Materiały źródłowe

• #1 Gynecomastia: Etiology, Diagnosis, and Treatment – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279105/

  Gynecomastia is a relatively common disorder. Its causes range from benign physiological processes to rare neoplasms. To diagnose the etiology of the gynecomastia, the clinician must understand the hormonal factors involved in breast development. Parallel to female breast development, estrogen, growth hormone (GH), and IGF-1 are required for breast growth in males. Since a balance exists between estrogen and androgens in males, any disease state or medication that increases circulating estrogens or decreases circulating androgens, causing an elevation in the estrogen to androgen ratio, can induce gynecomastia. […] In a population-based study of healthy boys and adolescents, IGF-I levels were found to be elevated in boys with pubertal gynecomastia compared with boys without gynecomastia suggesting that the GH-IGF-I axis may be involved in the pathogenesis of pubertal gynecomastia.

• #1 Gynecomastia: Etiology, Diagnosis, and Treatment – Endotext – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK279105/

  Gynecomastia, breast development in males, can occur normally during three phases of life. […] The mechanism by which pubertal gynecomastia occurs may be due to either decreased production of androgens or increased aromatization of circulating androgens, thus increasing the estrogen to androgen ratio. […] Pathologic gynecomastia is due to an increase in the circulating and/or local breast tissue ratio of estrogen to androgen. […] Increased estrogen levels will increase glandular proliferation by several mechanisms. These include direct stimulation of glandular tissue and by suppressing LH, therefore decreasing testosterone secretion by the testes and exaggerating the already high estrogen to androgen ratio. […] Thus, any cause of estrogen excess from overproduction to peripheral aromatization of androgens can initiate the cascade to breast development.

• #2 Gynecomastia: Pathophysiology, Evaluation, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2770912/

  Gynecomastia, defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications. […] The imbalance between estrogen action relative to androgen action at the breast tissue level appears to be the main etiology of gynecomastia. Elevated serum estrogen levels may be a result of estrogen-secreting neoplasms or their precursors (eg, Leydig or Sertoli cell tumors, human chorionic gonadotropin [hCG]producing tumors, and adrenocortical tumors) but more commonly are caused by increased extragonadal conversion of androgens to estrogens by tissue aromatase (as occurs in obesity). […] Levels of free serum testosterone are decreased in patients with gonadal failure, which can be primary (Klinefelter syndrome, mumps orchitis, castration) or secondary (hypothalamic and pituitary disease). Androgen resistance syndromes due to impaired activity of enzymes involved in the biosynthesis of testosterone can also be associated with gynecomastia.

• #2 Gynecomastia: Pathophysiology, Evaluation, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2770912/

  The balance between free testosterone and estrogen is also affected by serum levels of sex hormone-binding globulin, which is the proposed mechanism of gynecomastia in certain conditions, such as hyperthyroidism, chronic liver disease, and the use of some medications such as spironolactone. […] Eventually, the exposure to the hormonal imbalance leads to proliferation of glandular tissues, ie, ductal hyperplasia.

• #3 Gynecomastia: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/120858-overview

  Gynecomastia results from an altered estrogen-androgen balance, in favor of estrogen, or from increased breast sensitivity to a normal circulating estrogen level. […] The imbalance is between the stimulatory effect of estrogen and the inhibitory effect of androgen. […] Estrogens induce ductal epithelial hyperplasia, ductal elongation and branching, proliferation of the periductal fibroblasts, and an increase in vascularity. […] Estrogen production in males results mainly from the peripheral conversion of androgens (testosterone and androstenedione) to estradiol and estrone, which occurs through the action of the enzyme aromatase (mainly in muscle, skin, and adipose tissue). […] Thus, any cause of estrogen excess from overproduction to peripheral aromatization of androgens can initiate the cascade to breast development.

• #3 Gynecomastia: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/120858-overview

  Increased estrogen production and/or action can occur at the testicular level or at the periphery. […] Gynecomastia can be physiologic or pathologic. […] Pathologic gynecomastia can be caused by an increase in the production and/or action of estrogen, by a decrease in the production and/or action of testosterone accompanied by increased aromatization and high estrogen, or by drug use. […] Conditions that result in primary or secondary hypogonadism can lead to gynecomastia in different mechanisms. […] The associated reduction in testosterone production leads to a decrease in the serum testosterone concentration and a compensatory rise in leuteinizing hormone (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 estradiol; the net effect is an increase in estradiol relative to testosterone secretion.

