Feedback Hormones from Testicles
There are feedback hormones—testosterone and
inhibin—that keep a check and balance on GnRH, LH, and
FSH levels. Once the Leydig cells in the testicles produce
enough testosterone, the hormone control systems cut
back on GnRH and LH production. When the Sertoli
cells, which respond to FSH stimulation, produce enough
inhibin, the pituitary cuts back FSH production.
Fertility Factor: The Hormone Balancing Act
Several things can go wrong with the hypothalamus—
¾ The brain can fail to pulse GnRH properly
¾ The pituitary can fail to produce enough LH and FSH to
¾ The testes Leydig cells may not produce testosterone in
response to LH (pituitary) stimulation
¾ The body may produce other hormones and chemical
compounds which interfere with sex-hormone balance.
Congenital obstruction/absence of ducts 2
Erection, orgasm, ejaculation:
Problem % Infertile population %
Hyperprolactinemia (elevated prolactin) 10-40
Congenital adrenal hyperplasia 1
Any one of these conditions can impair sperm
An Overview of Hormonal Treatment
If the pituitary hormones (LH and FSH) are low, but the
hypothalamus and pituitary gland are working fine, then
clomiphene citrate (cc) is administered to stimulate the
hypothalamus to pulse GnRH at regular intervals. When the
hypothalamus properly releases GnRH, the pituitary gland
will respond by producing LH and FSH. If clomiphene
citrate does not improve LH and FSH levels, then one can
suspect that the pituitary gland may be malfunctioning.
If the pituitary cannot manufacture the missing sex
hormones, one has to take hormone supplements—hCG
Diagnosing and Beating Specific
Hyperprolactinemia (elevated prolactin) can be difficult to
diagnose because FSH, LH, and testosterone levels will be
normal. We find elevated prolactin, a hormone associated
with nursing mothers, in 10 to 40% of infertile males. Mild
prolactin elevation produces no symptoms; however,
greater elevations can reduce sperm production, impair
sex drive, and cause impotence. Hyperprolactinemia
responds well to bromocriptine. A prolactin-secreting
tumor will also respond to bromocriptine; however,
surgery and/or radiation therapy may be necessary.
Found in 1% of infertile men, hypothyroidism (low thyroid
hormone) can cause poor semen quality, poor testicular
function, and/or disturbances in sex drive. The person
will be lethargic, intolerant of cold, and overweight.
Because the pituitary gland is trying its best to stimulate
the unresponsive thyroid gland, the pituitary-produced
TSH (thyroid-stimulating hormone) level will be elevated.
Elevated prolactin levels, frequently found with this
disorder, may cause impotence.
Correcting the diet or beginning thyroid hormone
replacement therapy should elevate sperm count to
Congenital Adrenal Hyperplasia
Found in 1% of infertile males, congenital adrenal
hyperplasia may be suspected when a semen analysis
shows a low sperm count, an increased number of
immature sperm cells, sperm with long tapered heads, and
low motility. These abnormalities occur when the pituitary
is suppressed by increased levels of adrenal androgens.
Men with this disease may also have hypertension (high
blood pressure) and edema (water retention). Early onset
of the disease may result in ambiguous genitalia at birth
or reaching puberty at an early age. Adult onset may be
characterized by infertility, high blood pressure, and/or
Cortisone replacement therapy will lower the androgens
and allow the pituitary to function normally. Therefore,
indirectly, cortisone replacement therapy will elevate
Hypogonadotropic Hypopituitarism
Hypogonadotropic hypopituitarism is a spectrum of
diseases with a complicated name that means low (hypo)
pituitary gland output of LH and FSH. Other stages of
this disease are called isolated gonadotropin defect and
panhypopituitarism, in which the entire (pan-) pituitary
These diseases arrest sperm development and cause the
progressive loss of germ cells from the testes. In addition,
the seminiferous tubules and Leydig cells (which produce
FIG. 24.9: Male hormones, feedback and effects
a long time, there will be no sperm production at all. When
the disease is associated with a pituitary tumor, elevated
prolactin levels may also cause impotence.
