Gynecomastia

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Gynecomastia
Classification and external resources

A male with gynecomastia
ICD-10 N62
ICD-9 611.1
MedlinePlus 003165

Gynecomastia /ˌɡnɨkɵˈmæstiə/ is the benign enlargement of breast tissue in males.[2][3][lower-alpha 1] It may occur transiently in newborns. Half or more of adolescent boys have some breast development during puberty.[2][4] Gynecomastia may arise as an abnormal condition associated with disease, such as Klinefelter syndrome, metabolic disorders, as a side-effect of medication, or as a result of the natural decrease of testosterone production in older males.[2][5] In adolescent boys, the condition is often a source of psychological distress; however, 75% of pubertal gynecomastia cases resolve within two years of onset without treatment.[3]

Signs and symptoms

Gynecomastia may occur unilaterally or bilaterally,[6] presenting with swollen breast tissue or breast tenderness, which may lead affected individuals to be concerned about the possibility of having breast cancer.[7][8] An increase in the diameter of the areola or asymmetry of chest tissue are other possible signs of gynecomastia.[9]

Causes

Gynecomastia is caused by excessive estrogen actions and is often the result of an increased ratio of estrogen to androgen.[4] In approximately 25% of cases, the cause of gynecomastia is unknown.[6][8]

About 10%-25% of cases are estimated to result from the use of medications.[10] This is known as non-physiologic gynecomastia.[8] Those medications include ketoconazole, cimetidine, gonadotropin-releasing hormone analogues, human growth hormone, human chorionic gonadotropin, antiandrogens such as bicalutamide, flutamide, and spironolactone, and 5-alpha-reductase inhibitors such as finasteride or dutasteride.[10][11][12] Medications with probable associations to gynecomastia include risperidone, calcium channel blockers such as verapamil, amlodipine, and nifedipine, anabolic steroids,[13] alcohol, opioids, efavirenz, alkylating agents, and omeprazole.[10][14] Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia.[15] Hyperprolactinemia has also been associated with the development of gynecomastia.[16]

Other causes of gynecomastia may include:

Hypogonadism
Conditions that interfere with normal testosterone production, such as Klinefelter syndrome or pituitary insufficiency, can be associated with gynecomastia.[5][8]
Aging
Hormone changes that occur with normal aging, such as declining testosterone levels, can cause gynecomastia. This is also known as senile gynecomastia and is typically found in men between the ages of sixty and eighty.[6]
Endocrine tumors
Testicular tumors such as Leydig cell tumors or Sertoli cell tumors[17] (such as in Peutz-Jeghers syndrome)[3] or hCG-secreting choriocarcinoma[14] may result in gynecomastia. Other tumors such as adrenocortical tumors, pituitary gland tumors (such as a prolactinoma), or bronchogenic carcinoma, can produce hormones that alter the male-female hormone balance and cause gynecomastia.[6]
Hyperthyroidism
In this condition, the thyroid gland produces too much of the hormone thyroxine and is thought to influence the level of sex-hormone binding globulin.[5] 10-40% of individuals with hyperthyroidism may experience gynecomastia; returning to a normal thyroid state leads to resolution of the gynecomastia within a few months.[8]
Kidney failure
Renal failure patients often experience a state of malnutrition, which may contribute to gynecomastia development. Dialysis may attenuate malnutrition of renal failure. Additionally, many renal failure patients experience a hormonal imbalance due to the suppression of testosterone production and testicular damage from high levels of urea also known as uremia-associated hypogonadism.[8][18]
Liver failure and cirrhosis
In individuals with liver failure or cirrhosis, the liver's ability to properly metabolize hormones such as estrogen may be impaired. Additionally, those with alcoholic liver disease are further put at risk for development of gynecomastia; ethanol may directly disrupt the synthesis of testosterone and the presence of phytoestrogens in alcohol may also contribute to a higher estrogen to testosterone ratio.[8]
Malnutrition and starvation
When the human body is deprived of adequate nutrition, testosterone levels drop, and the liver's ability to degrade estrogen is diminished, causing a hormonal imbalance. Gynecomastia can occur once normal nutrition resumes but usually resolves within one to two years. Conditions that can cause malabsorption such as cystic fibrosis or ulcerative colitis may also produce gynecomastia.[8]
Neonatal breast development
Many newborn infants of both sexes show breast development at birth or in the first weeks of life.[19] This occurs in about 60-90% of males and is believed to be due to maternal or placental estrogens.[20][21] In some infants fluid ("witch's milk") can be expressed.[6]