• #3 Gynecomastia: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/120858-overview

  Secondary hypogonadism due to a hypothalamic or pituitary abnormality may also be associated with gynecomastia. […] The following are some of the conditions associated with gynecomastia: Klinefelter syndrome, congenital anorchia, testicular trauma, viral orchitis, Kallmann syndrome, pituitary tumors or abnormalities, malignancies that increase the serum level of hCG, renal failure, hyperthyroidism, malnutrition, environmental pollutants, androgen insensitivity syndrome, and aromatase excess syndrome. […] Various drugs are implicated in gynecomastia and can be classified into categories. […] The pathophysiologic mechanism for some drugs, such as estrogens or antiandrogens, is quite clear. […] However, for others such as spironolactone, the mechanism is more complex. […] Spironolactone can increase the aromatization of testosterone to estradiol, decrease testosterone production by the testes, increasing the rate of testosterone clearance by displacing it from SHBG, and also binding to androgen receptors leading to gynecomastia through estrogen/testosterone imbalance.

• #4 Gynecomastia – Wikipedia

  https://en.wikipedia.org/wiki/Gynecomastia

  Gynecomastia is thought to be caused by an altered ratio of estrogens to androgens mediated by an increase in estrogen action, a decrease in androgen action, or a combination of these two factors. […] The causes of common gynecomastia remain uncertain, but are thought to result from an imbalance between the actions of estrogen, which stimulates breast tissue growth, and androgens, which inhibit breast tissue growth. […] One of the main mechanisms for imbalance between estrogens and androgens is the overproduction of estrogens. […] Primary hypogonadism (indicating an intrinsic problem with the testes in males) leads to decreased testosterone synthesis and increased conversion of testosterone to estradiol potentially leading to a gynecomastic appearance. […] Dysfunctions in the androgen receptor prevent the effects of testosterone from acting on its target tissues. […] Medications are known to cause gynecomastia through several different mechanisms. […] Individuals who have cirrhosis or chronic liver disease may develop gynecomastia for several reasons.

• #5 Gynaecomastia: Causes, Symptoms, and Treatment | Doctor

  https://patient.info/doctor/gynaecomastia

  Gynaecomastia is a benign proliferation of the glandular tissue of the breast in men. […] Pathological causes involve an imbalance between the activity of androgens and oestrogens – the former is decreased compared with the latter. […] Oestrogen stimulates breast tissue growth whilst androgens inhibit it. The important factor is the ratio of active androgens to oestrogens. The ratio can be altered as a result of reduced testosterone production/action or enhanced oestrogen production/action or both. Increased levels of oestrogen suppress luteinising hormone, which causes further suppression of testicular production of oestrogen. […] Gynaecomastia may therefore be caused by conditions which cause raised oestrogen levels, conditions which cause low testosterone levels, conditions which affect levels of sex hormone-binding globulin (SHBG), conditions which cause androgen resistance, and conditions which cause an increased conversion of androgens to oestrogens. […] Once this ratio falls, breast tissue is stimulated to grow. This leads to proliferation of breast ducts and fibroblastic stroma. If the stimulus to proliferation continues then the ducts and fibroblastic stroma are replaced by fibrosis and gynaecomastia becomes well established and irreversible.

• #6 SciELO Brazil – Gynecomastia: physiopathology, evaluation and treatment Gynecomastia: physiopathology, evaluation and treatment

  https://www.scielo.br/j/spmj/a/PFcc79gBghNMHmXs7RPs89g/

  Gynecomastia (GM) is characterized by enlargement of the male breast, caused by glandular proliferation and fat deposition. […] A hormonal imbalance between estrogens and androgens is the key hallmark of GM generation. […] The etiology of GM is attributable to physiological factors, endocrine tumors or dysfunctions, non-endocrine diseases, drug use or idiopathic causes. […] The estrogen/androgen imbalance may be attributable to increased levels of free estrogens secreted by the testes or adrenal glands, extraglandular aromatization of estrogen precursors, decreased estrogen degradation, exposure to estrogen-like chemicals or exogenous estrogens and use of drugs that cause displacement of more estrogen than androgen from sex hormone-binding globulin (SHBG). […] On the other side, the imbalance may result from decreased androgen production in the testes, increased binding of androgens (relative to estrogens) by SHBG, altered androgen metabolism, drug-induced displacement of androgens from their receptors and androgen receptor defects.

