The effect of Ding-kun-dan comparing with Marvelon on primary dysmenorrhea: A prospective, double-blind, multicenter, randomized controlled trial

Abstract

Ethnopharmacological relevance: Ding-kun-dan (DKD), as one of well-known traditional Chinese medicine (TCM), is considered as an effective prescription to regulate menstruation, benefit Qi and nourish the blood. Previous studies had showed that DKD could improve sex hormone levels, insulin resistance, metabolism abnormalities and regulate immunity in animal models with polycystic ovary syndrome or endometriosis, however, little study conducted to reveal its clinical efficacy in Primary Dysmenorrhea (PD).

Aim of the study: To compare the effect of Ding-kun-dan (DKD) with Marvelon on relief of symptoms and change of serum pain-related factors in patients with primary dysmenorrhea.

Materials and method: 136 patients with primary dysmenorrhea were randomly assigned to the DKD group (n = 73, take one tablet per day from 5th day of the menstrual cycle for 10 days every 28 days) and the Marvelon group (n = 63, take one tablet per day from 5th day of the menstrual cycle for 21 days every 28 days), the therapeutic effects were analyzed through evaluating the change of VAS scores, CMSS scores and the level of PGF_2a, PGE₂, PGF_2a/PGE₂ and NO during the 12 weeks intervention.

Results: Both DKD and Marvelon could effectively relief pain and other associated symptoms at each visit (Baseline, 4^th week, 8^th week and 12^th week). Although Marvelon was significantly superior to DKD in reducing VAS scores, the total CMSS, CMSS severity and duration scores at each posttreatment follow-up (P < 0.01), VAS scores in the DKD group decreased significantly over time while scores in the COC group only dropped rapidly after the first two months of treatment. Efficacy gap between two interventions continuously narrowed over time and the efficacy of DKD became non-inferior at the 12^th week compared to that of Marvelon (the difference between groups, - 0.78%; 95% confidence interval (CI), -13.67%-12.75%; non-inferiority margin, 15%). DKD group had better efficacy on mild pain compared to that of the COC group with no statistical difference (75% VS 61.9%, P > 0.05). DKD and Marvelon could effectively reduce PGF_2a, PGE₂ and higher PGF_2a/PGE₂ in patients with PD. There was no statistical difference in the level of PGF_2a, PGE₂, PGF_2a/PGE₂ and NO between DKD and Marvelon group at each follow-up. No serious adverse effect was observed.

Conclusion: Ding-kun-dan is another available, effective and safe method for patients with primary dysmenorrhea to choose, especially for those who are suffered from mild pain and/or contraindicated to hormonal agents.

Keywords: CMSS; Ding-kun-dan; Marvelon; PGE(2); PGF(2a); PGF(2a)/PGE(2); Primary dysmenorrhea; VAS.