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 may be unilateral or bilateral and is diagnosed on examination as a palpable mass of tissue that has been variably defined as >0.5, >1 and >2 cm in diameter. Thus, a clinically useful definition of gynecomastia is palpable breast tissue that extends outside the area under the nipple or recent breast tissue growth (virtually always accompanied by tenderness) independent of size. Some boys and men are bothered by <2 cm of palpable nontender breast tissue whereas others are unperturbed by ≥2 cm of palpable nontender breast tissue. Many boys and men will report breast tenderness as bothersome or worrisome.
The clinical features and evaluation of gynecomastia will be reviewed here. Epidemiology, causes, pathogenesis, and management of gynecomastia and an overview of gynecomastia in children and adolescents are discussed separately. (See "Epidemiology, pathophysiology, and causes of gynecomastia" and "Management of gynecomastia" and "Breast masses in children and adolescents".)
CLINICAL FEATURES — Most gynecomastia is discovered incidentally on physical examination, but adolescents commonly experience painful, tender gynecomastia (see "Gynecomastia in children and adolescents", section on 'Definition and characteristic features'). In contrast, gynecomastia-associated pain is usually not severe in adults, and most men are asymptomatic. Varying degrees of tenderness and nipple sensitivity with rubbing against a shirt are more common than pain. However, severe symptoms in men are a potential indication for earlier therapeutic intervention, even though these symptoms are usually self-limited, because fibrotic changes begin to develop after 6 to 12 months. (See "Management of gynecomastia", section on 'Initial management'.)
Physical findings — In true gynecomastia, a ridge of glandular tissue will be felt that is reasonably symmetrical to the nipple-areolar complex. Gynecomastia can usually be detected when the size of the glandular tissue exceeds 0.5 cm in diameter. There are four typical features on examination: the glandular tissue is centrally located, symmetrical in shape, usually bilateral, and tender to palpation (during the early, growth phase) (figure 1). A study of 506 adolescent and adult males presenting to emergency departments with trauma who underwent a chest computed tomography (CT) scan showed that some breast glandular tissues in males is a normal finding with 90th, 95th, and 97.5th percentiles of normal breast tissue being 2.2, 2.6, and 3.6 cm, respectively [1].
Although gynecomastia is usually bilateral, some patients present with unilateral enlargement or asymmetric enlargement. One side may enlarge weeks to months before the other [2].
Imaging features — Imaging is not routinely recommended unless there is concern for possible breast cancer (new onset or rapid growth of a unilateral, nontender, and/or fixed mass that is eccentric to an areola). The mammographic features of gynecomastia are described as "a fan-shaped density emanating from the nipple, gradually blending into surrounding fat" [3]. It may have extensions into surrounding fat and an appearance similar to that of a heterogeneously dense female breast.
The usual imaging studies are mammography and ultrasound. Mammography is difficult to perform if there is not significant gynecomastia. Mammography is the most sensitive imaging modality for detecting malignancy, but ultrasonography is more specific [4].
Histology — Histologic studies show that the glandular changes in the breast are the same regardless of etiology, and the extent of glandular proliferation depends upon the intensity and duration of the growth stimulation. The histologic picture changes from the growth phase to the late fibrotic phase.
●Initially, there is extensive ductal epithelial hyperplasia, proliferation and lengthening of the ducts, an increase in the stromal and periductal connective tissue, and proliferation of periductal inflammatory cells (picture 1A-B). There is also extensive periductal edema and stromal fibroblastic proliferation. This is the early or florid stage of gynecomastia, generally is present for the first six months after onset, and is associated with pain and/or tenderness [5-8].
●After 12 or more months, the breast tissue evolves into the late or quiescent, fibrotic stage. There is a slight increase in the number of ducts, with marked dilatation of the ducts and little or no epithelial cell proliferation. There is also an increase in the amount of stroma, stromal fibrosis, and a disappearance of the inflammatory reaction. Pain and tenderness are uncommon during this stage.
It is unlikely that any medical therapy will result in significant regression in the late fibrotic stage. As a result, medical therapies, if used, should be tried early in the course. (See "Management of gynecomastia".)
DIAGNOSIS — The diagnosis of gynecomastia is made on physical examination as a palpable mass of tissue at least 0.5 cm in diameter (usually underlying the nipple). The examiner places his or her thumb and forefinger or the fingers of each hand on each side of the breast and slowly brings them together (figure 1) [9]. For men with large breasts, the authors recommend having the man lie recumbent with hands resting behind his head. Gynecomastia is felt as a concentric, rubbery-to-firm disk of tissue, often mobile, located directly beneath the areolar area.
