Gynecomastia: pathogenesis and approaches to treatment
S. Kh. Eristavi,
R. V. Rozhivanov,
E. R. Rozhivanova,
E. N. Andreeva,
G. A. Mel’nichenko,
N. G. Mokrysheva https://doi.org/10.14341/brh12752
Abstract
Gynecomastia is a benign enlargement of the breast glands in men that can be physiologic, pathologic, or idiopathic. Physiologic gynecomastia can occur in children and during puberty. Pathologic gynecomastia is associated with various endocrine, genetic disorders, systemic diseases, paraneoplastic processes, or may be iatrogenic. Common causes of pathologic gynecomastia are hypogonadism, testicular or adrenal tumors producing estrogens, androgen excess syndromes with aromatization, androgen deficiencies, hepatopathy, and nephropathy. Most commonly, the underlying cause of gynecomastia is an imbalance between estrogens and androgens. It is known that the treatment of syndromes causing gynecomastia depends on the etiology and pathogenesis, but gynecomastia itself is eliminated, as a rule, surgically. The use of drug therapy for gynecomastia is debated. It would probably be appropriate in cases of gynecomastia due to an imbalance between estrogens and androgens, given the initial stage of gynecomastia development. The main candidates for drug treatment of gynecomastia are anti-estrogens and aromatase inhibitors. These aspects are discussed in the review.
About the Authors
S. Kh. Eristavi
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Saida Kh. Eristavi, MD
11 Dm. Ulyanova street, 117036 Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
R. V. Rozhivanov
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Roman V. Rozhivanov, MD, PhD]
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
E. R. Rozhivanova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Ekaterina R. Rozhivanova, MD
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
E. N. Andreeva
Endocrinology Research Centre; Russian University of Medicine
Russian Federation
Competing Interests:
Russian Federation
Elena N. Andreeva, MD, PhD, Professor
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
G. A. Mel’nichenko
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Galina A. Mel’nichenko, MD, PhD, Professor
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
N. G. Mokrysheva
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Natalya G. Mokrysheva, MD, PhD, Professor
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
References
1. Mieritz MG, Christiansen P, Jensen MB, et al. Gynaecomastia in 786 adult men: clinical and biochemical findings. Eur J Endocrinol. 2017;176(5):555-566. doi: https://doi.org/10.1530/EJE-16-0643
2. Braunstein GD. Clinical practice. Gynecomastia. N Engl J Med. 2007;357(12):1229-1237. doi: https://doi.org/10.1056/NEJMcp070677
3. Nuttall FQ. Gynecomastia as a physical finding in normal men. J Clin Endocrinol Metab. 1979;48(2):338-40. doi: https://doi.org/10.1210/jcem-48-2-338
4. Jerome ML, Valcarce V, Lach L, et al. Infant body composition: A comprehensive overview of assessment techniques, nutrition factors, and health outcomes. Nutr Clin Pract. 2023;38 Suppl 2(Suppl 2):S7-S27. doi: https://doi.org/10.1002/ncp.11059
5. Valeyeva FV, Sharipova YuU, Gazizova GR. Gynecomastia in Men: Causes, Diagnosis, Treatment. Effective pharmacotherapy. 2023;19(52):30–39. (In Russ.). doi: https://doi.org/0.33978/2307-3586-2023-19-52-30-39
6. Kanakis GA, Nordkap L, Bang AK, et al. EAA clinical practice guidelines-gynecomastia evaluation and management. Andrology. 2019;7(6):778-793. doi: https://doi.org/10.1111/andr.12636
7. Nachtigall C. Verlaufsbeobachtungen über die physiologische Brustdrüsenschwellung der Neugeborenen [Progress observations on physiological swelling of the breast in newborn infants]. Monatsschr Kinderheilkd (1902). 1965;113(8):497-498
8. Jayasinghe Y, Cha R, Horn-Ommen J, et al. Establishment of normative data for the amount of breast tissue present in healthy children up to two years of age. J Pediatr Adolesc Gynecol. 2010;23(5):305-311. doi: https://doi.org/10.1016/j.jpag.2010.03.002
9. Biro FM, Lucky AW, Huster GA, et al. Hormonal studies and physical maturation in adolescent gynecomastia. J Pediatr. 1990;116(3):450-455. doi: https://doi.org/10.1016/s0022-3476(05)82843-4
