Some nonhormonal therapies may offer relief from hot flashes, but with possible adverse effects

A meta-analysis of previously published studies examining the use of nonhormonal therapies for treating menopausal hot flashes finds that some therapies are effective, but less so than estrogen, and have possible adverse effects that may restrict their use, according to an article in the May 3 issue of JAMA.

Hot flashes are the most common symptom related to menopausal transition. They are experienced by more than 50 percent of menopausal women, can persist for several years after menopause, and for some women can interfere with activities or sleep to such a degree that treatment is requested, according to background information in the article. Estrogen has been used as a hormone supplement for nearly 60 years to treat menopausal symptoms. However, recent studies reporting adverse effects such as cardiovascular events and breast cancer have raised important concerns about its use and have led to increased interest in other therapies for improving menopausal symptoms. Evidence of the efficacy and adverse effects of nonhormonal therapies is generally lacking or unclear.

Heidi D. Nelson, M.D., M.P.H., of the Oregon Health and Science University and Providence Health System, Portland, Ore., and colleagues conducted a meta-analysis of randomized controlled trials to compare the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes. The researchers identified 43 relevant trials, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts.

The researchers found: "This systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of nonhormonal therapies provides supportive evidence for the efficacy of selective serotonin reuptake inhibitors (SSRIs) or serotonin noradrenergic reuptake inhibitors (SNRIs) [such as paroxetine, venlafaxine, fluoxetine and citalopram], clonidine, and gabapentin in reducing the frequency and severity of menopausal hot flashes based on a small number of fair and good [quality] trials (SSRIs or SNRIs and gabapentin) or poor and fair [quality] trials (clonidine). The trials do not support the efficacy of red clover isoflavone extracts and present mixed results for soy isoflavone extracts. Evidence for other therapies is limited due to the small number of trials and their deficiencies. Few trials compare different therapies head-to-head and relative efficacy cannot be determined."

"Despite increasing interest in therapies for menopausal hot flashes that avoid use of estrogen, the efficacy and safety of other options currently are not well supported. The SSRIs or SNRIs, clonidine, and gabapentin provide some evidence of efficacy. However, effects are less than those for estrogen therapy, few trials have been published and most have methodological deficiencies, and generalizability beyond the small clinical populations studied could be limited. Adverse effects and cost may prohibit use for many women. Although these therapies may be most useful for highly symptomatic women who cannot take estrogen, they are not optimal choices for most women," the authors conclude.

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(JAMA. 2006;295:2057-2071. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: For funding/support and financial disclosure information, please see the JAMA article.

Editorial: Alternatives to Estrogen for Treatment of Hot Flashes - Are They Effective and Safe?

In an accompanying editorial, Jeffrey A. Tice, M.D., and Deborah Grady, M.D., M.P.H., of the University of California, San Francisco, discuss the findings of Nelson et al.

"Women with hot flashes should understand that most symptoms resolve over several months to several years. Those women with mild symptoms may find adequate relief by wearing layered clothing and keeping the home and bedroom cool. For women with more bothersome symptoms, clinicians should understand the advantages and disadvantages of both hormone therapy and nonhormonal alternatives. Hormone therapy is more effective than nonhormonal alternatives but should probably be avoided by women at high risk for venous thromboembolic events, cardiovascular disease, and breast cancer. Nonhormonal alternatives are less effective than estrogen, generally have more symptomatic adverse effects, and long-term adverse effects are not as well documented. With all medicines or dietary supplements used for symptomatic treatment, the lowest effective dose should be used and stopped as soon as symptoms improve or resolve. A better understanding of the pathophysiology of hot flashes will likely be necessary for the development of nonhormonal therapies that equal or surpass the efficacy of hormones."

(JAMA. 2006;295:2076-2078. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: For financial disclosure information, please see the JAMA article.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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