• #6 SciELO Brazil – Gynecomastia: physiopathology, evaluation and treatment Gynecomastia: physiopathology, evaluation and treatment

  https://www.scielo.br/j/spmj/a/PFcc79gBghNMHmXs7RPs89g/

  Continuous environmental exposure to substances with weak estrogen-agonist action, probably due to epigenetic mechanisms, theoretically can induce the development of GM. […] There is evidence that enlarged male breast glands contain luteinizing hormone (LH) and human chorionic gonadotropin (hCG) receptors. […] Another hormonal action that stimulates breast tissue in men is observed secondary to hyperprolactinemia. […] GM is a multifactorial disease and many conditions may be associated with it. […] Relative excess of serum levels of estrogens compared with androgens is implicated in the pathogenesis, due to estradiol production rising sooner than testosterone production. […] Older men over the age of 65 years often present relative hypogonadism with a decline in plasma testosterone levels, elevation of SHBG and decrease in free testosterone.

• #6 SciELO Brazil – Gynecomastia: physiopathology, evaluation and treatment Gynecomastia: physiopathology, evaluation and treatment

  https://www.scielo.br/j/spmj/a/PFcc79gBghNMHmXs7RPs89g/

  Benign testicular tumors (Sertoli or Leydig cell tumors) may secrete estradiol. […] Severe hyperthyroidism increases serum SHBG. […] Primary gonadal failure as a result of testicular trauma, chemotherapy, mumps, orchitis and leprosy can cause GM by lowering the serum testosterone levels, inducing elevation of LH and stimulating the remaining Leydig cells to secrete estrogens. […] The chief sex hormone abnormalities in cases of liver cirrhosis are decreased serum testosterone levels and increased estradiol levels. […] Drug-induced GM merits deep consideration as it may account for as many as 25% of all cases of new-onset GM in adults. […] Given the high frequency of idiopathic GM, we hypothesize that multiple environmental endocrine disruptors are likely to be involved in excessive breast development in men.

• #7 Gynecomastia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Gynecomastia_pathophysiology

  The main pathophysiology behind gynecomastia is increased estrogen to androgen ratio which can occur through multiple mechanisms. These mechanisms can be physiological, pathological or pharmacological. […] It is thought that gynecomastia can result from any condition, drug or disease state that causes an increase in circulating estrogen, a decrease in androgen or the sensitivity of the breast tissue to the circulating estrogen. […] The imbalance of estrogen/androgen can be due to increased levels of free estrogen secreted by the adrenals or testes, decreased estrogen breakdown, increased availability of estrogen precursors, exposure to estrogen like products or use of drugs that displaces more estrogen than androgen from sex hormone-binding globulin (SHBG). […] On the other hand, the imbalance can result from altered androgen metabolism, decreased androgen production, increased androgen binding (relative to estrogen) by SHBG, or androgen receptor defects.

• #8 Gynaecomastia – OzRadOnc

  http://ozradonc.wikidot.com/pathology-gynaecomastia

  Reduced action of androgens, usually due to administration of androgen receptor antagonists which prevent binding of androgens to their receptor. […] Sequestration of androgens through sex hormone binding globulin. This mechanism is thought to explain gynaecomastia due to otherwise unrelated conditions, such as hyperthyroidism, liver disease and non-hormonal pharmaceuticals. […] This occurs commonly in obesity due to conversion of androgens to oestrogens by tissue aromatase. Rarely, oestrogen producting tumours may develop in the testis (Sertoli-cell, Leydig-cell, hCG producing tumours) or adrenal glands. […] In neonates, oestrogen from the mother is responsible for gynaecomastia, which resolves rapidly after birth in nearly all cases. […] There is a suggestion that there is less free testosterone available in adolescents who develop gynaecomastia.

• #9 Gynecomastia in adolescent males: current understanding of its etiology, pathophysiology, diagnosis, and treatment

  https://e-apem.org/journal/view.php?number=1034

  A study reported that men with a body mass index (BMI) of 25 kg/m2 or higher are far more likely to develop GM or pseudogynecomastia, with a reported prevalence as high as 80%. […] AES is a rare genetic disease characterized by pre- or peripubertal onset of GM and is transmitted as an X-linked recessive or autosomal dominant trait. This condition is most likely caused by a genetic defect in the 5′-end of the P450 aromatase gene. […] GM can develop as a result of exposure to medications that lower the level of androgens, increase estradiol levels, or displace androgens from breast androgen receptors. […] The development of GM may theoretically be induced by ongoing environmental exposure to chemicals that have a mild estrogen-agonist effect. […] GM has been linked to chronic illnesses such cystic fibrosis, ulcerative colitis, liver disease, chronic renal failure, and human immunodeficiency virus (HIV).

