Gynecomastia

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Gynecomastia
Classification and external resources
Gynecomastia 001.jpg
A young adult male with gynecomastia
ICD-10 N62
ICD-9 611.1
MedlinePlus 003165

Gynecomastia /ˌɡnɨkɵˈmæstiə/ is a common condition characterized by the benign enlargement of breast tissue in males.[1][2][a] It may occur transiently in newborns. Half or more of adolescent boys have some breast development during puberty.[1][4] Newborn and adolescent males frequently experience temporary gynecomastia due to the influence of maternal hormones and hormonal changes during puberty, respectively.

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.[1][5][6] 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.[2]

Signs and symptoms[edit]

The hallmark feature of gynecomastia is male breast enlargement with rubbery or firm subcutaneous chest tissue extending outward from the areola of the nipple.[7] This enlargement may occur on one side or on both sides,[8] and may lead to significant stress and anxiety in affected individuals who may be concerned about the possibility of having breast cancer.[7][9] An increase in the diameter of the areola and asymmetry of chest tissue are other possible signs of gynecomastia.[10]

Causes[edit]

Gynecomastia is thought to be caused by an altered ratio of estrogens to androgens, an increase in estrogen production, a decrease in androgen production, or a combination of these factors with estrogen acting as a growth hormone to increase the size of male breast tissue.[4][7] The cause of gynecomastia is unknown in around 25% of cases.[8][9]

Physiologic[edit]

Many newborn infants of both sexes show breast development at birth or in the first weeks of life.[11] During pregnancy, the placenta converts the hormones DHEA and DHEA sulfate to the estrogens estrone and estradiol, respectively; after these estrogens are produced by the placenta, they are transferred into the baby's circulation thereby leading to temporary gynecomastia in the baby.[7][12] In some infants fluid ("witch's milk") can be expressed.[8] The temporary gynecomastia seen in newborn babies usually resolves after two or three weeks.[7] Gynecomastia in adolescents usually starts between the ages of ten and twelve and commonly goes away after eighteen months.[7] Declining testosterone levels and an increase in the level of subcutaneous fatty tissue seen as part of the normal aging process can lead to gynecomastia in older men. This is also known as senile gynecomastia.[7] Increased fatty tissue in these men leads to increased conversion of androgenic hormones such as testosterone to estrogens.[7] When the human body is deprived of adequate nutrition, testosterone levels drop while the adrenal glands continue to produce estrogens thereby causing a hormonal imbalance.[7] Gynecomastia can also occur once normal nutrition is restarted (this is known as refeeding gynecomastia).[7]

Non-physiologic[edit]

About 10–25% of cases are estimated to result from the use of medications.[13] This is known as non-physiologic gynecomastia.[9] 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 and dutasteride.[13][14][15] Medications that are probably associated with gynecomastia include risperidone, calcium channel blockers such as verapamil, amlodipine, and nifedipine, anabolic steroids,[16] alcohol, opioids, efavirenz, alkylating agents, and omeprazole.[13][17] Certain components of personal care products such as lavender or tea tree oil and certain supplements such as Dong Quai and Tribulus terrestris have been associated with gynecomastia.[9]

Chronic disease[edit]

Patients with kidney failure are often malnourished, which may contribute to gynecomastia development. Dialysis may attenuate malnutrition of renal failure. Additionally, many kidney 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.[9][18]

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.[9] Conditions that can cause malabsorption such as cystic fibrosis or ulcerative colitis may also produce gynecomastia.[9]

Tumors[edit]

Testicular tumors such as Leydig cell tumors or Sertoli cell tumors[19] (such as in Peutz-Jeghers syndrome)[2] or hCG-secreting choriocarcinoma[17] 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.[8]

Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia.[20]

Pathophysiology[edit]

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.[6][13] Adolescent gynecomastia is caused by the faster rise in estradiol than testosterone seen during early puberty. However, this skewed estrogen/androgen ratio is normally corrected with the expected increase in testosterone seen later in puberty.[7] In rare cases, the gynecomastia persists throughout puberty and such cases are often associated with a family history of a similar occurrence.[7]

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.[7] Klinefelter syndrome is a notable example of a disorder that causes hypogonadism, gynecomastia, and has a higher risk of breast cancer in males (10-20 times higher than males without the disorder).[7] Secondary hypogonadism (indicating a problem with the brain) leads to decreased production and release of luteinizing hormone (LH) (a stimulatory signal for endogenous steroid hormone synthesis) which leads to decreased production of testosterone and estradiol in the testes.[7]

