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Epidemiology, pathophysiology, and causes of gynecomastia

Epidemiology, pathophysiology, and causes of gynecomastia
Literature review current through: Jan 2024.
This topic last updated: Apr 25, 2023.

INTRODUCTION — Gynecomastia, a benign proliferation of the glandular tissue of the male breast, is common in infancy, adolescence, and in middle-aged to older males. Pseudogynecomastia, which is often seen in males with obesity, refers to fat deposition without glandular proliferation. Gynecomastia must be differentiated from breast carcinoma, which is far less common.

The epidemiology and pathogenesis will be reviewed here. The causes, evaluation, and management are discussed separately. (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults" and "Management of gynecomastia".)

DEFINITIONS — Gynecomastia is defined histologically as a benign proliferation of the glandular tissue of the male breast and clinically by the presence of a rubbery or firm mass extending concentrically from the nipple(s) (figure 1) [1]. Fat deposition without glandular proliferation is termed pseudogynecomastia (lipomastia) and is often seen in obese males.

The most important differentiation is between gynecomastia and breast carcinoma. Carcinoma is much less common, generally unilateral, eccentric in location rather than symmetrical to the nipple, nontender, hard or firm, often fixed to the underlying tissue, and may be associated with skin dimpling, nipple retraction or discharge, and axillary lymphadenopathy [2,3]. Less common conditions leading to breast enlargement include neurofibromas, lymphangiomas, hematomas, lipomas, and dermoid cysts. (See "Clinical features, diagnosis, and evaluation of gynecomastia in adults", section on 'Breast cancer'.)

EPIDEMIOLOGY — Gynecomastia is common in infancy, puberty, and in middle-aged to older males. One estimate is that between 60 to 90 percent of infants have transient gynecomastia due to the high estrogenic milieu of pregnancy [4]. Male infants also have a "mini-puberty" with adult serum concentrations of gonadotropins and a transient rise of serum estradiol more than serum testosterone concentrations [3]. After delivery, gynecomastia regresses in two to three weeks. (See "Gynecomastia in children and adolescents".)

The second peak is during puberty, with a prevalence ranging from 4 to 69 percent, with a median from several studies of 33 percent (figure 2) [4-12]. This wide variation is probably due to differences in what is considered normal subareolar glandular tissue, observer differences, and, probably most importantly, differences in the age distribution of the adolescents examined. Pubertal gynecomastia usually has an onset between ages 10 and 12 years and peaks between ages 13 and 14 years, usually at Tanner pubertal stage 3 (table 1). It generally regresses within 18 months but may persist into adulthood in approximately 20 percent of affected individuals [6]. (See "Gynecomastia in children and adolescents".)

The third peak of gynecomastia occurs in middle-aged and older males. The highest prevalence is at 50 to 80 years, with as many as 24 to 65 percent of males being affected (figure 2) [13-18].

Although gynecomastia is usually bilateral, it is often asymmetrical and can even be unilateral [19,20]. In a study of 36 male patients who underwent subcutaneous mastectomy for a unilateral breast mass, 30 (83 percent) had gynecomastia, four (11 percent) had lipoma, and two had breast cancer [20]. The majority of patients with gynecomastia were receiving medications that have been associated with gynecomastia (table 2).

PATHOPHYSIOLOGY

Sex hormone action in breast — Estrogens and androgens are the major hormones that determine breast growth and development in females and males. An increased breast tissue ratio of estrogen to androgen effect is necessary to induce breast growth.

There are three lines of evidence indicating that androgens antagonize the effects of estrogen in breast glandular tissue. First, in vitro data with breast cancer cell lines have predominately shown that androgens have apoptotic and antiproliferative effects [21,22]. Second, in postmenopausal females receiving estrogen and progesterone plus a placebo patch for six months, breast fine needle aspiration biopsies showed a five-fold increase in breast cell proliferation [23]. However, in a group receiving a testosterone patch with the estrogen and progesterone, no increase in cell proliferation was observed. Lastly, in a study of 40 patients with idiopathic gynecomastia, approximately three-quarters had at least a partial resolution of the breast enlargement when treated with dihydrotestosterone, a nonaromatizable androgen [24].

The various conditions associated with gynecomastia are usually thought to represent an imbalance between the stimulatory effect of estrogen and the inhibitory effect of androgen [25,26]. An imbalance between estrogen and androgen action will occur if there is an increase in free estrogens or a decrease of free androgens that result in an increase in the free estrogen-to-free androgen ratio; androgen insensitivity; or an estrogenic or an antiandrogenic effect of drugs (figure 3).