• #9 Gynecomastia in adolescent males: current understanding of its etiology, pathophysiology, diagnosis, and treatment

  https://e-apem.org/journal/view.php?number=1034

  Gynecomastia (GM) is a common and continuously evolving condition that commonly occurs during adolescence. GM is characterized by enlargement of the male breast due to the proliferation of glandular ducts and stromal components. The main cause of GM during adolescence is physiological or pubertal GM, which is primarily attributed to an imbalance between estrogen and androgen activity. […] Most cases of pubertal GM are assumed to be caused by an imbalance between the activities of the hormones estrogen and androgen in the breast tissue. Pubertal GM is caused by either increased estrogen production, decreased testosterone production, or a combination of both. […] However, some studies have indicated that a significant number of adolescents with pubertal GM had normal estrogen level, and they linked GM to increased susceptibility of the breast tissue to normal level of circulating estrogen. These studies also claimed that the presence of local tissue factors in the breast increased the aromatization of androgens to estrogen in the breast tissue itself, which was corroborated by the presence of elevated aromatase activity in the fibroblasts in the pubic skin of GM patients.

• #9 Gynecomastia in adolescent males: current understanding of its etiology, pathophysiology, diagnosis, and treatment

  https://e-apem.org/journal/view.php?number=1034

  According to reports, more than 50% of KS patients have GM as a result of both increased aromatase activity and decreased androgen production. […] GM is uncommon in males with 11-hydroxylase deficiency and is extremely unusual in children with 21-hydroxylase deficiency. […] Graves disease (GD) is a contributing factor to hyperthyroidism in adolescents. […] Prolactin-producing pituitary adenomas (prolactinomas) induce GM via their indirect role in change of the androgen/estrogen ratio. […] Testicular trauma, mumps, orchitis, and chemotherapy can all result in primary gonadal failure, which lowers serum testosterone level, increases lutenizing hormone (LH) level, and stimulates Leydig cells to produce estrogens, resulting in GM. […] Testicular feminization syndrome is commonly associated with the development of female breast appearance in males with an XY karyotype as a result of gonadal estrogen production.

• #9 Gynecomastia in adolescent males: current understanding of its etiology, pathophysiology, diagnosis, and treatment

  https://e-apem.org/journal/view.php?number=1034

  Patients with type 1 diabetes who have had the condition for a long time may develop diabetic mastopathy (DMP), presenting as hard, diffuse enlargements in one or both breasts. […] GM without testicular swelling is the main symptom in 7%-11% of subjects with testicular tumors, and it may be the only clinical finding on physical examination at the time of diagnosis. […] Feminizing adrenocortical tumors (FATs) are extremely rare and have a median age at diagnosis of 6 years. […] Breast cancer in adolescents accounts for 0.1% of all breast cancer cases and less than 1% of all pediatric cancer cases. […] Identifying patients with underlying pathological conditions is crucial, and can be achieved through a comprehensive medical history, clinical examination, and laboratory tests as appropriate.

• #10 Unilateral gynecomastia as an initial presentation of hyperthyroid Graves’ disease in: Endocrinology, Diabetes & Metabolism Case Reports Volume 2021 Issue 1 (2021)

  https://edm.bioscientifica.com/view/journals/edm/2021/1/EDM20-0140.xml

  Thyroid hormones, particularly T4, influence plasma SHBG level by increasing hepatic production of SHBG. […] The pathophysiology described above explains the observed upregulation of both serum estradiol and total testosterone level in this patient. […] The occurrence of gynecomastia in hyperthyroid can be as high as 40% as reported in the literature and this number is enough to warrant hyperthyroidism as a common differential diagnosis for the cause of pathologic bilateral gynecomastia. […] The etiologies and mechanisms involved in the development of unilateral gynecomastia in hyperthyroidism remain to be elucidated. […] The development of unilateral gynecomastia poses a challenge in diagnosis, since the growth of one breast is commonly associated with malignancy and rarely presented as a symptom of hyperthyroidism. […] In conclusion, this case highlights the rare presentation of unilateral gynecomastia in hyperthyroidism from GD and the importance of precise diagnosis for prompt treatment of this reversible condition.