Differential diagnosis
Pseudogynecomastia — Gynecomastia needs to be distinguished from pseudogynecomastia (lipomastia), which is due to an increase in breast fat, not glandular tissue. These patients have diffuse breast enlargement without any subareolar glandular tissue. When examining the patient with pseudogynecomastia, the fingers will not meet any resistance until they reach the nipple, eg, there is no discrete mass (figure 1) [9].
Breast cancer — Gynecomastia needs to be differentiated from other causes of breast masses, most importantly, breast cancer. Gynecomastia almost always can be distinguished from breast cancer by physical examination. Breast cancers are typically unilateral, nontender, and often fixed masses found eccentric to the nipple-areolar complex. In addition, they are firm-to-hard in texture and may be associated with skin dimpling, nipple discharge, and regional lymphadenopathy (algorithm 1). If the differentiation cannot be made by physical examination, ultrasonography or mammography should be done. (See 'Further evaluation to rule out breast cancer' below.)
EVALUATION TO DETERMINE CAUSE — Once gynecomastia has been diagnosed, the combination of a careful history, physical examination, and a few diagnostic tests allows one to identify the cause of gynecomastia in most patients [9]. Unilateral gynecomastia should be evaluated in the same fashion as bilateral gynecomastia. The causes of gynecomastia are shown in the tables and reviewed separately (table 1 and table 2). (See "Epidemiology, pathophysiology, and causes of gynecomastia".)
History and examination — Additional evaluation includes reviewing all medications, including over-the-counter drugs, dietary supplements, and herbal products that can cause gynecomastia (table 2) (see "Epidemiology, pathophysiology, and causes of gynecomastia"). Improvement in gynecomastia after discontinuance or substitution of a drug (with good evidence for being associated with gynecomastia) for one to several months suggests, but does not prove, that the drug was responsible.
In adolescent boys, breast enlargement is almost always due to pubertal gynecomastia, which resolves spontaneously in most cases.
The patient should be asked about symptoms of liver and kidney disease, as well as overt hyperthyroidism (eg, weight loss and palpitations) and hypogonadism (eg, decreased libido and strength).
In addition to the breast examination (see 'Physical findings' above), which allows one to make the diagnosis of gynecomastia, the examination should focus on the following:
●Signs of liver and kidney disease, as well as hyperthyroidism (eg, weight loss, tachycardia, goiter, tremor, lid lag, or exophthalmos). The patient should also be closely evaluated for signs that suggest hypogonadism (eg, small, firm testes that suggest Klinefelter syndrome]). (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Chest findings' and "Overview of the clinical manifestations of hyperthyroidism in adults", section on 'Genitourinary' and "Clinical features and diagnosis of male hypogonadism", section on 'Physical findings'.)
●An abdominal mass might suggest adrenocortical carcinoma, and a testicular mass or change in testicular size or consistency might indicate a neoplasm. If any of these conditions are found, it is the likely cause of the gynecomastia. (See "Clinical presentation and evaluation of adrenocortical tumors", section on 'Clinical presentation' and "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Clinical manifestations'.)
Biochemical testing — Diagnostic tests for asymptomatic gynecomastia discovered during a physical examination in a patient without one of the known underlying pathologic conditions, such as hypogonadism, cirrhosis or malnutrition, testicular tumors, or hyperthyroidism (table 1), and who is not ingesting a drug associated with gynecomastia (table 2) have a low yield.
Because of the finding of hypogonadism in 2 to 5 percent of middle-aged to older men, we suggest measurement of a morning serum total testosterone concentration in older men who present for evaluation of gynecomastia [10] (see "Approach to older men with low testosterone"). If it is low, then it should be repeated at least once between 8:00 to 9:00 AM, and free or bioavailable testosterone and luteinizing hormone (LH) levels should be considered, especially in men who are obese or have diabetes mellitus, as they might have a low sex hormone-binding globulin (SHBG) level resulting in a low total testosterone. A man with low SHBG and total testosterone levels but with a normal hypothalamic-pituitary-testicular axis will have normal free or bioavailable testosterone and LH concentrations. (See "Clinical features and diagnosis of male hypogonadism", section on 'Effect of abnormal SHBG'.)