Determinants of sex hormone exposure — The factors that define the net estrogen/androgen balance are (table 3):

Physiologic stage - physiologic gynecomastia is common and has a trimodal distribution occurring in neonatal, pubertal, and older males

The circulating concentration and sex-steroid-hormone binding of sex hormone-binding globulin (SHBG)

The extraglandular conversion of androgens to estrogens, such as in adipose tissue

The hormone target cells' ability to respond to androgens and estrogens

Physiologic stage

Neonatal gynecomastia During pregnancy, the placenta transforms dehydroepiandrosterone and dehydroepiandrosterone sulfate (derived from both the mother and fetus) to estrone (E1) and estradiol (E2), which enter the fetal circulation and stimulate breast glandular proliferation, resulting in transient neonatal gynecomastia. (See "Placental development and physiology", section on 'Steroid hormones'.)

Pubertal gynecomastia In boys who develop gynecomastia during early puberty, a relative increase in extratesticular production of estrogen plays a role in the development of gynecomastia. The major androgen secreted by the adrenal glands is androstenedione. Most of the circulating E1 and E2 in early male puberty are derived from the extraglandular conversion of androstenedione and testosterone via aromatization to E1 and E2, respectively, by tissues that have aromatase including liver, skin, fat, muscle, bone, and kidney. In mid- to late pubertal adolescent boys a greater relative increase in testicular production of estrogen compared with testosterone is the major cause of gynecomastia; after early puberty in males, 95 percent of the circulating testosterone, 15 percent of the E2, and less than 5 percent of E1 is directly secreted by the testes (figure 3) [5,27-29]. (See "Male reproductive physiology", section on 'Testosterone synthesis'.)

Middle-aged and older males As noted, gynecomastia is most common in middle-aged and older males. The highest prevalence is at 50 to 80 years. This is likely due to a number of factors including the effects of aging and increasing BMI on SHBG (figure 2). (See 'Epidemiology' above.)

Role of SHBG — The majority of androgens and estrogens that enter the circulation are relatively tightly bound to sex hormone-binding globulin (SHBG) and are weakly bound to albumin. Conditions that increase SHBG concentrations (estrogenic drugs, many antiseizure medications, aging) will decrease free testosterone in males with impaired testosterone production. In addition, SHBG has a higher affinity for androgens than for estrogens, and therefore, any substance that displaces sex hormones from SHBG will tend to displace quantitatively more estrogens than androgens. The unbound or weakly bound androgens and estrogens enter the target cells and lead to hormone action [30,31]. (See "Male reproductive physiology", section on 'Transport of gonadal steroids'.)

Obesity — In some studies, higher body mass index (BMI) was associated with gynecomastia and breast diameter in adolescents and adults [16,32]. Breast adipose tissue contains the aromatase enzyme complex that converts testosterone and androstenedione to E2 and E1, respectively. Thus, it has been hypothesized, but not proven, that an increase in breast adipose tissue due to generalized weight gain might increase local estrogen production, which in turn may stimulate breast glandular tissue proliferation in a paracrine fashion.

In addition, the increase in breast fat with weight gain may lead to pseudogynecomastia that might be mistaken for gynecomastia. (See "Causes of secondary hypogonadism in males", section on 'Obesity'.)

Tissue – specific regulation — Some patients with gynecomastia appear to have enhanced sensitivity of the breast tissue to normal circulating estrogen levels even in the presence of normal circulating androgen concentrations. This might reflect increased local aromatization of androgens to estrogens in the breast tissue as increased aromatase activity has been found in pubic skin fibroblasts of patients with pubertal gynecomastia [33].

CAUSES OF GYNECOMASTIA

Common etiologies — In adult patients with persistent gynecomastia seeking consultation for the condition, current estimates suggest the following etiologies, all of which are discussed in detail below (table 3):

Persistent pubertal gynecomastia – 25 percent

Drugs – 10 to 25 percent (table 2)

No detectable abnormality – 25 percent

Cirrhosis or malnutrition – 8 percent

Hypogonadism – Primary (8 percent), secondary (2 percent)

Testicular tumors – 3 percent

Hyperthyroidism – 1.5 percent

Chronic kidney disease – 1 percent

A series of 786 males with gynecomastia seen at a single institution has confirmed these prevalent etiologies [34].

Physiologic — As noted above, physiologic gynecomastia is common and has a trimodal distribution occurring in neonatal, pubertal, and older males [1,16]. (See 'Epidemiology' above.)