10. Mieritz MG, Rakêt LL, Hagen CP, et al. A Longitudinal Study of Growth, Sex Steroids, and IGF-1 in Boys With Physiological Gynecomastia. J Clin Endocrinol Metab. 2015;100(10):3752-3759. doi: https://doi.org/10.1210/jc.2015-2836
11. Tinggaard J, Mieritz MG, Sørensen K, et al. The physiology and timing of male puberty. Curr Opin Endocrinol Diabetes Obes. 2012;19(3):197- 203. doi: https://doi.org/10.1097/MED.0b013e3283535614
12. Lee KO, Chua DY, Cheah JS. Oestrogen and progesterone receptors in men with bilateral or unilateral pubertal macromastia. Clin Endocrinol (Oxf ). 1990;32(1):101-105. doi: https://doi.org/10.1111/j.1365-2265.1990.tb03755.x
13. Georgiadis E, Papandreou L, Evangelopoulou C, et al. Incidence of gynaecomastia in 954 young males and its relationship to somatometric parameters. Ann Hum Biol. 1994;21(6):579-587. doi: https://doi.org/10.1080/03014469400003582
14. Bannayan GA, Hajdu SI. Gynecomastia: clinicopathologic study of 351 cases. Am J Clin Pathol. 1972;57(4):431-437. doi: https://doi.org/10.1093/ajcp/57.4.431
15. Narula HS, Carlson HE. Gynaecomastia — pathophysiology, diagnosis and treatment. Nat Rev Endocrinol. 2014;10(11):684-698. doi: https://doi.org/10.1038/nrendo.2014.139
16. Kanhai RC, Hage JJ, van Diest PJ, et al. Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men. Am J Surg Pathol. 2000;24(1):74-80. doi: https://doi.org/10.1097/00000478-200001000-00009
17. Rochefort H, Garcia M. The estrogenic and antiestrogenic activities of androgens in female target tissues. Pharmacol Ther. 1983;23(2):193-216. doi: https://doi.org/10.1016/0163-7258(83)90013-x
18. Hellmann P, Christiansen P, Johannsen TH, et al A. Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia. Arch Dis Child. 2012;97(5):403-409. doi: https://doi.org/10.1136/archdischild-2011-300584
19. Mathur R, Braunstein GD. Gynecomastia: pathomechanisms and treatment strategies. Horm Res. 1997;48(3):95-102. doi: https://doi.org/10.1159/000185497
20. Ismail AA, Barth JH. Endocrinology of gynaecomastia. Ann Clin Biochem. 2001;38(Pt 6):596-607. doi: https://doi.org/10.1258/0004563011900993
21. Sasano H, Kimura M, Shizawa S, et al. Aromatase and steroid receptors in gynecomastia and male breast carcinoma: an immunohistochemical study. J Clin Endocrinol Metab. 1996;81(8):3063-3067. doi: https://doi.org/10.1210/jcem.81.8.8768875
22. Sattin RW, Roisin A, Kafrissen ME, et al. Epidemic of gynecomastia among illegal Haitian entrants. Public Health Rep. 1984;99(5):504-510
23. Niewoehner CB, Nuttal FQ. Gynecomastia in a hospitalized male population. Am J Med. 1984;77(4):633-638. doi: https://doi.org/10.1016/0002-9343(84)90353-x
24. Forest MG, Lecoq A, Saez JM. Kinetics of human chorionic gonadotropin-induced steroidogenic response of the human testis. II. Plasma 17 alpha-hydroxyprogesterone, delta4-androstenedione, estrone, and 17 beta-estradiol: evidence for the action of human chorionic gonadotropin on intermediate enzymes implicated in steroid biosynthesis. J Clin Endocrinol Metab. 1979;49(2):284-291. doi: https://doi.org/10.1210/jcem-49-2-284
25. Vargatu I. Williams textbook of endocrinology. Acta Endocrinol (Buchar). 2016;12(1):113. doi: https://doi.org/10.4183/aeb.2016.113
26. Boddi V, Barbaro V, McNieven P, Maggi M, Rotella CM. Present and future association between obesity and hypogonadism in Italian male. Arch Ital di Urol e Androl. 2014;86(1):26. doi: https://doi.org/10.4081/aiua.2014.1.26
27. Leisegang K, Bouic PJ, et al. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort. Reprod Biol Endocrinol. 2014;12:34. doi: https://doi.org/10.1186/1477-7827-12-34
28. Kim SD, Cho KS. Obstructive Sleep Apnea and Testosterone Deficiency. World J Mens Health. 2019;37(1):12-18. doi: https://doi.org/10.5534/wjmh.180017
29. Ferreira M, Mesquita M, Quaresma M, et al. Prolactin receptor expression in gynaecomastia and male breast carcinoma. Histopathology. 2008;53(1):56-61. doi: https://doi.org/10.1111/j.1365-2559.2008.03059.x
30. Kidd GS, Glass AR, Vigersky RA. The hypothalamic-pituitary-testicular axis in thyrotoxicosis. J Clin Endocrinol Metab. 1979;48(5):798-802. doi: https://doi.org/10.1210/jcem-48-5-798
31. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702-755. doi: https://doi.org/10.1210/er.2009-0041
