initiated at puberty, they continue, at least to some extent,
throughout adult life. There is a steady decrease, however, in tes-
tosterone secretion, beginning at about 40 years of age, which
ects slow deterioration of testicular function and
failure of the gonads to respond to the pituitary gonadotropins.
Along with the decreasing testosterone levels, libido decreases,
and sperm become less motile. Despite these events, many men
continue to be fertile in their seventies and eighties.
With aging, some men manifest increased emotional
problems, such as depression, and this is sometimes referred to
). It is not clear, how-
ever, what role hormone changes play in this phenomenon.
We have already discussed erectile dysfunction and
prostate cancer. Several additional conditions highlight the
pathophysiology of male reproduction.
A decrease in testosterone release from the testes can be
caused by a wide variety of disorders. In general, they can be
classiﬁ ed into testicular failure (primary hypogonadism) or
a failure to supply the testes with appropriate gonadotropic
stimulus (secondary hypogonadism). The loss of normal
testicular androgen production before puberty can lead to a
failure to develop secondary sex characteristics (deepening of
the voice, pubic and axillary hair, and increased libido) as well
as a failure to develop normal sperm production.
A relatively common genetic cause of hypogonadism
The most common cause of this
disorder, occurring in 1 in 500 male births, is an extra X
chromosome (XXY) caused by meiotic nondisjunction.
The classic form is caused by the failure of the two sex
chromosomes to separate during the ﬁ rst meiotic division
in gametogenesis (from Steps g to h in Figure 17–2). The
extra X chromosome can come from either the egg or the
sperm. That is, if nondisjunction occurs in the ovary leading
to an XX ovum, an XXY genotype will result if fertilized
by a Y sperm. If nondisjunction occurs in the testes leading
to an XY sperm, an XXY genotype will result if that sperm
fertilizes a normal (single X) ovum.
The XXY genotype leads to a male child of normal
appearance before puberty. However, after puberty, the
testes remain small and ﬁ rm. Because of abnormal Leydig
cell function, testosterone levels are low. The lack of local
testosterone production in addition to the abnormal
development of the seminiferous tubules leads to decreased
sperm production. Normal secondary sex characteristics
do not appear, and breast size increases (
). These men have relatively high
gonadotropin levels (LH and FSH) due to loss of androgen
and inhibin negative feedback. Men with Klinefelter’s
syndrome can be treated with androgen replacement therapy
to increase libido and decrease breast size. This will not
restore normal spermatogenesis, however.
Hypogonadism in men can also be caused by a decrease
in LH and FSH secretion (secondary hypogonadism).
Although there are many causes of this loss of function of the
pituitary cells that secrete LH and FSH,
(increased prolactin in the blood) is one of the most
ADDITIONAL CLINICAL EXAMPLES
common. Although prolactin has minimal effects in men
under normal conditions, the pituitary gland still has cells
that secrete prolactin (lactotrophs). Pituitary tumors arising
from prolactin-secreting cells can develop and secrete very
high levels of prolactin. One of the effects of high prolactin
is to inhibit LH and FSH secretion. (This occurs in men
and women.) Sometimes, these tumors can get so big that
they can press on the optic chiasm and cause loss of vision.
One potential treatment takes advantage of the fact that
the primary controller of prolactin release is inhibition by
hypothalamic dopamine. Dopamine agonists can be given
to reduce the size and activity of prolactin-secreting tumors.
Once these tumors are reduced in size, they can be removed
by surgery, although the tumors often recur.
Klinefelter’s syndrome in a 20-year-old man. Note relatively
increased lower/upper body segment ratio, gynecomastia, small
penis, and sparse body hair with a female pubic hair pattern.
Courtesy of Glenn D. Braunstein, MD.