Management of gynecomastia

INTRODUCTION — 

Gynecomastia, a benign proliferation of the glandular tissue of the male breast, is caused by an increase in the ratio of estrogen to androgen activity. It is categorized as physiologic (occurring normally during infancy, puberty, and older age) or pathologic (due to drugs or disorders such as androgen deficiency, testicular tumors, hyperthyroidism, and chronic kidney disease). In adult males seeking consultation for gynecomastia, approximately 40 percent of cases are due to persistent pubertal gynecomastia or medications and 25 percent are idiopathic (table 1) [1].

True gynecomastia should be differentiated from pseudogynecomastia (lipomastia), which refers to fat deposition without glandular proliferation. Gynecomastia must also be differentiated from breast carcinoma, which is far less common.

The management of gynecomastia will be reviewed here. An overview of gynecomastia in children and adolescents, the epidemiology, causes, evaluation, and diagnosis of gynecomastia in adults, and the management of gynecomastia in Klinefelter syndrome are discussed separately. (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults" and "Gynecomastia in children and adolescents" and "Epidemiology, pathophysiology, and causes of gynecomastia" and "Clinical features, diagnosis, and management of Klinefelter syndrome", section on 'Gynecomastia'.)

GENERAL PRINCIPLES — 

The management of gynecomastia depends upon its etiology, duration, severity, and the presence or absence of tenderness (algorithm 1).

●Distinguish gynecomastia from lipomastia – A careful breast examination is the first step to distinguishing true gynecomastia (enlargement of the glandular tissue) from pseudogynecomastia (excessive adipose tissue) (figure 1). Additional details on the breast examination and evaluation of the patient with gynecomastia are reviewed separately. (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults", section on 'Evaluation to determine cause'.)

●Assessment of gynecomastia size – Assessment of baseline and changes in the size of gynecomastia is assessed by measurement of the width (diameter) of palpable glandular breast tissue in the non-compressed state.

●Pubertal gynecomastia – Pubertal gynecomastia (a benign, physiologic process) is common in adolescent boys, often developing between ages 10 and 12 years, with a peak prevalence of 65 percent between ages 13 and 14 years, followed by regression in approximately 80 percent within six months to two years. Observation alone is usually the first step in management of pubertal gynecomastia (figure 2). (See "Gynecomastia in children and adolescents" and "Epidemiology, pathophysiology, and causes of gynecomastia".)

●Unilateral versus bilateral gynecomastia – The approach to unilateral gynecomastia is the same as for bilateral gynecomastia. Gynecomastia is sometimes asymmetric and may appear unilateral by observation alone, but on palpation, bilateral breast tissue is often found (emphasizing the importance of physical examination). It is especially important to distinguish unilateral gynecomastia from breast carcinoma and other lesions by physical examination, ultrasonography, and/or mammography. (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults", section on 'Breast cancer'.)

●Duration of gynecomastia – Gynecomastia of recent onset (<6 months) is the most symptomatic (pain and tenderness), when ductal hyperplasia and periductal inflammation are present. It often regresses spontaneously, so observation alone is often the initial step particularly for those with pubertal gynecomastia or those whose underlying cause has been corrected. Recent onset gynecomastia is also the most treatable with medications (table 2) [2]. (See 'Observation alone' below and 'Stop offending drugs' below.)

After approximately 12 months, fibrotic tissue eventually replaces glandular tissue, and tenderness resolves. Pharmacologic therapy is unlikely to be beneficial once fibrous tissue is present. (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults", section on 'Histology'.)

●Males with prostate cancer – The goal in males with prostate cancer undergoing hormone therapy (androgen deprivation therapy or antiandrogen monotherapy) is to prevent the development of gynecomastia. (See 'males with prostate cancer' below.)

INITIAL MANAGEMENT — 

Initial management of adult and adolescent males includes:

●Stopping causative medications (table 2) (see 'Stop offending drugs' below)

●Treating underlying medical problems (table 1) (see 'Treat underlying condition' below)

●In many cases, observation alone is the first step (see 'Observation alone' below)

After these initial steps, pharmacologic therapy and/or surgical intervention can be used if needed. (See 'Pharmacologic therapy' below and 'Surgery' below.)

Stop offending drugs — The first step in the management of new gynecomastia is to discontinue, if possible, any drugs that cause it, such as spironolactone (table 2). If the drug is identified as the cause of gynecomastia during the early, proliferative, and often painful phase, stopping it may result in regression of glandular tissue (within one month of stopping the drug) [1]. On the other hand, if the gynecomastia has been present for more than one year, stopping the offending drug is unlikely to result in spontaneous regression of glandular tissue, because fibrosis is likely to be present.

