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Research Shows Nonhormonal Therapies Reduce Hot Flash Frequency But With Possible Adverse Side Effects

An Oregon Health & Science University and Providence Health System researcher has found that some antidepressants, blood pressure and anti-seizure medications offer relief to women with menopausal hot flashes but also have possible adverse effects. An analysis of trials of these drugs indicate that they reduce the frequency of hot flashes, but less so than estrogen. Isoflavones from soy and red clover, however, were not found to be effective. The study will be published in the May 3 issue of the Journal of American Medical Association.


 "Menopausal hot flashes are very individualized experiences for women. Our analysis of published trials suggests that there are some options for women with frequent hot flashes to consider. For women who can not take estrogen, such as women with breast cancer, or a history of breast cancer or blood clots, these medicines may be effective alternatives," said Heidi D. Nelson, M.D., M.P.H., principal investigator and researcher at the Oregon Evidence-based Practice Center based at Oregon Health & Science University. Nelson is also a professor of medicine, (medical informatics and clinical epidemiology, and general internal medicine and geriatrics), OHSU School of Medicine; and medical director of Providence Women and Children's Program and Providence Women and Children's Health Research Center.

Many women enrolled in the trials had five or more hot flashes a day. The study found that using some antidepressants and hypertensive blood pressure medicine resulted in approximately one fewer hot flash a day; antiseizure medicine eliminated about two hot flashes a day; and red clover or soy did not prove to be effective. The most common adverse side effects for some women using antidepressants included: headache, nausea, sleep disturbances, dry mouth, decreased appetite, dizziness. Blood pressure medication included: dry mouth, sleep disturbances, headache, constipation. And on the antiseizure medication included sleepiness and fatigue.

Hot flashes are the most common - and often the most annoying - symptom women suffer as they go through menopause. More than 50 percent of menopausal women experience hot flashes, or flushes, often for several years. A hot flash is a sudden feeling of warmth often associated with perspiration, palpitations and anxiety. It is associated with declining estrogen production.

Nelson worked with eight co-investigators at the Oregon Evidence-based Practice Center. They examined 4,249 abstracts with 43 trials meeting the study criteria, including 10 trials of antidepressants, 10 trials of clonidine (high blood pressure medicine), six trials of other medications and 17 trials of isoflavone extracts from red clover and soy.

Nelson said that there needs to be more studies of nonhormonal therapies for menopausal hot flashes. Few well-designed trials are currently available, and they are generally small, of short duration, and may not apply to women in the community. Many potential therapies have not been studied, or have been inadequately studied.

The methods of this study were similar to the Oregon Evidence-based Practice Center estrogen study by Nelson in 2004. This analysis of estrogen trials indicated an overall reduction of 2.5 to 3 fewer hot flashes per day. Estrogen is still approved for treatment of some menopausal symptoms and clinicians are advised to use the lowest effective dose for a limited time.

The study was funded by the National Institutes of Health Office of Medical Applications of Research through the Agency for Healthcare Research and Quality Evidence-based Practice Centers program. The Oregon Evidence-based Practice Center (EPC) is funded by the Agency for Healthcare Research and Quality (AHRQ) to provide systematic evidence reviews on health care topics related to screening and prevention services.


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