Effectiveness and safety of commercial Chinese polyherbal preparations combined with menopausal hormone therapy for perimenopausal symptoms: a network meta-analysis of randomized controlled trials.

Background: Perimenopause is a natural physiological transition associated with declining ovarian function and bothersome systemic symptoms. Menopausal hormone therapy (HT) remains the primary treatment, but safety concerns persist. Commercial Chinese polyherbal preparations (CCPPs) combined with HT are increasingly used, yet comparative evidence remains limited. This network meta-analysis (NMA) evaluated the effectiveness and safety of CCPPs plus HT for perimenopausal symptoms. Methods: Chinese and English databases were searched for randomized controlled trials (RCTs) evaluating CCPPs plus HT. The study followed the reporting guideline for network meta-analyses and was registered in PROSPERO (CRD420261335785). Risk of bias was assessed using the revised Cochrane risk-of-bias tool. Data were synthesized in Stata 18.0, and surface under the cumulative ranking curve values were estimated as exploratory summaries. Results: Seventy-three RCTs (n = 8,314) involving 11 CCPPs were included. Most studies had some concerns or high risk of bias, mainly owing to inadequate blinding and subjective-outcome vulnerability. Five CCPP + HT regimens significantly reduced the Kupperman Index (KI) compared with HT alone. Linglianhua Granule plus HT showed the largest KI estimate, but was supported by only two trials and low-certainty evidence. Given the very large standardized mean differences and the subjective nature of KI assessment in mostly unblinded trials, these results should be interpreted cautiously. For the Menopause-Specific Quality of Life questionnaire, only Kuntai Capsule plus HT showed significant improvement. The overall effective rate was treated as auxiliary because definitions varied. Dingkun Pill plus HT and Kuntai Capsule plus HT showed favorable estimates versus HT alone for estradiol elevation and follicle-stimulating hormone/luteinizing hormone reduction, respectively. CCPP + HT did not significantly increase reported short-term adverse reactions, but monitoring and follow-up were insufficient to establish safety superiority, equivalence, or long-term safety. Conclusion: CCPP + HT may be associated with improvements in selected symptom-related and endocrine outcomes compared with HT alone, but the evidence was generally of low to moderate certainty and derived mostly from unblinded trials. Ranking results, particularly for KI, should be considered exploratory summaries and not clinically actionable treatment hierarchies. Further high-quality blinded RCTs with standardized outcome assessment, adverse-event monitoring, and longer follow-up are needed. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261335785, identifier CRD420261335785.