Real-World Effectiveness and Safety of Liuwei Dihuang Pill for Menopausal Syndrome: Protocol for a Prospective, Observational, Multicenter Cohort Study (Preprint)

<sec> <title>BACKGROUND</title> Menopausal syndrome (MPS) results from declining ovarian function and estrogen fluctuations during the menopausal transition, typically presenting with vasomotor, psychological, and metabolic symptoms that impair quality of life. Current treatments, including hormone replacement therapy and nonhormonal medications, are limited by safety concerns and adverse effects. The Liuwei Dihuang (LWDH) pill, a classical traditional Chinese medicine formula, is widely used for kidney-yin deficiency and menopausal symptoms such as hot flashes, insomnia, depression, and anxiety. Preliminary studies suggest favorable efficacy and safety; however, robust real-world evidence, particularly in combination with conventional Western therapy, remains insufficient. </sec> <sec> <title>OBJECTIVE</title> This study aims to evaluate the real-world effectiveness and safety of LWDH in combination with conventional Western therapy for MPS. </sec> <sec> <title>METHODS</title> This prospective, multicenter, real-world, observational cohort study will be conducted at 8 centers in China from March 9, 2025, to December 2026. A total of 1000 patients with MPS in a real-time clinical setting will be allocated to either the exposure group (conventional therapy plus LWDH) or the nonexposure group (conventional therapy alone). The primary outcome is the change in the modified Kupperman Index. The secondary outcomes encompass changes in the Menopausal Quality of Life Scale, serum sex hormone levels, traditional Chinese medicine syndrome scores, and metabolic parameters. Metabolomics analyses will be conducted to explore potential mechanisms. Safety will be assessed by monitoring adverse events and clinically significant abnormalities in vital signs or laboratory parameters. Assessments will be conducted at baseline and at 2 and 4 weeks, with a subsequent 2-week follow-up. Propensity score–based inverse probability of treatment weighting will be applied to balance baseline covariates, and weighted regression models will be used for comparative analyses. </sec> <sec> <title>RESULTS</title> Participant recruitment and enrollment began in March 2025. It is expected that by December 2026, a total of 1000 participants will be recruited. At present, patient recruitment is ongoing, and preliminary organization and analysis of medical record data are underway. Blood sample collection for metabolomics analysis is also in progress. Final data collection is expected to be completed in March 2027. We expect to generate evidence to support clinical decision-making, with results anticipated to be published in esteemed, peer-reviewed health research journals by December 2027. </sec> <sec> <title>CONCLUSIONS</title> This study will assess the clinical effectiveness, safety, and potential mechanisms of LWDH in the treatment of MPS in real-world settings, providing a scientific basis for its use in clinical practice. </sec> <sec> <title>CLINICALTRIAL</title> ClinicalTrials.gov NCT06874738; https://clinicaltrials.gov/study/NCT06874738 </sec> <sec> <title>INTERNATIONAL REGISTERED REPORT</title> DERR1-10.2196/84803 </sec>