A randomised placebo-controlled trial of a traditional chinese herbal formula in the treatment of primary dysmenorrhoea

[[abstract]]Background. Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang) is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial. Methodology/Principal Findings. A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang) group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow-up cycle, at which the reduced peak-pain in the Four-Agents-Decoction (Si Wu Tang) group did not differ significantly by treatment length. However, the reduced peak-pain did differ profoundly among women treated for four menstrual cycles (2.69(2.06) cm, mean (standard deviation), for the 20 women with Four-Agents-Decoction and 4.68 (3.16) for the 22 women with placebo, p=.020.) There was no difference in adverse symptoms between the Four-Agents-Decoction (Si Wu Tang) and placebo groups. Conclusion/significance. Four-Agents-Decoction (Si Wu Tang) therapy in this pilot post-market clinical trial, while meeting the standards of conventional medicine, showed no statistically significant difference in reducing menstrual pain intensity of primary dysmenorrhoea at the end of treatment. Its use, with our dosage regimen and treatment length, was not associated with adverse reactions. The finding of statistically significant pain-reducing effect in the first follow-up cycle was unexpected and warrants further study. A larger similar trial among primary dysmenorrheic young women with longer treatment phase and multiple batched study products can determine the definitive efficacy of this historically documented formula. Trial Registration