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 men seeking consultation for gynecomastia, approximately 40 percent of cases of gynecomastia 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 and the epidemiology, causes, and evaluation of gynecomastia in adults are discussed separately. (See "Gynecomastia in children and adolescents" and "Epidemiology, pathophysiology, and causes of gynecomastia" and "Clinical features, diagnosis, and evaluation of gynecomastia in adults".)

GENERAL PRINCIPLES — The management of gynecomastia depends upon its etiology, duration, severity, and the presence or absence of tenderness.

●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'.)

●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. In up to 20 percent, pubertal gynecomastia persists into adulthood (figure 2).

●The simplest method to prevent or manage gynecomastia is to avoid or discontinue drugs that cause it (table 2). (See 'Stop offending drugs' below.)

●Gynecomastia of recent onset (<6 months) often regresses spontaneously, so observation alone is the initial step for many patients, especially those with pubertal gynecomastia or following the correction of the cause, such as discontinuation of a medication known to be associated with gynecomastia [2]. (See 'Observation only' below.)

●Potential indications for early medical therapy include significant breast enlargement (>4 cm in diameter in young men), pain, tenderness, and embarrassment that interfere with the patient's normal daily activities (see 'Pharmacologic therapy' below). Surgical intervention might be needed in patients with persistent gynecomastia, including those with pubertal gynecomastia that persists into late adolescence or early adulthood.

●Gynecomastia is the most symptomatic (pain and tenderness) and treatable in its early stages (first six months). 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. Surgery effectively removes excess breast tissue at any time, but it is delayed until the underlying cause of gynecomastia has been addressed (to avoid recurrence after surgery) [3]. (See 'Pharmacologic therapy' below.)

●Severe gynecomastia, with large pendulous breasts and skin redundancy, is unlikely to respond to pharmacologic therapy and nearly always requires surgery for an optimal cosmetic result. (See 'Surgery' below.)

●The approach to unilateral gynecomastia is the same as for bilateral gynecomastia. 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".)

INITIAL MANAGEMENT — The approach to management begins with the simplest and least invasive steps, including observation only, stopping causative medications, and treating underlying medical problems associated with gynecomastia. If gynecomastia does not resolve within three months with these measures and the patient has pain and tenderness, medical therapy is typically the next step. Surgical intervention should be considered in men whose gynecomastia does not regress spontaneously, is causing considerable discomfort or psychological distress, or is longstanding (greater than 12 months) and in which the fibrotic stage has been reached [4,5].

A major factor that should influence the initial approach to management is the duration of gynecomastia. Histologic studies show that the glandular changes in the breast are the same regardless of etiology and that the extent of glandular proliferation depends upon the intensity and duration of the stimulation (see "Clinical features, diagnosis, and evaluation of gynecomastia in adults", section on 'Histology'). Gynecomastia is the most symptomatic in the early stages (first six months), when ductal hyperplasia and periductal inflammation are present. During this time period, gynecomastia is also the most treatable with medications.

The goal in men with prostate cancer undergoing hormone therapy (androgen deprivation therapy or antiandrogen monotherapy) is to prevent the development of gynecomastia. The best options include tamoxifen and radiation therapy. (See 'Men with prostate cancer' 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.

Observation only — Gynecomastia often regresses spontaneously, so observation alone is often the initial step (if there are no possible inciting drugs). This is only effective if the gynecomastia is in the early proliferative phase (eg, present for less than one year). Otherwise, fibrosis is likely to be present and glandular tissue will not regress spontaneously. We suggest observation without medical therapy after stopping offending medications and/or treating any underlying disorders. Patients with recent-onset gynecomastia should be seen at three-month intervals to determine if the gynecomastia is resolving spontaneously or if a medication trial should be initiated.

Pubertal gynecomastia (a benign, physiologic process) typically develops between ages 10 and 12 years, with a peak prevalence of 65 percent between ages 13 and 14 years, followed by regression in 80 percent within six months to two years. It may persist into adulthood in up to 20 percent of individuals (figure 2). Observation alone is a reasonable approach in most adolescent boys.

Regression of gynecomastia is also common in adults. In one report, regression of breast tissue occurred in 85 percent of adult men with gynecomastia due to various causes [2]. In contrast, in therapeutic trials, complete spontaneous regression in men receiving drug therapy or placebo is much less frequent. (See 'Pharmacologic therapy' below.)

Treat underlying condition — In men with gynecomastia due to an underlying treatable disorder such as hypogonadism or hyperthyroidism, 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.

Pharmacologic therapy — Three classes of medications, selective estrogen receptor modulators (SERMs), aromatase inhibitors, and androgens (for men with hypogonadism), have been studied for the treatment of gynecomastia. For men with indications for medical therapy, we suggest tamoxifen, unless they have hypogonadism, in which case we suggest testosterone therapy. Potential indications for early intervention with pharmacotherapy include pain, tenderness, and embarrassment that interfere with the patient's normal daily activities. Although they may not induce complete regression of gynecomastia, they may result in partial regression and relief of tenderness. None are approved for the treatment of gynecomastia.

