Abstract
Objective: Unkeito is a Kampo formula used to treat several menstrual disorders and menopausal symptoms. Our aim was to determine the effects of unkeito on trabecular bone mineral density (BMD) and uterus in the ovariectomized (OVX) mouse to predict the effects of unkeito on women in the post-reproductive period. Design: Ten-week-old Balb/c mice were ovariectomized to induce both osteoporosis and loss of ovarian function. Two weeks after surgery, the mice were divided into control and experimental groups. The control mice were given unlimited access to tap water. The experimental mice were given an estrogen solution (6.25 or 12.5 μg/day), unkeito suspension (60, 120, 240, or 480 mg/day), or a combination of 12.5 μg/day estrogen and unkeito (240 or 480 mg/day) orally for two weeks. The trabecular BMD, uterine weight, and endometrial thickness were then measured. Results: Trabecular BMD, uterine weight, and endometrial thickness in OVX mice were markedly decreased as compared with the sham-operated mice. The trabecular BMD in OVX mice that received unkeito was significantly increased in comparison with that of OVX mice that did not receive unkeito. No significant differences in uterine weight or endometrial thickness were noted between the unkeito groups and the OVX groups. Moreover, the increment in both uterine weight and endometrial thickness in OVX mice induced by estradiol was reduced by oral administration of unkeito. Conclusion: OVX mice showed recovery from trabecular BMD loss without both uterine weight gain and increase in endometrial thickness, after treatment with unkeito for two weeks. Thus, we found for the first time that unkeito exhibits a selective estrogen receptor modulator-like activity.