Male Breast Enlargement in Patients With HIV/AIDS
from The AIDS Reader ®
Initiation of early treatment (Table 3) is important. If gynecomastia is present for more than 1 year, glandular tissue will be replaced by fibrosis, rendering medical therapy unsuccessful. A rapid and complete resolution of gynecomastia can be expected if treatment of the underlying cause is started early. When medical treatment is unlikely to be successful, surgery remains an option.
The identification and removal of the causative agent is the main-stay of treatment for medication-associated gynecomastia. Antiretroviral therapy-associated gynecomastia may resolve when all or a part of the antiretroviral combination is switched.[4,6,7] For instance, switching current treatment with ritonavir to nelfinavir and switching ritonavir and lamivudine to didanosine and efavirenz led to complete resolution of true gynecomastia in 2 patients. In addition, Donovan and colleagues reported 4 cases of gynecomastia associated with saquinavir therapy. In 3 of these cases, switching saquinavir to nevirapine led to a complete resolution of the gynecomastia. However, switching the PI component of HAART may not always be successful. In one study, switching zidovudine, lamivudine, and nelfinavir to stavudine, didanosine, and nevirapine did not result in a resolution of the gynecomastia. Clearly, in the cases where gynecomastia is associated with PI-containing HAART, it is prudent to switch the PI for a nonnucleoside reverse transcriptase inhibitor (NNRTI). When the gynecomastia is associated with an NNRTI-containing regimen, switching to abacavir may be an option.
Both androgens (particularly, danazol) and antiestrogens (namely, tamoxifen) have been used in the management of idiopathic gynecomastia. In a recent analysis, Ting and associates compared the efficacy of these 2 agents. Tamoxifen, 20 mg once daily, resulted in complete resolution of breast masses in 78% of patients; danazol, 400 mg once daily, in 40%, although the relapse rate was higher for tamoxifen.
However, tamoxifen has many metabolites, and some of these have estrogen agonist activity. This probably explains its side effects, especially its prothrombotic nature, and may explain its lack of ability to maintain resolution of gynecomastia. Newer and purer antiestrogens with little or no agonist activity are currently being developed.
Aromatization of androgens to estrogen in peripheral tissue, as mentioned earlier, has been noted to play a role in the development of gynecomastia. Delta1-Testolactone was one of the earliest aromatase inhibitors to be developed and used. Given at a dosage of 450 mg once daily for 2 to 6 months to pubertal patients, Delta1-testolactone was associated with breast glandular tissue softening and a decrease in breast diameter.
The triazoles anastrozole and letrozole and the steroid exemestane are newer potent aromatase inhibitors. These can substantially inhibit in situ aromatase by more than 95% without significant effects on other endocrine pathways and are known to have a relatively good side-effect profile. The role of these newer agents has yet to be evaluated in the management of idiopathic gynecomastia, and they may prove to be of great benefit in HIV-associated gynecomastia.
Prophylactic breast bud irradiation has long been used in the management of patients with metastatic carcinoma of the prostate before the commencement of diethylstilbestrol therapy. Its place in the treatment of gynecomastia in HIV disease is not known, and the potential for carcinogenesis in breast tissue that was previously benign should not be disregarded.
Surgery is the last line of therapy in benign gynecomastia. Circumareolar breast reduction is the surgical method of choice. The indications for surgical intervention are:
Progression despite medical intervention.
Suspected underlying malignancy.
Clearly, excluding medical and often reversible causes is important in the treatment of gynecomastia. However, once true gynecomastia has been ascribed to HAART, switching antiretroviral therapy appears to be the most promising treatment strategy. One must bear in mind, however, that many cases do resolve spontaneously; so, it is important not to be too hasty with regimen change, because this has implications for resistance and future treatment options. Furthermore, some patients may be on salvage regimens with few therapeutic alternatives; in these cases, antiestrogens or aromatase inhibitors may be an option.