• #11

  https://journals.lww.com/trap/fulltext/2014/11030/a_curious_case_of_gynaecomastia_.9.aspx

  Gynecomastia is a benign proliferation of the glandular tissue of the male breast and is caused by a relative increase in the ratio of estrogen to androgen activity. […] The pathogenesis of gynecomastia in patients with Graves’s disease is multifactorial. There is several-fold increase in levels of sex hormone-binding globulin (SHBG) as a result of primary hepatic stimulation by thyroid hormones. […] Higher affinity of testosterone to SHBG relative to estrogen contributes to elevated total testosterone levels, normal or low free testosterone levels, and elevated free estradiol levels. […] There is also enhanced aromatization of testosterone to estradiol and of androstenedione to estrone in extraglandular tissues. […] Increased serum LH levels in Graves’ disease also contribute to further increased estradiol relative to testosterone production by Leydig cells.

• #12 Drug-induced Gynecomastia: Data Mining and Analysis of the FDA Adverse | CLEP

  https://www.dovepress.com/drug-induced-gynecomastia-data-mining-and-analysis-of-the-fda-adverse–peer-reviewed-fulltext-article-CLEP

  The analysis revealed that drug-induced gynecomastia represented only 0.17% of all adverse event reports, emphasizing its rarity in clinical practice. Moreover, the incidence of serious outcomes, such as fatal and life-threatening incidents, was strikingly low, with rates of 0.51% and 0.39% respectively among the cases analyzed. […] In our study, nervous system drugs were identified as the primary contributors to drug-induced gynecomastia. Furthermore, among the 165 drugs that induced more than 5 cases of gynecomastia, nervous system agents were the most prevalent, with a total of 38 drugs (23.0%). […] The development of antipsychotic-induced gynecomastia is primarily considered a symptom of hyperprolactinemia, a condition triggered by antipsychotics blocking pituitary dopamine D2 receptors. This blockade inhibits prolactin suppression and may reduce GnRH secretion by the hypothalamus, potentially leading to hypogonadism.

• #12 Drug-induced Gynecomastia: Data Mining and Analysis of the FDA Adverse | CLEP

  https://www.dovepress.com/drug-induced-gynecomastia-data-mining-and-analysis-of-the-fda-adverse–peer-reviewed-fulltext-article-CLEP

  Gynecomastia arises from a disruption in the equilibrium between estrogen and androgen activities within breast tissue. Estrogens promote the growth of breast tissue, a process that is typically mitigated by androgens. An elevation in the estrogen-to-androgen ratio, whether caused by heightened estrogenic influences or diminished androgenic effects, precipitates the development of gynecomastia. This hormonal imbalance can result from various factors, including endocrine disorders, obesity, certain medications, and aging. […] Drug-induced gynecomastia accounted for approximately 9.3% to 25% of all reported cases. The mechanism of drug-induced gynecomastia varied depending on the specific medication. It may involve androgen antagonism, estrogen receptor activation, or hormone synthesis alteration.

• #13 Management of Gynaecomastia: An Update

  https://www.medscape.org/viewarticle/560809

  Gynaecomastia is a benign proliferation of the glandular component of the male breast and is caused by an increase in the ratio of oestrogen to androgen activity. […] Gynaecomastia is common. In two case series, palpable breast tissue was detected on physical examination in 36% of healthy younger adult men, 57% of healthy older men and more than 70% of hospitalised elderly men. […] In general gynaecomastia can be observed in three peaks during life.

• #14 Gynecomastia: What It Is, Causes, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/symptoms/16227-enlarged-male-breast-tissue-gynecomastia

  Gynecomastia most often happens due to an imbalance of testosterone and estrogen. […] Gynecomastia is the enlargement of glandular tissue in your breast(s). Estrogen is responsible for the growth of glandular breast tissue. Estrogen also suppresses the release of testosterone. This is because it suppresses luteinizing hormone (LH), the hormone responsible for the release of testosterone in your testicles. In other words, an increase in estrogen and a decrease in testosterone most often leads to gynecomastia. […] Gynecomastia is more likely to happen during periods of hormonal fluctuations, especially at or during: Birth: More than half of male newborns have enlarged breasts, or breast buds. It typically happens due to exposure from their mother. Gynecomastia in newborns usually goes away within a few weeks.

