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Gynecomastia is hypertrophy of breast glandular tissue in men. It must be differentiated from pseudogynecomastia, which is increased breast fat, but no enlargement of breast glandular tissue.
Pathophysiology of Gynecomastia
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 6 months to 2 years. 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
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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 of Gynecomastia
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
Medications (particularly spironolactone, anabolic steroids, and antiandrogens—see table Medications (particularly spironolactone, anabolic steroids, and antiandrogens—see tableCommon Medication 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 |
|---|---|---|
History of chronic kidney disease | Serum electrolytes, BUN, and creatinine Urinalysis Possibly urine culture and urinary levels of sodium, potassium, and creatinine | |
Often history of liver disease, alcohol use, or both Ascites, spider angiomas, dilated abdominal veins | Routine laboratory testing Sometimes liver biopsy | |
Medications and substances (see table Common Medication Causes of Gynecomastia) | History of use | Trial of stopping the medication |
Feminizing adrenocortical tumor | Palpable mass, testicular atrophy | Imaging (MRI or CT) |
Tremor, heat intolerance, diarrhea, tachycardia, weight loss, goiter, exophthalmos | Thyroid function tests | |
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 Diagnosis) | |
Paraneoplastic ectopic production of hCG | Possibly signs of primary tumor or symptoms and signs of hypogonadism | Evaluation for suspected primary tumor |
Testicular mass Possibly symptoms and signs of hypogonadism | Scrotal ultrasound | |
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 months Possibly serum testosterone level |
Data from Dickson G. Gynecomastia. Am Fam Physician 2012;85(7):716-722. | ||
BUN = blood urea nitrogen; CT = computed tomography; FSH = follicle-stimulating hormone; hCG = human chorionic gonadotropin; LH = luteinizing hormone; MRI = magnetic resonance imaging. | ||
Common Medication Causes of Gynecomastia*
Category | Medication (or recreational drug) |
|---|---|
Antiandrogen medications (inhibit androgen synthesis or activity) | Cyproterone (an antiandrogen used to treat prostate cancer or transgender females; not available in the United States) Dutasteride and finasteride (5 alpha reductase inhibitors)Dutasteride and finasteride (5 alpha reductase inhibitors) Goserelin, histrelin, leuprolide, and triptorelin (GnRH agonists); degarelix, relugolix (GnRH antagonists)Goserelin, histrelin, leuprolide, and triptorelin (GnRH agonists); degarelix, relugolix (GnRH antagonists) Flutamide, bicalutamide, enzalutamide, abiraterone, darolutamide, apalutamide, and nilutamide (oral antiandrogens used to treat Flutamide, bicalutamide, enzalutamide, abiraterone, darolutamide, apalutamide, and nilutamide (oral antiandrogens used to treatprostate cancer) |
Antimicrobials | EfavirenzEfavirenz EthionamideEthionamide IsoniazidIsoniazid KetoconazoleKetoconazole MetronidazoleMetronidazole |
Antineoplastic medications | Alkylating agents ImatinibImatinib GnRH agonists and antagonists MethotrexateMethotrexate Vinca alkaloids |
Antiulcer medications† | CimetidineCimetidine Ranitidine OmeprazoleOmeprazole |
Cardiovascular medications | ACE inhibitors (eg, captopril, enalapril)ACE inhibitors (eg, captopril, enalapril) AmiodaroneAmiodarone Calcium channel blockers (eg, nifedipine, diltiazem)Calcium channel blockers (eg, nifedipine, diltiazem) MethyldopaMethyldopa Reserpine SpironolactoneSpironolactone |
CNS-acting medications | DiazepamDiazepam HaloperidolHaloperidol MethadoneMethadone Phenothiazines Tricyclic antidepressants |
Hormones | Androgens Anabolic steroids Estrogens Human growth hormone |
OTC herbals | Lavender oil Tea tree oils |
Amphetamines EthanolEthanol Heroin Marijuana | |
Other medications | AuranofinAuranofin DiethylpropionDiethylpropion Domperidone MetoclopramideMetoclopramide PhenytoinPhenytoin PenicillaminePenicillamine SulindacSulindac TheophyllineTheophylline |
* Not all medications that have been associated with gynecomastia have been shown to cause gynecomastia through challenge-rechallenge testing. | |
† Medications are listed in order of frequency of association. | |
ACE = angiotensin-converting enzyme; CNS = central nervous system; GnRH = gonadotropin-releasing hormone; LH = luteinizing hormone; OTC = over-the-counter. | |
Evaluation of Gynecomastia
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 over-the-counter medications.
Physical examination
Complete examination is performed, including assessment of vital signs, skin, and general appearance. The neck is examined for goiter. The abdomen is examined for ascites, venous distention, and 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. If there is any uncertainty or concern, differentiation of true masses from accumulation of fatty tissue is detected by mammography or ultrasound imaging. 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 medications. Other examination findings may also be helpful (see Interpretation of Some Findings in Gynecomastia).
Interpretation of Some Findings in Gynecomastia
Finding | Possible Causes |
|---|---|
Fragile skin | |
Skin discoloration | |
Tachycardia, tremor, goiter, exophthalmos | |
Testicular atrophy | Hypogonadism (postpubertal onset) |
Underdeveloped secondary sexual characteristics | Hypogonadism (prepubertal onset) |
Weight loss | Refeeding after undernutrition |
Testing
If breast cancer is suspected, mammography should be performed. If another disorder is suspected, appropriate testing should be performed (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 medication or evident pathologic cause, measurement of serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and human chorionic gonadotropin (hCG) are recommended. Patients with physiologic or idiopathic gynecomastia are evaluated again in 6 months.
Treatment of Gynecomastia
In most cases, no specific treatment is needed because gynecomastia usually remits spontaneously or disappears after any causative medication (except perhaps anabolic steroids) is stopped or underlying disorder is treated. Some clinicians try tamoxifen 10 mg orally twice a day if pain and tenderness are very troublesome in men or adolescents, but this treatment is not always effective. In most cases, no specific treatment is needed because gynecomastia usually remits spontaneously or disappears after any causative medication (except perhaps anabolic steroids) is stopped or underlying disorder is treated. Some clinicians try tamoxifen 10 mg orally twice a day 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 with medical therapy is unlikely after 12 months. Thus, after 12 months, if cosmetic appearance is unacceptable, surgical removal of excess breast tissue (eg, suction lipectomy alone or with cosmetic surgery) may be used.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 with medical therapy is unlikely after 12 months. Thus, after 12 months, 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 medications can cause gynecomastia.
Patients should be evaluated for clinically suspected genital or systemic disorders.
