A. Estrogen Excess

1. Generally due to imbalance of free estrogen and free androgen on breast tissue
2. Elevated estrogen production
   1. Obesity
   2. Estrogen secreting tumors: Leydig or Sertoli cell tumors
   3. Human chorionic gonadotropin (hCG) producing (germ cell) tumors
   4. Adrenal tumors
   5. Obesity - adiopose tissue contains aromatase (testosterone --> estrodiol conversion)
   6. Advancing age also associated with increased aromatase activity
3. Increased environmental estrogen
4. Hypogonadism
5. Increased Sex Hormone Binding Globulin
   1. Hyperthyroidism
   2. Cirrhosis and some other liver diseases
6. Androgen receptor mutations

B. Elevated Prolactin

1. Most commonly from a prolactinoma
2. Dopamine antagonists: enhance prolactin production
   1. First generation antipsychotic agents
   2. Antinausea agents: phenothiazines, butyrphenones
3. Thyroid Dysfunction -
4. Rena Disease
5. Estrogen excess can also induce hyperprolactinemia

C. Medications

1. Spironolactone (Aldactone®)
2. Androgen Blockade
   1. Finasteride
   2. Bicalutamide
3. Digitalis (Digoxin®)
4. Cimetidine (Tagamet®)

D. Breast Disease

1. Gynecomastia must involve tissue directly under the aereola
2. Therefore, most cancers will not cause true gynecomastia
3. Cystic Breast Disease
4. Neoplastic Breast Disease

E. Treatment [1]

1. Identify specific cause and remove it
2. The proliferative process is often painful; treatment in this phase may lead to regression
3. Medications for Treatment During Proliferative Phase
   1. Tamoxifen 20mg qd x 3 months causes 80% partial and 60% complete regression
   2. Danazol ~40% resolution
   3. Testosterone or dihydrodestosterone
   4. Clomiphene citrate
4. Gynecomastia >1 year is unlikely to regress (or progress)
   1. Surgery - subcutaneous mastectomy
   2. Ultrasound-assisted liposuction
   3. Suction-assisted lipectomy

References

1. Braunstein GD. 2007. NEJM. 357(12):1229
2. Hayes FJ and Eichhorn JH. 2000. NEJM. 342(16):1196 (Case Record)