ABSTRACT
Introduction
Herbal medicine containing Vitex agnus-castus (VAC) extract is widely used by women with premenstrual syndrome (PMS) in Europe, however, in Japan, clinical evidence remains to be determined. This study attempted to investigate the efficacy and safety profiles of VAC extract in Japanese patients with PMS.
Methods
A multi-center, prospective, open-label, single-arm, phase 3 study was performed in Japanese women with PMS and aged 18–44 years. The patients received Prefemin® (Max Zeller Söhne AG, Romanshorn, Switzerland), containing 20 mg of VAC extract, once daily for three menstrual cycles. The efficacy profile was examined based on the intensity of ten PMS symptoms—irritability, depressed mood, anger, headache, bloating, breast fullness, skin disorder, fatigue, drowsiness, and sleeplessness—recorded by patients via a visual analog scale (VAS). In addition, the responder rate was calculated based on the total VAS score defined by the sum of the VAS scores of the first six symptoms mentioned above. Furthermore, physician’s global assessment (PGA) scores were recorded. Adverse events including vital signs and laboratory test values were monitored as safety evaluation.
Results
Sixty-nine patients received Prefemin®. After the first menstrual cycle, a statistically significant decrease in total VAS score was observed (P < 0.001), and the score continued to diminish for the following two cycles. Each of the ten symptom scores decreased significantly in this manner. In addition, the responder rate increased in a time-dependent manner; the rate at the third menstrual cycle was 91.0%, and almost all of the patients were without symptoms or exhibited only mild symptoms based on PGA. Eight patients exhibited non-serious adverse events, one of which was allergic dermatitis whose causal relationship with VAC was not ruled out.
Conclusion
VAC extract improved PMS symptoms in Japanese patients, with no substantial adverse events. This is the first study to report the effect of VAC extract in Japanese patients.
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Acknowledgments
We hereby acknowledge the contribution of the following principal investigators: Dr. Kiyoko Iesaka, Dr. Katsumi Yazaki, Dr. Hitoshi Tamura, and Dr. Taiichi Sato. We also thank Max Zeller Söhne AG for providing information on Prefemin®. The study and article processing charges were funded and supported by Zeria Pharmaceutical Co., Ltd., Tokyo, Japan. Editorial assistance in the preparation of this manuscript was provided by Ms. Ayako Fujita and Mr. Satoshi Katou of Zeria Pharmaceutical Co., Ltd., Tokyo, Japan. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.
Conflict of interest
Mikio Momoeda has received consulting fees from Zeria Pharmaceutical Co., Ltd. Kazunori Ochiai has received consulting fees from Zeria Pharmaceutical Co., Ltd. Hidetaka Sasaki is an employee of Zeria Pharmaceutical Co., Ltd. Eiko Tagashira is an employee of Zeria Pharmaceutical Co., Ltd. Masayuki Ogishima is an employee of Zeria Pharmaceutical Co., Ltd. Yuichi Takano is an employee of Zeria Pharmaceutical Co., Ltd.
Compliance with ethics guidelines
This study was approved by the institutional review board of Yoshii Chuo Shinryojo, Gunma, Japan. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008, and Good Clinical Practice guidelines. Informed consent was obtained from all patients for being included in the study.
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Trial registration: JAPIC Clinical Trials Information number: Japic CTI-090757.
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Momoeda, M., Sasaki, H., Tagashira, E. et al. Efficacy and Safety of Vitex agnus-castus Extract for Treatment of Premenstrual Syndrome in Japanese Patients: A Prospective, Open-label Study. Adv Ther 31, 362–373 (2014). https://doi.org/10.1007/s12325-014-0106-z
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DOI: https://doi.org/10.1007/s12325-014-0106-z