If gynecomastia and breast tenderness does not resolve within three months after stopping the causative drug or if the causative medication cannot be discontinued, medical therapy can be considered. (See 'Pharmacologic therapy' below.)

Treat underlying condition — In males with gynecomastia due to an underlying treatable disorder such as hypogonadism or hyperthyroidism (table 1), we suggest treatment of the underlying disorder first, followed by observation with a follow-up breast examination in three months to see if the gynecomastia is resolving. (See "Testosterone treatment of male hypogonadism" and "Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Hyperthyroidism'.)

Observation alone

●Adolescent males - We start with observation alone in most adolescent boys with pubertal gynecomastia, as regression occurs in approximately 80 percent within six months to two years (figure 2). (See "Gynecomastia in children and adolescents", section on 'Pubertal gynecomastia'.)

●Adult males – For adult males with recent onset gynecomastia (less than 6 to 12 months), we also suggest observation but only after medications and/or underlying medical disorders have been addressed. Patients whose gynecomastia has been present for a year or more are not candidates for observation only, as fibrosis is likely to be present and glandular tissue will not regress spontaneously.

Patients with recent-onset gynecomastia should be seen after three months to determine if the gynecomastia is resolving spontaneously. If tender, painful gynecomastia does not resolve within three months of observation, we typically start medical therapy. (See 'Pharmacologic therapy' below.)

In one report, regression of breast tissue occurred in 85 percent of adult males with gynecomastia due to various causes [2]. However, complete spontaneous regression is uncommon.

PHARMACOLOGIC THERAPY

Options — If gynecomastia persists after the initial steps of stopping offending drugs (table 2), treating the underlying condition, and a period of observation, pharmacologic therapy and/or surgical interventions are considered.

Pharmacologic therapies that have been studied for the treatment of gynecomastia include selective estrogen receptor modulator (SERMs), testosterone (only for males with hypogonadism), and aromatase inhibitors. Tamoxifen is the preferred SERM. Aromatase inhibitors are not recommended. (See 'Aromatase inhibitors' below.)

Patients and parents/caregivers should be told that these drugs are not approved for the treatment of gynecomastia.

SERMs — Although selective estrogen receptor modulators (SERMs) may not result in complete regression of breast tissue, they may be effective for patients with painful gynecomastia. Tamoxifen is effective in the early active phase of gynecomastia (for relief of tenderness and partial regression) but not in the late fibrotic stage (after 12 months).

We choose tamoxifen over other SERMs, such as raloxifene, since it is the best studied of the SERMs and is reasonably well tolerated.

Adolescent males — We suggest tamoxifen therapy for adolescent males with significant breast enlargement (glandular tissue >4 cm in diameter) that is causing pain, tenderness, and embarrassment that interfere with the patient's normal daily activities.

We start with a three-month trial of tamoxifen (20 mg daily) and re-evaluate after three months to determine if the therapy is effective.

In a systematic review of six studies of tamoxifen therapy for pubertal gynecomastia, tamoxifen was beneficial and well tolerated [3]. A retrospective chart review of tamoxifen and raloxifene therapy for pubertal gynecomastia reported that both drugs decreased glandular tissue, but neither resulted in complete resolution of the gynecomastia [4].

Adult males without hypogonadism — We also suggest tamoxifen therapy for adult eugonadal males with tender gynecomastia with no known underlying cause that has persisted more than three months.

Although clinical trial data are limited, tamoxifen and raloxifene seem to decrease breast volume in most males with acute gynecomastia. Tamoxifen therapy for up to three months has been reported to result in pain relief (for those with gynecomastia associated with pain and tenderness) and at least partial regression of glandular tissue in approximately 80 percent of males [1,5-9]. In another study, a complete response occurred in 90 percent of males [10].

In a retrospective series, tamoxifen appeared to be more effective than danazol therapy [7]. Adverse events in males taking tamoxifen for six months or less are rare but include epigastric distress, hot flashes, and one report of a posttraumatic deep venous thrombosis [1,9].

Testosterone therapy

Adult males with hypogonadism — We only suggest testosterone therapy for the management of gynecomastia in adult males who are also hypogonadal. Testosterone replacement in hypogonadal males often improves gynecomastia [11-13], but there is no rationale for its use in eugonadal males, in whom it may actually worsen the gynecomastia due to aromatization of the testosterone to estradiol.