Pathophysiology

Pathology: A large glandular mass of male breast tissue, surgically removed
Micrograph showing gynecomastoid hyperplasia, the changes seen in gynecomastia. H&E stain

The causes of common gynecomastia remain uncertain, but are thought to result from an imbalance between the actions of estrogen and androgens at the breast tissue.[5][10] The imbalance in the estrogen:testosterone ratio results from increased estrogens or estrogenic precursors secondary to excess secretion by the testicles or adrenal glands; decreased androgens due to decreased secretion or increased metabolism by high levels of sex hormone-binding globulin (SHBG) in some cases may also play a role.[22] This mechanism has been the proposed cause of gynecomastia in certain associated conditions such as hyperthyroidism, chronic liver disease, and the use of certain medications such as spironolactone.[5][23] Breast prominence can result from hypertrophy of glandular breast tissue, chest adipose tissue (fat) and skin, and is typically a combination.[14] Breast prominence due solely to excessive adipose is often termed pseudogynecomastia[22] or sometimes lipomastia.[24]

Diagnosis

To reach a diagnosis of gynecomastia, other causes of male breast enlargement such as mastitis,[8][25] breast cancer, pseudogynecomastia, lipoma, sebaceous cyst, dermoid cyst, hematoma, metastasis, ductal ectasia, fat necrosis, or a hamartoma are typically excluded.[8] Ultrasonography has supplanted mammography as the method of choice for radiologic examination of male breast tissue in the diagnosis of gynecomastia.[22] Gynecomastia usually presents with bilateral involvement of the breast tissue but may occur unilaterally as well.[8] Histological examination of tissue attained by fine needle aspiration cytology may demonstrate dilated ducts with periductal fibrosis, increased subareolar fat, and hyalinization of the stroma.[9]

Gynecomastia should also be distinguished from muscle hypertrophy of the pectoralis muscles. When surgery is performed, the gland is routinely sent to the lab to confirm the presence of gynecomastia and to check for tumors under a microscope. The utility of pathologic examination of breast tissue removed from male adolescent gynecomastia patients has recently been questioned due to the rarity of breast cancer in this population.[26]

A review of the medications or illegal substances an individual takes may reveal the cause of gynecomastia.[8] Recommended laboratory investigations to find the underlying cause of gynecomastia include tests for aspartate transaminase and alanine transaminase to rule out liver pathology, serum creatinine to evaluate if kidney damage is present, and thyroid-stimulating hormone levels to evaluate for hyperthyroidism. Medical imaging may be indicated in a subset of patients to rule out adrenal tumors, pituitary tumors, or male breast cancer.[27] Additional tests that may be considered are markers of testicular, adrenal, or other tumors such as urinary 17-ketosteroid, serum beta human chorionic gonadotropin, or serum dehydroepiandrosterone. Serum testosterone levels (free and total), estradiol, luteinizing hormone, and follicle stimulating hormone may also be evaluated to determine if hypogonadism may be the cause of gynecomastia.[8]

Classification

The spectrum of gynecomastia severity has been categorized into a grading system:[27]

  • Grade I: Minor enlargement, no skin excess
  • Grade II: Moderate enlargement, no skin excess
  • Grade III: Moderate enlargement, skin excess
  • Grade IV: Marked enlargement, skin excess

Treatment

Male with asymmetrical gynecomastia, after excision of the gland and liposuction of the waist

Medical treatment of gynecomastia that has been present for over one year is usually futile. If chronic gynecomastia is treated, surgical removal of glandular breast tissue is usually required.[10] Surgical approaches to the treatment of gynecomastia include subcutaneous mastectomy, liposuction-assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma, surgical wound infection, breast asymmetry, changes in sensation in the breast, necrosis of the areola or nipple, seroma, noticeable or painful scars, and contour deformities.[27]

Selective estrogen receptor modulators may be beneficial in the treatment of gynecomastia but are not approved by the Food and Drug Administration for use in gynecomastia.[10] Aromatase inhibitors such as testolactone have been approved for the treatment of gynecomastia in children and adolescents.[3] Tamoxifen may be used for painful gynecomastia in adults.[10]

Radiation therapy and tamoxifen have been shown to help prevent gynecomastia and breast pain from developing in prostate cancer patients who will be receiving androgen deprivation therapy. The efficacy of these treatments is limited once gynecomastia has occurred and are therefore are most effective when used prophylactically.[28]

