Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

adults

1st line – observation and reassurance

Back
ACUTE
|
adults
|
idiopathic
1st line – 

observation and reassurance

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

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.

2nd line – tamoxifen

Back
ACUTE
|
adults
|
idiopathic
2nd line – 

tamoxifen

Persistent pain and psychological distress are primary indications for treatment.

Tamoxifen may be trialed in patients with rapid-onset nonpathological 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]

European guidelines do not recommend the use of tamoxifen in the treatment of idiopathic gynecomastia because of limited randomized controlled trial evidence.[3]

Primary options

tamoxifen: 10-20 mg orally once daily

3rd line – breast reduction surgery

Back
ACUTE
|
adults
|
idiopathic
3rd line – 

breast reduction 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]

Not generally recommended in pubertal and adolescent groups.

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.

1st line – discontinuation of exposure

Back
ACUTE
|
adults
|
with exogenous androgen or estrogen exposure
1st line – 

discontinuation of exposure

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

Men who have taken high doses of exogenous androgen for body building frequently are found to be unresponsive to therapies other than surgical reduction.

Consider – androgen therapy

Back
ACUTE
|
adults
|
with exogenous androgen or estrogen exposure
Consider – 

androgen therapy

Treatment recommended for SOME patients in selected patient group

Candidates for testosterone therapy should have the following measured prior to beginning therapy: prostate-specific antigen (PSA [if ages >40 years]) to exclude prostate cancer; hematocrit or hemoglobin, to determine risk for polycythaemia.[74]

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]

Adjust dose according to serum testosterone levels.

Primary options

testosterone transdermal: (gel) consult specialist for guidance on dose; several formulations exist

2nd line – tamoxifen

Back
ACUTE
|
adults
|
with exogenous androgen or estrogen exposure
2nd line – 

tamoxifen

Persistent pain and psychological distress are primary indications for treatment.

Decreases symptoms and breast diameter, sometimes with complete resolution.[76]

Well tolerated. Modestly effective.

Primary options

tamoxifen: 10-20 mg orally once daily

3rd line – breast reduction surgery

Back
ACUTE
|
adults
|
with exogenous androgen or estrogen exposure
3rd line – 

breast reduction surgery

May be the only effective treatment for patients who misuse androgen.

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]

Not generally recommended in pubertal and adolescent groups.

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.

1st line – tamoxifen

Back
ACUTE
|
adults
|
with prostate cancer on antiandrogen therapy
1st line – 

tamoxifen

More effective for prevention of gynecomastia and chest pain than radiation when administered concurrently with antiandrogens bicalutamide or flutamide, which are used to treat prostate cancer.​[34][57][58][60]​​[84]​​[86][101]​​The aromatase inhibitor anastrozole does not appear to be as effective.[34][55]​​

Also used for treatment in men with prostate cancer given antiandrogen therapy who develop gynecomastia.[58] 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]

Primary options

tamoxifen: 10-20 mg orally once daily

2nd line – prophylactic radiation therapy to breasts

Back
ACUTE
|
adults
|
with prostate cancer on antiandrogen therapy
2nd line – 

prophylactic radiation therapy to breasts

Radiation is more expensive, but is an alternative in men with high cardiovascular risk, history of thrombosis, or intolerance to tamoxifen.[57]​ However, this is less effective than tamoxifen.[60]

Adverse effects from radiation therapy include skin reaction, erythema, pruritus, and hyperpigmentation, usually mild and transient.[57][58][86]

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]

1st line – androgen therapy

Back
ACUTE
|
adults
|
with hypogonadism
1st line – 

androgen therapy

Candidates for testosterone therapy should have the following measured prior to beginning therapy: prostate-specific antigen (PSA [if ages >40 years]) to exclude prostate cancer; hematocrit or hemoglobin, to determine risk for polycythemia.[74]

Gynecomastia is more likely to resolve in these patients 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.

Adjust dose according to serum testosterone levels.

Primary options

testosterone transdermal: (gel) consult specialist for guidance on dose; several formulations exist

Secondary options

testosterone cypionate: 150-200 mg intramuscularly every 2 weeks, or 75-100 mg intramuscularly once weekly

OR

testosterone enanthate: 150-200 mg intramuscularly every 2 weeks, or 75-100 mg intramuscularly once weekly

1st line – discontinuation or change of drug

Back
ACUTE
|
adults
|
with nonhormonal drug exposure
1st line – 

discontinuation or change of drug

Withdrawal of a contributing drug may be sufficient to alleviate gynecomastia.[3][4][27]

Most effective when treatment is instituted early, especially in the first year.[82]​​

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.

2nd line – tamoxifen

Back
ACUTE
|
adults
|
with nonhormonal drug exposure
2nd line – 

tamoxifen

Persistent pain and psychological distress are primary indications for treatment.

Decreases symptoms and breast diameter, sometimes with complete regression.

Well tolerated. Modestly effective.

More effective than the weak androgen danazol.[77]

Primary options

tamoxifen: 10-20 mg orally once daily

3rd line – breast reduction surgery

Back
ACUTE
|
adults
|
with nonhormonal drug exposure
3rd line – 

breast reduction 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]

Not generally recommended in pubertal and adolescent groups.

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.

Final breast contour may not be apparent for 1 year.

pubertal idiopathic gynecomastia

1st line – observation and reassurance

Back
ACUTE
|
pubertal idiopathic gynecomastia
1st line – 

observation and reassurance

Asymptomatic patients require no treatment as the gynecomastia is self-limited and benign. 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]

Consider – selective estrogen receptor modulator (SERM)

Back
ACUTE
|
pubertal idiopathic gynecomastia
|
with significant psychological distress
Consider – 

selective estrogen receptor modulator (SERM)

Treatment recommended for SOME patients in selected patient group

Often, breast tissue reduction rather than complete resolution. 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 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]

Primary options

tamoxifen: 10-20 mg orally once daily

OR

raloxifene: 60 mg orally once daily

Consider – breast reduction surgery

Back
ACUTE
|
pubertal idiopathic gynecomastia
|
with significant psychological distress
Consider – 

breast reduction surgery

Treatment recommended for SOME patients in selected patient group

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.

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]

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]

infantile and prepubertal gynecomastia

1st line – observation and reassurance

Back
ACUTE
|
infantile and prepubertal gynecomastia
|
newborn infants to 6 months
1st line – 

observation and reassurance

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

1st line – evaluation and treatment on case-by-case basis

Back
ACUTE
|
infantile and prepubertal gynecomastia
|
prepubertal boys
1st line – 

evaluation and treatment on case-by-case basis

A detailed history for environmental exposure should be followed by physical exam for a testicular mass, differences in sex development, or precocious puberty.[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.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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