Testosterone regimens and dosing are the same as for any male with hypogonadism. (See "Testosterone treatment of male hypogonadism", section on 'Choice of testosterone regimen'.)

The nonaromatizable androgen dihydrotestosterone (available as a gel in some countries) has been reported to be effective for gynecomastia in uncontrolled studies [14,15], but there is insufficient information to recommend its use.

Aromatase inhibitors — Aromatase inhibitors block estrogen biosynthesis and should theoretically be effective for gynecomastia by decreasing the estrogen-to-androgen ratio [16]. However, clinical trials to date have not demonstrated an important clinical benefit in adolescents with pubertal gynecomastia or males with prostate cancer who develop gynecomastia due to antiandrogen monotherapy [1,17]. (See 'males with prostate cancer' below.)

Aromatase excess syndrome — Aromatase excess syndrome is one very rare exception when aromatase inhibitors are used. For boys and adolescents with this syndrome, we suggest aromatase inhibitor therapy [18]. (See "Epidemiology, pathophysiology, and causes of gynecomastia", section on 'Sex hormone action in breast'.)

Therapy should be initiated before puberty at the onset of gynecomastia. In a case series of seven boys with congenital aromatase excess syndrome, early initiation of anastrozole resulted in resolution of gynecomastia and optimization of growth and virilization [18]. There was a relapse of gynecomastia when anastrozole was discontinued. It is not known whether aromatase inhibitors are safe to administer long term in this rare syndrome.

SURGERY

Indications — Surgery effectively removes excess breast tissue at any time, but should be delayed until the underlying cause of gynecomastia has been addressed (to avoid recurrence after surgery) [19].

Candidates for surgical intervention include:

●Patients with persistent gynecomastia, including those with pubertal gynecomastia that persists into late adolescence or early adulthood. We consider surgery when the gynecomastia has persisted >12 months, the nontender, fibrotic stage has been reached, and is causing considerable psychological distress [11,20,21].

However, for adolescents, we avoid surgery for treatment of gynecomastia until adult testicular size is attained, as there may be regrowth of the breast tissue if the surgery is performed before puberty is completed.

●Patients with severe gynecomastia, with large pendulous breasts and skin redundancy, because they are unlikely to respond to pharmacologic therapy. These patients nearly always require surgery for an optimal cosmetic result.

In the United States, there was a 19 percent increase in gynecomastia surgery between 2000 and 2019, with 24,123 male breast reduction surgeries being performed in 2019 [22].

Extent of surgery — The extent of surgery depends upon the severity of the breast enlargement and whether there is also excess adipose tissue present. Multiple classification schemes have been published to grade the degree of gynecomastia. Males with moderate (6 to 11 cm in diameter) to severe gynecomastia (>11 cm) are unlikely to undergo spontaneous regression. Surgical outcomes are generally better for those with minimal or moderate breast enlargement without skin redundancy than those with severe enlargement and stretched, redundant skin [16].

Procedure — Many patients are treated with a combination of direct surgical excision of the glandular tissue and liposuction of any coexisting adipose tissue through a periareolar incision [20,21,23].

More extensive cosmetic surgery, including skin excision, is required for patients with marked gynecomastia or who develop excessive sagging of the breast tissue, as occurs with weight loss [21,24,25]. A transverse ellipse of excessive skin, fat, and glandular tissue is excised, and the nipple-areola complex is removed as a full thickness graft and replaced in the appropriate anatomic position following removal of the redundant tissue [24]. Alternatively, the nipple-areola complex may remain attached to the surrounding dermis and blood supply and be rotated upward into its proper position after the excessive tissue is excised.

Complications — Potential complications of surgical for gynecomastia include sloughing of tissue due to compromise of the blood supply, contour irregularity, hematoma or seroma formation, and numbness of the nipple-areolar area [20,23-27]. However, when surgery is performed by an experienced cosmetic surgeon, complication rates are low, as illustrated in a series of 107 males with gynecomastia treated in one center [23]. Only one patient had a postoperative complication (dehiscence of the surgical wound). All but 2 of the 107 patients were considered to have a satisfactory cosmetic result (excellent in 94 patients, good in 11).

Histopathologic findings — The histopathologic findings from surgical breast specimens almost always show gynecomastia; breast cancer is extremely rare. In a report of 3719 surgical procedures performed for gynecomastia (5113 breast specimens), the most common pathologic diagnosis was gynecomastia (94.1 percent), followed by pseudogynecomastia (5.3 percent) [28]. The overall prevalence of invasive breast carcinoma, ductal carcinoma in situ, and atypical ductal hyperplasia was 0.11, 0.18, and 0.4 percent (4, 7, and 18 cases), respectively.

