A Multi-center,Randomized,Controlled and Open Clinical Trial of Heyan Kuntai Capsule (和颜坤泰胶囊) and Hormone Therapy in Perimenopausal Women

Objective： To evaluate the efficacy and safety of Heyan Kuntai Capsule（和颜坤泰胶囊, HYKT） and hormone therapy（HT） on perimenopausal syndromes（PMSs）. Methods： From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol（E2） below 30 ng/L, and follicle stimulating hormone（FSH） above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index（KMI） scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life（MENQOL） scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment. Results： After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline（P〈0.01） and there was no significant difference between groups（P〉0.05）, except that KMI of HYKT group was higher after 3-month treatment（P〈0.05）. After treatment, hot flush and insomnia scores were both improved significantly in two groups（P〈0.01）; and HT had a better performance than HYKT in improving hot flush（P〈0.05）. MENQOL were significantly improved in both groups after treatment（P〈0.01）; but there was no significant difference between two groups（P〉0.05）. The incidence of adverse event in the HYKT group was much lower than that in the HT group（P〈0.01）. Conclusions： HYKT could effectively relieve PMSs and improve patient quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.

Effects of Heyan Kuntai Capsule(和颜坤泰胶囊)on Follicular Development and Oocyte Cohesin Levels in Aged Mice

Objective： To evaluate the effect of Heyan Kuntai Capsule （和颜坤泰胶囊, HYKT） on the ovarian function of aged mice and expressions of cohesion complexes in oocytes. Methods： Twenty-five 9-month-old female C57BL/6J mice were randomly divided into 5 groups by block randomization method （n=5 per group）, including the control group （saline）, 17β-estradiol group [E2, 100 μg/（kg·d）], and low-, medium-, and high- dose of HYKT groups [0.3, 0.9, 2.7 g/（kg·d）, respectively]. All mice were treated by intragastric administration for 4 weeks. Hematoxylin and eosin staining and anti-VASA staining were used to detect the amounts of follicles. The apoptosis of follicles was measured by anti-gamma H2A histone family member X （γ, H2AX） staining and TdT-mediated dUTP Nick-End Labeling （TUNEL） assay. The density of cohesin subunits, REC8 meiotic recombination protein （REC8）, structural maintenance of chromosome （SMC） 1 β and SMC3 in oocytes were evaluated by immunofluorescent staining. Results： After administration of E2 and high-dose of HYKT, the total number of follicles as well as the number of primordial and primary follicles were significantly increased （P〈0.05）. Anti-γ/H2AX staining and TUNEL assay demonstrated that high-dose of HYKT and E2 partly suppressed the apoptosis of follicles （P〈0.05）. Furthermore, it showed an increased trend in the levels of REC8 and SMC1 β, after administration with E2 and HYKT, and no obvious change in the level of SMC3. Conclusion： HYKT could enhance the number of follicles, suppress apoptosis of oocytes and have a trend to elevate the meiotic-specific cohesin subunits （REC8 and SMC1 β） in oocytes of aged mice, indicating a beneficial effect on the ovarian function in terms of the quantity and quality of follicles.