Gynecomastia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]
Overview
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.
Pathophysiology
Hormones involved in breast development
- Estrogen and progesterone act in a coordinated manner to support breast development. Estrogen helps duct growth and progesterone promotes alveolar development which only occurs in female as gynecomastia doesn't have alveolar development. [1][2]
- Growth hormone which acts through IGF-1 acts as a mediator in the presence of estrogen and progesterone for ductal breast duct development.[3] The IGF-1 levels have been found higher in boys with pubertal gynecomastia which shows the role of GH and IGF-1 in the pathogenesis of gynecomastia.[4]
- Prolactin in the presence of estrogen and progesterone also supports breast development. It also plays an indirect role as it causes central hypogonadism which alters the androgen/estrogen balance.[5] [6]
- Aromatase catalyzes the conversion of androgens to estrogen and promotes the breast development. So, gynecomastia can also result from overexpression of aromatase.[7][8]
| Breast Tissue | |||||||||||||||||||||||||||||||||||||||||||
| Stimulatory Action | Inhibitory Action | ||||||||||||||||||||||||||||||||||||||||||
| Estrogen | Androgens | ||||||||||||||||||||||||||||||||||||||||||
| GH & IGF-1 | |||||||||||||||||||||||||||||||||||||||||||
Pathogenesis
- 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.[5]
- 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.[9] [10] [5]
Some examples regarding gynecomastia development based on the pathophysiology include:
| Conditions causing increased estrogen | Conditions causing decreased testosterone |
|---|---|
Genetics
Genes involved in the pathogenesis of aromatase overexpression form of gynecomastia is encoded by a chromosome 15q21.2.[8] As a result, any mutation in the mentioned loci result in aromatase overexpression.
Associated Conditions
Gynecomastia is associated with psychological stress such as:[11][12][13][14]
- Depression
- Decreased self-esteem
- Body dissatisfaction
Gross Pathology
On gross pathology, characteristic findings of gynecomastia include:
- Excessive breast tissue and subareolar mass
- Well circumscribed borders
- Firm surfaces
Microscopic Pathology
On microscopic inspection, gynecomastia histology shows:[15]
- Ductal hyperplasia
- Lengthening of the ducts
- inflammation surrounding the ducts
- Increase in periductal connective tissue
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References
- ↑ Bocchinfuso WP, Korach KS (1997). "Mammary gland development and tumorigenesis in estrogen receptor knockout mice". J Mammary Gland Biol Neoplasia. 2 (4): 323–34. PMID 10935020.
- ↑ Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O (1993). "Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene". Proc. Natl. Acad. Sci. U.S.A. 90 (23): 11162–6. PMC 47942. PMID 8248223.
- ↑ Kleinberg DL, Feldman M, Ruan W (2000). "IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis". J Mammary Gland Biol Neoplasia. 5 (1): 7–17. PMID 10791764.
- ↑ Mieritz MG, Sorensen K, Aksglaede L, Mouritsen A, Hagen CP, Hilsted L, Andersson AM, Juul A (2014). "Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia". Clin. Endocrinol. (Oxf). 80 (5): 691–8. doi:10.1111/cen.12323. PMID 24033660.
- ↑ 5.0 5.1 5.2 De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Swerdloff RS, Ng J. PMID 25905330. Vancouver style error: initials (help); Missing or empty
|title=(help) - ↑ Barros AC, Sampaio Mde C (2012). "Gynecomastia: physiopathology, evaluation and treatment". Sao Paulo Med J. 130 (3): 187–97. PMID 22790552.
- ↑ Li X, Wärri A, Mäkelä S, Ahonen T, Streng T, Santti R; et al. (2002). "Mammary gland development in transgenic male mice expressing human P450 aromatase". Endocrinology. 143 (10): 4074–83. doi:10.1210/en.2002-220181. PMID 12239119.
- ↑ 8.0 8.1 Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K; et al. (2003). "Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene". N Engl J Med. 348 (19): 1855–65. doi:10.1056/NEJMoa021559. PMID 12736278.
- ↑ Johnson RE, Murad MH (2009). "Gynecomastia: pathophysiology, evaluation, and management". Mayo Clin Proc. 84 (11): 1010–5. doi:10.1016/S0025-6196(11)60671-X. PMC 2770912. PMID 19880691.
- ↑ Mathur R, Braunstein GD (1997). "Gynecomastia: pathomechanisms and treatment strategies". Horm Res. 48 (3): 95–102. PMID 11546925.
- ↑ Wassersug, Richard J.; Oliffe, John L. (2009). "The Social Context for Psychological Distress from Iatrogenic Gynecomastia with Suggestions for Its Management". The Journal of Sexual Medicine. 6 (4): 989–1000. doi:10.1111/j.1743-6109.2008.01053.x. ISSN 1743-6095.
- ↑ Strømsvik, Nina; Råheim, Målfrid; Øyen, Nina; Engebretsen, Lars Fredrik; Gjengedal, Eva (2010). "Stigmatization and Male Identity: Norwegian Males' Experience after Identification as BRCA1/2 Mutation Carriers". Journal of Genetic Counseling. 19 (4): 360–370. doi:10.1007/s10897-010-9293-1. ISSN 1059-7700.
- ↑ Hack, Thomas F.; Sawatzky, Jo-Ann; Pedersen, Allison E. (2010). "The Sequelae of Anxiety in Breast Cancer: A Human Response to Illness Model". Oncology Nursing Forum. 37 (4): 469–475. doi:10.1188/10.ONF.469-475. ISSN 0190-535X.
- ↑ Senín-Calderón, Cristina; Rodríguez-Testal, Juan F.; Perona-Garcelán, Salvador; Perpiñá, Conxa (2017). "Body image and adolescence: A behavioral impairment model". Psychiatry Research. 248: 121–126. doi:10.1016/j.psychres.2016.12.003. ISSN 0165-1781.
- ↑ Nicolis GL, Modlinger RS, Gabrilove JL (1971). "A study of the histopathology of human gynecomastia". J Clin Endocrinol Metab. 32 (2): 173–8. doi:10.1210/jcem-32-2-173. PMID 5539033.