Pubertal gynecomastia — It is likely that a transient imbalance of estrogen to androgen accounts for much of the estrogen/androgen imbalance that leads to pubertal gynecomastia. Most studies in pubertal boys with gynecomastia have found no differences in single-point measurements of serum concentrations of testosterone, estradiol (E2), estrone (E1), or gonadotropins from those in normal boys [7,9,35,36]. However, during early puberty, the serum E2 concentrations rise to adult levels before the testosterone concentration, and some reports have shown a transient increase in E2 concentration at the onset of puberty in boys who develop gynecomastia [7]. These boys may also have wider fluctuations of E2 levels, with an absolute increase in 24-hour concentration of E2, which may reflect increased conversion of adrenal androgens to estrogens [10,37]. (See "Gynecomastia in children and adolescents".)

Leptin and insulin-like growth factor-1 (IGF-1) are elevated in boys with pubertal gynecomastia compared with those without [38-41]. The finding that pubertal gynecomastia occurs in a temporal association with peak height velocity (the time when IGF-1 levels also peak) suggests that, together with estrogens, IGF-1, and/or leptin might play a role in the genesis of pubertal gynecomastia.

Persistent pubertal gynecomastia — Pubertal gynecomastia usually resolves spontaneously within six months to two years of onset but, in some instances, it may persist after completion of puberty into adulthood, resulting in persistent pubertal gynecomastia. (See "Gynecomastia in children and adolescents".)

Drugs — There are many drugs that have been associated with gynecomastia (table 2). Drugs with the best evidence for an association with gynecomastia are drugs that are known to affect androgen or estrogen concentrations or effects including spironolactone, cimetidine, ketoconazole, recombinant human growth hormone, estrogens, human chorionic gonadotropin (hCG), antiandrogens, gonadotropin-releasing hormone (GnRH) agonists, and 5-alpha-reductase inhibitors [42,43]. The pathophysiologic mechanism for some, such as estrogens or antiandrogens, is quite clear. However, for others such as spironolactone, the mechanisms are multifactorial.

For many of the drugs listed in the table, a clear-cut relationship between the drug ingestion and gynecomastia has not been established (table 2). For most drugs, the presumed relationship has been based upon epidemiologic studies or challenge-rechallenge studies in small numbers of individual patients [42,44,45].

Spironolactone Spironolactone can increase the aromatization of testosterone to E2, decrease the testosterone production rate by the testes, and displace testosterone from sex hormone-binding globulin (SHBG), thereby increasing its metabolic clearance rate. Spironolactone also acts as an antiandrogen by binding to androgen receptors and displacing or preventing binding of testosterone and dihydrotestosterone to their receptors (table 2) [30,44].

In a placebo-controlled trial of low-dose spironolactone (25 to 50 mg/day) for heart failure, endocrine side effects (gynecomastia, breast pain, impotence, and decreased libido) were seen in 10 percent compared with 3 percent in the placebo group [46]. Gynecomastia will occur in almost every male who takes a large dose of spironolactone (≥100 mg/day), eg, to treat males with liver failure or hypertension due to aldosterone excess [47].

In contrast, in a study of eplerenone (a selective mineralocorticoid receptor antagonist without antiandrogen effects) in over 6500 patients with heart failure, gynecomastia, impotence, or breast pain occurred with equal frequency in the eplerenone and placebo groups (1.0 versus 1.1 percent) [48]. A large meta-analysis confirmed these findings [49]. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Mineralocorticoid receptor antagonist'.)

Statins A large epidemiological study has suggested that statin use might be associated with increased risk of gynecomastia. This case-control study adjusted for a number of factors that are associated with gynecomastia and demonstrated an increased relative risk (20 to 40 percent) of gynecomastia with current, recent, or past use of a statin [50].

Calcium channel blockers – Drugs within the same class do not cause gynecomastia to the same extent. Among the calcium channel blockers, nifedipine has the highest frequency of gynecomastia and diltiazem the lowest [44,51]. Thus, in an older man who is at increased risk of gynecomastia simply on the basis of age, diltiazem would be preferable to nifedipine.

H2-receptor or proton-pump blockers Another example is the use of H2-receptor or proton-pump blockers; the incidence of gynecomastia is highest with cimetidine and lowest with omeprazole [52]. Thus, omeprazole would be a better choice in an older individual with other risk factors for developing gynecomastia (table 2).