Medical therapy may be effective in the early active phase of gynecomastia but not in the late fibrotic stage (after 12 months). Surgical intervention might be necessary in patients with persistent gynecomastia, including those with pubertal gynecomastia that persists into late adolescence or early adulthood.

Androgens — Testosterone replacement in hypogonadal men often improves gynecomastia [4,6,7], but there is no rationale for its use in eugonadal men, in whom it may actually worsen the gynecomastia due to aromatization of the testosterone to estradiol. (See "Testosterone treatment of male hypogonadism".)

The nonaromatizable androgen dihydrotestosterone (available as a gel in some countries) has been reported to be effective for gynecomastia in uncontrolled studies [8,9], but there is insufficient information to recommend its use.

Selective estrogen receptor modulators (SERMs) — For adolescent boys with severe breast enlargement that is confirmed to be glandular tissue and is causing substantial tenderness and/or embarrassment, we suggest a brief trial (three months) of a SERM. A systematic review of six studies of tamoxifen therapy suggests that tamoxifen is beneficial and well tolerated [10]. A retrospective chart review of tamoxifen and raloxifene therapy reported that both drugs decreased glandular tissue, but neither resulted in complete resolution of the gynecomastia [11].

We currently use tamoxifen (20 mg once daily or 10 mg twice daily) for three months because there is inadequate experience with raloxifene in this population. Patients and parents/caregivers should be told that these drugs are not approved for this purpose.

For adults in whom no cause can be identified and the gynecomastia is tender and persists more than three months, we suggest a brief trial (three to six months) of tamoxifen for relief of symptoms. Although clinical trial data are limited, tamoxifen and raloxifene appear to decrease breast volume in adults with gynecomastia. However, despite some positive reports, complete breast regression may not be achieved with this approach, and these drugs are not approved for the treatment of gynecomastia [12].

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 men [1,13-17].

In a retrospective series, tamoxifen appeared to be more effective than danazol therapy [15]. Adverse events in men taking tamoxifen are rare but include epigastric distress and one report of a posttraumatic deep venous thrombosis [1,17].

In summary, although SERMs may not result in complete regression of breast tissue, they may be effective for patients with painful gynecomastia. We suggest a three-month trial of tamoxifen for adolescents with severe breast enlargement that is confirmed to be glandular tissue and is causing substantial tenderness and/or embarrassment. We suggest a similar approach for men prior to considering surgery. We typically choose tamoxifen over other SERMs, such as raloxifene, since it is the best studied of the SERMs and is reasonably well tolerated. We evaluate patients after three months to determine if the therapy is effective.

Aromatase inhibitors — We do not suggest aromatase inhibitors for the prevention or treatment of gynecomastia. Aromatase inhibitors block estrogen biosynthesis and should theoretically be effective for gynecomastia by decreasing the estrogen-to-androgen ratio [18]. However, clinical trials to date have not demonstrated an important clinical benefit of these drugs for gynecomastia in either adolescents or men with prostate cancer. The reason for this is unknown. (See "Epidemiology, pathophysiology, and causes of gynecomastia" and 'Men with prostate cancer' below.)

Surgery — Surgical therapy should be considered in men whose gynecomastia does not regress spontaneously, is causing considerable discomfort or psychological distress, or is longstanding (greater than 12 months) and the fibrotic stage has been reached [5,19]. There was a 19 percent increase in gynecomastia surgery between 2000 and 2019, with 24,123 male breast reduction surgeries being performed in 2019 [20]. (See 'Pharmacologic therapy' above.)

For adolescents, surgery is generally not recommended until adult testicular size is attained, as there may be regrowth of the breast tissue if the surgery is performed before puberty is completed.

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. Men 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 with stretched, redundant skin [18].

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 [5,19,21].

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 [19,22,23]. 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 [22]. 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.

Outcome — Potential complications of surgical therapy 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 [5,21-25]. However, when surgery is performed by an experienced cosmetic surgeon, complication rates are low, as illustrated in a series of 107 men with gynecomastia treated in one center [21]. 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).

Pathology — 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 pathology diagnosis was gynecomastia (94.1 percent), followed by pseudogynecomastia (5.3 percent) [26]. 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.

Men with prostate cancer — Gynecomastia is common in men with prostate cancer undergoing androgen deprivation. The prevalence of gynecomastia is approximately 15 percent in men treated with total androgen blockade (gonadotropin-releasing hormone [GnRH] agonists combined with an antiandrogen) [27]. However, the prevalence is as high as 75 percent when antiandrogen monotherapy is used [28-30]. Much higher doses of antiandrogens are used for monotherapy (eg, bicalutamide 150 versus 50 mg if combined with a GnRH agonist). (See "Overview of systemic treatment for recurrent or metastatic castration-sensitive prostate cancer".)

Prevention of gynecomastia is the goal of therapy, although effective treatment strategies are available for men who did not receive prophylaxis. Strategies that have been used for prevention include pharmacologic therapy (SERMs [tamoxifen]) or radiotherapy [27,31,32]. Aromatase inhibitors have been studied but do not appear to be effective.

