Definition
Gynecomastia is a common disease of the male breast
where there is a benign glandular enlargement of that breast
at some time in the male’s life. It usually consists of the
appearance of a flat pad of glandular tissue beneath a
nipple which becomes tender at the same time. The
development may be unilateral or bilateral. There is rarely
a continued growth of the breast tissue; ordinarily the
process is of brief duration and stops short of the
production of permanent enlargement of the breast.
Causes
A great number of patients who suffer from this
disease have a disturbance in the proper ratio of androgen
and estrogen levels. The normal ratio of the two hormones
in plasma is approximately 100:1. “The etiology of
gynecomastia in patients with a known documented cause
appears to be related to increased estrogen stimulation,
decreased testosterone levels, or some alteration of the
estrogens and androgen so that the androgen-estrogen ratio
is decreased”(Williams 373). From this information it was
discovered that there is also a lower ratio of weaker
adrenal androgens (delta 4-androstenedione and
dehydroepiandrosterone) found in youths with this disease.
It was once believed that there was an imbalance in the
ratios of testosterone to estrogen or estradiol, but this is
now know to be untrue.
There are three areas the can be attributed to the
cause of gynecomastia: physiologic, pathologic and
pharmacologic. “Enlargement of the male breast can be a
normal physiologic phenomenon at certain stages of life or
the result of several pathologic states.”(Isselbacher, 2037)
In the case of physiologic gynecomastia the disease
can occur in a newborn baby, at puberty or at any time in a
man’s life. In the newborn, transient enlargement of the
breast is due to the action of maternal and/or placental
estrogens. The enlargement usually disappears within a few
weeks. Adolescent gynecomastia is common during puberty
with the onset at the median age of 14. It is often
asymmetrical and frequently tender. It regresses so that by
the age of 20 only a small number of men have palpable
vestiges of gynecomastia in one or both the breasts.
Gynecomastia of aging also occurs in otherwise healthy men.
Forty percent or more of aged men have gynecomastia. One
explanation is the increase in age in the conversion of
androgens to estrogens in extra-
glandular tissues. Drug therapy and abnormal liver
functioning can also be causes of gynecomastia in older men.
When the disease is pathologic the patient can have
increased estrogen secretions, increased conversion of
androgens to estrogens or decreased androgen activity due to
a failure in protein receptors. Increased estrogen
secretions are found in such diseases and disorders as
Hermaphroditism, Kleinfelter’s syndrome, congenital adrenal
hyperlasia, and adrenal carcinoma or testicular tumors. In
the second case some examples are adrenal carcinoma, liver
disorders, malnutrition and thyroidtoxicosis. Decreased
androgen activity can be found in complete testicular
feminization, incomplete testicular feminization and
Reifenstein’s syndrome.
Many drugs can cause gynecomastia by several
mechanisms. The drugs can either act directly as estrogens
or cause and increase in plasma estrogen levels. “Boys and
young men are particularly sensitive to estrogen, and can
develop gynecomastia after the use of dermal ointments
containing estrogen or after the ingestion of milk or meat
from estrogen-treated animals.”(Isselbacher, 2038) Some
examples of drugs that may have cause gynecomastia include
Cannabinoids (methane and marijuana), Psychotropics
(pheno-thiazine, butyrophenone and reserpine),
Antihypertensives (reserpine, alpha-methyldopa and
spironolactone), Cardiac (digitalis), Gastrointestinal
(cimetidine, metoclopramide and domperidone),
Antituburculous (isoniazid), Cytoxic (cyclophospha-mide,
mustine, vincristine and mitotane) and Hormonal (sex
steroids, gonadotropins and antiandrogens). Use of these
drugs, however, will rarely cause gynecomastia. In some
instances, the feminization is due to effects of drugs on
liver functions.
