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Which nonhormonal treatments are effective for hot flashes?
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).
EVIDENCE SUMMARY
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).
Phytoestrogens: The jury is still out
A meta-analysis of 43 RCTs (4364 patients) evaluated phytoestrogens that included dietary soy, soy extracts, red clover extracts, genistein extracts, and other types of phytoestrogens.3 The data from the only 5 RCTs (300 patients) that could be combined showed no effect from red clover extract on hot flash frequency. However, another 4 individual trials that couldn’t be combined each found that extracts with high levels of the phytoestrogen genistein (>30 mg/d) did reduce frequency. Investigators reported that many of the trials were small and had a high risk of bias.
A meta-analysis of 16 RCTs (2027 patients) that assessed black cohosh found that it didn’t reduce hot flash frequency (3 RCTs, 393 patients) or symptom severity scores (4 RCTs, 357 patients).4 Investigators reported high heterogeneity and recommended further research.
Nonpharmacologic therapies and vitamin E don’t help
Systematic reviews found that relaxation therapy (4 RCTs, 281 patients), exercise (3 RCTs, 454 patients), and acupuncture (8 RCTs, 414 patients) didn’t reduce hot flashes.5-7 In another review, vitamin E (1 RCT, 105 patients), homeopathy (2 RCTs, 124 patients), and magnetic devices (1 RCT, 11 patients) also produced no benefit.1
1. Rada G, Capurro D, Pantoja T, et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev. 2010;(9):CD004923.
2. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies of menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295:2057-2071.
3. Lethaby A, Marjoribanks J, Kronenberg F, et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;(12):CD001395.
4. Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev. 2012;(9):CD007244.
5. Saensak S, Vutyavanich T, Somboonporn W, et al. Relaxation for perimenopausal and postmenopausal symptoms. Cochrane Database Syst Rev. 2014;(7):CD008582.
6. Daley A, Stokes-Lampard H, Thomas A, et al. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev. 2014:(11):CD006108.
7. Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flashes. Cochrane Database Syst Rev. 2013;(7):CD007410.
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).
EVIDENCE SUMMARY
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).
Phytoestrogens: The jury is still out
A meta-analysis of 43 RCTs (4364 patients) evaluated phytoestrogens that included dietary soy, soy extracts, red clover extracts, genistein extracts, and other types of phytoestrogens.3 The data from the only 5 RCTs (300 patients) that could be combined showed no effect from red clover extract on hot flash frequency. However, another 4 individual trials that couldn’t be combined each found that extracts with high levels of the phytoestrogen genistein (>30 mg/d) did reduce frequency. Investigators reported that many of the trials were small and had a high risk of bias.
A meta-analysis of 16 RCTs (2027 patients) that assessed black cohosh found that it didn’t reduce hot flash frequency (3 RCTs, 393 patients) or symptom severity scores (4 RCTs, 357 patients).4 Investigators reported high heterogeneity and recommended further research.
Nonpharmacologic therapies and vitamin E don’t help
Systematic reviews found that relaxation therapy (4 RCTs, 281 patients), exercise (3 RCTs, 454 patients), and acupuncture (8 RCTs, 414 patients) didn’t reduce hot flashes.5-7 In another review, vitamin E (1 RCT, 105 patients), homeopathy (2 RCTs, 124 patients), and magnetic devices (1 RCT, 11 patients) also produced no benefit.1
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).
EVIDENCE SUMMARY
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).
Phytoestrogens: The jury is still out
A meta-analysis of 43 RCTs (4364 patients) evaluated phytoestrogens that included dietary soy, soy extracts, red clover extracts, genistein extracts, and other types of phytoestrogens.3 The data from the only 5 RCTs (300 patients) that could be combined showed no effect from red clover extract on hot flash frequency. However, another 4 individual trials that couldn’t be combined each found that extracts with high levels of the phytoestrogen genistein (>30 mg/d) did reduce frequency. Investigators reported that many of the trials were small and had a high risk of bias.
A meta-analysis of 16 RCTs (2027 patients) that assessed black cohosh found that it didn’t reduce hot flash frequency (3 RCTs, 393 patients) or symptom severity scores (4 RCTs, 357 patients).4 Investigators reported high heterogeneity and recommended further research.
Nonpharmacologic therapies and vitamin E don’t help
Systematic reviews found that relaxation therapy (4 RCTs, 281 patients), exercise (3 RCTs, 454 patients), and acupuncture (8 RCTs, 414 patients) didn’t reduce hot flashes.5-7 In another review, vitamin E (1 RCT, 105 patients), homeopathy (2 RCTs, 124 patients), and magnetic devices (1 RCT, 11 patients) also produced no benefit.1
1. Rada G, Capurro D, Pantoja T, et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev. 2010;(9):CD004923.
2. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies of menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295:2057-2071.
3. Lethaby A, Marjoribanks J, Kronenberg F, et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;(12):CD001395.
4. Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev. 2012;(9):CD007244.
5. Saensak S, Vutyavanich T, Somboonporn W, et al. Relaxation for perimenopausal and postmenopausal symptoms. Cochrane Database Syst Rev. 2014;(7):CD008582.
6. Daley A, Stokes-Lampard H, Thomas A, et al. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev. 2014:(11):CD006108.
7. Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flashes. Cochrane Database Syst Rev. 2013;(7):CD007410.
1. Rada G, Capurro D, Pantoja T, et al. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev. 2010;(9):CD004923.
2. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies of menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295:2057-2071.
3. Lethaby A, Marjoribanks J, Kronenberg F, et al. Phytoestrogens for menopausal vasomotor symptoms. Cochrane Database Syst Rev. 2013;(12):CD001395.
4. Leach MJ, Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane Database Syst Rev. 2012;(9):CD007244.
5. Saensak S, Vutyavanich T, Somboonporn W, et al. Relaxation for perimenopausal and postmenopausal symptoms. Cochrane Database Syst Rev. 2014;(7):CD008582.
6. Daley A, Stokes-Lampard H, Thomas A, et al. Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev. 2014:(11):CD006108.
7. Dodin S, Blanchet C, Marc I, et al. Acupuncture for menopausal hot flashes. Cochrane Database Syst Rev. 2013;(7):CD007410.
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