A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Effects of Kamishoyosan, a Traditional Japanese Medicine, on Menopausal Symptoms: The KOSMOS Study

Kiyoshi Takamatsu; Mariko Ogawa; Satoshi Obayashi; Takashi Takeda; Masakazu Terauchi; Tsuyoshi Higuchi; Kiyoko Kato; Toshiro Kubota

doi:10.1155/2021/8856149

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Effects of Kamishoyosan, a Traditional Japanese Medicine, on Menopausal Symptoms: The KOSMOS Study

Evid Based Complement Alternat Med. 2021 Feb 26:2021:8856149. doi: 10.1155/2021/8856149. eCollection 2021.

Authors

Kiyoshi Takamatsu¹, Mariko Ogawa¹, Satoshi Obayashi², Takashi Takeda³, Masakazu Terauchi⁴, Tsuyoshi Higuchi⁵, Kiyoko Kato⁶, Toshiro Kubota⁷

Affiliations

¹ Department of Obstetrics and Gynecology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan.
² Department of Obstetrics and Gynecology, Dokkyo Medical University, Tochigi, Japan.
³ Division of Women's Health, Research Institute of Traditional Asian Medicine, Kindai University, Osaka, Japan.
⁴ Department of Women's Health, Tokyo Medical and Dental University, Tokyo, Japan.
⁵ Department of Nursing Science, Hirosaki University Graduate School of Health Sciences, Aomori, Japan.
⁶ Department of Obstetrics and Gynecology, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
⁷ Department of Gynecology, Tokyo Kyosai Hospital, Tokyo, Japan.

Abstract

Objective: The KOSMOS study, a multicenter, randomized, double-blind, placebo-controlled trial, investigated the effects and safety of kamishoyosan (TJ-24), a traditional Japanese medicine, in the treatment of climacteric disorder.

Methods: Japanese women with climacteric disorder were administered a placebo during a 4-week run-in period, after which they were classified as placebo responders (R group) if their score on the modified Questionnaire for the Assessment of Climacteric Symptoms in Japanese Women (m-QACS) with excitability and irritability as the primary outcome improved by ≥ 3 points and as placebo nonresponders (NR group) otherwise. Members of the NR group were randomly allocated to receive either TJ-24 or placebo. After 12 weeks, their m-QACS scores, anxiety and depression, sleep, and overall quality of life (QOL) were compared.

Results: The TJ-24 and placebo arms in the NR group included 20 patients each. The change in the m-QACS scores of members of the NR group for excitability and irritability at 12 weeks versus baseline was -3.1 ± 1.7 in the TJ-24 arm, a significant decrease, but compared with -2.7 ± 2.2 in the placebo arm, no significant difference was between two arms. However, the proportion of participants whose score improved by ≥3 points was significantly higher in the TJ-24 arm. In the subgroup analysis of premenopausal women, the changes in the score for excitability and irritability were significantly larger in the TJ-24 arm. The incidence of adverse drug reactions or adverse events did not differ between the two arms, and no serious events were reported.

Conclusion: Although no significant difference was identified for the primary outcome, a significantly higher proportion of patients who received TJ-24 displayed improvement. Its high level of safety and effects on excitability and irritability in premenopausal women suggest that TJ-24 may be a useful treatment.