Signs and Symptoms
There are very few signs and symptoms that are
associated with the this disease. Signs may appear at any
time in a male’s life, although the most common time of
onset is during puberty. At the first indication of the
disease the patient will feel pain and tender-
ness in the breast area due to the rapid development of the
breast. The breasts grow because of the enlargement of the
glandular tissue. “The concentric arrangement of the
connective tissue around the ducts is a characteristic
feature of the active phase of gynecomastia.”(Delany, 67)
The enlargement of the breast is usually bilateral but some
cases have unilateral enlargement. In the case of
unilateral enlargement, “Induration, fixation, or bloody
discharge should raise the possibility of
carcinoma.”(Wyngaarden, 1450) Carcinoma is a cancerous
growth of the epithelial tissues.
It may be hard to distinguish true breast tissue
from masses of adipose tissue without true enlargement
(lipomastia). In such cases, a real case of gynecomastia
can be distinguished by mammography or by sonography.
Early gynocomastia is characterized by
“proliferation of both the fibrobalstic stroma and the duct
system, which elongates, buds, and duplicates. As the
disease progresses, fibrosis and hyalinization are
associated with the regression of epithelial proliferation.”
Eventually the number of ducts decreases, resolution occurs
by reduction in size of epithelial content leaving temporary
hyaline bands behind. (Isselbacher, 2037)
Diagnosis
A satisfactory diagnosis can be made in only half or
less of patients referred for gynecomastia. This is a
result of insufficient diagnostic techniques, causes that
are still undefined and/or difficult to diagnose, or in some
instances, gynecomastia may be normal rather than due to a
pathologic state. This disease should only be worked up
only if there is a negative drug history, if the breast is
tender (indicating rapid growth), or if the breast mass is
larger than 4 cm in diameter. A decision to perform an
endocrine evaluation depends on the clinical context. An
example would be gynecomastia associated with signs of under
androgenization.
Obesity can often be confused with gynecomastia. To
prevent this, the doctor can palpate the breast to see if
there is a lack of glandular elements that would indicate
only obesity.
Once the signs become evident, the doctor needs to
assess the patient with a number of test to give a proper
diagnosis since many other diseases and disorders are
commonly involved. This can be done with a physical
examination. The head and neck area may show signs of a
pituitary tumor or goiter which is found in Graves disease.
The skin and abdomen may reveal signs of liver failure and
the testes should be examined for asymmetric enlargement in
Klinefelter’s syndrome. The doctor may consider liver
function tests of a karyotype if Kleinfelter’s is suspected.
Other diseases related to gynecomastia include: testicular
tumors, hypo and hyperthyroidism, Cushing’s disease,
cirrhosis, spinal cord lesions, Hodgkin’s disease, enzymatic
defects in androgen synthesis and androgen resistance
syndromes, and many others.
The evaluation of patients with gynecomastia should
include a careful drug history, measurement and examination
of the testes, evaluation of liver function and endocrine
evaluation to include measurement of serum androstenedione
or 24-h urinary 17-keto-steriods, plasma estradiol and hCG,
and plasma luteinizing hormone (LH) and testoster-
one. If LH is high and testosterone is low, the diagnosis
is usually testicular failure. If LH and testosterone are
both low, the diagnosis is usually increased estrogen
production. If they are both high, the diagnosis is either
an androgen-resistance state or a gonadotropin -secreting
tumor. In true gynecomastia these tests would prove to be
unnecessary because the symptoms would regress.
Treatment
When the primary cause can be identified and
corrected, breast enlargement usually diminishes until it
usually disappears. For example, “androgen replacement
therapy may produce dramatic improvement in men with
testicular insufficiency. However, if the gynecomastia is
of long duration (and fibrosis has replaced the original
ductal hyperplasia), correction of the primary defect may
not be followed by resolution.” (Isselbacher, 2038) In this
case, surgery would be the only effective treatment.
Candidates for surgery include those with several
psychologic and/or cosmetic problems, continued growth, or a
suspected malignancy.
The treatment selected for this disease is related
to how the patient was affected by the disease. The
treatment for a person who contracted the disease through
certain drug use will be treated different from a person who
is affected from a related disease. If gynecomastia is
contracted through drug use, the patient will needs to
discontinue the medications that are associated with the
disease. The only exception is when there is a life
threatening illness involved, and there is no alternative
medication available.
