Efficacy and safety of HYYK formula for residual follicle revival in premature ovarian insufficiency: a multicenter, randomized, double-blind, placebo-controlled trial protocol

BackgroundPremature ovarian insufficiency (POI), a condition impacting women under 40, is rising globally, posing significant risks to fertility, bone health, and cardiovascular function. Conventional hormone replacement therapy (HRT) alleviates symptoms but fails to restore ovarian function. Our prior studies have demonstrated that the Huyang Yangkun (HYYK) formula effectively supports menstrual cycle frequency and alleviates menopause-related symptoms in POI patients. This study aims to evaluate the efficacy and safety of the HYYK formula, a traditional Chinese medicine (TCM) approach, in enhancing residual follicle activity in POI patients.MethodsThis multicenter, randomized, double-blind, placebo-controlled trial will enroll 102 women with POI, who will be randomly assigned to receive either the HYYK formula or a placebo for 24 weeks. Primary outcomes will be assessed through Hoogland and Skouby scores (indicative of residual follicle activity) and menstrual cycle regularity. Secondary outcomes include hormone levels (AMH, FSH, LH, E2), ovarian volume, antral follicle count, and clinical symptom scales, such as the Greene Scale and the Female Sexual Function Index. Safety assessments will involve routine physical exams and adverse event monitoring.DiscussionThis is the first multicenter, randomized, double-blind, placebo-controlled study to investigate the efficacy of TCM in stimulating residual follicle recovery in POI patients. The trial rigorously investigates the potential of the HYYK formula as a therapeutic alternative for POI, aiming to deliver high-quality evidence that supports the use of TCM in POI management. This study will concentrate on stimulating residual follicle development in POI patients, offering a viable approach to delaying ovarian decline and generating compelling clinical evidence.Trial registrationChinese Clinical Trials.gov ChiCTR2100049604 Registered on August 6, 2021 (http://www.chictr.org.cn).