Approach

Treatment goals are pain reduction and cosmetic improvement. Full resolution is not always possible.

Candidates for testosterone therapy should have the following measured prior to beginning therapy:[74]

  • Prostate-specific antigen (PSA [if ages >40 years]) to exclude prostate cancer

  • Hematocrit or hemoglobin, to determine risk for polycythemia.

Adults with idiopathic gynecomastia

Patients without pain or psychological distress require no treatment as the gynecomastia is self-limited and benign.

Spontaneous regression of gynecomastia has been reported in adult men, although this is rare in controlled trials. Asymptomatic men without an obvious cause in whom treatment is deferred should be re-examined in 6 months to be certain the gynecomastia is stable or improving.

Persistent pain and psychological distress are indications for treatment.

Pharmacotherapy

Tamoxifen, a selective estrogen receptor modulator (SERM), may be trialed in patients with rapid-onset nonpathologic gynecomastia.[27]​ In one prospective cohort study of 81 men with idiopathic gynecomastia (mean age 42.8 years), 90% experienced complete resolution with tamoxifen therapy.[76]​ Pruritus, constipation, and/or diarrhea may occur.[3]​ However, European guidelines do not recommend the use of tamoxifen in the treatment of idiopathic gynecomastia because of limited randomized controlled trial evidence.[3]

Observational data indicate that danazol (a weak androgen) is less effective than tamoxifen in adult patients (n=68; median age 39.5 years) with idiopathic gynecomastia (complete resolution of gynecomastia reported in 78.2% of tamoxifen-treated patients and 40% of danazol-treated patients).[77]​ Danazol has been associated with weight gain, which may exacerbate gynecomastia.[78]​ European guidelines, and many experts, do not recommend the use of danazol in the treatment of idiopathic gynecomastia.[3]

Indications for surgery

A comprehensive workup should be performed before surgery to exclude an underlying cause; surgical treatment should not be considered until an observation period has been allowed.[3][70]

Patients with long-lasting gynecomastia that fails to regress following medical therapy, or in whom there is continuing significant pain or psychological distress, may be candidates for surgery.[3][4]​​​[27]​ The surgical procedure depends on the type and extent of tissue to be removed.[3]

Minimally-invasive approaches (including ultrasound-assisted liposuction, suction lipectomy, and laparoscopic or endoscopic methods) may be appropriate for patients with small to moderate enlargement, without skin excess.[79]​ Low-quality evidence suggests that these techniques are associated with high levels of patient satisfaction, low complication rates, and inconspicuous scarring.[79][80]

Open surgical excision is required for excision of large volumes of fat, in cases with more extensive glandular tissue, and for patients with the potential for significant skin redundancy. Transposition of the nipple-areola complex may be required. Complications of surgery include hematoma, seroma, infection, permanent sensory loss, skin redundancy, abnormal breast contour, and scarring.[79]​​[81]​ Final breast contour may not be apparent for 1 year.

Adults with exogenous androgen or estrogen exposure

Withdrawal of a contributing drug or exposure, or treatment of an underlying disorder, may be sufficient to alleviate some cases of gynecomastia.[3][4]​​[27]​

Environmental manipulations (e.g., removal of occupational estrogenizing agents) are most effective when treatment is instituted early, especially in the first year, while gynecomastia is still in the proliferative phase.[82]​​ Persistent pain and psychological distress are primary indications for treatment. Tamoxifen reduces pain and breast tissue diameter where removal of estrogenizing compounds may be untenable or ineffective as therapy.

Testosterone replacement therapy

May be required in some men who have taken prolonged high-dose exogenous androgen to enhance performance in recreational sport, or for bodybuilding, because of prolonged hypogonadism following discontinuation of high doses of androgen.[64]​ Replacement testosterone is ideally administered transdermally (intermittent intramuscular administration is associated with high testosterone peaks) to avoid severe symptoms of androgenic-anabolic steroid withdrawal hypogonadism including including sexual dysfunction, fatigue, depressed mood, and possibly clinical depression.[64]​ These men are often found to be unresponsive to therapies other than surgical reduction.[39][40][41]​​​[83] Factors that predict refractory gynecomastia in this setting include longstanding (>12 months) fibrotic gynecomastia or extensive (>6 cm) amounts of glandular tissue in the breasts. In these patients referral to a surgeon is advisable. 

Adults with prostate cancer

Men with prostate cancer who develop gynecomastia and breast pain after antiandrogen therapy respond to tamoxifen. Tamoxifen is also effective for prevention of gynecomastia and breast pain in these patients.​[34][58][84]​​​​​​​ The aromatase inhibitor anastrozole does not appear to be as effective.[34][55]​​

The prevalence of breast pain and gynecomastia are lower when tamoxifen is given prophylactically rather than at the onset of symptoms after antiandrogen therapy is begun, but some men who might never have developed significant symptoms will be treated unnecessarily.[85] 

Systematic reviews and meta-analyses indicate that tamoxifen is more effective than radiation therapy for the prevention of gynecomastia and chest pain associated with androgen deprivation in men with prostate cancer.[34][57]​​​​[86]​ Adverse effects occur more frequently with tamoxifen (dizziness, hot flashes, constipation, asthenia, and rare cardiologic or neurologic effects) than with radiation therapy, but are usually mild.[57][58]​ Adverse effects from radiation therapy include skin reaction, erythema, pruritus, and hyperpigmentation, usually mild and transient.[57][58][86]

Radiation is more expensive, but is an alternative in men with high cardiovascular risk, history of thrombosis, or intolerance to tamoxifen.[57]​ The long-term efficacy and effect of these treatments on cancer progression and survival is unknown; further studies are indicated.[86]​ Caution is warranted when considering radiation therapy in young patients for whom long-term cancer risk is greater.[86]

Adults with hypogonadism

Androgen replacement for gynecomastia may be effective treatment in hypogonadal men, though contraindicated in men with prostate cancer. Topical administration of testosterone is preferred.