• #14 Gynecomastia: What It Is, Causes, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/symptoms/16227-enlarged-male-breast-tissue-gynecomastia

  Puberty: More than half of male adolescents have some degree of breast enlargement during puberty. It likely happens due to a faster rise in estrogen than in testosterone. But this imbalance usually regulates with time about six months to two years. […] Late adulthood: Gynecomastia is common in males over 50. With age, your body produces less testosterone. People over 50 are also more likely to be taking medications that can cause gynecomastia. […] Gynecomastia may be a symptom or result of the following health conditions: Adrenal tumors. […] Male hypogonadism (low testosterone). […] Gynecomastia may be a side effect of certain medications, including: Cimetidine (for heartburn and acid reflux). […] If an underlying condition is the cause, like a tumor or hypogonadism, treatment for the condition may also treat gynecomastia. […] If you have gynecomastia due to a hormonal imbalance, exercise likely won’t make a difference. This is because an imbalance of estrogen and testosterone is responsible for an increase in your breast tissue, and exercise can’t override that.

• #15 Grade 2 Gynecomastia: Causes, Symptoms & Treatment Options

  https://gynecomastiala.com/grade-2-gynecomastia/

  Gynecomastia can appear in infancy due to maternal estrogen and usually disappears within weeks. Another peak period is during puberty (ages 10 to 17), when hormonal shifts can cause a temporary imbalance between estradiol and testosterone, often resolving by age 17. […] Successful treatment often requires careful surgical techniques to address these issues.

• #16 Enlarged breasts in men (gynecomastia) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/gynecomastia/symptoms-causes/syc-20351793

  Aging. Hormone changes that happen with aging can cause gynecomastia, especially in people who are overweight. […] Some tumors can make hormones that shift the body’s hormone balance. These include tumors involving the testes, adrenal glands or pituitary gland. […] Changes in hormone levels related to liver problems and cirrhosis medicines are linked with gynecomastia. […] When the body doesn’t get enough nutrition, testosterone levels drop. But estrogen levels stay the same. This causes an imbalance in the hormones.

• #17 Gynecomastia | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0401/p716.html

  Gynecomastia is defined as benign proliferation of glandular breast tissue in men. […] Gynecomastia, which can be physiologic or nonphysiologic, occurs when the estrogen-to-testosterone ratio in men is disrupted, leading to proliferation of glandular breast tissue. […] Nonphysiologic gynecomastia can occur at any age as a result of a number of medical conditions, medication use, or substance use. […] Liver injury may impair hepatic degradation of estrogens and increase levels of sex hormone-binding globulin that contribute to increased peripheral estrogens. […] Gynecomastia may be the only presenting symptom in men with primary hypogonadism. […] Although testicular tumors are rare, approximately 10 percent of persons with testicular tumors present with gynecomastia alone. […] Gynecomastia occurs in 10 to 40 percent of men with hyperthyroidism, although it is rarely the only symptom at presentation.

• #17 Gynecomastia | AAFP

  https://www.aafp.org/pubs/afp/issues/2012/0401/p716.html

  Hormonal dysfunction is common in men with renal failure because of overall suppression of testosterone production and direct testicular damage secondary to uremia. […] Conditions that impair absorption, such as ulcerative colitis and cystic fibrosis, may result in gynecomastia. […] New research suggests that leptin and aromatase activity associated with obesity contribute to increased circulating estrogens, causing gynecomastia.

• #18 Gynecomastia: An Uncommon but Important Clinical Manifestation for Testicular Tumors

  https://file.scirp.org/Html/2%EF%BC%8D1940004_16951.htm

  Gynecomastia is benign enlargement of male breast tissue due to the proliferation of the ductal component. […] The pathogenesis of gynecomastia is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state. […] The pathogenesis of gynecomastia in Sertoli cell tumors is due to the increased ratio of estrogen to androgen by increasing the aromatization of estrogen precursors by the tumor cells. […] The pathogenesis of gynecomastia in testicular germ cell tumors is largely due to the increased level of human chorionic gonadotropin. […] The underlying mechanism is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state, which includes the absolute increase of estrogen or its precursors, increase of the aromatization of estrogen precursors or increased secretion of hCG.

• #19 Gynecomastia as a presenting symptom of Graves’ disease in a 49-year-old man in: Endocrinology, Diabetes & Metabolism Case Reports Volume 2021 Issue 1 (2021)

  https://edm.bioscientifica.com/view/journals/edm/2021/1/EDM20-0181.xml

  Two different mechanisms contribute to the development of gynecomastia in thyrotoxicosis. The first and major contributing factor to this disbalance is a thyroid hormone-induced increased production of the plasma protein SHBG in the liver. […] The exact pathway behind thyroid hormone increased SHBG levels remains unclear, but hepatocyte nuclear factor-4 (HNF4A) seems to play an essential role. […] The second underlying pathophysiological cause is due to an increased activity of aromatase by thyroid hormones, that converts androgens into estrogens in peripheral tissue. Thus, dysregulating the hormonal balance by increasing estrogen levels.

