Gynecomastia 

Gynecomastia is a benign enlargement of the male breast resulting from a proliferation of the glandular component of the breast. Gynecomastia is defined clinically by the presence of a rubbery or firm mass extending concentrically from the nipples. Although the condition is usually bilateral, it can be unilateral. The condition known as pseudogynecomastia, or lipomastia, is characterized by fat deposition without glandular proliferation. (See Etiology, Presentation, and Workup.)

Patient education

Reassure patients with physiologic gynecomastia regarding the benign nature of their condition, and inform them that most cases spontaneously resolve. (See Prognosis.)

Counsel patients regarding the various treatment modalities available for gynecomastia, and highlight the risks, adverse effects, success rates, and benefits of each modality. For patient education information, see the Men's Health Center. (See Treatment and Medication.)

Gynecomastia results from an altered estrogen-androgen balance, in favor of estrogen, or from increased breast sensitivity to a normal circulating estrogen level.^[1] The imbalance is between the stimulatory effect of estrogen and the inhibitory effect of androgen. (The normal production ratio of testosterone to estrogen is approximately 100:1; the normal ratio of testosterone to estrogen in the circulation is approximately 300:1.)

Estrogens induce ductal epithelial hyperplasia, ductal elongation and branching, proliferation of the periductal fibroblasts, and an increase in vascularity. The histologic picture is similar in male and female breast tissue after exposure to estrogen.^[2]

Estrogen production in males results mainly from the peripheral conversion of androgens (testosterone and androstenedione) to estradiol and estrone, which occurs through the action of the enzyme aromatase (mainly in muscle, skin, and adipose tissue).

Increased estrogen production and/or action can occur at the testicular level or at the periphery and is characterized as follows:

• From the testes - Can be due to testicular tumors or to ectopic production of human chorionic gonadotropin (hCG), as is reported with carcinoma of lung, kidney, gastrointestinal (GI) tract, and extragonadal germ cell tumors
• From peripheral conversion - Can be due to increased substrate or increased activity of aromatase, as in chronic liver disease, malnutrition, hyperthyroidism, adrenal tumors, and familial gynecomastia

Gynecomastia can be physiologic or pathologic.^{[3, 4]} Physiologic gynecomastia is seen in newborn infants, pubescent adolescents,^{[5, 6]} and elderly individuals.

Gynecomastia in adults is often multifactorial. Increased aromatization of testosterone to estradiol and the gradual decrease of testosterone production in the aging testes most often account for gynecomastia in adult males. Older men are also more likely to take medications associated with gynecomastia than are younger men.

Pathologic gynecomastia

Pathologic gynecomastia can be caused by a decrease in the production and/or action of testosterone, by an increase in the production and/or action of estrogen, or by drug use. However, gynecomastia can also be idiopathic.^[1]

Conditions that result in primary or secondary hypogonadism and cause decreased testosterone production and/or action include the following:

• Klinefelter syndrome
• Congenital anorchia
• Testicular trauma
• Testicular torsion
• Viral orchitis
• Kallmann syndrome - A form of hypogonadotropic hypogonadism, Kallmann syndrome is usually associated with varying degrees of abnormality in olfactory perception; this results from the defective migration of gonadotropin-releasing hormone–secreting cells (which comigrate with the cells of the olfactory epithelium) during embryogenesis
• Pituitary tumors
• Malignancies that increase the serum level of hCG (eg, large cell lung cancer, gastric carcinoma, renal cell carcinoma, hepatoma)^[1]
• Renal failure^[1]
• Hyperthyroidism
• Malnutrition
• Androgen insensitivity syndrome
• Five-alpha-reductase deficiency syndrome

Various drugs are implicated in gynecomastia and can be classified into the following categories (although drugs in the same class do not all cause gynecomastia to the same extent)^{[7, 8]} :

• Estrogens or drugs with estrogenlike activity - Include diethylstilbestrol, digitalis, and phytoestrogens, as well as estrogen-contaminated food and estrogen-containing cosmetics
• Drugs that enhance estrogen synthesis - Include gonadotropins, clomiphene, phenytoin, and exogenous testosterone
• Drugs that inhibit testosterone synthesis or action - Include ketoconazole, metronidazole, alkylating agents, cisplatin, spironolactone, cimetidine, flutamide, finasteride, and etomidate
• Drugs that act by unknown mechanisms - Include isonicotinic acid hydrazide, methyldopa, busulfan, tricyclic antidepressants, diazepam, penicillamine, omeprazole, phenothiazines, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, alcohol, marijuana, and heroin

A study by Den Hond et al on the effects of pollutants on sexual maturation indicated that higher blood levels of lead increased the risk of gynecomastia in the study's subjects, while higher serum levels of hexachlorobenzene decreased the risk. The report involved 1679 adolescents, aged 14-15 years.^[3]

Estimates suggest the following etiologies in males seeking medical attention for gynecomastia:

• Persistent pubertal gynecomastia - 25%
• Drugs - 10-25%
• No detectable abnormality - 25%
• Cirrhosis or malnutrition - 8%
• Primary hypogonadism - 8%
• Testicular tumors - 3%
• Secondary hypogonadism - 2%
• Hyperthyroidism - 1.5%
• Chronic renal insufficiency - 1%

Occurrence in the United States

Gynecomastia is the most common reason for male breast evaluation. The condition is common in infancy and adolescence, as well as in middle-aged to older adult males. One estimate is that 60-90% of infants have transient gynecomastia due to the high estrogen state of pregnancy.

The next peak of occurrence is during puberty,^{[5, 6]} with a prevalence ranging from 4-69%. Some reports have shown a transient increase in estradiol concentration at the onset of puberty in boys who develop gynecomastia. Pubertal gynecomastia usually has an onset in boys aged 10-12 years. It generally regresses within 18 months, and persistence is uncommon in men older than 17 years. The third peak occurs in older men, with a prevalence of 24-65%. [#Clinical]

Other than the associated risk of breast cancer, gynecomastia does not cause any long-term complications. In approximately 90% of cases, pubertal gynecomastia resolves within a period of months to several years. However, macromastia seldom resolves completely and often requires surgery.

Gynecomastia that occurs secondary to an underlying, treatable cause (eg, drug-induced gynecomastia) usually responds to treatment or removal of the primary cause. Men with Klinefelter syndrome have a 10- to 20-fold increased risk for breast cancer.