Complete pituitary gland failure (panhypopituitarism)
lowers growth hormone, ACTH level, thyroid-stimulating
hormone (TSH), and LH and FSH levels. Person having
this rare disease will have multiple symptoms that include
impotence, decreased sex drive, loss of secondary sex
characteristics, and normal or undersized testicles.
Hypothyroidism (low thyroid hormone) will cause to
gain weight, be intolerant of cold, and feel lethargic. If the
disorder began early enough in your life it may even cause
dwarfism. The hormonal deficiency is often caused by a
tumor, surgery, or trauma to the pituitary gland.
Kallmann’s syndrome is a congenital hypothalamic
dysfunction. A person born with this unusual condition
will have underdeveloped testicles and possibly a harelip,
cleft palate, color blindness, and/or the inability to smell.
Affected men have varying degrees of sexual infantilism
(prepuberty) and no sperm production. Since the
hypothalamus fails to stimulate the pituitary adequately,
FSH, LH, and testosterone levels are low.
Kallmann’s syndrome is treated similarly to
hypogonadotropic hypopituitarism. Although at first it
seems hopeless, men afflicted with Kallmann’s syndrome
can achieve normal puberty and eventually become fertile.
Individuals with isolated pituitary growth hormone
deficiency do not sexually mature until their mid-to-late
twenties. Hormone supplements can make them look
virile, but until they go through puberty, they would not
be fertile. The LH/FSH and/or hCG injections can bring on
puberty, although if left alone, sexual maturity and fertility
Although virilization (acquisition of adult sex
characteristics) will be moderately advanced, but the
individual will not have completed sexual maturation and
testicular growth. Here, the arrest of sperm production and
low testosterone levels are caused by an LH deficiency.
Treating Unresponsive Testicles
What Causes Testicular Failure?
Let us suppose that the hypothalamus and pituitary are
working well. The fact is that some conditions prevent
the testicles from responding to pituitary hormone
stimulation. Testicular failure, as it is called, can be caused
by genetic abnormalities or by damage from drugs, injury,
radiation, excess heat, adult mumps, a varicocele, or toxins
from your environment. Sensing abnormal testicular
function, your brain responds by telling your pituitary to
pump out more FSH to stimulate sperm production. In
fact, elevated FSH is the primary diagnostic indicator for
Varicocele is a varicose vein that allows blood to pool in your
scrotum. It is thought that poor circulation may lead to a
build-up of blood toxins or increase your scrotal temperature.
Either of these conditions may result in infertility.
Undescended testicles occur in 8 out of 1,000 boys. Hence,
Mumps, tuberculosis, brucellosis, gonorrhea, typhoid,
influenza, smallpox, and syphilis can cause the testes to
atrophy. With some of these infections, LH and testosterone
(virility) levels may remain normal. However, if FSH is
high, then prognosis for testicular recovery is poor.
Torsion of the testis and/or blood vessels supplying
the testis (spermatic cord) is a common problem that
Each cell in a normal man’s body has only one Y (male)
and one X (female) chromosome. People with Klinefelter’s
syndrome, however, have one Y and two X chromosomes
in each cell. In the beginning stages of this rare disorder
FSH is only slightly elevated, indicating minimal testicular
failure. However, eventually all other active testicular
structures will atrophy, including germ cells, tubules,
Leydig cells, and Sertoli cells; the testes themselves actually
shrink. After testicular failure occurs (causing FSH levels to
rise dramatically), improving fertility is impossible.
Cushing’s syndrome occurs when the adrenal gland
secretes excessive amounts of cortisol. People with
this rare disorder will have a moon-shaped face and
will suffer from water retention, obesity, impotence,
feminized characteristics, loss of sex drive, and infertility.
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