structures will atrophy, including germ cells, tubules, Leydig cells, and Sertoli cells; the testes themselves actually The Endocrine System 763 shrink. After testicular failure occurs (causing FSH levels to

 

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.

Where Can Things Go Wrong?

Fertility Factor: The Hormone Balancing Act

Several things can go wrong with the hypothalamus—

pituitary endocrine system:

¾ The brain can fail to pulse GnRH properly

¾ The pituitary can fail to produce enough LH and FSH to

stimulate the testes

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.

Testicular failure 14

Smoking, heat, drugs ?

Sperm delivery:

Obstructed ducts 7

Congenital obstruction/absence of ducts 2

Erection, orgasm, ejaculation:

Sexual problems 5

Ejaculation problems 2

Problem % Infertile population %

Hormone:

Endocrine 9

Hyperprolactinemia (elevated prolactin) 10-40

Congenital adrenal hyperplasia 1

Stress ?

Sperm production:

Varicocele 40

Contd...

Contd...

The Endocrine System 761

Any one of these conditions can impair sperm

production.

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

or Pergonal (LH + FSH).

Diagnosing and Beating Specific

Hormonal Problems

Hyperprolactinemia

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.

Hypothyroidism

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

previous levels.

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

water retention.

Cortisone replacement therapy will lower the androgens

and allow the pituitary to function normally. Therefore,

indirectly, cortisone replacement therapy will elevate

sperm count.

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

gland is affected.

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

762 Concise Book of Medical Laboratory Technology: Methods and Interpretations testosterone) also deteriorate. If the condition persists for

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.

Panhypopituitarism

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

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.

Delayed Puberty

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

will be achieved in time.

Fertile Eunuch

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.

Fertility Factor 2

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

testicular failure.

Varicocele

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.

Cryptorchidism

Undescended testicles occur in 8 out of 1,000 boys. Hence,

it causes infertility.

Infection

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

Torsion of the testis and/or blood vessels supplying

the testis (spermatic cord) is a common problem that

threatens fertility.

Klinefelter’s Syndrome

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

The Endocrine System 763

shrink. After testicular failure occurs (causing FSH levels to

rise dramatically), improving fertility is impossible.

Cushing’s Syndrome

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.