Obstetrics and gynecology.

Background
Hot flushes and night sweats are common symptoms experienced by menopausal women. Hormone therapy (HT), containing oestrogens alone or oestrogens together with progestogens in a cyclic or continuous regimen, is often recommended for their alleviation.

Objectives
To examine the effect of oral HT compared to placebo on these vasomotor symptoms and the risk of early onset side-effects.

Search methods
We searched the Cochrane Menstrual Disorders Group and Subfertility Group trials register (searched May 2002). This register is based on regular searches of MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, the handsearching of 20 relevant journals and conference proceedings, and searches of several key grey literature sources. We also contacted all relevant pharmaceutical companies, The Journal of the International Menopause Society and Climacteric.

Selection criteria
Double-blind, randomised, placebo-controlled trials of oral HT for at least three months duration.

Data collection and analysis
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 115 references originally identified, 24 trials meeting the selection criteria were included in the review. Study participants totaled 3,329. Trial duration ranged from three months to three years.

Main results
There was a significant reduction in the weekly hot flush frequency for HT 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) for HT relative to placebo. 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 events, commonly 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.

Authors' conclusions
Oral HT 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 because of the large placebo effect seen in well conducted randomised controlled trials, and also because during menopause symptoms may fluctuate and after menopause symptoms often decline. Withdrawals due to side-effects were only marginally increased in the HT groups despite the inability to tailor HT in these fixed dose trials. Comparisons of hormonal doses, product types or regimens require analysis of trials with these specific "within study" comparisons.

Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes

A new methodological approach to the evaluation of quality of life in postmenopausal women.

Objective: To examine the effectiveness of oral hormone replacement therapy (HRT) with regard to hot flushes and night sweats, which are vasomotor symptoms commonly experienced by menopausal women. Methods: Double-blind, randomized, placebo-controlled trials of oral HRT for at least 3 months' duration and reporting vasomotor outcomes were identified using a search strategy developed by the Menstrual Disorders Group and Subfertility Group of the Cochrane Collaboration. Twenty-one trials meeting the selection criteria were included in the review. Study participants totalled 2511. Trial duration ranged from 3 months to 3 years. Results: There was a significant reduction in the weekly hot flush frequency for HRT compared with placebo (weighted mean difference 17.46, 95% confidence interval (CI) 24.72 to 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 with placebo (odds ratio (OR) 0.13, 95% CI 0...

Oral estrogen replacement therapy versus placebo for hot flushes: a systematic review.

Background 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. Objectives To examine the effect of oral HRT compared to placebo on these vasomotor symptoms and the risk of early onset side-effects. Search strategy As developed by the Menstrual Disorders Group and Subfertility group of the Cochrane Collaboration. Selection criteria Double-blind, randomised, placebo-controlled trials of oral HRT therapy for at least three months duration. Data collection and analysis 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. Main results 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. Reviewer's conclusions 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.

Oral oestrogen replacement therapy versus placebo for hot flushes.

Menopausal hot flushes : a double blind comparison of placebo, ethinyl oestradiol and norgestrel

: The aetiology of hollow visceral myopathy remains poorly understood despite the review of histology and is often misdiagnosed. It is characterized by impaired intestinal function and motility in absence of mechanical obstruction, which may be familial (transmitted by a dominant or recessive gene) or sporadic. Familial visceral myopathy is a rare hereditary myopathic degeneration of both gastrointestinal (and urinary tracts) that causes chronic intestinal obstruction. Typically, it presents after the first decade of life with symptoms of abdominal distension, abdominal pain, vomiting, constipation, and diarrhoea. It is, therefore, a rare cause of chronic intestinal pseudo-obstruction. Secondary chronic intestinal pseudo-obstruction is typically managed by treating the underlying condition, however, decompression by colostomy or tube gastrostomy/enterostomy/ caecostomy may be performed; this also allows for feeding and irrigation of the alimentary tract. This case study emphasizes the atypical presentation of hollow visceral myopathy and the importance of thorough investigations, the various findings during surgery (including a para-duodenal volvulus), and the different approaches to decompression of the intestinal tract that may be considered for such a patient.

G. Hyman

Papers

Menopausal hot flushes : a double blind comparison of placebo, ethinyl oestradiol and norgestrel

Case Report Hollow Visceral Myopathy: Diagnosis and Management