Gynecomastia is hypertrophy of breast glandular tissue in males. It must be differentiated from pseudogynecomastia, which is increased breast fat, but no enlargement of breast glandular tissue.

Pathophysiology

During infancy and puberty, enlargement of the male breast is normal (physiologic gynecomastia). Enlargement is usually transient, bilateral, smooth, firm, and symmetrically distributed under the areola; breasts may be tender. Physiologic gynecomastia that develops during puberty usually resolves within about 6 mo to 2 yr. Similar changes may occur during old age and may be unilateral or bilateral. Most of the enlargement is due to proliferation of stroma, not of breast ducts. The mechanism is usually a decrease in androgen effect or an increase in estrogen effect (eg, decrease in androgen production, increase in estrogen production, androgen blockade, displacement of estrogen from sex-hormone binding globulin, androgen receptor defects).

Sidebar 1
Pearls & Pitfalls During infancy and puberty, bilateral, symmetric, smooth, firm, and tender enlargement of breast tissue under the areola is normal.

If evaluation reveals no cause for gynecomastia, it is considered idiopathic. The cause may not be found because gynecomastia is physiologic or because there is no longer any evidence of the inciting event.

Etiology

In infants and boys, the most common cause is

• Physiologic gynecomastia

In men, the most common causes are (see Table 2: Male Reproductive Endocrinology and Related Disorders: Some Causes of Gynecomastia)

• Persistent pubertal gynecomastia
• Idiopathic gynecomastia
• Drugs (particularly spironolactoneSome Trade Names
  ALDACTONE
  Click for Drug Monograph
  , anabolic steroids, and antiandrogens—see Table 3: Male Reproductive Endocrinology and Related Disorders: Common Drug Causes of Gynecomastia*)

Breast cancer, which is uncommon in males, may cause unilateral breast abnormalities but is rarely confused with gynecomastia.

Table 2
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Some Causes of Gynecomastia Cause Suggestive Findings Diagnostic Approach Chronic kidney disease History of chronic kidney disease Serum electrolytes, BUN, and creatinine Urinalysis Possibly urine culture and urinary levels of Na, K, and creatinine Cirrhosis Often history of liver disease, alcohol use, or both Ascites, spider angiomas, dilated abdominal veins Routine laboratory testing Sometimes liver biopsy Drugs (see Table 3: Male Reproductive Endocrinology and Related Disorders: Common Drug Causes of Gynecomastia*) History of use Trial of stopping the drug Feminizing adrenocortical tumor Palpable mass, testicular atrophy Imaging (MRI or CT) Hyperthyroidism Tremor, heat intolerance, diarrhea, tachycardia, weight loss, goiter, exophthalmos Thyroid function tests Hypogonadism Prepubertal onset: Underdeveloped secondary sexual characteristics Postpubertal onset: Decreased libido, erectile dysfunction, mood changes, decreased muscle and increased fat mass, osteopenia, testicular atrophy, mild cognitive changes Serum FSH, LH, and testosterone levels (see Male Reproductive Endocrinology and Related Disorders: Diagnosis) Paraneoplastic ectopic production of human chorionic gonadotropin (hCG) Possibly signs of primary tumor or symptoms and signs of hypogonadism Evaluation for suspected primary tumor Testicular tumors Testicular mass Possibly symptoms and signs of hypogonadism Ultrasonography Feeding after undernutrition Muscle and fat wasting, hair loss, skin changes, frequent infections, fatigue, signs of vitamin deficiencies (eg, osteopenia) Clinical evaluation Selective laboratory testing Idiopathic gynecomastia No abnormal findings other than gynecomastia, no symptoms, no apparent cause Repeat clinical evaluation in 6 mo Possibly serum testosterone level FSH = follicle-stimulating hormone; LH = lutenizing hormone.

