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

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.

Effects of the kampo formula tokishakuyakusan on headaches and concomitant depression in middle-aged women.

Objectives. To identify the correlates of headaches in middle-aged women and investigate the effects of Tokishakuyakusan (TJ-23), a formula of traditional Japanese herbal therapy Kampo, on headache and concomitant depression. Methods. We examined cross-sectionally the baseline records of 345 women aged 40-59 years who visited our menopause clinic. Among them, 37 women with headaches were treated with either hormone therapy (HT) or TJ-23; the data of these women were retrospectively analyzed to compare the effects of the treatment. Results. The women were classified into 4 groups on the basis of their headache frequency, and no significant intergroup differences were noted in the physical or lifestyle factors, except age. Multiple logistic regression analysis revealed that the significant contributors to the women's headaches were their age (adjusted OR 0.92 (95% CI 0.88-0.97)) and their depressive symptoms (adjusted OR 1.73 (95% CI 1.39-2.16)). Compared to women treated with HT, women treated with TJ-23 reported relief from headaches (65% versus 29%) and concomitant depression (60% versus 24%) more frequently. Improvement in the scores of headaches and depression correlated significantly with TJ-23 treatment. Conclusions. Headache in middle-aged women is significantly associated with depression; TJ-23 could be effective for treating both of these symptoms.

Effects of the Kampo medication keishibukuryogan on blood pressure in perimenopausal and postmenopausal women.

OBJECTIVE: To examine the effects of keishibukuryogan (TJ-25)-a medicine of the Kampo tradition (the Japanese adaptation of Chinese herbal medicine)-on middle-aged women with high blood pressure. METHODS: The records of 77 peri- and postmenopausal women with high-normal blood pressure or hypertension were analyzed retrospectively. The women had participated in the Systematic Health and Nutrition Education Program at the Tokyo Medical and Dental University in Tokyo, Japan, and had received education only (controls; n = 47) or education and treatment with TJ-25 (n = 30). RESULTS: The baseline characteristics of the 2 groups were comparable. After approximately 6 months, women in the TJ-25 group showed significant reductions in their systolic blood pressure (from 148.4mm Hg to 134.8mm Hg), diastolic blood pressure (from 89.7 mm Hg to 83.7 mm Hg), pulse rate (from 79.5 beats/min to 73.5 beats/min), and resting energy expenditure (from 1552 kcal/day to 1373 kcal/day). Several menopausal symptoms including perspiration, difficulty in initiating sleep, nonrestorative sleep, and headaches/dizziness were also improved. In addition, women in the TJ-25 group had increased health-related quality of life scores in the domains of physical health and life satisfaction. CONCLUSION: TJ-25 alleviates menopausal symptoms and concurrently lowers the blood pressure of middle-aged women with high blood pressure.

Effects of three Kampo formulae: Tokishakuyakusan (TJ-23), Kamishoyosan (TJ-24), and Keishibukuryogan (TJ-25) on Japanese peri- and postmenopausal women with sleep disturbances.

PURPOSE: To assess the effects of Kampo, a traditional Japanese adaptation of Chinese herbal medicine, on peri- and postmenopausal women with sleep disturbances. METHODS: Among the records of 1,523 peri- and postmenopausal women who are enrolled in the Health and Nutrition Education Program at the Tokyo Medical and Dental University, Menopause Clinic, during 1995-2009, about 151 women suffering from moderate to severe sleep disturbances were retrospectively analyzed. These women had received only health/nutrition education (control; n = 77) or received treatment with one of the three major Kampo formulae: Tokishakuyakusan (TJ-23; n = 42), Kamishoyosan (TJ-24; n = 16), or Keishibukuryogan (TJ-25; n = 16) according to their "Sho" or symptom patterns. Subjective sleep parameters, menopausal symptoms, health-related quality of life, body composition, blood pressure, and pulse rate were compared before and after the intervention. RESULTS: The TJ-25 group had significantly higher body weight, body mass index, body fat, lean body mass, resting energy expenditure, and relatively high blood pressure and heart rate at baseline than the other groups. After ~5-month follow up, TJ-23 reduced the sleep disruption frequency, increased lean body mass, and decreased diastolic pressure. TJ-24 alleviated subjective sleep disturbances; improved difficulties in initiating sleep, disrupted sleep, and non-restorative sleep; and relieved headache/dizziness. TJ-25 improved subjective sleep disturbances, alleviated perspiration, and reduced systolic/diastolic pressure and heart rate. CONCLUSIONS: Each of the Kampo formulae effectively alleviated sleep disturbances in Japanese peri- and postmenopausal women. Middle-aged female patients having sleeping disorder could successfully be treated using Kampo medicines.

Linalyl acetate as a major ingredient of lavender essential oil relaxes the rabbit vascular smooth muscle through dephosphorylation of myosin light chain.

In a preliminary experiment, we found that lavender essential oil relaxes vascular smooth muscle. Thus, the present experiments were designed to investigate the relaxation mechanism of linalyl acetate as the major ingredient of lavender essential oil in rabbit carotid artery specimens. Linalyl acetate produced sustained and progressive relaxation during the contraction caused by phenylephrine. The relaxation effect of linalyl acetate at a concentration near the EC50 was partially but significantly attenuated by nitroarginine as an inhibitor of nitric oxide synthase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one as an inhibitor of guanylyl cyclase, or by the denudation of endothelial cells. In specimens without endothelium, the phenylephrine-induced contraction and phosphorylation of myosin light chain (MLC) were significantly attenuated after the pretreatment with linalyl acetate. The relaxation caused by linalyl acetate in the endothelium-denuded specimens was clearly inhibited by calyculin A as an inhibitor of MLC phosphatase, although not by ML-9 as an inhibitor of MLC kinase. Furthermore, suppression of the phenylephrine-induced contraction and MLC phosphorylation with linalyl acetate was canceled by the pretreatment with calyculin A. These results suggest that linalyl acetate relaxes the vascular smooth muscle through partially activation of nitric oxide/cyclic guanosine monophosphate pathway, and partially MLC dephosphorylation via activating MLC phosphatase.