Effectiveness and safety of Bushen Huoxue granules in treatment of premature ovarian insufficiency: study protocol for a randomized, double-blinded, placebo-controlled, and multicenter clinical trial

Introduction: Premature ovarian insufficiency (POI) seriously affects the quality of life, endocrine function, and fertility of women of childbearing age. Currently, hormone replacement therapy for POI has some limitations, either with low efficacies or high side effects. Bushen Huoxue (BSHX) plays an important role in alleviating clinical symptoms and improving health status of POI patients. This placebo-controlled, randomized, double-blind, and multicenter clinical trial protocol aims to evaluate the effectiveness and safety of BSHX in women with POI. Methods and design: We plan to recruit 150 women with POI from four participating hospitals in China. Participants will be randomized in a 1:1 to receive oral BSHX or BSHX placebo. All participants will be treated for 3 months and will be followed up for another 3 month. The primary outcome is questionnaire scores based on the changes in the total symptoms, which is the Chinese version of the Menopause-Specific Quality of Life (CMS) (Nie G, Yang H, Liu J, Zhao C, Wang X, Menopause 24(5):546-554, 2017). CMS will be measured before the intervention, at 3 months and 6 months after randomization for all participants. The other measurements include serum sex hormone levels, anti-Mullerian hormone (AMH) levels, ovarian peak systolic velocity (PSV; cm/s), and antral follicle count (AFC). In this study, the regulatory effects of traditional Chinese medicine on hormones were evaluated by the changes of serum sex hormone levels, which include serum estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). These indicators will be measured before intervention and at 3 months after randomization. Ethics and dissemination: This study was approved by the Research Ethics Committee of Jiangsu Province Hospital on Integration of Chinese and Western Medicine (2019LWKY014). All participants will provide written informed consent prior to randomization. The results of this research will be presented to academic conferences and peer-reviewed journals.