Strategies for managing hot flashes

A meta-analysis published in 2009 that included 4 RCTs reported significant heterogeneity from one study to another, but comparisons of gabapentin and placebo showed reductions of 20% to 30% in the frequency and severity of hot flashes with gabapentin.³⁶ The most commonly reported adverse effects included somnolence, dizziness, ataxia, fatigue, nystagmus, and peripheral edema.

Clonidine
Clonidine has been studied in oral and transdermal forms for the treatment of hot flashes in menopausal women, especially in women with breast cancer.^37-39 Data from one meta-analysis revealed significant reductions in daily hot flashes in the clonidine group compared with placebo at 4 weeks (mean difference [MD]=-0.95; 95% CI, -1.44 to -0.47) and at 8 weeks (MD=-1.63; 95% CI, -2.76 to -0.50).³⁰ Adverse effects included dry mouth, drowsiness, and dizziness. The transdermal route may avoid some of these side effects.⁴⁰

Alternative remedies

Phytoestrogen and isoflavones. Phytoestrogens are sterol molecules produced by plants. They are similar in structure to human estrogens and have been shown to have estrogen-like activity.⁴⁰ They are available as dietary soy, soy extract, and red clover extracts. Isoflavones are a type of phytoestrogen.

Comparing trials of effects of soy or isoflavone is difficult, as various formulations and amounts of these products have been used. Combining the data from these trials yielded nonsignificant results for Promensil, a red clover extract (WMD=-0.6; 95% CI, -1.8 to 0.6), and inconsistent results (sometimes favoring the intervention, other times the placebo) for soy food and soy extracts.^41-43

There is no evidence of estrogenic stimulation of the endometrium with phytoestrogens used for up to 2 years.⁴¹ Nevertheless, in the absence of evidence on the safety of long-term use, women with a personal or strong family history of hormone-dependent cancers (breast, uterine, or ovarian) or thromboembolic events should be cautious about using soy-based therapies.⁴² Long-term safety of these products has to be established before any evidence-based recommendations can be made.

Black cohosh. Actaea racemosa (formerly Cimicifuga racemosa) is the most studied and perhaps the most widely used herbal remedy for hot flashes. It is commonly known as black cohosh and has been used traditionally by Native Americans for the treatment of various medical conditions, including amenorrhea and menopause.^44,45

Remifemin is an available standardized extract. Evidence for effectiveness is limited and contradictory. Data from a recent meta-analysis showed that although there was significant heterogeneity between included trials, preparations containing black cohosh improved vasomotor symptoms overall by 26% (95% CI, 11%-40%).⁴⁵

A recent well-conducted RCT concluded that neither black cohosh nor red clover significantly reduced the frequency of symptoms compared with placebo.⁴⁶ The same study found that both botanicals were safe as administered for a 12-month period. Some case reports have identified serious adverse events including acute hepatocellular damage, which warrants further investigation, although no causal relationship has been established.⁴⁷

Evidence for safety and efficacy of antidepressants, gabapentin, clonidine, isoflavones, black cohosh, yoga, acupuncture, and herbal remedies is summarized in TABLE 2.^{30,36,41,47-55}

For more on the treatment of hot flashes, see “Clinical approach to managing hot flashes”.⁴⁰