The very limited data available do not indicate an increased risk of breast cancer recurrence with single-agent estrogen use in patients with a history of breast cancer.[17,18] A series of double-blind placebo-controlled trials suggests that low-dose megestrol acetate (i.e., 20 mg by mouth twice a day) and selective serotonin reuptake inhibitors (SSRIs) are among the more promising agents for hot flash management in this population. Limited data suggest that brief cycles of intramuscular depot medroxyprogesterone acetate also play a role in the management of hot flashes.[Level of evidence: I] Risk associated with progestin use is unknown.
Other pharmacologic interventions
Numerous nonestrogenic, pharmacologic treatment interventions for hot flash management in women with a history of breast cancer and in some men who have undergone androgen deprivation therapy have been evaluated. Options with reported efficacy include androgens, progestational agents, gabapentin, SSRIs, selective serotonin norepinephrine inhibitors, alpha adrenergic agonists (e.g., methyldopa, clonidine), beta-blockers, and veralipride (an antidopaminergic agent). Inferior efficacy, lack of large definitive studies, and potential side effects limit the use of many of these agents.[20,21,22][Level of evidence: I]
Agents that have been found to be helpful in large, randomized, placebo-controlled clinical trials include venlafaxine, paroxetine, citalopram, fluoxetine, gabapentin, pregabalin, and clonidine.[20,21,22] These agents demonstrate a 40% to 60% reduction in hot flash frequency and score (a measure combining severity and frequency). Agents conferring a 55% to 60% reduction in hot flashes are venlafaxine extended release, 75 mg daily; paroxetine, 12.5 mg controlled release  or 10 mg daily; gabapentin, 300 mg tid;[27,28][Level of evidence: I];[Level of evidence: II] and pregabalin, 75 mg bid.[Level of evidence: I] Other effective agents resulting in about a 50% reduction in hot flashes include citalopram, 10 to 20 mg per day, which was studied in clinical trial NCCTG-N05C9;[Level of evidence: I] and fluoxetine, 20 mg per day. Clonidine, 0.1 mg transdermal  or oral daily,[Level of evidence: I] can reduce hot flashes by about 40%.