Clinical Inquiries

Which nonhormonal treatments are effective for hot flashes?

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Selective serotonin reuptake inhibitors (SSRIs [fluoxetine, sertraline, paroxetine]) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine, as well as clonidine and gabapentin, reduce hot flashes by about 25% (approximately one per day) in women with and without a history of breast cancer. No studies compare medications against each other to determine a single best option (strength of recommendation [SOR]: A, systematic reviews and meta-analyses of randomized controlled trials [RCTs]). In comparison, estrogen reduces the frequency of hot flashes by about 75%, or 2.5 to 3 per day.

The phytoestrogens (soy isoflavones, red clover extract, black cohosh), vitamin E, and nonpharmacologic measures (relaxation therapy, exercise, acupuncture, homeopathy, magnet therapy) lack evidence of effectiveness (SOR: A, meta-analyses of RCTs, many of which were low quality).


A systematic review of 6 RCTs that evaluated SSRIs and SNRIs (fluoxetine, sertraline, paroxetine, venlafaxine) found them all to be effective for reducing hot flash frequency and symptom scores in women with previous breast cancer1 (TABLE1,2).

A 2006 meta-analysis combined the results of 7 RCTs (each evaluating a single SSRI [fluoxetine, paroxetine] or SNRI [venlafaxine]) and found that as a group, they reduced mean hot flash frequency (–1.13 hot flashes/d; 95% confidence interval [CI], –1.70 to –0.57) in women with and without breast cancer.2 No trial compared medications head to head, and the populations differed among studies, so that investigators couldn’t determine a single best agent.

Clonidine and gabapentin decrease hot flash frequency

The 2006 meta-analysis also included 10 RCTs (743 patients) that studied clonidine in women with and without a history of breast cancer, and 2 RCTs (479 patients) that evaluated gabapentin in women with breast cancer.2 Both drugs reduced mean hot flash frequency (clonidine: –0.95 hot flashes/d, 95% CI, –1.44 to –0.47 at 4 weeks and –1.63 hot flashes/d, 95% CI, –2.76 to –0.05 at 8 weeks; gabapentin: –2.05 hot flashes/d; 95% CI, −2.80 to –1.30).


Evidence-based answers from the Family Physicians Inquiries Network

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