EVIDENCE-BASED ANSWER
Regular exercise may reduce vasomotor symptoms of menopause (strength of recommendation [SOR]: C—single observational study).1
Soy products/isoflavones, either through diet or supplementation, may reduce the incidence of hot flushes (SOR: D—inconsistent results of randomized trials).2
Clonidine, as an oral or transdermal preparation, reduces hot flushes (SOR: A—randomized clinical trials),3 as does gabapentin (SOR: A— single randomized clinical trial).4
In cancer patients who have had surgical menopause, selective serotonin reuptake inhibitors5 and megestrol6 (Megase) have been effective in reducing hot flushes (SOR: A; B for extrapolation to the general population).
Other therapies—including Bellergal (a combination of belladonna, ergotamine, and phenobarbital), methyldopa, evening primrose oil, mai quan, flaxseed, ginseng, and topical wild yam extract—have not been effective.7 Black cohosh may be effective, but the evidence for this is of poor quality (SOR: C). (See Table.)
TABLE
Nonhormonal therapies for postmenopausal vasomotor symptoms
| Agent | Effective | SOR † | Comments |
|---|---|---|---|
| Soy/isoflavones | Maybe | D | Multiple RCTs with conflicting results, no formal meta-analysis. Does have a positive effect on lipid profile |
| Clonidine (Catapres) | Yes | A | Multiple small RCTs |
| Venlafaxine* (Effexor) | Yes | B | Single RCT |
| Fluoxetine* (Prozac) | Yes | B | Single RCT |
| Gabapentin (Neurontin) | Yes | A | Single RCT |
| Megestrol* (Megace) | Yes | B | Single RCT |
| Exercise | Maybe | C | Single observational study |
| Black cohosh | Maybe | C | German E commission recommenda tion positive in 1989, but only 1 of 7 trials cited had placebo control. Recent RCT showed no benefit |
| Other: Bellergal, methyldopa, evening of effect | No | C | All have been advocated but no positive trials for any evidence primrose oil, ginseng, wild yam extract, mai quan, flaxseed |
| *Trials conducted only with patients with breast cancer and interventional menopause, most of whom were on anti-estrogen therapy. | |||
| †See page 290 for a description of strength of recommendation. | |||
| SOR, strength of recommendation; RCT, randomized controlled trial | |||
Evidence summary
Hormone replacement therapy (HRT) is the standard treatment for vasomotor symptoms of menopause, and it is effective for this indication. With recent studies showing no benefit from long-term HRT for menopausal women and increased adverse effects with its use (especially for women at risk for coronary heart disease), there has been increased interest in nonhormonal treatments for these symptoms.
A small number of randomized clinical trials have studied treatments other than HRT for the control of vasomotor symptoms of menopause. As a group, these trials have been short-term and have involved small numbers of patients. A disproportionate number of trials have been completed in breast cancer survivors, since these patients tend to have more severe vasomotor symptoms as a result of their anti-estrogenic therapies. Whether these results can be generalized to all postmenopausal women with vasomotor symptoms cannot be determined from the evidence.
Eleven randomized trials of soy protein/isoflavone used placebo controls. Results were mixed, with 7 trials showing no effect and 4 showing a reduction in hot flushes in comparison with placebo. Studies reporting a positive effect showed approximately a 15% reduction in episodes in comparison with placebo. In one 6-month trial, there was a correlation between hot flushes and urinary isoflavone excretion regardless of treatment group, suggesting a confounding effect of dietary intake of isoflavone.
Five of six randomized controlled trials of cloni-dine have shown a reduction in frequency of hot flushes ranging from 14%–50% compared with placebo. One trial, which used oral clonidine 0.1 mg daily, also reported an improved quality of life for the treatment group. A single randomized trial has shown that gabapentin, at a dose of 900 mg/day, is effective in reducing both frequency and severity of hot flashes.4
Trials of specific selective serotonin reuptake inhibitors have been completed in patients with vasomotor symptoms secondary to breast cancer therapies. Individual randomized controlled trials of venlafaxine and fluoxetine have proven these agents effective, and a preliminary open-labeled trial of paroxetine has also suggested benefit.
Several reviews suggest black cohosh may be effective for short-term treatment, and it is used in Germany for this indication. The trials we found were not placebo-controlled, however, and the safety of this agent is controversial. A single English-language placebo-controlled trial did not show any benefit for black cohosh.