If the gynecomastia is of recent onset, is painful or tender, or is greater than 4 cm, then serum concentrations of human chorionic gonadotropin (hCG; measured by an assay that detects all forms of hCG and its beta subunit [11]), LH, testosterone, and estradiol should be measured (algorithm 1) unless the cause is clearly apparent after the above clinical evaluation. An elevated hCG plus a suppressed LH concentration suggest a testicular or extragonadal germ cell tumor. A high serum estradiol plus a suppressed LH concentration should prompt further evaluation for a testicular tumor (Leydig or Sertoli cell) or adrenal tumor (algorithm 1). Gynecomastia associated with a mild elevation of serum estradiol and a normal LH is unlikely to be related to a tumor.
Further evaluation to rule out breast cancer — Mammography or ultrasonography should be performed in the patient with unilateral breast enlargement if there is uncertainty whether the palpable, nonfat tissue represents gynecomastia or another lesion. If uncertainty persists, we suggest referral to a surgeon with experience in managing male breast cancer and other breast lesions (eg, neurofibroma, dermoid cyst, hematoma).
Men with Klinefelter syndrome and a palpable breast mass deserve careful attention because they have a 20- to 60-fold increase in breast cancer risk compared with normal men. Although the relative risk is increased, their absolute risk of breast cancer is still considerably lower than it is in women, and routine mammography is not recommended. (See "Causes of primary hypogonadism in males", section on 'Klinefelter syndrome' and "Breast cancer in men", section on 'Epidemiology and risk factors'.)
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 5th to 6th 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 10th to 12th 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 men) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition – 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. A clinically useful definition of gynecomastia is palpable breast tissue that extends outside the area under the nipple or recent breast tissue growth (virtually always accompanied by tenderness) independent of size. (See 'Introduction' above.)
●Clinical features – Most gynecomastia is discovered incidentally on physical examination, but adolescents commonly experience painful, tender gynecomastia. Gynecomastia can usually be detected when the size of the glandular tissue exceeds 0.5 cm in diameter, but virtually always when the size of the glandular tissue exceeds 2 cm in diameter. There are four typical features on examination: the glandular tissue is centrally located, symmetrical in shape, usually bilateral, and tender to palpation (during the early growth phase) (figure 1). (See 'Clinical features' above.)
Histologic studies show that the glandular changes in the breast are the same regardless of etiology, and the extent of glandular proliferation depends upon the intensity and duration of the growth stimulation. The histologic picture changes from the growth phase to the late fibrotic phase. (See 'Histology' above.)
●Diagnosis – The diagnosis of gynecomastia is made on physical examination as a palpable mass of tissue of 2 cm or more, usually underlying the nipple. Breast glandular tissue that is nontender and 2 to 4 cm is a frequent finding in the normal population, and this finding does not generally require diagnostic evaluation. Of note, some individuals are bothered by <2 cm of palpable breast tissue while others are not bothered by >2 cm of palpable breast tissue that is nontender. The examination is performed by placing the thumb and forefinger on each side of the breast and slowly bringing them together (figure 1 and algorithm 1). (See 'Diagnosis' above.)
●Differential diagnosis
•Pseudogynecomastia – Gynecomastia needs to be distinguished from pseudogynecomastia (lipomastia, diffuse breast enlargement without any glandular tissue). When examining the patient with pseudogynecomastia, the fingers will not meet any resistance until they reach the nipple. There is no discrete mass (figure 1). (See 'Pseudogynecomastia' above.)
•Breast cancer – Breast cancers are typically unilateral, nontender, and often fixed masses found eccentric to the nipple-areolar complex. They are firm-to-hard in texture and may be associated with skin dimpling, nipple discharge, and regional lymphadenopathy (algorithm 1). If the differentiation cannot be made by physical examination, mammography or ultrasonography should be done. (See 'Further evaluation to rule out breast cancer' above.)
●Evaluation to determine cause – Once gynecomastia has been diagnosed, the combination of a careful history, physical examination, and a few diagnostic tests allows one to identify the cause of gynecomastia in most patients (algorithm 1) [9]. Unilateral gynecomastia should be evaluated in the same fashion as bilateral gynecomastia. The causes of gynecomastia are shown in the tables and reviewed separately (table 1 and table 2). (See 'Evaluation to determine cause' above and "Epidemiology, pathophysiology, and causes of gynecomastia".)
