Vitamin E for dysmenorrhoea
Bandolier was asked to comment on a media report that vitamin E had proved to be a useful treatment for dysmenorrhoea, and because vitamin E is sold as a nutritional treatment. A literature search showed that 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.
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.
Results
Three studies were found, one from 1955 performed in Cardiff [1], and two recent studies from Tehran [2,3]. Details of the studies are in Table 1. 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.
Table 1: Randomised trials of vitamin E for primary dysmenorrhoea
Reference |
Design |
Treatment |
Results |
| Butler & McKnight, 1955 [1] | Randomised,
double-blind,
parallel group
(QS=5/5) Undergraduates (n=100) with spasmodic dysmenorrhea, but normal regular menses |
50 mg vitamin
E three times
a day (150 mg
total) or matching
placebo, for three
consecutive months
for 14 days starting
10 days before
period Only withdrawals due to vacation |
After 3 months
more women had
improved by two
or more pain stages
(out of four)
with vitamin E 22/37 vitamin E 5/35 placebo Better results at three rather than one or two months Adverse events were not reported |
| Ziaei et al, 2001 [2] | Randomised,
double-blind,
parallel group
(QS=4/5) High-school students, mean age 17 years (n=100) with mild to severe pain |
100 units vitamin E five times a day (500 units total) for two consecutive months for 5 days starting two days before period | Significant
fall in average
pain for both
vitamin E and
placebo, but significantly
greater fall with
vitamin E Adverse events were not reported |
| Ziaei et al, 2005 [3] | Randomised,
double-blind,
parallel group
(QS=5/5) High-school students, mean age 17 years (n=278) with mild to severe pain |
200 units vitamin
E twice daily
(400 units total)
for four consecutive
months for 5 days
starting two days
before period Minimal withdrawals |
Initial average
pain score of
6/10 (VAS) did
not change with
placebo, but fell
to 3 at two months
and 0.5 at four
n=months with
vitamin E. Duration of pain initally averaged 18 hours, and did not change with placebo, but fell to 4 hours at two months and 2 hours at four months with vitamin E Use of supplementart ibuprofen: 4% vitamin E 89% placebo Adverse events not reported |
All three studies found that 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 amount [1], or non-use of analgesics [3].
Pooling these two (Figure 1) showed a highly significant result. A good result occurred in 155/176 (88%) of women on vitamin E and 20/174 (11%) of women on placebo by three or four months. The relative benefit was 7.7 (95%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).
Figure 1: Trials of vitamin E for dysmenorrhoea, improvement or much reduced pain or no analgesic use
Comment
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 trial [4], using only 1.5 mg 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 that 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 E [5]. 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-analyses [6] using only larger studies found no difference in mortality.
So any move to using vitamin E for treating 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:
- EB Butler, E McKnight. Vitamin E in the treatment of primary dysmenorrhoea. Lancet 1955 i: 844-847.
- S Ziaei 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.
- S Ziaei 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.
- Z Harel 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.
- ER Miller et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of Internal Medicine 2005 142: 37-46.
- DP Vivekananthan et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003 361: 2017-2023.