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Gynecomastia

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).

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 GynecomastiaTables)

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

Table 2

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*Tables)

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

Undernutrition followed by refeeding

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

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
, 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

PC-SPES

Tea tree oils

Other drugs

AuranofinSome Trade Names
RIDAURA
Click for Drug Monograph

Diethylpropion

Domperidone

Etretinate

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 and atrophy.

The breasts are examined while patients are recumbent with their hands behind their head. Examiners bring their thumb and forefinger together from opposite sides of the nipple until they meet. 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
  • Symptoms or signs of hyperthyroidism
  • 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 GynecomastiaTables).

Table 4

Interpretation of Some Findings in Gynecomastia

Finding

Possible Causes

Tachycardia, tremor, goiter, exophthalmos

Hyperthyroidism

Weight loss

Cirrhosis

Chronic kidney disease

Hyperthyroidism

Refeeding after undernutrition

Fragile skin

Undernutrition

Chronic kidney disease

Ascites, vascular spiders

Cirrhosis

Underdeveloped secondary sexual characteristics

Hypogonadism (prepubertal onset)

Skin discoloration

Cirrhosis

Chronic kidney disease

Testicular atrophy

Hypogonadism (postpubertal onset)

Cirrhosis

Testicular mass

Testicular tumor

Testing: If breast cancer is considered, 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 GynecomastiaTables). 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 January 2010 by Bradley D. Anawalt, MD

Content last modified June 2007

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