Aetiology

The cause of gynaecomastia is likely to be an imbalance between oestrogen activity (increased) and androgen activity (decreased) in the breast tissue (1).

Summary of causes (2):

Benign gynaecomastia can be secondary to multiple medical and recreational drugs, as well as many chronic medical conditions.

Physiological

• neonatal: due to placental oestrogen transfer
• pubertal: pubertal oestrogen production begins prior to testosterone production due to early maturation of aromatase (catalyzes conversion of androgens to oestrogens). Regression occurs in 90% of cases
• senile: Age 70+. Up to 65% of men. Due to the reduction in testosterone relative to oestrogen

Drug induced - 10-20% of gynaecomastia is due to prescribed drugs

• for example
  • Oestrogen containing drugs eg. Bicalutamide, Buserelin, Goserelin
  • Androgen receptor blocking drugs e.g. Cyproterone acetate, spironolactone, flutamide
  • Androgen production inhibiting e.g. Finasteride, ketoconazole, dutasteride

Drug induced - recreational drugs such as marijuana, amphetamines, heroin, methadone

Pathological

• Adrenal or testicular tumours <3% of gynaecomastia
  • a. Oestrogen or androgen producing tumours
  • b. Aromatase producing tumours
  • c. hCG producing tumours
• Endocrine
  • a. Primary hypogonadism [10% of gynaecomastia]
  • b. Secondary hypogonadism
  • c. Prolactinoma
  • d. Thyrotoxicosis
  • e. Acromegaly
  • f. Androgen insensitivity
• Systemic illness
  • a. Liver cirrhosis
  • b. Renal failure
  • c. Malnutrition
  • d. Obesity
  • e. HIV

More detailed information relating to aetiological factors is presented in linked items below.

The aetilogy of gynaecomastia can be classified as:

• physiological
• pathological
• drug-induced
• idiopathic - especially in the elderly

Reference:

• (1) Johnson RE, Kermott CA, Murad MH. Gynecomastia - evaluation and current treatment options. Ther Clin Risk Manag. 2011;7:145-8.
• (2) Association of Breast Surgery Summary Statement (June 2019). Investigation and management of gynaecomastia in primary and secondary care.