Gynecomastia   Last updated: August 14, 2003

THE ANALYST TM
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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 on one or both breasts. 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.

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 and 40% of the cases affect pubescent boys.. 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%. In one study, more than 80% of hospitalized patients with a body mass index (BMI) of 25 or greater had gynecomastia. About 70% of pubertal males required no treatment. If the threshold for judging that the breast is enlarged is set at 2cm in diameter, the incidence is 32 to 36% in normal aged men 17 to 58 years.

Many 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 to 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. From this information it was discovered that there is also a lower ratio of weaker adrenal androgens (delta 4 androstenedione and dehydroepiandrosterone [DHEA]) 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 known 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.

In the case of <b>physiologic</b> 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 around age 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 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 <b>pathologic</b> 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 hyperplasia, and adrenal carcinoma or testicular tumors. In the second case some examples are adrenal carcinoma, liver disorders, malnutrition and thyrotoxicosis. Decreased androgen activity can be found in complete testicular feminization, incomplete testicular feminization and Reifenstein's syndrome.

Many <b>drugs</b> 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. There have been examples where the mother prepared sandwiches for her boys after applying estrogen cream to her skin. Small amounts of estrogen were consumed by the boys and reversible gynecomastia resulted. Some examples of drugs that may have cause gynecomastia include Cannabinoids (methane and marijuana), Psychotropics (phenothiazine, butyrophenone and reserpine), Antihypertensives (reserpine, alphamethyldopa and spironolactone), Cardiac (digitalis), Gastrointestinal (cimetidine, metoclopramide and domperidone), Antituburculous (isoniazid), Cytoxic (cyclophosphamide, 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 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 tenderness 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. 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 cancer.

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.

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 or difficult to diagnose, or in some instances, gynecomastia may be normal rather than due to a pathologic state. This disease should only be investigated carefully if there is a negative drug history, if the breast is tender (indicating rapid growth), or if the breast mass is larger than 4cm 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. Other diseases related to gynecomastia include: testicular tumors, hypothyroidism 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 hour urinary 17ketosteriods, plasma estradiol and HCG, and plasma luteinizing hormone (LH) and testosterone. 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.

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. In this case, surgery would be the only effective treatment. Candidates for surgery include those with several psychologic or cosmetic problems, continued growth, or a suspected malignancy.

<b>Conventional Treatment</b>
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 need 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 tamoxifen 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. In patient with painful gynecomastia and who are not candidates for other therapy, treatments 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 producing tumor or treatment of thyrotoxicosis 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.

In most cases of true gynecomastia the signs and symptoms should regress in about a year. However, in the case of severe gynecomastia where the breast has an increase of fibrous tissue stroma the patient will require a surgical reduction mammoplasty. 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 cancer of the breast is increased in men with gynecomastia, it is rare nevertheless.

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.