Many insurance companies deny coverage for surgery for gynecomastia treatment or male breast reduction on the basis that it is a cosmetic procedure.[29][30][31][32]

Prognosis

Gynecomastia is not physically harmful, but in some cases it may be an indicator of other more serious underlying conditions, such as testicular cancer.[4] Growing glandular tissue, typically from some form of hormonal stimulation, is often tender or painful. Furthermore, it can frequently present social and psychological difficulties such as low self-esteem or shame for the sufferer.[26][27][33] Weight loss can alter the condition in cases in which it is triggered by obesity, but losing weight will not reduce the glandular component and patients cannot target areas for weight loss. Massive weight loss can result in sagging tissues about the chest known as chest ptosis.

Epidemiology

Gynecomastia has a trimodal peak of incidence and commonly presents in newborns, adolescents, and men older than 50 years of age,[27] but most cases of newborn gynecomastia are self-limiting and resolve on their own.[8] Thirty to sixty percent of male are estimated to exhibit sign of gynecomastia during their adolescence.[14] Most cases of adolescent gynecomastia resolve within six months to two years.[8] The prevalence of gynecomastia in men may have increased in recent years, but the epidemiology of gynecomastia is not fully understood.[14] The use of anabolic steroids and exposure to xenoestrogens present in cosmetic products, organochlorine pesticides, and industrial chemicals have been suggested as possible factors driving this increase.[14][32] According to the American Society of Plastic Surgeons, breast reduction surgeries to correct gynecomastia are becoming increasingly common. In 2006, there were 14,000 procedures of this type performed in the United States.[32]

Society and culture

Derogatory terms for gynecomastia can include moobs (for male boobs) and bitch tits.[34]