HAART The breast enlargement that is seen in males with human immunodeficiency virus (HIV) receiving highly active antiretroviral therapy (HAART) is usually due to fat tissue (lipomastia or pseudogynecomastia) as part of a fat redistribution syndrome (lipodystrophy) [53]. However, cases of true gynecomastia have also been described, thought to be due to coexisting hypogonadism or possible estrogen-like effects of some drugs, in particular, efavirenz (table 2) [54]. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy" and "Treatment of HIV-associated lipodystrophy".)

Prostate cancer: androgen deprivation therapy Gynecomastia is common in males with prostate cancer undergoing androgen deprivation therapy, in particular with bicalutamide. The prevalence is as high as 75 percent when antiandrogen monotherapy is used but is only approximately 15 percent in males treated with total androgen blockade (combined GnRH agonist with an antiandrogen). This difference might be due to higher doses of antiandrogen plus persistent normal to elevated endogenous production of estrogen with antiandrogen therapy. When antiandrogens are used as monotherapy, much higher doses are used, eg, bicalutamide 150 mg/day versus 50 mg/day if combined with a GnRH agonist. (table 2) (See "Side effects of androgen deprivation therapy", section on 'Gynecomastia'.)

Herbal products Tea tree oil and lavender oil, plant-derived oils that are available as over-the-counter skin care products (lotions, soaps, and shampoos), have been associated with gynecomastia. A few prepubertal boys have been reported to develop gynecomastia after repeated use of skin products containing the oils [55]. In vitro studies demonstrated weak estrogenic and antiandrogenic properties of both oils, and the gynecomastia resolved when the skin products were discontinued. Other environmental substances with estrogenic or antiandrogenic properties have also been reported to cause gynecomastia [56-58].

However, in a cross-sectional study of 556 children with a mean age of 6.3 years, 74 percent of whom had been exposed to lavender oil, tea tree oil or both, no cases of prepubertal gynecomastia or premature thelarche were diagnosed [59]. In addition, one study of soy protein formula, which contains phytoestrogens, was not associated with gynecomastia in one study of children [60].

Idiopathic — Gynecomastia in adults is usually multifactorial. There tends to be a gradual decrease in testosterone production in older males and an increase in SHBG levels, resulting in a fall in the total and free testosterone concentration with a reciprocal increase in the luteinizing hormone (LH) level that results in increased aromatization of testosterone to estradiol [28,61]. In addition, aging is associated with increased body fat relative to the lean body mass. Adipose tissue is a site of extraglandular aromatization of androstenedione to E1 and testosterone to E2. These two factors probably account for most patients who have "idiopathic" gynecomastia. Older males are also more likely to take medications associated with gynecomastia than are younger males.

Cirrhosis — The prevalence of gynecomastia in cirrhotic patients is as high as 67 percent; however, this may not be significantly different from noncirrhotic, age-matched control patients [26,62]. Cirrhosis is accompanied by several changes that probably explain the development of gynecomastia, including an increased production rate of androstenedione from the adrenals, enhanced aromatization of androstenedione to E1, and increased conversion of E1 to E2 [63]. Additionally, many patients receive high doses of spironolactone, which can contribute to the pathogenesis of gynecomastia in this population. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Chest findings'.)

Starvation and refeeding — Several studies were carried out on American prisoners of war who were freed at the end of World War II. Approximately 10 percent had developed gynecomastia during starvation, while between 5 and 50 percent noted breast tenderness, pain, and enlargement within two to three months of refeeding after release [64]. Prior to refeeding, approximately 80 percent reported erectile dysfunction, 85 percent had decreased libido, and 73 percent showed testicular atrophy [65]. (See "Causes of secondary hypogonadism in males".)

During starvation, both gonadotropin and testosterone levels were probably reduced, while estrogen production was probably normal due to normal estrogen production from adrenal precursors. These changes will promote the development of gynecomastia. During refeeding, gonadotropins rise, resulting in both an increase in testosterone secretion and a marked elevation in E2 product (due to LH-induced increases in aromatization of testosterone) that mimics normal puberty [65]. Thus, patients who develop refeeding gynecomastia may be said to have undergone a "second puberty." (See "Normal puberty", section on 'Boys'.)

Male hypogonadism — Primary hypogonadism can be due to a congenital abnormality, such as Klinefelter syndrome or an enzymatic defect in the testosterone biosynthetic pathway, or to testicular trauma, infection, infiltrative disorders, vascular insufficiency, or aging (see "Causes of primary hypogonadism in males"). The associated reduction in testosterone production leads to a decrease in the serum testosterone concentration and a compensatory rise in LH release. The excess LH results in enhanced Leydig cell stimulation with inhibition of the 17,20-lyase and 17-hydroxylase activities and increased aromatization of testosterone to E2; the net effect is an increase in E2 relative to testosterone secretion [66].

