[Adam F]

MEDICAL TREATMENT
If the gynecomastia is severe, does not resolve, and does not have a treatable underlying cause, some medical therapies may be attempted.

There are 3 classes of medical treatment for gynecomastia: androgens (testosterone, dihydrotestosterone, danazol), anti-estrogens (clomiphene citrate, tamoxifen) and aromatase inhibitors such as testolactone.

Testosterone treatment of hypogonadal men with gynecomastia often fails to produce breast regression once gynecomastia is established. Unfortunately, testosterone treatment may actually produce the side effect of gynecomastia by being aromatized to estradiol. Thus, although testosterone is used to treat hypogonadism, its use to specifically counteract gynecomastia is limited.

Dihydrotestosterone, a non-aromatizable androgen, has been used in patients with prolonged pubertal gynecomastia with good response rates. Since dihydrotestosterone is given either intramuscularly or percutaneously, this may restrict its usefulness.

Danazol, a weak androgen that inhibits gonadotropin secretion, resulting in decreased serum testosterone levels, has been studied in a prospective placebo-controlled trial, whereby gynecomastia resolved in 23 percent of the patients, as opposed to 12 percent of the patients on placebo. Unfortunately, undesirable side effects including edema, acne, and cramps have limited its use.

Investigators have reported a 64 percent response rate with 100 mg/day of clomiphene citrate, a weak estrogen and moderate antiestrogen. Lower doses of clomiphene have shown varied results, indicating that higher doses may need to be administered, if clomiphene is to be attempted.

Tamoxifen, also an antiestrogen, has been studied in 2 randomized, double-blind studies in which a statistically significant regression in breast size was achieved, although complete regression was not documented.

One study compared tamoxifen with danazol in the treatment of gynecomastia. Although patients taking tamoxifen had a greater response with complete resolution in 78 percent of patients treated with tamoxifen, as compared to only a 40 percent response in the danazol-treated group, the relapse rate was higher for the tamoxifen group.

Although complete breast regression may not be achieved and a chance of recurrence exists with therapy, tamoxifen, due to relatively lower side effect profile, may be a more reasonable choice when compared to the other therapies. If used, tamoxifen should be given at a dose of 10 mg twice a day for at least 3 months.

An aromatase inhibitor, testolactone, has also been studied in an uncontrolled trial with promising effects. Further studies must be performed on this drug before any recommendations can be established on its usefulness in the treatment of gynecomastia.

Newer aromatase inhibitors such as anastrozole and letrozole may have therapeutic potential but no study has been published to confirm its efficacy in treatment of gynecomastia.