Tamoxifen — Tamoxifen is effective for preventing antiandrogen-associated gynecomastia. In three trials of men with prostate cancer receiving high doses (150 mg/day) of the antiandrogen bicalutamide alone or with tamoxifen (10 to 20 mg/day) [32-34], 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 [35].

Tamoxifen is more effective given daily than weekly [36], and prophylaxis with tamoxifen 10 mg/day started with bicalutamide is more effective than 20 mg/day started one month after gynecomastia first develops [37].

Anastrozole — Anastrozole reduces the incidence of antiandrogen-associated gynecomastia but is less effective than tamoxifen. This was illustrated in a trial of 88 men 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 [34]. Gynecomastia developed in 73, 51, and 10 percent of men receiving bicalutamide alone, bicalutamide with anastrozole, or bicalutamide with tamoxifen, respectively.

Radiotherapy — Prophylactic radiotherapy prevents antiandrogen-associated gynecomastia in some, but not all, men [31]. 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 [32,33,38,39].

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 [40].

A Norwegian registry-based study did not demonstrate an increased risk of breast cancer in patients who received prophylactic breast radiotherapy [41]. However, the study had a relatively short follow-up period (median = 4 years), and the study was too small to detect changes in incidence in breast cancer, a disease that is rare in men.

Tamoxifen versus radiotherapy — For men at high risk for venous thromboembolism, we suggest radiotherapy rather than tamoxifen [42]. (See "Overview of the causes of venous thrombosis", section on 'Tamoxifen'.)

Data on the efficacy of tamoxifen versus radiotherapy for preventing gynecomastia in men receiving high-dose bicalutamide monotherapy (150 mg/day) after radical prostatectomy are conflicting [32,33,43]. In one trial of 102 men, gynecomastia developed in 68, 8, and 34 percent of patients receiving bicalutamide alone, bicalutamide combined with tamoxifen (10 mg/day), or prophylactic radiotherapy, respectively, suggesting that tamoxifen is superior to radiotherapy [32].

Results of two meta-analyses suggest that while tamoxifen 20 mg/day is the most effective agent for preventing gynecomastia, it is also associated with more side effects than radiotherapy or aromatase inhibitors [43,44]. Weekly tamoxifen (as opposed to daily) and aromatase inhibitors were ineffective. One meta-analysis of nine trials including 1573 men suggested that radiotherapy was more effective than tamoxifen for treatment of bicalutamide-induced gynecomastia [44].

Based upon these meta-analyses and the known risks of tamoxifen and radiotherapy, we recommend tamoxifen over radiotherapy for prevention of gynecomastia in patients being treated with high-dose bicalutamide monotherapy.

Surgical intervention — Surgical prophylaxis of gynecomastia has been described, but surgery (subcutaneous mastectomy, liposuction) is most often considered for established disease [29,45]. (See 'Surgery' above.)

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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 — The management of gynecomastia depends upon a number of factors, including its etiology, duration, severity, and the presence or absence of tenderness. When gynecomastia persists beyond 12 months, the breast glandular tissue has typically become fibrotic and medical therapy is unlikely to be effective. (See 'Pharmacologic therapy' above.)

●Pubertal gynecomastia (a benign, physiologic process) typically develops 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. Its persistence into adulthood is uncommon (figure 2). Thus, observation without treatment is a reasonable approach in most adolescent boys.

●For most men with gynecomastia, we suggest initial observation without treatment with follow-up re-evaluation (Grade 2C), especially in men with drug-induced gynecomastia or men with an underlying treatable disorder such as hypogonadism or hyperthyroidism, once the drug has been stopped and/or the underlying disorder has been treated.

●For adolescent boys with severe breast enlargement that is confirmed to be glandular tissue and is causing substantial tenderness and/or embarrassment, we suggest a brief trial (three months) of tamoxifen (10 mg twice daily) for relief of tenderness (Grade 2C). We do not use aromatase inhibitors, as they do not appear to be effective.

●For men in whom no cause can be identified and the gynecomastia is tender and persists more than three months, we suggest a brief trial (three to six months) of a selective estrogen receptor modulator (SERM) for relief of tenderness (Grade 2C). We currently use tamoxifen (10 mg twice daily) because there is inadequate experience with raloxifene. Patients should be told that SERMs are not approved for this purpose.

●In men with persistent gynecomastia (>1 to 2 years) that the patient finds troubling psychologically, we suggest surgery because the breast tissue has probably become fibrotic and unresponsive to drug therapy (Grade 2C).

●For prevention of gynecomastia in men with advanced prostate cancer undergoing high-dose antiandrogen monotherapy, we suggest tamoxifen therapy to reduce the risk of developing gynecomastia (Grade 2C). However, for men with known risk factors for venous thromboembolism, we suggest radiotherapy rather than tamoxifen.

•We suggest not using aromatase inhibitors for prevention, because they do not appear to be effective in this setting.

•For men who have already developed gynecomastia on antiandrogen therapy, we use tamoxifen therapy (if it is of recent onset and likely to be in its proliferative phase).