Secondary hypogonadism due to a hypothalamic or pituitary abnormality is less commonly associated with gynecomastia. In these patients, the production of LH is deficient, resulting in a low testosterone production rate and low E2 production from the testes. However, the adrenal cortex continues to produce estrogen precursors that are aromatized in extraglandular tissue; the result is an increased estrogen-to-androgen ratio.

Men with hyperprolactinemia may develop gynecomastia due to prolactin's effect on reducing the secretion of gonadotropins, leading to secondary hypogonadism. Prolactin itself will stimulate milk production in breast tissue that has been primed by estrogen and progesterone but does not directly cause gynecomastia.

Testicular neoplasms — Germ cell tumors account for approximately 95 percent of testicular neoplasms; between 7 and 11 percent of affected patients have gynecomastia determined by physical examination and 23.4 percent by computed tomography (CT) imaging criteria at the time of presentation [67]. The gynecomastia is associated with secretion of hCG by foci of choriocarcinoma or trophoblastic cells in germ cell tumors (table 2). (See "Anatomy and pathology of testicular tumors".)

The high levels of hCG lead to Leydig cell dysfunction through inhibition of the cytochrome P450c17 enzyme, which mediates the 17,20-lyase and 17-hydroxylase activities in the testes [66]. hCG also stimulates interstitial (Leydig) cell aromatase activity, which converts androgen precursors to E1 and E2. The net effect is a relative increase in E2 to testosterone production.

Gynecomastia is a poor prognostic sign if present at the time of diagnosis of the tumor [67], although this has been disputed [68]. It also occurs in approximately 15 percent of patients after successful treatment with surgery, chemotherapy, or radiation therapy; post-therapy gynecomastia does not affect predicted survival [69]. This form of gynecomastia results from hypogonadism secondary to the chemotherapy or radiation; hCG is not found in the serum. It often spontaneously resolves within one year [69]. (See "Epidemiology and risk factors for testicular cancer".)

Gynecomastia is also found in 20 to 30 percent of patients with the less common (2 percent of all testicular tumors) Leydig cell tumors of the testes [70,71]. These tumors are found in 6- to 10-year-old boys who present with precocious puberty and in 26- to 35-year-old males who present with a testicular mass, gynecomastia, erectile dysfunction, and loss of libido. Approximately 10 percent of these tumors are malignant. In boys, Leydig cell tumors may secrete testosterone and/or E2, but they usually secrete relatively increased quantities of E2. They also aromatize androgen precursors to estrogens [72,73]. In adults, testosterone production is generally decreased because the increased E2 levels inhibit gonadotropin secretion, which in turn leads to secondary hypogonadism. (See "Anatomy and pathology of testicular tumors".)

Large cell calcifying Sertoli cell (sex-cord) tumors of the testes are associated with gynecomastia and feminization through excessive aromatase activity, converting androstenedione to E1 and testosterone to E2. These tumors may occur sporadically or as manifestations of two autosomal dominant disorders: Peutz-Jeghers syndrome and the Carney complex. (See "Testicular sex cord stromal tumors", section on 'Sertoli cell tumors'.)

Hyperthyroidism — Gynecomastia has been reported in as many as 25 to 40 percent of males with hyperthyroidism due to Graves' disease, although one study suggests that the prevalence is less than 10 percent [74-77]. Serum LH levels are often elevated, contributing to increased E2 relative to testosterone production by Leydig cells [78,79]. There is also enhanced aromatization of testosterone to E2 and of androstenedione to E1 in extraglandular tissues [80]. This results in increased concentration of SHBG. Free testosterone levels are normal or low, while free E2 levels are elevated. Thus, gynecomastia results from the combination of decreased free androgen levels combined with the overproduction of estrogens. (See "Overview of the clinical manifestations of hyperthyroidism in adults", section on 'Genitourinary'.)

Chronic kidney disease — Gynecomastia occurs in approximately 50 percent of patients treated with maintenance hemodialysis [81]. The primary cause of the gynecomastia appears to be Leydig cell dysfunction. Serum testosterone levels are low, and gonadotropins are appropriately elevated; the metabolic clearance of LH is also reduced [82]. Gynecomastia may occur following renal transplantation as gonadal function improves ("refeeding gynecomastia") and/or the use of transplantation medications such as cyclosporine.

