Strategies for managing hot flashes
Hormone therapy—at the lowest possible dose for the shortest period of time—remains the best option for menopausal women with moderate to severe vasomotor symptoms.
In subsequent studies, the magnitude of the associated risk was substantially greater for the estrogen-progestogen preparation, and also higher for longer-term exposure.13 Additionally, a meta-analysis of 8 studies of the risk of breast cancer with combination HT resulted in an odds ratio (OR) of 1.39 (95% CI, 1.12-1.72). Estimates were higher for more than 5 years of use (OR=1.63; 95% CI, 1.22-2.18) when compared with estimates for less than 5 years of use (OR=1.35; CI, 1.16-1.57).14 Recent studies have reported a decline in the incidence of breast cancer in the United States, which has been attributed to a parallel reduction in HT use.15
In contrast to the findings for women taking combination HT, the estrogen-only arm of the WHI study showed a decrease in the overall risk of breast cancer.16 A new analysis of data on participants in the estrogen-only arm of the study shows that, 10 years after the intervention ended, a decreased risk of breast cancer persists. In addition, the increased risk of stroke and deep vein thrombosis found in the original study had dissipated, and the decreased risk of hip fracture was not maintained.
Age matters. Health outcomes in this new analysis were more favorable for younger women for coronary heart disease, heart attack, colorectal cancer, total mortality, and a global index of chronic diseases.17 Pooled results of systematic reviews and meta-analyses on HT risks are available in TABLE 1.14,16,18-21
Progestins
Progesterone in the form of injections (Depo-Provera 150 mg, for example) or oral medroxyprogesterone acetate 20 mg daily has shown a significant reduction in hot flashes compared with placebo.22 However, associated side effects (withdrawal bleeding and weight gain) and concerns about breast cancer often limit the use of this medication.23 Because of the paucity of evidence, transdermal progesterone creams should not be recommended.24
Tibolone
Tibolone is a synthetic steroid that is structurally related to 19-nortestosterone derivatives. It has weak estrogenic, progestogenic, and androgenic properties and has shown significant reduction in hot flashes and night sweating compared with placebo.25 Tibolone has also been shown to enhance mood and sexual function.26 However, evidence of its safety on outcomes such as breast cancer and cardiovascular events is obscure and has shown conflicting results, especially for breast cancer.25,26
A recent double-blinded trial on women with breast cancer found that although tibolone significantly improved vasomotor symptoms, it was associated with an increased risk of breast cancer recurrence (HR=1.40; 95% CI, 1.14-1.70]; P=.001).27 Tibolone is not approved for sale in the United States.
Nonhormonal options
Lifestyle modifications
According to recent reviews, exercise is less effective than HT in relieving hot flashes, but does seems to have beneficial effects on mood, sleep, and overall quality of life.28,29 Other lifestyle modifications such as smoking cessation and weight loss may also be of use.5
Antidepressants
Data from one meta-analysis showed that selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) were significantly more effective than placebo in reducing daily frequency of hot flashes (WMD=-1.13; 95% CI, -1.70 to -0.57).30 Efficacy varied for individual drugs.
Venlafaxine, an SNRI, has been shown to be more effective than placebo in managing hot flashes.31 The effect on hot flashes was noticed after 4 weeks of treatment with the 75- and 150-mg doses, but the higher dosage was associated with more adverse effects such as dry mouth, sleeplessness, and decreased appetite.32 Even so, 93% of the participants in the venlafaxine group chose to continue treatment, because the reduction in hot flashes had significantly improved their daily lives.31 Desvenlafaxine, a metabolite of venlafaxine, has been shown to reduce the number of hot flashes by almost 65% from baseline at Weeks 4 and 12, with dosages of 100 and 150 mg/d.33
The SSRIs fluoxetine, citalopram, and paroxetine in 10-, 20-, and 30-mg doses and paroxetine CR (12.5 and 25 mg) have been studied in many RCTs. All have demonstrated a significant decrease in hot flashes compared with placebo with various dosages used. SSRIs reduce hot flashes by as much as 50% to 60%, compared with 80% for estrogen.34 The duration of treatment ranged from 4 weeks to 6 months.
Gabapentin
Gabapentin is approved by the FDA for the treatment of partial seizures and postherpetic neuralgia.35 A meta-analysis of multiple studies published in 2006 showed that gabapentin reduced the mean number of daily hot flashes by 2.05 (95% CI, -2.80 to -1.30).30 Two recent reviews evaluated the efficacy and safety of gabapentin in the treatment of hot flashes in menopausal women and reported that gabapentin in daily doses ranging from 900 to 2400 mg and titration periods lasting 3 to12 days was well tolerated and effective.35,36
