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At the heart of general practice since 1960

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Vitamin E was in the news recently amid claims that it can provide relief for painful periods ­

Bandolier editors Dr Andrew Moore and Professor Henry McQuay look at the evidence behind the headlines

We were asked to comment on a media report that vitamin E, which is sold as a nutritional supplement, had proved to be a useful treatment for dysmenorrhoea. A literature search showed at least three randomised trials had been performed over 50 years, so a quick systematic review seemed in order.

The upshot seems to be that this is an effective treatment, with consistent results from three trials.

Our search

The search was confined to PubMed and Cochrane library, and used broad terms of vitamin E and dysmenorrhoea or dysmenorrhea. Abstracts were read and possible randomised trials were obtained and read in detail. For inclusion, studies had to be both randomised and double-blind, investigate vitamin E at any sensible dose or duration of use, in women with primary dysmenorrhoea, and use pain or some related measure as an outcome.

The shortlist

Three studies were found, one from 1955 performed in Cardiff1, and two recent studies from Tehran2,3.

All of them studied young women, for between two and four months, using different doses of vitamin E, for different periods before and during menstruation, and used different measures of pain.

All three studies found menstrual pain was diminished by vitamin E more than placebo, and the two longer studies found that maximum effect occurred by about three months. The two longer studies had dichotomous outcomes, of pain reduction by a useful amount1, or non-use of analgesics3.

Pooling these two showed a highly significant result. A good result occurred in 155/176 (88 per cent) of women on vitamin E and 20/174 (11 per cent) of women on placebo by three or four months. The relative benefit was 7.7 (95 per cent CI 5.1 to 12) and the number needed to treat for one woman to benefit compared with placebo was 1.3 (1.2 to 1.4).

Conclusions and caveats

On the face of it, this looks like a useful result. Well-conducted trials, 50 years apart, in different parts of the world gave similar results. Nor is it just a shade of statistical significance, but a result of large clinical relevance, with benefits to the majority of young women receiving vitamin E. So far, so good. We should note that a fourth tria · 4, using only 1.5mg vitamin E along with lots of fish oils, failed to show any benefit.

There are some caveats, however. First is that none of the studies mentioned adverse events, and that is something that should always be important.

It may be that there were none, but no trial stated there were none. They just failed to mention adverse events. The second caveat is whether vitamin E could be harmful. A meta-analysis of vitamin E supplementation trials indicated a small increase of mortality in people taking vitamin E5. The size of the increase was not great (39 per 10,000 persons), was barely statistically significant, applied only to high-dose studies (400 IU/day or more), used for long periods, and mostly in small studies in older patients with chronic diseases. Other meta-analyses6 using only larger studies found no difference in mortality.

So any move to using vitamin E to treat dysmenorrhoea needs to be cautious, and young women thinking of self-treating should be advised to use small doses for a few days before and during their period, and no longer.

References

1 EB Butler, E McKnight. Vitamin E in the treatment of primary dysmenorrhoea.

Lancet 1955 i: 844-847

2 Ziaei S et al. A randomised placebo-controlled trial to determine the effect of vitamin E in treatment of primary dysmenorrhoea.

British Journal of Obstetrics and Gynaecology 2001 108: 1181-1183

3 Ziaei S et al. A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. British Journal of Obstetrics and Gynaecology 2005 112: 466- 469

4 Harel Z et al. Supplementation with omega-3 polyunsaturated fatty acids in the

management of dysmenorrhea in adolescents. American Journal of Obstetrics and Gynecology 1996 174: 1335-1338

5 Miller ER et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of Internal Medicine 2005 142: 37-46

6 Vivekananthan DP et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: metaanalysis of randomised trials. Lancet 2003 361: 2017-2023

Andrew Moore is honorary professor of health sciences at University College Swansea and editor-in-chief of Bandolier

Henry McQuay is professor of pain relief at the Oxford pain relief unit and co-editor of Bandolier

Bandolier(www.ebandolier.com) is an independent monthly journal on evidence-based health care. Subscription costs £36 for 12 issues and subscribers receive the print journal three months before articles are available on the website.

A subscription form is available on the website or from: maura.moore@pru.ox.ac.uk

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