Hormone replacement therapy is recommended for patients with hot flushes and night sweats, when pharmacological treatment is needed and who do not have contraindications. Discontinuing of treatment as early as symptoms allow is recommended for preventing long-term adverse effects.
The recommendation is strong because of large effect size on patient-important outcomes: hot flushes and night sweats may deteriorate sleep and working ability and strongly decrease quality of life.
A Cochrane review [Abstract] 1 included 24 studies with a total of 3 329 subjects. There was a significant reduction in the weekly hot flush frequency for hormone replacement therapy (HRT) compared to placebo (WMD -17.92, 95% CI -22.86 to -12.99). This was equivalent to a 75% reduction in frequency (95% CI 64.3 to 82.3). Symptom severity was also significantly reduced compared to placebo (OR 0.13, 95% CI 0.07 to 0.23). Withdrawal for lack of efficacy occurred significantly more often on placebo therapy (OR 10.51, 95% CI 5.00 to 22.09). Withdrawal for adverse effects (breast tenderness, oedema, joint pain and psychological symptoms) was not significantly increased (OR 1.25, 95% CI 0.83 to 1.90), although the occurrence of any adverse events was significantly increased for HT (OR 1.41, 95% CI 1.00 to 1.99). In women who were randomised to placebo treatment, a 57.7% (95% CI 45.1 to 67.7) reduction in hot flushes was observed between baseline and end of study.
Another Cochrane review [Abstract] 2 included 23 studies with a total of 5 779 subjects mostly with moderate to severe hot flushes. All studies compared unopposed 17 beta-estradiol (beta-estradiol, a bioidentical hormone) versus placebo or conjugated equine estrogens (CEE). Beta-estradiol in various forms and doses was more effective than placebo for treating moderate to severe menopausal hot flushes (table T1). Higher doses of beta-estradiol tended to be associated with greater effectiveness but also with higher risk of adverse effects. There was no good evidence of a difference in effectiveness between beta-estradiol and 0.625 mg conjugated equine estrogens, but the data were unsuitable for analysis (2 trials of patch versus CEE and 1 trial of oral beta-estradiol versus CEE).
| Outcome: Frequency of hot flushes Form of beta-estradiol | Anticipated absolute effects (95% CI) | №of participants (studies) |
|---|---|---|
| Patch 0.0375-0.10 mg/day | Fewer hot flushes in the beta-estradiol group. Effect size moderate: SMD -0.68, 95% CI -0.83 to -0.53 | 793 (4) |
| Gel 0.27-1.5 mg/day | Data unsuitable for analysis reported a benefit in the beta-estradiol gel group (P value < 0.05) | 930 (3) |
| Oral 0.5-1.0 mg/day | Fewer hot flushes in the beta-estradiol group. Effect size moderate: SMD -0.80, 95% CI -1.03 to -0.57 | 356 (2) |
| Intranasal 0.021 mg/day, 0.029 mg/day or 0.040 mg/day | The mean rate of hot flushes per day was lower in the beta-estradiol group: MD - 3.04, 95% CI -4.05 to -2.03 | 458 (1) |
A controlled trial 3 randomized 727 women, aged 42 to 58, within 3 years of their final menstrual period, to receive oral conjugated estrogens (o-E) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Moderate to severe hot flashes (from 44% at baseline to 28.3% for placebo, 7.4% for t-E2, and 4.2% for o-E) and night sweats (from 35% at baseline to 19% for placebo, 5.3% for t-E2, and 4.7% for o-E) were reduced significantly by 6 months in women randomized to either active hormone compared with placebo (P < 0.001 for both symtoms). Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus placebo, with o-E being more effective than placebo at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than placebo at 48 months (P = 0.004).
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