Nonhormonal therapies may offer some relief from hot flashes, but less so than estrogen, and the side effects and cost of these agents may limit their use, conclude researchers in a report published today.

“These therapies may be most useful for highly symptomatic women who cannot take estrogen, but are not optimal choices for most women,” they write in the Journal of the American Medical Association.

Hot flashes are the most common symptom related to the transition to menopause. Experienced by more than half of menopausal women, hot flashes can persist for several years after menopause, and for some women can interfere with daily activities and sleep.

Concern regarding the adverse effects of estrogen and other hormones for treating hot flashes and other menopausal symptoms has led to a demand for nonhormonal options. However, the efficacy and adverse effects of these therapies remain unclear.

Dr. Heidi D. Nelson from the Oregon Health and Science University in Portland and colleagues pulled together data on 43 trials that evaluated the value of various nonhormonal treatments for hot flashes. They included in their analyses 10 trials of antidepressants, 10 trials of clonidine (a blood pressure drug), 17 trials of isoflavone extracts derived from red clover and soy, and 6 trials of other prescription medications, including the anti-seizure drug gabapentin.

According to the findings, antidepressants reduce hot flashes “by approximately one per day,” Nelson noted in comments to Reuters Health. This was observed for drugs such as such as paroxetine, venlafaxine, fluoxetine and citalopram.

The antihypertensive agent clonidine also reduces hot flashes by about one per day, while the anti-epileptic gabapentin reduces hot flashes by approximately two per day.

“Compared with a similar meta-analysis of estrogen trials, estrogen reduces hot flashes by approximately 2.5 to 3 per day,” Nelson reported. However, isoflavones from red clover and soy sources “are not effective,” she warned.

The most common adverse effects of antidepressants are headache, nausea, insomnia/drowsiness, dry mouth, decreased appetite and dizziness. Side effects of clonidine include dry mouth, insomnia/drowsiness, headache and constipation. Sleepiness and fatigue are the most common side effects of gabapentin. For isoflavones, gastrointestinal symptoms associated with soy are the most frequently seen side effects.

For women with “more bothersome” hot flashes, both hormone therapy and nonhormonal alternatives have advantages and disadvantages, which women should discuss with their doctor, the comment the authors of a related editorial.

While hormone therapy is more effective than nonhormonal alternatives for menopausal symptoms, hormones should probably be avoided by women who have a high risk for blood clots, cardiovascular disease or breast cancer, advise Drs. Jeffrey Tice and Deborah Grady from the University of California, San Francisco.

“Nonhormonal alternatives are less effective than estrogen, generally have more symptomatic adverse effects, and long-term adverse effects are not well documented,” they warn.

SOURCE: Journal of the American Medical Association May 3, 2006.