A Cochrane review 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 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 ). 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) |