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 gynaecomastia is self-limiting and benign.

Asymptomatic men without an obvious cause in whom treatment is deferred should be re-examined in 6 months to be certain the gynaecomastia 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 trialled in patients with rapid-onset non-pathological gynaecomastia.[27]​ In one prospective cohort study of 81 men with idiopathic gynaecomastia (mean age 42.8 years), 90% experienced complete resolution with tamoxifen therapy.[74]

Pruritus, constipation, and/or diarrhoea may occur.[74]

European guidelines do not recommend the use of tamoxifen in the treatment of idiopathic gynaecomastia because of limited randomised 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 work-up 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 gynaecomastia 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.[77]​ Low-quality evidence suggests that these techniques are associated with high levels of patient satisfaction, low complication rates, and inconspicuous scarring.[77][78]

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 haematoma, seroma, infection, permanent sensory loss, skin redundancy, abnormal breast contour, and scarring.[77][79]

Final breast contour may not be apparent for 1 year.

1st line – discontinuation of exposure

Back
ACUTE
|
adults
|
with exogenous androgen or oestrogen 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 gynaecomastia.[27]​ Environmental manipulations (e.g., removal of occupational oestrogenising agents) are most effective when treatment is instituted early, especially in the first year, while gynaecomastia is still in the proliferative phase.[80]​​

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

Consider – androgen therapy

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

androgen therapy

Additional 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 aged >40 years]) to exclude prostate cancer; haematocrit or hemoglobin, to determine risk for polycythaemia.[73]

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. Available formulations and brands may differ between countries; consult your local drug formulary for more information.

Primary options

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

2nd line – tamoxifen

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

tamoxifen

Persistent pain and psychological distress are primary indications for treatment.

Decreases symptoms and breast diameter, sometimes with complete resolution.[74]

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 oestrogen exposure
3rd line – 

breast reduction surgery

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

A comprehensive work-up 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 gynaecomastia 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.[77]​ Low-quality evidence suggests that these techniques are associated with high levels of patient satisfaction, low complication rates, and inconspicuous scarring.[77][78]

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 haematoma, seroma, infection, permanent sensory loss, skin redundancy, abnormal breast contour, and scarring.[77][79]

Final breast contour may not be apparent for 1 year.

1st line – tamoxifen

Back
ACUTE
|
adults
|
with prostate cancer on anti-androgen therapy
1st line – 

tamoxifen

More effective for prevention of gynaecomastia and chest pain than radiation when administered concurrently with anti-androgens bicalutamide or flutamide, which are used to treat prostate cancer.​[34][57]​​[58][60]​​[82]​​​​​[84][99]​​​​​The aromatase inhibitor anastrozole does not appear to be as effective.[34]​​​​​[55]

Also used for treatment in men with prostate cancer given anti-androgen therapy who develop gynaecomastia.[58] The prevalence of breast pain and gynaecomastia are lower when tamoxifen is given prophylactically rather than at the onset of symptoms after anti-androgen therapy is begun, but some men who might never have developed significant symptoms will be treated unnecessarily.[83]

Systematic reviews and meta-analyses indicate that tamoxifen is more effective than radiotherapy for the prevention of gynaecomastia and chest pain associated with androgen deprivation in men with prostate cancer.[34][57]​​[84]​​

Adverse effects occur more frequently with tamoxifen (dizziness, hot flushes, constipation, asthenia, and rare cardiological or neurological effects) than with radiotherapy, but are usually mild.[57][58]​​​​​

Primary options

tamoxifen: 10-20 mg orally once daily

2nd line – prophylactic radiotherapy to breasts

Back
ACUTE
|
adults
|
with prostate cancer on anti-androgen therapy
2nd line – 

prophylactic radiotherapy 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 radiotherapy include skin reaction, erythema, pruritus, and hyperpigmentation, usually mild and transient.[57][58]​​​​[84]

The long-term efficacy and effect of these treatments on cancer progression and survival is unknown; further studies are indicated.[84]​ Caution is warranted when considering radiotherapy in young patients for whom long-term cancer risk is greater.[84]

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 aged >40 years]) to exclude prostate cancer; haematocrit or haemoglobin, to determine risk for polycythaemia.[73]

Gynaecomastia 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 gynaecomastia.

