Evaluation of the efficacy, safety, and clinically recommended dose of dienogest in the treatment of primary dysmenorrhea: a randomized, double-blind, multicenter, placebo-controlled study

Objective: To evaluate the efficacy, safety, and clinically recommended dose of dienogest (DNG; 0.5 mg/d, 1 mg/d, and 2 mg/d) in the treatment of primary dysmenorrhea.

Design: A phase II, randomized, double-blind, multicenter, placebo-controlled study.

Setting: Twenty study sites.

Patients: A total of 235 patients with primary dysmenorrhea.

Intervention(s): Patients were randomized to receive orally a placebo, DNG (0.5 mg/d, 1 mg/d, or 2 mg/d) or ethinylestradiol 0.02 mg/drospirenone 3 mg (an open-label reference drug) for 12 weeks.

Main outcome measure(s): The primary endpoint was the change from baseline in the dysmenorrhea score at week 12 of treatment. The secondary endpoint was the change from baseline in the visual analogue scale at week 12 of treatment. Subjects were assessed for lower abdominal pain and/or low back pain.

Results: All DNG arms were superior to the placebo arm in terms of the change from baseline in the dysmenorrhea score. The results suggest an equal or greater effect of DNG 1 and 2 mg/d in relieving pain, when compared to the reference drug. In the safety profile of DNG, including irregular uterine bleeding, there was no obvious difference among the doses of DNG. A significant decrease in the serum estradiol concentration compared to that in the placebo arm was not observed in the DNG 1 mg/d arm but was observed in the DNG 2 mg/d arm.

Conclusion(s): The results suggest that DNG at a dose of 1 mg/d is an effective and well-tolerated treatment for primary dysmenorrhea.

Trial registration: JapicCTI-152977 (en).