The TU-025 keishibukuryogan clinical trial for hot flash management in postmenopausal women: results and lessons for future research

Objective: The aim of this study was to assess the efficacy of TU-025, keishibukuryogan, a Japanese prescription herbal medicine used for hot flash management, in American women. Methods: This randomized, double-blind, placebo-controlled, phase II trial enrolled 178 postmenopausal women aged 45 to 58 years with a Mayo hot flash score greater than 28 per week who met other inclusion criteria. After a 1-week placebo run-in period, participants were randomly assigned placebo, or 7.5 g/day, or 12.5 g/day groups, for 12 weeks. Primary and secondary outcomes were measured using the Mayo Clinic Hot Flash Diary, the Greene Climacteric Index, and the Pittsburgh Sleep Quality Index. Results: At 3 months, hot flash scores, climacteric symptoms, and sleep quality improved by 34% in the placebo group, 40% in the 7.5 g/day group, and 38% in the 12.5 g/day group. (P < 0.001). However, the differences in changes between groups were not statistically significant (P = 0.990). Diarrhea unexpectedly developed in 20% of participants receiving active medication. Conclusions: For American women, unlike the clinical experience for Japanese women, TU-025 did not significantly reduce the frequency and severity of hot flash symptoms, improve climacteric symptoms, or benefit sleep quality. This study identified several potentially significant methodological factors to be considered in future scientific assessments of traditional Asian medicines.