Oral oestrogen replacement therapy versus placebo for hot flushes

Hot flushes and night sweats are common symptoms experienced by menopausal women. Hormone replacement therapy (HRT), containing oestrogens alone or oestrogens together with progestogens in a cyclic or continuous regimen, is often recommended for their alleviation.

To examine the effect of oral HRT compared to placebo on these vasomotor symptoms and the risk of early onset side-effects.

As developed by the Menstrual Disorders Group and Subfertility group of the Cochrane Collaboration.

Double-blind, randomised, placebo-controlled trials of oral HRT therapy for at least three months duration.

Study quality and outcome data were assessed independently. Random effects models were considered appropriate due to the variety of trial methodologies. The meta-analyses were explored for sensitivity to trial quality and therapy duration. Symptom frequency and severity were assessed separately, together with withdrawals and side-effects. Frequency data were analysed using the Weighted Mean Difference (WMD) between treatment and placebo outcomes. For severity data, odds ratios were estimated from the proportional odds model. From 99 references originally identified, 21 trials meeting the selection criteria were included in the review. Study participants totalled 2,511. Trial duration ranged from three months to three years.

There was a significant reduction in the weekly hot flush frequency for HRT compared to placebo (WMD -17.46, 95% CI -24.72, -10.21). This was equivalent to a 77% reduction in frequency (95% CI 58.2, 87.5) for HRT relative to placebo. Symptom severity was also significantly reduced compared to placebo (OR 0.13, 95% CI 0.08, 0.22). Withdrawal for lack of efficacy occurred significantly more often on placebo therapy (OR 17.25, 95% CI 8.23, 36.15). Withdrawal for adverse events, commonly breast tenderness, oedema, joint pain and psychological symptoms, was not significantly increased for HRT therapy (OR 1.38, 95% CI 0.87, 2.21). In women who were randomised to placebo treatment, a 50.8% (95% CI 41.7, 58.5) reduction in hot flushes was observed between baseline and end of study.

Oral HRT is highly effective in alleviating hot flushes and night sweats. Therapies purported to reduce such symptoms must be assessed in blinded trials against a placebo or a validated therapy. Withdrawals due to side-effects were only marginally increased in the HRT groups despite the inability to tailor HRT in these fixed dose trials. Comparisons of hormonal doses, product types or regimens require analysis of trials with these specific "within study" comparisons.