Table 3
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Common Drug Causes of Gynecomastia* Category Drugs Drugs that inhibit androgen synthesis or activity CyproteroneSome Trade Names No US trade name Click for Drug Monograph (an antiandrogen) DutasterideSome Trade Names AVODART Click for Drug Monograph and finasterideSome Trade Names PROPECIA PROSCAR Click for Drug Monograph (5α-reductase inhibitors) FlutamideSome Trade Names EULEXIN Click for Drug Monograph , bicalutamideSome Trade Names CASODEX Click for Drug Monograph , enzalutamide, and nilutamideSome Trade Names NILANDRON Click for Drug Monograph (antiandrogens used to treat prostate cancer) Antimicrobials EfavirenzSome Trade Names SUSTIVA Click for Drug Monograph EthionamideSome Trade Names TRECATOR Click for Drug Monograph IsoniazidSome Trade Names INH NYDRAZID Click for Drug Monograph KetoconazoleSome Trade Names NIZORAL Click for Drug Monograph MetronidazoleSome Trade Names FLAGYL Click for Drug Monograph Antineoplastic drugs Alkylating drugs ImatinibSome Trade Names GLEEVEC Click for Drug Monograph MethotrexateSome Trade Names RHEUMATREX Click for Drug Monograph Vinca alkaloids Cardiovascular drugs ACE inhibitors (eg, captoprilSome Trade Names CAPOTEN Click for Drug Monograph , enalaprilSome Trade Names VASOTEC Click for Drug Monograph ) AmiodaroneSome Trade Names CORDARONE Click for Drug Monograph Ca channel blockers (eg, nifedipineSome Trade Names ADALAT PROCARDIA Click for Drug Monograph , diltiazemSome Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph ) MethyldopaSome Trade Names ALDOMET Click for Drug Monograph ReserpineSome Trade Names SERPASIL Click for Drug Monograph SpironolactoneSome Trade Names ALDACTONE Click for Drug Monograph CNS-acting drugs DiazepamSome Trade Names VALIUM Click for Drug Monograph HaloperidolSome Trade Names HALDOL Click for Drug Monograph MethadoneSome Trade Names DOLOPHINE Click for Drug Monograph Phenothiazines Tricyclic antidepressants Antiulcer drugs† CimetidineSome Trade Names TAGAMET Click for Drug Monograph RanitidineSome Trade Names ZANTAC Click for Drug Monograph OmeprazoleSome Trade Names PRILOSEC Click for Drug Monograph Hormones Androgens Anabolic steroids EstrogensSome Trade Names PREMARIN Click for Drug Monograph Human growth hormone Recreational drugs Amphetamines Ethanol Heroin Marijuana OTC herbal drugs Lavender oil Tea tree oils Other drugs AuranofinSome Trade Names RIDAURA Click for Drug Monograph Diethylpropion Domperidone MetoclopramideSome Trade Names REGLAN Click for Drug Monograph PhenytoinSome Trade Names DILANTIN Click for Drug Monograph PenicillamineSome Trade Names CUPRIMINE Click for Drug Monograph SulindacSome Trade Names CLINORIL Click for Drug Monograph TheophyllineSome Trade Names ELIXOPHYLLIN THEO-DUR Click for Drug Monograph *Not all drugs that have been associated with gynecomastia have been shown to cause gynecomastia through challenge-rechallenge testing. †Drugs are listed in order of frequency of association.

Evaluation

History: History of present illness should help clarify the duration of breast enlargement, whether secondary sexual characteristics are fully developed, the relationship between onset of gynecomastia and puberty, and the presence of any genital symptoms (eg, decreased libido, erectile dysfunction) and breast symptoms (eg, pain, nipple discharge).

Review of systems should seek symptoms that suggest possible causes, such as weight loss and fatigue (cirrhosis, undernutrition, chronic kidney disease, hyperthyroidism); skin discoloration (chronic kidney disease, cirrhosis); hair loss and frequent infections (undernutrition); fragility fractures (undernutrition, hypogonadism); mood and cognitive changes (hypogonadism); and tremor, heat intolerance, and diarrhea (hyperthyroidism).

Past medical history should address disorders that can cause gynecomastia and include a history of all prescribed and OTC drugs.

Physical examination: Complete examination is done, including assessment of vital signs, skin, and general appearance. The neck is examined for goiter. The abdomen is examined for ascites, venous distention, and suspected adrenal masses. Development of secondary sexual characteristics (eg, the penis, pubic hair, and axillary hair) is assessed. The testes are examined for masses or atrophy.

