Gynecomastia refers to enlargement of one or both breasts in boys or men caused by nonmalignant hyperplasia of the glandular tissue, which is sometimes accompanied by adipose tissue hyperplasia. It must be differentiated from the deposition of the adipose (fatty) tissue alone, which is referred to as adipomastia (pseudogynecomastia).
Causes and PathogenesisTop
1) Increased levels of free (biologically active) estradiol in relation to free testosterone as a result of:
a) Increased estrogen biosynthesis (during puberty [a physiological phenomenon], in testicular cancer [tumors producing estrogens or gonadotropins], in adrenal hyperplasia or tumors).
b) Decreased androgen biosynthesis (in hypogonadism and in elderly men).
c) Increased hepatic production of sex hormone–binding globulin (SHBG) (eg, in hyperthyroidism).
d) Decreased estrogen and androgen metabolism (eg, in cirrhosis or chronic renal failure).
e) Antiandrogen effects of medications used to treat prostatic hypertrophy (eg, finasteride, dutasteride) and prostate cancer (eg, flutamide, bicalutamide).
f) Direct action on estrogen receptors (eg, digoxin).
2) Locally increased activity of aromatase (the enzyme converting testosterone to estradiol; eg, in obesity).
3) Increased sensitivity of the breast to estrogens.
4) A congenital androgen receptor defect or androgen receptor inhibition by exogenous factors, for instance, drugs that have antiandrogenic effects (spironolactone, ketoconazole, enalapril, verapamil, ranitidine, omeprazole).
Classification by the age of onset and most frequent causes:
1) Boys aged 13 to 14 years: Pubertal gynecomastia.
2) Postpubertal men: Persistent postpubertal gynecomastia; idiopathic gynecomastia; drug-induced gynecomastia; gynecomastia as a symptom of hormone disturbances or other conditions (symptomatic), for instance, cancer.
3) Elderly men: Hormone changes.
1. History and physical examination: Take a medication history. Determine the rate of progression of breast enlargement and establish if breast tenderness and tension are present. Perform a thorough examination of the breasts to distinguish true gynecomastia from pseudogynecomastia (texture, elasticity, mobility of the glandular tissue in relation to surrounding tissues; check for discharge by gently pressing the nipple), as well as testicles, external genitals, and peripheral lymph nodes. Look for manifestations of hyperthyroidism, Cushing syndrome, liver failure, renal failure, and a central nervous system tumor.
2. Diagnostic studies:
1) Laboratory tests: Complete blood count (CBC); liver and kidney function tests; serum levels of estradiol, total testosterone, prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). If a germ cell tumor is suspected, assess relevant tumor markers (eg, alpha-fetoprotein [AFP], beta human chorionic gonadotropin [beta-hCG], lactate dehydrogenase [LDH]).
2) Imaging studies: Ultrasonography of both breasts (to exclude a breast tumor and differentiate between gynecomastia and adipomastia) and testicles (to exclude a tumor). If a hormone-secreting tumor is suspected, perform ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI) of the adrenal glands; MRI of the pituitary gland; and chest radiography.
3) Breast biopsy: Perform if breast cancer is suspected (particularly if the lesion is not movable in relation to the surrounding tissues and is irregular).
1. Treatment of pathologic gynecomastia depends on the underlying cause.
2. Treatment of idiopathic and physiologic gynecomastia involves sympathetic reassurance and observation. Follow-up should be biannual until resolution.
3. Pubertal gynecomastia has a favorable prognosis with spontaneous complete or partial resolution.
4. Discontinuation or conversion of the inciting drug is recommended in drug-induced gynecomastia.
5. For selected cases of persistent gynecomastia that is causing substantial tenderness or embarrassment, medications and/or surgical intervention may be considered.
6. Drug therapy with tamoxifen may be considered at an early stage, usually for limited time (3-6 months).
7. For gynecomastia persisting >1 year, surgical excision is the treatment of choice, as it is less likely to regress spontaneously.