MALES WITH PROSTATE CANCER

Prevalence — Gynecomastia is common in males with prostate cancer undergoing androgen deprivation therapy (table 1). The prevalence of gynecomastia is approximately 15 percent in males treated with total androgen blockade (gonadotropin-releasing hormone [GnRH] agonists combined with an antiandrogen) [29]. However, the prevalence is as high as 75 percent when antiandrogen monotherapy is used [30-32]. Much higher doses of antiandrogens are used for monotherapy (eg, bicalutamide 150 versus 50 mg if combined with a GnRH agonist). Gynecomastia causes significant alterations in body image and is often associated with breast tenderness as well [5]. (See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer", section on 'Androgen deprivation therapy'.)

Prevention of gynecomastia — Prevention of gynecomastia is the goal of therapy, although effective treatment strategies are available for males who did not receive prophylaxis.

Strategies that have been used for prevention include pharmacologic therapy (SERMs [tamoxifen] and aromatase inhibitors [anastrozole]) and radiotherapy [29,33-35]. Surgical prophylaxis of gynecomastia has been described, but it is not typically used to prevent gynecomastia for these patients.

Medications

●Tamoxifen – Tamoxifen is effective for preventing antiandrogen-associated gynecomastia. In three trials of males with prostate cancer receiving high doses (150 mg/day) of the antiandrogen bicalutamide alone or with tamoxifen (10 to 20 mg/day) [34,36,37], gynecomastia occurred in 86 of 124 patients (69 percent) treated with bicalutamide alone compared with 11 of 122 patients (9 percent) treated with bicalutamide plus tamoxifen. Tamoxifen must be continued for the duration of antiandrogen therapy as its effect does not persist after it is discontinued [38].

Tamoxifen is more effective given daily than weekly [39], and prophylaxis with tamoxifen 10 mg/day started with bicalutamide is more effective than 20 mg/day started one month after gynecomastia first develops [40].

●Anastrozole – Anastrozole, an aromatase inhibitor, reduces the incidence of antiandrogen-associated gynecomastia but is less effective than tamoxifen. This was illustrated in a trial of 88 males with prostate cancer who were randomly assigned to bicalutamide alone or to bicalutamide plus either anastrozole (1 mg/day) or tamoxifen (20 mg/day) for 48 weeks [37]. Gynecomastia developed in 73, 51, and 10 percent of males receiving bicalutamide alone, bicalutamide with anastrozole, or bicalutamide with tamoxifen, respectively.

Radiotherapy — Prophylactic radiotherapy prevents antiandrogen-associated gynecomastia in some, but not all, males [33]. In four trials of prophylactic, low-dose bilateral breast radiotherapy (10 to 15 Gy in either one fraction or over three days), gynecomastia occurred in 155 of 215 patients (72 percent) treated with bicalutamide alone compared with 105 of 322 patients (33 percent) treated with bicalutamide plus prophylactic radiotherapy [34,36,41,42].

Treatment of established gynecomastia with higher radiation doses (eg, 20 Gy in five fractions) may improve pain and tenderness but is less effective at reducing the volume of tissue [43].

A Norwegian registry-based study did not demonstrate an increased risk of breast cancer in patients who received prophylactic breast radiotherapy [44]. However, the study had a relatively short follow-up period (median = four years), and the study was too small to detect changes in incidence in breast cancer, a disease that is rare in males.

Tamoxifen versus radiotherapy

●For prevention of gynecomastia in males with advanced prostate cancer undergoing high-dose antiandrogen monotherapy, we suggest tamoxifen therapy rather than radiotherapy. We use tamoxifen 20 mg daily (for up to one year).

●However, for males at high risk for venous thromboembolism (VTE), we use radiotherapy rather than tamoxifen, as tamoxifen is associated with an increased risk of VTE [35]. (See "Overview of the causes of venous thrombosis in adults".)

Available evidence suggests that both tamoxifen and radiotherapy are effective for preventing gynecomastia in males receiving high-dose bicalutamide monotherapy (150 mg/day) [34-36,45]. In one trial of 102 males, gynecomastia developed in 68, 8, and 34 percent of patients receiving bicalutamide alone, bicalutamide combined with tamoxifen (10 mg/day), or bicalutamide with prophylactic radiotherapy, respectively, suggesting that tamoxifen may be superior to radiotherapy [34].