Individuals who have cirrhosis or chronic liver disease may develop gynecomastia for several reasons. It is not uncommon for such individuals to have increased secretion of the androgenic hormone androstenedione from the adrenal glands, increased conversion of this hormone into various types of estrogen, and increased levels of the protein sex hormone binding globulin (SHBG), which leads to decreased levels of free testosterone (the active form).[7] Approximately 10-40% of individuals with Graves disease (a common form of hyperthyroidism) experience gynecomastia.[7] Increased conversion of testosterone to estrogen by increased aromatase activity, increased levels of SHBG, and increased production of testosterone and estradiol by the testes due to elevated levels of LH cause the gynecomastia. Proper treatment of the hyperthyroidism can lead to the resolution of the gynecomastia.[7]

Medications known to cause gynecomastia act through several different mechanisms. These mechanisms include increasing estrogen levels, mimicking estrogen, decreasing levels of testosterone or other androgens, blocking androgen receptors, increasing prolactin levels, or through unidentified means.[7] High levels of prolactin in the blood (which may occur as a result of certain tumors or as a side effect of certain medications) has been associated with gynecomastia.[7] A high level of prolactin in the blood can cause central hypogonadism and receptors for prolactin have been found in male breast tissue, however, the prolactin's role in the development of gynecomastia remains unclear.[7] Breast prominence can result from enlargement of glandular breast tissue, chest adipose tissue (fat) and skin, and is typically a combination.[17]

Diagnosis[edit]

To diagnose gynecomastia, other causes of male breast enlargement such as mastitis,[9][21] breast cancer, pseudogynecomastia, lipoma, sebaceous cyst, dermoid cyst, hematoma, metastasis, ductal ectasia, fat necrosis, or a hamartoma are typically excluded.[9] 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.[9]

Early histological features expected to be seen on examination of gynecomastic tissue attained by fine-needle aspiration biopsy include the following: proliferation and lengthening of the ducts, an increase in connective tissue, an increase in inflammation and swelling surrounding the ducts, and an increase in fibroblasts in the connective tissue.[7] Chronic gynecomastia may show different histological features such as increased connective tissue fibrosis, an increase in the number of ducts, less inflammation than in the acute stage of gynecomastia, increased subareolar fat, and hyalinization of the stroma.[7][10]

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.[23]

A review of the medications or illegal substances an individual takes may reveal the cause of gynecomastia.[9] 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.[24] 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.[9]

Classification[edit]

The spectrum of gynecomastia severity has been categorized into a grading system:[24]

  • 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[edit]

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

Mild cases of gynecomastia may be treated with advice on lifestyle habits such as proper diet and exercise with reassurance, but in more severe cases, medical treatmeant is required, perhaps including surgical intervention.[7] 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.[13] 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.[24]

Selective estrogen receptor modulators such as tamoxifen may be beneficial in the treatment of gynecomastia but are not approved by the Food and Drug Administration for use in gynecomastia.[13] Aromatase inhibitors such as testolactone have been approved for the treatment of gynecomastia in children and adolescents.[2] Tamoxifen may be used for painful gynecomastia in adults.[13]

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 most effective when used prophylactically.[25]

Many insurance companies deny coverage for surgery for gynecomastia treatment or male breast reduction on the basis that it is a cosmetic procedure.[26][27][28][29]

Prognosis[edit]

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.[23][24] 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[edit]

Gynecomastia has a trimodal peak of incidence and commonly presents in newborns, adolescents, and men older than 50 years of age,[24] but most cases of newborn gynecomastia resolve on their own.[9] Newborn gynecomastia occurs in about 60-90% of male babies.[7] Thirty to sixty percent of males are estimated to exhibit signs of gynecomastia during their adolescence.[17] Senile gynecomastia is estimated to be present in 24-65% of men between the ages of fifty and eighty.[7] The prevalence of gynecomastia in men may have increased in recent years, but the epidemiology of gynecomastia is not fully understood.[17] The use of anabolic steroids and exposure to chemicals that mimic estrogen in cosmetic products, organochlorine pesticides, and industrial chemicals have been suggested as possible factors driving this increase.[17][29] 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.[29]

Society and culture[edit]