32. Bercovici JP, Tater D, Khoury S, et al. Leydig cell tumor with gynecomastia: hormonal effects of an estrogen-producing tumor. J Clin Endocrinol Metab. 1981;53(6):1291-1296. doi: https://doi.org/10.1210/jcem-53-6-1291
33. Lafemina J, Brennan MF. Adrenocortical carcinoma: past, present, and future. J Surg Oncol. 2012;106(5):586-594. doi: https://doi.org/10.1002/jso.23112
34. Iglesias P, Carrero JJ, Díez JJ. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options. J Nephrol. 2012;25(1):31-42. doi: https://doi.org/10.5301/JN.2011.8481
35. Hou SH, Grossman S, Molitch ME. Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or chronic ambulatory peritoneal dialysis. Am J Kidney Dis. 1985;6(4):245-249. doi: https://doi.org/10.1016/s0272- 6386(85)80181-5
36. Maruyama Y, Adachi Y, Aoki N, et al. Mechanism of feminization in male patients with non-alcoholic liver cirrhosis: role of sex hormone-binding globulin. Gastroenterol Jpn. 1991;26(4):435-439. doi: https://doi.org/10.1007/BF02782811
37. Castilla-García A, Santolaria-Fernández FJ, González-Reimers CE, et al. Alcohol-induced hypogonadism: reversal after ethanol withdrawal. Drug Alcohol Depend. 1987;20(3):255-260. doi: https://doi.org/10.1016/0376-8716(87)90035-4
38. Kasyanova YuV, Chernyak IYu, Voronina IK, et al. A clinical case of aromatase excess syndrome associated with 15Q21.2 duplication. Problems of Endocrinology. 2020;66(2):79-84. (In Russ.) doi: https://doi.org/10.14341/probl12446
39. Nuttall FQ, Warrier RS, Gannon MC. Gynecomastia and drugs: a critical evaluation of the literature. Eur J Clin Pharmacol. 2015;71(5):569-578. doi: https://doi.org/10.1007/s00228-015-1835-x
40. Nieschlag E, Vorona E. MECHANISMS IN ENDOCRINOLOGY: Medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. Eur J Endocrinol. 2015;173(2):R47-R58. doi: https://doi.org/10.1530/EJE-15-0080
41. Geyer H, Schänzer W, Thevis M. Anabolic agents: recent strategies for their detection and protection from inadvertent doping. Br J Sports Med. 2014;48(10):820-826. doi: https://doi.org/10.1136/bjsports-2014-093526
42. Henley DV, Lipson N, Korach KS, et al. Prepubertal gynecomastia linked to lavender and tea tree oils. N Engl J Med. 2007;356(5):479-485. doi: https://doi.org/10.1056/NEJMoa064725
43. Alesini D, Iacovelli R, Palazzo A, et al. Multimodality treatment of gynecomastia in patients receiving antiandrogen therapy for prostate cancer in the era of abiraterone acetate and new antiandrogen molecules. Oncology. 2013;84(2):92-99. doi: https://doi.org/10.1159/000343821
44. Wu FC, Tajar A, Beynon JM, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123-135. doi: https://doi.org/10.1056/NEJMoa0911101
45. Lawrence SE, Faught KA, Vethamuthu J, et al. Beneficial effects of raloxifene and tamoxifen in the treatment of pubertal gynecomastia. J Pediatr. 2004;145(1):71-76. doi: https://doi.org/10.1016/j.jpeds.2004.03.057
46. Derman O, Kanbur NO, Kutluk T. Tamoxifen treatment for pubertal gynecomastia. Int J Adolesc Med Health. 2003;15(4):359-363. doi: https://doi.org/10.1515/ijamh.2003.15.4.359
47. Khan HN, Rampaul R, Blamey RW. Management of physiological gynaecomastia with tamoxifen. Breast. 2004;13(1):61-65. doi: https://doi.org/10.1016/j.breast.2003.10.005
48. Braunstein GD. Aromatase and gynecomastia. Endocr Relat Cancer. 1999;6(2):315-324. doi: https://doi.org/10.1677/erc.0.0060315
49. Bel’cevich DG, Vanushko VE, Kuznecov NS, i dr. Ginekomastiya // Endokrinnaya hirurgiya. 2012;1:18-23 (In Russ.).
50. Webster MH. Plastic surgery of the breast. Practitioner. 1980;224(1342):406-408
51. Rahmani S, Turton P, Shaaban A, et al. Overview of gynecomastia in the modern era and the Leeds Gynaecomastia Investigation algorithm. Breast J. 2011;17(3):246-255. doi: https://doi.org/10.1111/j.1524-4741.2011.01080.x
52. Ordaz DL, Thompson JK. Gynecomastia and psychological functioning: A review of the literature. Body Image. 2015;15:141-148. doi: https://doi.org/10.1016/j.bodyim.2015.08.004
Supplementary files
Review
For citations:
Eristavi S.Kh., Rozhivanov R.V., Rozhivanova E.R., Andreeva E.N., Mel’nichenko G.A., Mokrysheva N.G. Gynecomastia: pathogenesis and approaches to treatment. Bulletin of Reproductive Health. 2025;4(1):32-38. (In Russ.) https://doi.org/10.14341/brh12752
Views:
241
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