Other rare causes

Feminizing adrenal tumors – These are rare tumors that are typically large at the time of presentation and are malignant in approximately 75 percent of cases, with a median survival of 1.5 years. In a series of 52 patients, 98 percent had gynecomastia, 58 percent had a palpable tumor, and approximately 50 percent had testicular atrophy [83]. Serum levels of dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, and E2 are increased, while total and free testosterone levels are reduced. Urinary 17-ketosteroid excretion is generally markedly elevated. Gonadotropin levels are usually normal or low. The combination of increased secretion of estrogens by the tumor and increased peripheral aromatization of adrenal androgens to estrogens accounts for the gynecomastia [84]. (See "Clinical presentation and evaluation of adrenocortical tumors".)

Ectopic hCG – Increased serum levels of immunoreactive hCG are found in approximately 18 percent of patients with a wide variety of nontrophoblastic neoplasms [85]. The levels of hCG are generally only modestly raised, and most patients do not exhibit clinical evidence of excess hCG production, in part because the majority of patients have production of the biologically inactive free beta subunit of hCG rather than the biologically active intact molecule. There are, however, a few exceptions:

Precocious puberty can occur in boys with hCG-secreting hepatoblastomas [85].

In adults, large cell carcinoma of the lung, gastric carcinoma, renal cell carcinoma, and, occasionally, hepatoma have been associated with gynecomastia and marked elevations of serum hCG.

The pathogenesis of the gynecomastia is similar to that found with hCG-secreting germ cell neoplasms of the testes. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Serum tumor markers'.)

Disorders of sex development – Individuals with a disorder of sex development born with both testicular and ovarian tissue may develop gynecomastia from excessive estrogen secretion by the ovarian component [86]. In addition, the increased estrogen production can suppress intratesticular P450c17 activity, as well as LH secretion, thereby reducing testosterone production.

The androgen insensitivity syndromes are a group of disorders due to defects in or absence of the intracellular androgen receptor in androgen target tissues [87,88]. The clinical manifestations are variable, but breast development is seen. This disorder is reviewed in detail separately. (See "Pathogenesis and clinical features of disorders of androgen action".)

Familial prepubertal gynecomastia – Familial prepubertal gynecomastia is a rare disorder of increased aromatase activity resulting in severe estrogen excess. The disorder appears to be due to heterozygous inversions or polymorphisms of the p450 aromatase gene (CYP19) with autosomal dominant inheritance [89-95].

This rare syndrome is characterized by pre- or peripubertal gynecomastia that is always bilateral [94,95]. Patients typically have small testes, advanced bone age with short stature as adults, and a high-pitched voice.

It is possible that some patients with the diagnosis of "idiopathic" gynecomastia actually represent excessive extraglandular aromatase activity [73].

Aromatase inhibitors, which have had limited success in the treatment of other causes of gynecomastia, may be effective in this disorder [89].

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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

Definitions Gynecomastia is defined histologically as a benign proliferation of the glandular tissue of the male breast and clinically by the presence of a rubbery or firm mass extending concentrically from the nipple(s) (figure 1). Fat deposition without glandular proliferation is termed pseudogynecomastia (lipomastia; often seen in obese males). (See 'Definitions' above.)

Epidemiology Gynecomastia is common in infancy and adolescence. It is estimated that between 60 to 90 percent of infants have transient gynecomastia due to the high estrogenic milieu of pregnancy. The second peak of occurrence is during puberty, affecting approximately one- to two-thirds of boys. Spontaneous regression of breast tissue occurs in most cases. (See "Gynecomastia in children and adolescents".)

Pathophysiology The basic pathophysiology of gynecomastia is an imbalance in androgen-to-estrogen concentrations or effect due to decreased androgen production, increased estrogen production, antiandrogen, or estrogenic drugs or compounds. (See 'Pathophysiology' above.)

Causes In adult patients seeking help for gynecomastia, current estimates suggest the following etiologies (table 3) (see 'Epidemiology' above and 'Causes of gynecomastia' above):

No detectable abnormality – 25 percent

Persistent pubertal gynecomastia – 25 percent

Drugs – 10 to 25 percent (table 2)

Cirrhosis or malnutrition – 8 percent

Male hypogonadism – 10 percent; (primary hypogonadism [8 percent], secondary hypogonadism [2 percent])

Testicular tumors – 3 percent

Untreated hyperthyroidism – 1.5 percent

Chronic kidney disease – 1 percent

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Topic 7466 Version 24.0

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