Gynecomastia or other signs of feminization in males may be due to an absolute or relative (in relation to androgens) surplus of estrogens. Gynecomastia is common during puberty in boys. Unless E1, E2, or testosterone levels exceed the adult male reference range, the condition is usually not due to hormonal disease (though it sometimes may still result in persistent breast tissue, which later needs to be surgically removed). For adults with gynecomastia, the workup should include testosterone and adrenal androgen measurements, in addition to E2 and E1 measurements. Causes for increased E1 or E2 levels include:
-High androgen levels caused by tumors or androgen therapy (medical or sport performance enhancing), with secondary elevations in E1 and E2 due to aromatization
-Obesity with increased tissue production of E1
-Decreased E1 and E2 clearance in liver disease
-Estrogen producing tumors
-Estrogen ingestion
Normal male E1 and E2 levels also may be associated with feminization or gynecomastia, if bioavailable testosterone levels are low due to primary/secondary testicular failure. This may occur, for example, when patients are receiving antiandrogen therapy or other drugs with antiandrogenic effects (eg, spironolactone, digitalis preparations).