The breasts are examined while patients are recumbent with their hands behind the head. Examiners bring their thumb and forefinger together from opposite sides of the nipple until they meet. Any nipple discharge is noted. Lumps are assessed and characterized in terms of location, consistency, fixation to underlying tissues, and skin changes. The axilla is examined for lymph node involvement in men who have breast lumps.

Red flags: The following findings are of particular concern:

• Localized or eccentric breast swelling, particularly with nipple discharge, fixation to the skin, or hard consistency
• Symptoms or signs of hypogonadism (eg, delayed puberty, testicular atrophy, decreased libido, erectile dysfunction, decreased proportion of lean body mass, loss of visual-spatial abilities)
• Symptoms or signs of hyperthyroidism (eg, tremor, tachycardia, sweating, heat intolerance, weight loss)
• Testicular mass
• Recent onset of painful, tender gynecomastia in an adult

Interpretation of findings: With pseudogynecomastia, the examiner feels no resistance between the thumb and forefinger until they meet at the nipple. In contrast, with gynecomastia, a rim of tissue > 0.5 cm in diameter surrounds the nipple symmetrically and is similar in consistency to the nipple itself. Breast cancer is suggested by swelling with any of the following characteristics:

• Eccentric unilateral location
• Firm or hard consistency
• Fixation to skin or fascia
• Nipple discharge
• Skin dimpling
• Nipple retraction
• Axillary lymph node involvement

Gynecomastia in an adult that is of recent onset and causes pain is more often caused by a hormonal abnormality (eg, tumor, hypogonadism) or drugs. Other examination findings may also be helpful (see Table 4: Male Reproductive Endocrinology and Related Disorders: Interpretation of Some Findings in Gynecomastia).

Table 4
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Interpretation of Some Findings in Gynecomastia Finding Possible Causes Tachycardia, tremor, goiter, exophthalmos Hyperthyroidism Weight loss Chronic kidney disease Cirrhosis Hyperthyroidism Refeeding after undernutrition Fragile skin Chronic kidney disease Undernutrition Ascites, vascular spiders Cirrhosis Underdeveloped secondary sexual characteristics Hypogonadism (prepubertal onset) Skin discoloration Chronic kidney disease Cirrhosis Testicular atrophy Cirrhosis Hypogonadism (postpubertal onset) Testicular mass Testicular (Leydig cell) tumor

Testing: If breast cancer is suspected, mammography should be done. If another disorder is suspected, appropriate testing should be done (see Table 2: Male Reproductive Endocrinology and Related Disorders: Some Causes of Gynecomastia). Extensive testing is often unnecessary, especially for patients in whom the gynecomastia is chronic and detected only on physical examination. Because hypogonadism is somewhat common with aging, some authorities recommend measuring the serum testosterone level in older men, particularly if other findings suggest hypogonadism. However, in adults with recent onset of painful gynecomastia without a drug or evident pathologic cause, measurement of serum levels of LH, FSH, testosterone, estradiol, and human chorionic gonadotropin (hCG) are recommended. Patients with physiologic or idiopathic gynecomastia are evaluated again in 6 mo.

Treatment

In most cases, no specific treatment is needed because gynecomastia usually remits spontaneously or disappears after any causative drug (except perhaps anabolic steroids) is stopped or underlying disorder is treated. Some clinicians try tamoxifenSome Trade Names
NOLVADEX
Click for Drug Monograph
10 mg po bid if pain and tenderness are very troublesome in men or adolescents, but this treatment is not always effective. TamoxifenSome Trade Names
NOLVADEX
Click for Drug Monograph
may also help prevent gynecomastia in men being treated with high-dose antiandrogen (eg, bicalutamideSome Trade Names
CASODEX
Click for Drug Monograph
) therapy for prostate cancer; breast radiation therapy is an alternative. Resolution of gynecomastia is unlikely after 12 mo. Thus, after 12 mo, if cosmetic appearance is unacceptable, surgical removal of excess breast tissue (eg, suction lipectomy alone or with cosmetic surgery) may be used.

Key Points

• Gynecomastia must be differentiated from increased fat tissue in the breast.
• Gynecomastia is often physiologic or idiopathic.
• A wide variety of drugs can cause gynecomastia.
• Patients should be evaluated for clinically suspected genital or systemic disorders.

Last full review/revision February 2013 by Irvin H. Hirsch, MD

Content last modified March 2013