For those suffering from gynecomastia, the doctor
may prescribe antiestrogens such as clomiphene citrate or
tamoxiten to eliminate tenderness of the breast. “The
non-aromatizable androgen dihydrotesosterone also has been
reported to reduce gynecomastia by reducing testicular
secretion of estradiol, by decreasing peripheral conversion
of precursors to estradiol and by increasing circulating
levels of androgen.”(Kohler, 295) In patient with painful
gynecomastia and who are not candidates for other therapy,
treat-ments with antiestrogens such as tamoxifen may be
used.
When other related diseases are the cause for the
onset of gynecomastia, treatment of these diseases will
often cure gynecomastia, too. The removal of a sex steroid
produc-ing tumor or treatment of thyroidtoxicosis are two
examples. Testosterone treatment of androgen deficiency
will also cause great improvement in this condition.
“Prophylactic radiation of the breasts prior to the
institution of diethylstilbestrol therapy is effective in
preventing gynecomastia and has a low complication rate in
elderly men.”(Isselbacher, 2039)
In most cases of true gynecomastia the signs and
symptoms should regress in about a year. However, in the
case of severe gynecomsatia where the breast has an increase
of fibrous tissue stroma the patient will require a surgical
reduction mammo-plasty. Once this has been done the tissue
is sent to a lab to be examined. The results should show
elongated circular ducts imbedded in cellular fibrous tissue
with a rubbery fatty quality. From these laboratory tests
it can be determined if there is any cribiform epithelial
hyperlasia or a case of carcinoma. Although the relative
risk of carcinoma of the breast is increased in men with
gynecomastia, it is rare nevertheless.
Statistical Data
Gynecomastia is found only in males, and the signs
can appear any time in a male’s lifetime. It is the leading
breast disorder in males and it accounts for 60% of all
disorders of the male breast. About 85% of male breast
masses are due to gynecomastia. Forty percent of the cases
affect pubescent boys occurring most often between the ages
of 14 to 15.5. Approximately 40% of normal men and up to
70% of hospitalized men have palpable breast tissue. Active
gynecomastia in autopsy data is between 5 and 9%. “More than
80% of their hospitalized patients with a body mass index of
25 kg/m2 or greater had gynocamastia.”(Williams, 373) About
70% of pubertal males required no treatment. “If the
threshold for judging that the breast is enlarged is set at
2.0cm in diameter, the incidence is 32-36% in normal aged
men 17-58 years.”(Williams, 340) A bloody discharge is
present in about 60% of patients, while a milky discharge is
present in about 1% of patients.
Recent Research
In the Wilford Hall USAF Medical Center a set of
experiments were done to see if there is a connection
between 3B-HSD deficiency and gynecomastia. The researchers
tested a male who had developed right side gynecomastia at
the age of twenty-four. When a series of tests were run, no
other underlying conditions were evident. He was found only
to have a deficiency of 3B-HSD. The patient also had
abnormally high ratios of estradiol, estrogen and
aldosterone and other serums. This showed the presence of
adrenal sex steroid production on the right side of his
body.
This is not to say that all males patients with a
deficiency of 3B-HSD will develop gynecomastia. Other
patients with the same deficiency showed no signs, and still
others with normal 3B-HSD levels have also been found to
have reduced breast tissue. Researchers, however, do
believe that the deficiency of 3B-HSD later in life is quite
possibly a frequently unrecognized cause of new-onset
gynecomastia.
There are so many causes and factors that lead to
the disease gynecomastia that it is very difficult for
researchers to try to agree upon one main factor. So many
of the cases differ from one another, and, perhaps, no one
cause will ever be agreed upon as the leading factor of the
disease. As long as there is no other underlying disease or
disorder, gynecomastia is not a life threatening disease.
Experimentation with hormone therapy is the main research
being tested at this time.
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