Hot flushes, which affect approximately 75 percent of postmenopausal women, usually start one to two years before menopause and can persist for six months to five years. Shanafelt and colleagues reviewed the pathophysiology of and treatment options for hot flushes.

Multiple placebo-controlled trials have demonstrated a reduction of about 25 percent in hot flushes after four weeks of placebo treatment. Studies have shown that estrogen has an even greater effect on vasomotor symptoms, relieving them by about 80 to 90 percent. The Women's Health Initiative demonstrated that long-term hormone replacement therapy had positive effects on women's bones but also put women at an increased risk of venous thromboembolic disease, breast cancer, stroke, and coronary artery disease.

Megestrol acetate, a progestational agent, was found to reduce hot flushes by 75 to 80 percent in a double-blind, placebo-controlled, crossover study of 97 women with a history of breast cancer and 66 men receiving androgen ablation therapy for prostate cancer. Currently, a large phase-3 trial of depomedroxyprogesterone acetate, a long-acting intramuscular progestin, is being conducted to confirm its role as a therapeutic option for hot flushes.

Transdermal progesterone cream has demonstrated improvement in the treatment of hot flushes when compared with placebo. Smaller trials of androgens including danazol and estrogen combined with methyltestosterone have shown that they successfully treat hot flushes, but larger trials are needed to confirm these results. The authors discuss five studies of soy proteins that produced mixed results, suggesting that evidence of a substantial benefit is currently lacking. A study of 191 patients showed that venlafaxine produced an improvement of up to 61 percent in hot flushes compared with placebo.

A study of fluoxetine showed a 50 percent reduction in hot flushes, while the placebo group had a 36 percent reduction. Pilot studies of paroxetine and gabapentin were promising, and randomized controlled trials of these drugs are being conducted. Although clonidine has been shown to moderately decrease hot flushes, adverse effects (such as mouth dryness, constipation, drowsiness, and pruritus at the site of the patch) have been reported. Tocopherol (vitamin E) slightly improved vasomotor symptoms in one study and produced no adverse effects. The herbal remedy black cohosh has not been shown to be more effective than placebo in a U.S. study of breast cancer patients; however, studies in Germany suggest that it improves menopausal symptoms. Questions about its potential estrogenic effects remain unanswered. Although a small benefit has been found from the combination of belladonna and phenobarbital, concern over adverse effects and possible addiction problems has limited its use.

The authors conclude that vitamin E is a reasonable therapeutic approach for women with mild symptoms, given its low cost, lack of side effects, and good placebo effect. In patients with severe symptoms, estrogen is recommended, followed by progesterone in patients with a history of breast or uterine cancer. Patients who are unwilling or unable to take hormones can be treated with an anti-depressant such as venlafaxine or fluoxetine.

editor's note: As we continue to discover the risks of hormone replacement therapy, it is important to investigate alternative treatments for vasomotor symptoms. Loprinzi and colleagues' study of gabapentin in 20 women demonstrated a 66 percent reduction in frequency of hot flushes. Although the side effect of dizziness caused four people to drop out of the study, this treatment appears to be promising.—S.M.S.