• #20 Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

  https://www.e-enm.org/journal/view.php?number=1660

  The development of external genitalia during sex differentiation is determined by the action of androgens and androgen receptors. The androgen receptor is essential for androgen action, thus mutations in the androgen receptor gene can alter receptor function, which leads to AIS. […] The androgen receptor gene mutation was identified as a somatic mosaicism (c.2128GA, [p.Glu710Lys]) in exon 4. […] Therefore, a male patient complaints of gynecomastia must be considered by physicians for physiological causes, drugs, systemic diseases such as liver cirrhosis, chronic kidney disease, hyperthyroidism and malignancy, as the common causes of gynecomastia.

• #21 Drug-induced gynecomastia | Pharmaco Vigilance

  https://www.pharmaco-vigilance.eu/content/drug-induced-gynecomastia

  Mammary glandular tissue proliferation is physiologically stimulated by oestrogens and inhibited by androgens. Therefore, gynecomastia is generally caused by increased ratio of free-circulating oestrogens/androgens or altered effects of these hormones on their correspondent intracellular receptors in the mammary tissue. […] Sometimes gynecomastia can be idiopathic (about 25% of cases) or, more rarely, secondary to pathologies influencing the levels of circulating sexual hormones (i.e. testicular or adrenal neoplasias, hepatic cirrhosis, hyperthyroidism, hypogonadism, obesity, refeeding syndrome). […] In the end, a consistent part of gynecomastia cases, around 20%, is iatrogenic.

• #22

  https://journals.lww.com/iphr/fulltext/2009/41060/gynecomastia__an_adr_due_to_drug_interaction.11.aspx

  Gynecomastia results from conditions that cause an imbalance of estrogenic and androgenic effects on the breast, resulting in an increased or unopposed estrogen action on breast tissue. […] Approximately 4-10% cases of gynecomastia are due to drugs. […] Mechanisms by which drugs cause gynecomastia include inhibition of androgen synthesis and/or metabolism (ketoconazole), antagonism at androgen receptor (flutamide, finastride), direct action at estrogen receptors by estrogen-like drugs (estrogen vaginal cream, clomiphine) and displacement of estrogen from sex hormone-binding globulin (thereby increasing the free estrogen level, e.g. spironolactone). […] The mechanism of digoxin-induced gynecomastia is believed to be a direct action at estrogen receptors due to similarity in the structure of digoxin and estrogen. […] Although furosemide is reported to cause gynecomastia, its exact mechanism is still not known.

• #23 Isoniazid-induced gynaecomastia: report of a paediatric case and review of literature | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-020-00639-9

  Among the drugs in the standard tuberculosis regimen, only isoniazid has been reported to be associated with gynaecomastia. […] Isoniazid is known to induce pyridoxine (vitamin B6) deficiency by inhibiting pyridoxal phosphokinase and by combining with pyridoxine to form isonicotinylhydrazide which is excreted in urine. […] Apart from causing the well-known side effect of peripheral neuropathy, isoniazid was also postulated to cause altered estrogen-androgen metabolism. The physiologically active form of vitamin B6, pyridoxal 5-phosphate (PLP), acts as a modulator of steroid hormone receptor-mediated gene expression. […] Another possible mechanism is refeeding gynaecomastia associated with weight gain during anti-tuberculosis therapy, but this was not seen in our case.

• #24 Gynecomastia Caused by Antiretroviral Therapy, Highly Suspected Efavirenz: A Case Report

  https://www.jmchemsci.com/article_184564.html

  Gynecomastia is an enlargement of breasts in men. This disease is commonly found in patients with impaired liver function and patients on additional hormonal use. Approximately, 10% to 25% of gynecomastia instances are attributed to the use of pharmaceutical substances. […] Efavirenz decreases androgen activity through unknown factors. Several assumed mechanisms include the direct mammotropic effect of ARTs, and elevated IL-2 and IL-6 production due to T-helper cytokine response, thereby increasing the estrogen production which stimulates breast growth. […] The primary reason for gynecomastia is the hormonal imbalance between estrogen and androgen within the breast tissue. Free testosterone and estrogen levels are influenced by binding globulin which can decrease in patients with long-term use of drugs such as the antiviral efavirenz for HIV.

