Burden of Menstrual Pain Measured by Heatmap Visualization of Daily Patient-Reported Data in Japanese Patients Treated with Ethinylestradiol/Drospirenone: A Randomized Controlled Study

Abstract

Purpose: Dysmenorrhea negatively affects women's quality of life and poses a considerable economic burden. A recent study in Japanese patients with dysmenorrhea (NCT01892904) reported a significant reduction in the number of days with menstrual pain after treatment with a flexible extended regimen of ethinylestradiol (EE)/drospirenone (DRSP) compared with a cyclic regimen. However, individual patients' menstrual pain patterns and intensities were not indicated. Heatmapping was used to visualize menstrual pain patterns and intensities by re-evaluating the previously published data from NCT01892904.

Patients and methods: NCT01892904 was a Phase III, multicenter, randomized, open-label, active-control study of 212 women aged ≥20 years randomized 1:1 to receive flexible extended or 28-day cyclic EE/DRSP treatment. Daily pain levels were recorded in patient diaries, and menstrual pain patterns and intensities were visualized using heatmapping. Patients were stratified by baseline dysmenorrhea scores and primary or secondary dysmenorrhea.

Results: The heatmap data demonstrated that EE/DRSP reduced the degree of menstrual pain. Regular peaks of menstrual pain were alleviated in the extended regimen group but were still observed in the cyclic regimen group. While a decrease in the days with menstrual pain was observed in patients with higher baseline dysmenorrhea scores (5-6), those with lower baseline scores (3-4) were more likely to experience lower intensities of menstrual pain. Although pain relief was less likely in patients with secondary dysmenorrhea, those who had lower baseline dysmenorrhea scores (3-4) and received the flexible extended regimen experienced a greater reduction in the number of days with menstrual pain than those who received the cyclic regimen.

Conclusion: Heatmapping effectively visualized the daily burden of menstrual pain in Japanese patients with dysmenorrhea. The analysis using heatmaps suggested that the flexible extended EE/DRSP treatment regimen was more likely to alleviate the regular occurrence of menstrual pain peaks compared with the cyclic regimen.

Keywords: dysmenorrhea; ethinylestradiol; pain measurement; patient-reported outcomes.

Conflict of interest statement

Mikio Momoeda is a paid medical advisor to Bayer Yakuhin, Ltd. for this study and outside of this study. Takeshi Fukai, Shigetomo Yamamoto, and Masami Kondo are employees of Bayer Yakuhin, Ltd. and Sayako Akiyama was an employee of Bayer Yakuhin, Ltd. during the conduct of this study. The authors report no other conflicts of interest related to this work.

© 2020 Momoeda et al.

Figures

Figure 1

Overall menstrual pain scores over 24 weeks in the full analysis set following treatment with the flexible extended regimen (A) and the 28-day cyclic regimen (B), as shown with heatmapping. The reference line at Day 0 indicates the first day of study drug administration. Lower baseline dysmenorrhea scores (3–4) are shown in the top half of the heatmap, and higher baseline dysmenorrhea scores (5–6) in the bottom half.

Figure 2

Mean cumulative function of the flexible extended regimen and the 28-day cyclic regimen.

Figure 3

Menstrual pain scores as shown by heatmapping after treatment with the flexible extended regimen (A) or the 28-day cyclic regimen (B) in the group with primary dysmenorrhea. Lower baseline dysmenorrhea scores (3–4) are shown in the top half of the heatmap, and higher baseline dysmenorrhea scores (5–6) in the bottom half.

Figure 4

Menstrual pain scores as shown by heatmapping after treatment with the flexible extended regimen (A) or the 28-day cyclic regimen (B) in the group with secondary dysmenorrhea. Lower baseline dysmenorrhea scores (3–4) are shown in the top half of the heatmap, and higher baseline dysmenorrhea scores (5–6) in the bottom half.