Adjust dose according to serum testosterone levels. Available formulations and brands may differ between countries; consult your local drug formulary for more information.

Primary options

testosterone topical: consult specialist for guidance on dose; several formulations exist

Secondary options

testosterone cipionate: consult specialist for guidance on dose

OR

testosterone enantate: consult specialist for guidance on dose

1st line – discontinuation or change of drug

Back
ACUTE
|
adults
|
with non-hormonal drug exposure
1st line – 

discontinuation or change of drug

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

Most effective when treatment is instituted early, especially in the first year.[80]​​

Commonly used medicines that may be considered as substitutions include, in order of increasing risk for gynaecomastia:[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 non-hormonal 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.[75]

Primary options

tamoxifen: 10-20 mg orally once daily

3rd line – breast reduction surgery

Back
ACUTE
|
adults
|
with non-hormonal drug exposure
3rd line – 

breast reduction surgery

A comprehensive work-up 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 gynaecomastia 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.[77]​ Low-quality evidence suggests that these techniques are associated with high levels of patient satisfaction, low complication rates, and inconspicuous scarring.[77][78]

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 haematoma, seroma, infection, permanent sensory loss, skin redundancy, abnormal breast contour, and scarring.

Final breast contour may not be apparent for 1 year.

pubertal idiopathic gynaecomastia

1st line – observation and reassurance

Back
ACUTE
|
pubertal idiopathic gynaecomastia
1st line – 

observation and reassurance

Asymptomatic patients require no treatment as the gynaecomastia is self-limiting and benign. Boys at puberty with normal sexual development need reassurance that gynaecomastia is normal and that the condition usually resolves within 2 to 3 years.[3][85][86]

Consider – selective oestrogen receptor modulator (SERM)

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

selective oestrogen receptor modulator (SERM)

Additional treatment recommended for SOME patients in selected patient group

Often, breast tissue reduction rather than complete resolution. Systematic reviews of tamoxifen treatment of pubertal gynaecomastia suggest that tamoxifen may be effective in select patients and appears to be safe.[87][88]​ 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 post-treatment.[88]​ High-quality evidence on pharmacological therapy for pubertal gynaecomastia is lacking.[88]

European guidelines do not recommend the use of SERMs (tamoxifen and raloxifene) in the treatment of gynaecomastia 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 gynaecomastia
|
with significant psychological distress
Consider – 

breast reduction surgery

Additional 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/oestrogen ratio to reach adult proportions.

A comprehensive work-up 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 gynaecomastia 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 gynaecomastia in adolescents significantly improved quality of life, particularly in younger and overweight/obese patients and those with moderate to severe gynaecomastia.[89]

Most medical centres require pathological examination 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 histopathological examination of tissue has been questioned.[90][91]​ 

infantile and pre-pubertal gynaecomastia

1st line – observation and reassurance

Back
ACUTE
|
infantile and pre-pubertal gynaecomastia
|
newborn infants to 6 months
1st line – 

observation and reassurance

Gynaecomastia is considered physiological and does not require assessment or intervention.

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

Back
ACUTE
|
infantile and pre-pubertal gynaecomastia
|
pre-pubertal boys
1st line – 

evaluation and treatment on 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.[92][93]​ Other rare but possible causes of pre-pubertal gynaecomastia include renal failure, hyperthyroidism, congenital adrenal hyperplasia, and Leydig cell testicular tumour.[94][95][96][97]

No underlying disorder is identified in most cases, and gynaecomastia recedes or resolves if the environmental exposure is removed.[20]​​[46][98]​​ If no cause is found, reassurance that gynaecomastia 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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