Evidence suggests that gynecomastia associated with hypogonadism is more likely to resolve with transdermal (patch) testosterone replacement than with intramuscular administration.[52]​​ However, transdermal patch formulations are no longer available in some countries, and an alternative formulation (e.g., transdermal gel) may be considered based upon patient preference and treatment burden.[64] ​It is unclear whether these alternative preparations have been studied in patients with gynecomastia.

Additional androgen treatment for eugonadal men is not effective and is not recommended.

Adults with nonhormonal drug exposure

Withdrawal of a contributing drug may be sufficient to alleviate gynecomastia.[3][4]​​[27]​ These measures are most effective when treatment is instituted early, especially in the first year, while gynecomastia is still in the proliferative phase.[82]​​

Treatment should proceed in a stepwise fashion with:

  1. Discontinuation or change of the medication

  2. Selective estrogen receptor modulation (SERM; e.g., tamoxifen)

  3. Surgery.

Commonly used medications that may be considered as substitutions include, in order of increasing risk for gynecomastia:[30][31][36][38]​​[52]​​​[53]

  • Calcium-channel blockers: diltiazem < nifedipine

  • Aldosterone antagonists: eplerenone < spironolactone

  • Testosterone replacement in hypogonadal men: transdermal patch or gel < intramuscular.

Patients ingesting herbal remedies (e.g., saw palmetto for prostate enlargement) should be identified, and consideration given to replacing the herbal remedy with conventional therapy (e.g., alpha blockade).

If further treatment is necessary, tamoxifen may be trialed.[77]

Patients with long-lasting gynecomastia that fails to regress following medical therapy, or in whom there is continuing significant pain or psychological distress, may be candidates for surgery.[3][4]​​[27]​ The surgical procedure depends on the type and extent of tissue to be removed.[3]

Pubertal gynecomastia

It is difficult to assess the effects of treatment in pubertal boys, because gynecomastia usually resolves spontaneously.[3]​

Boys at puberty with normal sexual development need reassurance that gynecomastia is normal and that the condition usually resolves within 2 to 3 years.[3][87][88]

Systematic reviews of tamoxifen treatment of pubertal gynecomastia suggest that tamoxifen may be effective in select patients, and appears to be safe.[89][90]​​​ Raloxifene, an alternative SERM, was superior to tamoxifen in one systematic review (with respect to size and pain reduction, adverse effect profile, and recurrence rate), but greater numbers of tamoxifen-treated patients have been studied and followed up posttreatment.[90]​ High-quality evidence on pharmacologic therapy for pubertal gynecomastia is lacking.[90]

European guidelines do not recommend the use of SERMs (tamoxifen and raloxifene) in the treatment of gynecomastia in general.​[3]

Surgical treatment is not generally recommended in pubertal and adolescent groups

Where it is indicated, in cases with persistent pain and extensive tissue deposition causing significant psychological distress, surgery may be deferred to allow an extended observation period of 2 years (or until the testicles are adult size and puberty is nearing completion).[3] This allows the testosterone/estrogen ratio to reach adult proportions.

Liposuction (with or without ultrasound) is used for removal of adipose tissue with a small glandular component. Direct surgical excision is needed for more extensive or redundant tissue. Combined surgery may be appropriate. One cohort study found that surgical treatment of gynecomastia in adolescents significantly improved quality of life, particularly in younger and overweight/obese patients and those with moderate to severe gynecomastia.[91]​ 

Most medical centers require pathologic exam of the excised breast tissue. However, given the extremely low incidence of cancer or other abnormal pathology in adolescent males under the age of 21 years, routine histopathologic examination of tissue has been questioned.[92][93]

Prepubertal boys

Gynecomastia should be evaluated on a case-by-case basis. A detailed history for environmental exposure should be followed by physical examination for a testicular mass, differences in sex development, or precocious puberty. Central precocious puberty is more likely to be due to a brain or pituitary tumor in boys than it is in girls.[94][95]​​​​ Other rare but possible causes of prepubertal gynecomastia include renal failure, hyperthyroidism, congenital adrenal hyperplasia, and Leydig cell testicular tumor.[96][97][98][99]​​

No underlying disorder is identified in most cases, and gynecomastia recedes or resolves if the environmental exposure is removed.[20][46]​​[100]​​​ If no cause is found, reassurance that gynecomastia may resolve during puberty is usually the only option.

Newborn infants to 6 months of age

Gynecomastia is considered physiologic and does not require assessment or intervention.

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