• #24 Gynecomastia Caused by Antiretroviral Therapy, Highly Suspected Efavirenz: A Case Report

  https://www.jmchemsci.com/article_184564.html

  The inhibition of cytochrome P-450 (CYP450) caused by HAART, especially the PI group, leads to an elevation in the estrogen-to-androgen ratio. This could be attributed to decreased estrogen metabolism, alterations in estrogen binding to globulins, and diminished testosterone biosynthesis, among other potential underlying factors. Efavirenz, which belongs to the NNRTI group, was found to have a 37% increase in the area under the curve (AUC) of circulating ethynyl estradiol, thereby affecting CYP450. […] Hence, it is plausible that efavirenz exerts an effect similar to estradiol within the human body, promoting the expansion of breast tissue and contributing to the development of gynecomastia.

• #25 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Gynecomastia.aspx

  Three types of gynecomastia have been identified. These include florid, fibrous, and intermediate. Florid gynecomastia is characterized by an increased volume of ductal tissue and vascularity. It is most commonly seen in the early stages of the condition. […] Fibrous gynecomastia is observed following a year of suffering from the condition and is characterized by the presence of stroma fibrosis with fewer ducts. As suggested by the name, intermediate gynecomastia is intermediate between the fibrous and florid types, with both features present. […] In most cases, if gynecomastia persists longer than a year, the fibrous type is more prevalent and irreversible, which may subsequently reduce the likelihood of success of medical treatment.

• #26 ESTROGEN AND PROGESTERONE RECEPTORS IN GYNECOMASTIA (40 CASES): – Turkish Journal of Pathology

  https://turkjpath.org/text.php?id=61

  Gynecomastia is defined as a potentially reversible enlargement of the male breast. It is characterized by an unencapsulated proliferation of ducts and connective tissue. […] The mean percentage of estrogen and progesterone receptor positive cells were significantly higher in gynecomastia than in carcinoma. […] Estrogen and progesterone receptor expression probably constitute steps in the pathogenesis of gynecomastia.

• #27 Plastic Surgery for Gynecomastia: Practice Essentials, History of the Procedure, Problem

  https://emedicine.medscape.com/article/1273437-overview

  The basic mechanisms of physiologic gynecomastia have been postulated to represent a decrease in androgen production, an absolute increase in estrogen production, and an increased availability of estrogen precursors for peripheral conversion to estradiol. […] The etiology of most cases of gynecomastia remains unknown. The number of breast malignancies does not appear to be increased in patients with idiopathic gynecomastia. Patients who present with gynecomastia and have Klinefelter syndrome do exhibit an increased incidence of breast malignancies. […] The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms. By contrast, patients with idiopathic gynecomastia did not demonstrate an increased number of estrogen or progesterone receptors.

• #28 Radiofrequency & Its Role in Treating Male Gynecomastia

  https://xthetics.ca/blog/radiofrequency-and-its-potential-role-in-treating-male-gynecomastia/

  Gynecomastia, the enlargement of male breast tissue, is a condition that can cause physical and psychological discomfort for affected individuals. […] Male gynecomastia is characterized by the enlargement of glandular tissue in the male breast, resulting in an appearance similar to female breasts. It can be caused by various factors, including hormonal imbalances, certain medications, obesity, or underlying medical conditions. […] Radiofrequency technology has gained recognition in the field of aesthetics for its ability to safely and effectively address various skin concerns. InModes Evolve X system, a leading radiofrequency device, combines multiple modalities, including radiofrequency energy, suction, and deep tissue heating, to provide comprehensive treatment for gynecomastia. By targeting the affected areas, this system offers a non-invasive alternative that can reduce glandular tissue and improve the contour of the male chest.

• #28 Radiofrequency & Its Role in Treating Male Gynecomastia

  https://xthetics.ca/blog/radiofrequency-and-its-potential-role-in-treating-male-gynecomastia/

  Several clinical papers have explored using radiofrequency devices, including Evolve X, in treating gynecomastia. […] The study concluded radiofrequency treatment with Evolve X was a promising non-surgical approach for male gynecomastia. […] These peer-reviewed studies provide valuable insights into the potential benefits of radiofrequency technology in gynecomastia treatment. […] Radiofrequency treatments, such as Evolve X, offer a non-surgical alternative to traditional gynecomastia interventions. […] Evolve Xs advanced technology allows for precise targeting of glandular tissue while simultaneously tightening the overlying skin. […] The controlled delivery of radiofrequency energy minimizes the risk of complications, making it a safer option compared to invasive surgical procedures.

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