Results of two meta-analyses suggest that tamoxifen 20 mg/day is the most effective agent for preventing gynecomastia in males treated with androgen deprivation therapy [35,45,46].

Tamoxifen is associated with more side effects (mostly dizziness and hot flashes), while adverse effects of radiotherapy are primarily local (erythema, pruritus, or hyperpigmentation of chest skin) [45,46].

Weekly tamoxifen (as opposed to daily) and aromatase inhibitors are relatively ineffective compared with tamoxifen or radiation therapy [35].

Management after gynecomastia develops — Tamoxifen and prophylactic radiation therapy (RT) are effective in most cases when initiated prior to the development of gynecomastia. However, both approaches have limited benefit once gynecomastia is established.

For males who have developed gynecomastia due to androgen deprivation therapy for prostate cancer, we suggest radiotherapy. In a meta-analysis of nine trials including 1573 males, radiotherapy was more effective than tamoxifen for treatment of bicalutamide-induced gynecomastia [46].

Surgery (subcutaneous mastectomy, liposuction) is typically reserved for those with contraindications to radiation therapy or tamoxifen [31,47].

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Gynecomastia (male breast development) (The Basics)")

●Beyond the Basics topics (see "Patient education: Gynecomastia (breast enlargement in males) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Initial management – We start with observation alone in most adolescent boys with pubertal gynecomastia, as regression occurs in approximately 80 percent within six months to two years. (See "Gynecomastia in children and adolescents", section on 'Physiologic gynecomastia'.)

For adult males with recent onset gynecomastia (less than 6 to 12 months) we also suggest observation, but only after medications (table 2), and/or underlying medical disorders have been addressed. Patients whose gynecomastia has been present for a year or more are not candidates for observation only, as fibrosis is likely to be present and glandular tissue will not regress spontaneously. (See 'Initial management' above.)

We start with observation alone in most adolescent boys with pubertal gynecomastia, as regression occurs in approximately 80 percent within six months to two years. (See "Gynecomastia in children and adolescents", section on 'Physiologic gynecomastia'.)

If gynecomastia persists in spite of these initial interventions, pharmacologic therapy and/or surgical interventions are considered. (See 'Pharmacologic therapy' above.).

●Pharmacologic therapy – Pharmacologic therapy is effective in the early active phase of gynecomastia (for relief of tenderness and partial regression) but not in the late fibrotic stage (after 12 months). (See 'Pharmacologic therapy' above.)

•Adolescent boys – For adolescent males with severe breast enlargement that is tender and/or causing significant embarrassment, we suggest a trial of tamoxifen therapy (Grade 2C). We treat with 20 mg once daily for three months and re-evaluate after three months to determine if the therapy is effective. (See 'Adolescent males' above.)

•Adult males without hypogonadism – For adult males with gynecomastia with no identifiable cause and breast tenderness that persists more than three months, we also suggest tamoxifen (Grade 2C). We use tamoxifen 20 mg once daily for three months and re-evaluate after three months to determine if the therapy is effective. (See 'Adult males without hypogonadism' above.)

•Adult males with hypogonadism – We suggest testosterone therapy only for adult males with gynecomastia who have hypogonadism (Grade 2C). There is no rationale for its use in eugonadal males with gynecomastia. Testosterone regimens and dosing are the same as for any male with hypogonadism. (See "Testosterone treatment of male hypogonadism", section on 'Choice of testosterone regimen' and 'Adult males with hypogonadism' above.)

●Surgery – Surgery is indicated in patients with persistent gynecomastia, including those with pubertal gynecomastia that persists into late adolescence or early adulthood. We consider surgery when the gynecomastia is causing considerable psychological distress, has persisted >12 months, and the nontender, fibrotic stage has been reached. (See 'Surgery' above.)

However, we avoid surgery in adolescents until adult testicular size is attained, as there may be regrowth of the breast tissue if the surgery is performed before puberty is completed. (See 'Surgery' above.)

●Males with prostate cancer

•Prevention – For most males with advanced prostate cancer undergoing high-dose antiandrogen monotherapy, we suggest tamoxifen therapy to reduce the risk of developing gynecomastia (Grade 2C). However, for males with known risk factors for venous thromboembolism, we suggest radiotherapy rather than tamoxifen. (See 'Prevention of gynecomastia' above.)

•Treatment – For males who have developed gynecomastia due to antiandrogen therapy for prostate cancer, we suggest radiation therapy (if the breast growth is recent and is in its tender, proliferative phase (Grade 2C). (See 'Management after gynecomastia develops' above.)