We searched sources including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, PsycINFO (all from inception to 23 March 2015), trial registries, and the reference lists of relevant articles.
We included 27 RCTs (3101 women). Most included studies were conducted amongst cohorts of students with primary dysmenorrhoea in their late teens or early twenties. Twenty-two studies were conducted in Iran and the rest were performed in other middle-income countries. Only one study addressed secondary dysmenorrhoea. Interventions included 12 different herbal medicines (German chamomile (Matricaria chamomilla, M recutita, Chamomilla recutita), cinnamon (Cinnamomum zeylanicum, C. verum), Damask rose (Rosa damascena), dill (Anethum graveolens), fennel (Foeniculum vulgare), fenugreek (Trigonella foenum-graecum), ginger (Zingiber officinale), guava (Psidium guajava), rhubarb (Rheum emodi), uzara (Xysmalobium undulatum), valerian (Valeriana officinalis), and zataria (Zataria multiflora)) and five non-herbal supplements (fish oil, melatonin, vitamins B1 and E, and zinc sulphate) in a variety of formulations and doses. Comparators included other supplements, placebo, no treatment, and NSAIDs.
We judged all the evidence to be of low or very low quality. The main limitations were imprecision due to very small sample sizes, failure to report study methods, and inconsistency. For most comparisons there was only one included study, and very few studies reported adverse effects.
Effectiveness of supplements for primary dysmenorrhoea
We have presented pain scores (all on a visual analogue scale (VAS) 0 to 10 point scale) or rates of pain relief, or both, at the first post-treatment follow-up.
Supplements versus placebo or no treatment
There was no evidence of effectiveness for vitamin E (MD 0.00 points, 95% CI −0.34 to 0.34; two RCTs, 135 women).
There was no consistent evidence of effectiveness for dill (MD -1.15 points, 95% CI −2.22 to −0.08, one RCT, 46 women), guava (MD 0.59, 95% CI −0.13 to 1.31; one RCT, 151 women); one RCT, 73 women), or fennel (MD −0.34 points, 95% CI −0.74 to 0.06; one RCT, 43 women).
There was very limited evidence of effectiveness for fenugreek (MD −1.71 points, 95% CI −2.35 to −1.07; one RCT, 101 women), fish oil (MD 1.11 points, 95% CI 0.45 to 1.77; one RCT, 120 women), fish oil plus vitamin B1 (MD −1.21 points, 95% CI −1.79 to −0.63; one RCT, 120 women), ginger (MD −1.55 points, 95% CI −2.43 to −0.68; three RCTs, 266 women; OR 5.44, 95% CI 1.80 to 16.46; one RCT, 69 women), valerian (MD −0.76 points, 95% CI −1.44 to −0.08; one RCT, 100 women), vitamin B1 alone (MD −2.70 points, 95% CI −3.32 to −2.08; one RCT, 120 women), zataria (OR 6.66, 95% CI 2.66 to 16.72; one RCT, 99 women), and zinc sulphate (MD −0.95 points, 95% CI −1.54 to −0.36; one RCT, 99 women).
Data on chamomile and cinnamon versus placebo were unsuitable for analysis.
Supplements versus NSAIDS
There was no evidence of any difference between NSAIDs and dill (MD 0.13 points, 95% CI −1.01 to 1.27; one RCT, 47 women), fennel (MD −0.70 points, 95% CI −1.81 to 0.41; one RCT, 59 women), guava (MD 1.19, 95% CI 0.42 to 1.96; one RCT, 155 women), rhubarb (MD −0.20 points, 95% CI −0.44 to 0.04; one RCT, 45 women), or valerian (MD points 0.62 , 95% CI 0.03 to 1.21; one RCT, 99 women),
There was no consistent evidence of a difference between Damask rose and NSAIDs (MD −0.15 points, 95% CI −0.55 to 0.25; one RCT, 92 women).
There was very limited evidence that chamomile was more effective than NSAIDs (MD −1.42 points, 95% CI −1.69 to −1.15; one RCT, 160 women).
Supplements versus other supplements
There was no evidence of a difference in effectiveness between ginger and zinc sulphate (MD 0.02 points, 95% CI −0.58 to 0.62; one RCT, 101 women). Vitamin B1 may be more effective than fish oil (MD −1.59 points, 95% CI −2.25 to −0.93; one RCT, 120 women).
Effectiveness of supplements for secondary dysmenorrhoea
There was no strong evidence of benefit for melatonin compared to placebo for dysmenorrhoea secondary to endometriosis (data were unsuitable for analysis).
Safety of supplements
Only four of the 27 included studies reported adverse effects in both treatment groups. There was no evidence of a difference between the groups but data were too scanty to reach any conclusions about safety.