Gynecomastia can result in psychological distress for those with the condition. Common derogatory terms for gynecomastia include moobs (for man boobs) and bitch tits. Support groups exist to help improve the self-esteem of affected individuals.[30]

See also[edit]

Notes[edit]

  1. ^ The term comes from the Greek γυνή gyné (stem gynaik-) meaning "female" and μαστός mastós meaning "breast."[3]

References[edit]

  1. ^ a b c 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. 
  2. ^ a b c d 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. 
  3. ^ 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. 
  4. ^ a b c Fauci, Anthony S.; Eugene Braunwald; Dennis L. Kasper; Stephen L. Hauser; Dan L. Longo; J. Larry Jameson; 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. 
  5. ^ Definition of Gynecomastia, 2014, retrieved 22 April 2014 
  6. ^ a b Johnson RE, Murad MH (November 2009). "Gynecomastia: pathophysiology, evaluation, and management". Mayo Clinic Proceedings 84 (11): 1010–1015. doi:10.1016/S0025-6196(11)60671-X. PMC 2770912. PMID 19880691. 
  7. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z Cuhaci N, Polat SB, Evranos B, Ersoy R, Cakir B (March 19, 2014). "Gynecomastia: Clinical evaluation and management". Indian J Endocrinol Metab 18 (2): 150–58. doi:10.4103/2230-8210.129104. PMID 24741509. 
  8. ^ a b c d Devalia HL, Layer GT (April 2009). "Current concepts in gynaecomastia". Surgeon 7 (2): 114–19. doi:10.1016/s1479-666x(09)80026-7. PMID 19408804. 
  9. ^ a b c d e f g h i j k l m Dickson, G (April 2012). "Gynecomastia.". American Family Physician 85 (7): 716–722. PMID 22534349. 
  10. ^ a b 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. 
  11. ^ Fleisher, Gary (2010). Textbook of pediatric emergency medicine (6th ed. ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health. p. 731. ISBN 9781605471594. 
  12. ^ Melmed, Shlomo (2011). Williams Textbook of Endocrinology: Expert Consult. pp. Chapter 19. ISBN 9781437736007. 
  13. ^ a b c d e f g Deepinder F, Braunstein GD (2012). "Drug-induced gynecomastia: an evidence-based review.". Expert opinion on drug safety 11 (5): 779–795. doi:10.1517/14740338.2012.712109. PMID 22862307. 
  14. ^ Nappi, JM; Sieg, A (2011). "Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure.". Vascular health and risk management 7: 353–363. doi:10.2147/VHRM.S13779. PMC 3119593. PMID 21731887. 
  15. ^ Aiman, U; Haseen, MA; Rahman, SZ (December 2009). "Gynecomastia: An ADR due to drug interaction.". Indian journal of pharmacology 41 (6): 286–287. doi:10.4103/0253-7613.59929. PMC 2846505. PMID 20407562. 
  16. ^ 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. 
  17. ^ a b c d e f Barros AC, Sampaio Mde C (2012). "Gynecomastia: physiopathology, evaluation and treatment". Sao Paolo Medical Journal 130 (3): 187–97. doi:10.1590/s1516-31802012000300009. PMID 22790552. 
  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. ^ 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. 
  20. ^ 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. 
  21. ^ Mayo Clinic Staff (2010). "Tests and diagnosis". Mayo Clinic. Retrieved 3 February 2013. 
  22. ^ 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. ^ a b 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. 
  24. ^ a b c d e 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. 
  25. ^ Viani, GA; Bernardes da Silva, LG; Stefano, EJ (July 2012). "Prevention of gynecomastia an breast pain caused by androgen deprivation therapy in prostate cancer: tamoxifen or radiotherapy?". International Journal of Radiation Oncology, Biology, Physics 83 (4): e519–e524. doi:10.1016/j.ijrobp.2012.01.036. PMID 22704706. 
  26. ^ "Coverage Determination Guideline Gynecomastia Treatment". United HealthCare Services, Inc. 2012. Retrieved 12 February 2013. 
  27. ^ "Clinical Policy Bulletin: Breast Reduction Surgery and Gynecomastia Surgery". Aetna Inc. 2012. Retrieved 12 February 2013. are
  28. ^ "Cigna Medical Coverage Policy". Surgical Treatment of Gynecomastia. Cigna. 2012. Retrieved 12 February 2013. 
  29. ^ a b c 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. 
  30. ^ 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. 

External links[edit]