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Gynecomastia

by Irvin H. Hirsch, MD

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).

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: Some Causes of Gynecomastia)

  • Persistent pubertal gynecomastia

  • Idiopathic gynecomastia

  • Drugs (particularly spironolactone, anabolic steroids, and antiandrogens—see Table: Common Drug Causes of Gynecomastia*)

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

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

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 Hypogonadism : 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.

Common Drug Causes of Gynecomastia*

Category

Drugs

Drugs that inhibit androgen synthesis or activity

Cyproterone (an antiandrogen)

Dutasteride and finasteride (5α-reductase inhibitors)

Goserelin, histrelin, leuprolide, and triptorelin (LH-RH agonists)

Flutamide, bicalutamide, enzalutamide, and nilutamide (antiandrogens used to treat prostate cancer)

Antimicrobials

Efavirenz

Ethionamide

Isoniazid

Ketoconazole

Metronidazole

Antineoplastic drugs

Alkylating drugs

Imatinib

Methotrexate

Vinca alkaloids

Cardiovascular drugs

ACE inhibitors (eg, captopril, enalapril)

Amiodarone

Ca channel blockers (eg, nifedipine, diltiazem)

Methyldopa

Reserpine

Spironolactone

CNS-acting drugs

Diazepam

Haloperidol

Methadone

Phenothiazines

Tricyclic antidepressants

Antiulcer drugs

Cimetidine

Ranitidine

Omeprazole

Hormones

Androgens

Anabolic steroids

Estrogens

Human growth hormone

Recreational drugs

Amphetamines

Ethanol

Heroin

Marijuana

OTC herbal drugs

Lavender oil

Tea tree oils

Other drugs

Auranofin

Diethylpropion

Domperidone

Metoclopramide

Phenytoin

Penicillamine

Sulindac

Theophylline

*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)

  • 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: Interpretation of Some Findings in Gynecomastia).

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: Some Causes of Gynecomastia). Extensive testing is often unnecessary, especially for patients in whom the gynecomastia is chronic and detected only during 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 tamoxifen 10 mg po bid if pain and tenderness are very troublesome in men or adolescents, but this treatment is not always effective. Tamoxifen may also help prevent gynecomastia in men being treated with high-dose antiandrogen (eg, bicalutamide) 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.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • DOLOPHINE
  • CLINORIL
  • No US brand name
  • NIZORAL
  • REGLAN
  • TENUATE
  • CASODEX
  • PRILOSEC
  • FLAGYL
  • DELATESTRYL
  • RIDAURA
  • XTANDI
  • CARDIZEM, CARTIA XT, DILACOR XR
  • HALDOL
  • ZOLADEX
  • No brand name
  • PROPECIA, PROSCAR
  • LANIAZID
  • VALIUM
  • TRECATOR
  • ADALAT CC, PROCARDIA
  • LUPRON
  • CORDARONE
  • NILANDRON
  • GLEEVEC
  • TAGAMET
  • CAPOTEN
  • OTREXUP
  • DILANTIN
  • SUSTIVA
  • VASOTEC
  • CUPRIMINE
  • ALDACTONE
  • AVODART
  • ELIXOPHYLLIN
  • ZANTAC
  • ESTRADERM, ESTROGEL, VIVELLE
  • NOLVADEX

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