary, or an ovotestis with a testis, an ovary or another ovotestis . 

    This
usually results from a mosaic XX:XY karyotype, and the predominance of either
ovarian or testicular tissue in the gonad depends on the percent- age of cell
lines in the mosaic. As can be seen from, the combination of gonads will
determine the degree of virilization: the greater the testicular component, the
more virilized the resulting development and the more likely the presence of
Müllerian inhibitor. 

    Thus, in the true hermaphrodite, it is possible to get
co-existent Müllerian and Wolffian structures in terms of internal development,
and varying degrees of masculinization of the external genitalia, depending on
the combination of gonads.

Internal genitalia abnormalities

    In males there are three fundamental changes
that may lead to abnormalities of the internal genitalia. The first of these is
androgen insensitivity. In this condition the fetus fails to develop androgen
receptors due to mutations in the androgen receptor gene. Failure to possess
the receptor means that although the testis will be producing testosterone, the
androgenic effect cannot be translated into the end organ as it is not
recognized by the cell wall. 

    The result here is that the fetus develops in the
default female state, as it is unable to recognize the androgenic impact. This
is the commonest type of XY female and the Wolffian ducts regress, as they also
have no androgen receptor. However, the Müllerian ducts also regress because
the testis is normal and produces Müllerian inhibitor. Girls with this
abnormality present with primary amenorrhoea at puberty.

    A further aberration in XY females also exists
with a condition known as 5a-reductase deficiency. As outlined above, this
enzyme is responsible for the conversion of testosterone to dihydrotestosterone
resulting in virilization of the cloaca. If this enzyme is absent, the external
genitalia will be female but the internal genitalia will be male. The Müllerian
ducts will regress. Here again, this female will present with primary
amenorrhoea.

    Finally, a rare condition known as Müllerian
inhibitory deficiency may mean that an XY male may have persistent Müllerian
structures, due to the absence of Müllerian inhibitory factor, and co-existent
male and female internal structures.

    In 46 XX females, a genetic defect that
results in failure of development of the uterus, cervix and vagina is known as
the Rokitansky syndrome. This is the second most common cause of primary
amenorrhoea in women, the first being Turner’s syndrome. Here the ovaries are
normal, and the external genitalia are normally female. 

    The internal genitalia
are either absent or rudimentary. Variations on this may lead to development of
the vagina without development of the uterus, or development of the uterus
without subsequent development of the cervix or vagina, and a functional uterus
may result. The aetiology of this developmental abnormality remains to be
clarified. 

    It is probably, however, a defect in the genes responsible for the
development of the internal fee genetalia These genes, known as the homeobox
genes, are likely to possess either deletions, which may be partial or
complete, or point mutations and, as a consequence of these variations, the
resulting structures of the internal genitalia will vary in their development. 

    However, the overall effect of this developmental abnormality is a failure of
uterine and vaginal development, leading to infertility. These patients will
present at puberty with either primary amenorrhoea or, in circumstances when a
small portion of uterus may be functional, with cyclical abdominal pain due to
retained menstrual blood.

    Two other developmental abnormalities may
occur. The first of these is maldevelopment of the uterus, in which fusion
defects occur from the extreme of a double uterus with a double cervix through
to the normally fused uniform uterus. 

    These abnormalities have been classified
and result from the failure of fusion of the paramesonephric ducts at their
lower border. A mal- developed uterus may be associated with some degree of
reproductive failure.

    The development of the vagina involves a
down-growth of the vaginal plate and subsequent union of this with the cloaca
and thereafter canalization. This process can also fail, leading to the second
developmental abnormality, transverse vaginal septae, in which the passage of
the vagina is interrupted and therefore at menstrual blood is trapped in an
upper vagina that does not connect to the lower vagina. 

    In the unusual
condition of a double uterus, a double vagina- can also exist, and failure to
develop the full double vaginal system may result in a blind hemivagina, again
leading to a collection of menstrual blood at puberty.