See also

Notes

  1. The term comes from the Greek γυνή gyné (stem gynaik-) meaning "female" and μαστός mastós meaning "breast."[1]

References

  1. Iaunow, E; Kettler, M; Slanetz, PJ (March 2011). "Spectrum of disease in the male breast". American Journal of Roentgenology 196 (3): W247–259. doi:10.2214/AJR.09.3994. PMID 21343472. 
  2. 2.0 2.1 2.2 Niewoehner, CB; Schorer, AE (March 2008). "Gynaecomastia and breast cancer in men". BMJ 336 (7646): 709–713. doi:10.1136/bmj.39511.493391.BE. PMC 2276281. PMID 18369226. 
  3. 3.0 3.1 3.2 3.3 Shulman, DI; Francis, GL; Palmert, MR; Eugster, EA; Lawson Wilkins Pediatric Endocrine Society Drug and Therapeutics Committee (April 2008). "Use of aromatase inhibitors in children and adolescents with disorders of growth and adolescent development.". Pediatrics 121 (4): e975–983. doi:10.1542/peds.2007-2081. PMID 18381525. 
  4. 4.0 4.1 4.2 Fauci, Anthony S.; Eugene Braunwald, Dennis L. Kasper , Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, and Kurt J. Isselbacher (2008). Chapter 340. Disorders of the Testes and Male Reproductive System Harrison's principles of internal medicine (17th ed. ed.). New York: McGraw-Hill. ISBN 978-0-07-147693-5. 
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  6. 6.0 6.1 6.2 6.3 6.4 Devalia, HL; Layer, GT (April 2009). "Current concepts in gynaecomastia". Surgeon 7 (2): 114–119. PMID 19408804. 
  7. Mayo Clinic Staff (2010). "Symptoms". Mayo Clinic. Retrieved 3 February 2013. 
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 8.10 8.11 8.12 8.13 8.14 Dickson, G (April 2012). "Gynecomastia.". American Family Physician 85 (7): 716–722. PMID 22534349. 
  9. 9.0 9.1 Cordova, A; Moschella, F (2008). "Algorithm for clinical evaluation and surgical treatment of gynaecomastia". Journal of plastic, reconstructive, & aesthetic surgery 61 (1): 41–49. doi:10.1016/j.bjps.2007.09.033. PMID 17983883. 
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  13. Basaria, S (2010). "Androgen abuse in athletes: detection and consequences.". The Journal of Clinical Endocrinology and Metabolism 95 (4): 1533–1543. doi:10.1210/jc.2009-1579. PMID 20139230. 
  14. 14.0 14.1 14.2 14.3 14.4 14.5 Barros AC, Sampaio Mde C (2012). "Gynecomastia: physiopathology, evaluation and treatment". Sao Paolo Medical Journal 130 (3): 187–97. PMID 22790552. 
  15. Saylor, PJ; Smith, MR (May 2009). "Metabolic complications of androgen deprivation therapy for prostate cancer.". The Journal of Urology 181 (5): 1998–2006. doi:10.1016/j.juro.2009.01.047. PMC 2900631. PMID 19286225. 
  16. Huang, W; Molitch, ME (June 2012). "Evaluation and management of galactorrhea.". American Family Physician 85 (11): 1073–1080. PMID 22962879. 
  17. Gourgari, E; Saloustros, E; Stratakis, CA (August 2012). "Large-cell calcifying Sertoli cell tumors of the testes in pediatrics.". Current Opinion in Pediatrics 24 (4): 518–522. doi:10.1097/MOP.0b013e328355a279. PMID 22732638. 
  18. Iglesias, P; Carrero, JJ; Diez, JJ (January–February 2012). "Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.". Journal of Nephrology 25 (1): 31–42. doi:10.5301/JN.2011.8481. PMID 21748720. 
  19. Fleisher, Gary (2010). Textbook of pediatric emergency medicine (6th ed. ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health. p. 731. ISBN 9781605471594. 
  20. Anawalt, BD; Braunstein, GD; Matusomoto, AM (January 2011). "Gynecomastia". Journal of Clinical Endocrinology & Metabolism 96 (1): 0. 
  21. Melmed, Shlomo (2011). Williams Textbook of Endocrinology: Expert Consult. pp. Chapter 19. ISBN 9781437736007. 
  22. 22.0 22.1 22.2 Hassan, HC; Cullen, IM; Casey, RG; Rogers, E (June 2008). "Gynaecomastia: an endocrine manifestation of testicular cancer". Andrologia 40 (3): 152–157. doi:10.1111/j.1439-0272.2007.00815.x. PMID 18477201. 
  23. Haynes, Bridgett; Macadam, F (August 2009). "Male Gynecomastia". Mayo Clinic proceedings. Mayo Clinic 84 (8): 672. doi:10.4065/84.8.672. PMC 2719518. PMID 19648382. 
  24. Gynecomastia at eMedicine
  25. Mayo Clinic Staff (2010). "Tests and diagnosis". Mayo Clinic. Retrieved 3 February 2013. 
  26. 26.0 26.1 Koshy, JC; Goldberg, JS; Wolfswinkel, EM; Ge, Y; Heller, L (January 2011). "Breast cancer incidence in adolescent males undergoing subcutaneous mastectomy for gynecomastia: is pathologic examination justified? A retrospective and literature review.". Plastic and reconstructive surgery 127 (1): 1–7. doi:10.1097/PRS.0b013e3181f9581c. PMID 20871489. 
  27. 27.0 27.1 27.2 27.3 27.4 Wollina, U; Goldman, A (June 2011). "Minimally invasive esthetic procedures of the male breast". Journal of cosmetic dermatology 10 (2): 150–155. doi:10.1111/j.1473-2165.2011.00548.x. PMID 21649820. 
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  29. "Coverage Determination Guideline Gynecomastia Treatment". United HealthCare Services, Inc. 2012. Retrieved 12 February 2013. 
  30. "Clinical Policy Bulletin: Breast Reduction Surgery and Gynecomastia Surgery". Aetna Inc. 2012. Retrieved 12 February 2013. 
  31. "Cigna Medical Coverage Policy". Surgical Treatment of Gynecomastia. Cigna. 2012. Retrieved 12 February 2013. 
  32. 32.0 32.1 32.2 Wassersug, RJ; Oliffe, JL (April 2009). "The social context for psychological distress from iatrogenic gynecomastia with suggestions for its management". Journal of Sexual Medicine 6 (4): 989–1000. doi:10.1111/j.1743-6109.2008.01053.x. PMID 19175864. 
  33. Wiesman, IM; Lehman, JA; Parker, MG; Tantri, MD; Wagner, DS; Pedersen, JC (August 2004). "Gynecomastia: an outcome analysis". Annals of Plastic Surgery 53 (2): 97–101. PMID 15269574. 
  34. Wassersug, Richard J.; Oliffe, John L. (1 April 2009). "The Social Context for Psychological Distress from Iatrogenic Gynecomastia with Suggestions for Its Management". Journal of Sexual Medicine 6 (4): 989–1000. doi:10.1111/j.1743-6109.2008.01053.x. PMID 19175864. 

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