Identification of a Predictive Biomarker for the Beneficial Effect of Keishibukuryogan, a Kampo (Japanese Traditional) Medicine, on Patients with Climacteric Syndrome
Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is one of the Kampo (Japanese traditional) medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA) repeat polymorphism of the estrogen receptor β gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients’ profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12？weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients’ climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype). No relationship between the patients’ profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it. 1. Introduction Climacteric syndrome, which is caused by a decrease of the estrogen level during menopause, often severely impairs a woman’s quality of life [1, 2]. Many climacteric women suffer from vasomotor symptoms, mood disorders, vaginal dryness, headache, shoulder stiffness, and other problems. Hormone replacement therapy (HRT) is one of the most effective treatments for climacteric symptoms, especially for vasomotor symptoms, mood problems, and vaginal dryness. In recent years, however, epidemiological studies have reported adverse reactions to HRT such as an increase in the risks for stroke, deep vein thrombosis, dementia, and breast cancer [3–6]. In Japan, the use of Kampo medications (Japanese herbal medicine) is one alternative for controlling these symptoms in women who reject HRT or who cannot receive HRT due to a history of breast cancer [7]. Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is a Kampo medicine that has been effective in patients with climacteric syndrome. KBG consists of five crude drugs: cinnamon bark (Cinnamomum cassia Blume), peony root (Peonia lactiflora Palls), peach kernel (Prunus persica Batsch), poria sclerotium (Poria cocos Wolf), and moutan bark (Peonia suffruticosa Andrews). However, at
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