Acupoint stimulation methods for premature ovarian insufficiency: a systematic review and network metaanalysis of randomized controlled trials

Zhenping DuGuancheng YeJingyuan WeiShutong LiShan ZhaoJun Wang^*

• Beijing University of Chinese Medicine, Beijing, China

Objective: The aim of this study was to evaluate and rank the efficacy of different acupoint stimulation (AS) therapies in the treatment of premature ovarian insufficiency (POI) by network meta-analysis (NMA), and to explore the optimal AS regimen for improving sex hormone levels and clinical symptoms.Methods: Randomized controlled trials (RCTs) in English and Chinese up to November 2024 were searched in eight databases, including the Cochrane Library, PubMed, and the China National Knowledge Infrastructure (CNKI), etc. Included studies were patients with POI diagnosed according to established international or Chinese guidelines. The intervention compared AS therapies (e.g., acupuncture, moxibustion) with conventional treatments (oral herbs or hormone replacement therapy) or/and placebo. Outcome indicators included antral follicle count (AFC), follicle-stimulating hormone (FSH) levels, luteinizing hormone (LH) levels, estradiol (E2) levels and Kupperman score. Literature quality and risk of bias were assessed using Review Manager (RevMan), Version 5.3. Statistical analysis was performed using Stata 16.0 software, mvmeta package and cumulative sorted area under the curve (SUCRA).Results: A total of 51 RCTs were retrieved, containing 3754 patients. Therapies combining multiple AS therapies (especially moxibustion-related therapies) improved ovarian function significantly. Acupuncture combined with moxibustion (Acu + Moxi) was effective in increasing AFC (MD=2.04, 95% CI [1.31, 2.77]; SUCRA=75.1%). Auricular seed therapy (AST) was most effective in reducing FSH (MD = 3.03, 95% CI [0.45, 5.60]; SUCRA = 83.7%). Acupuncture (Acu) was effective in reducing LH levels (MD = 1.52, 95% CI [0.27, 2.77]; SUCRA = 58.3%). Moxibustion combined with tuina (Moxi + MT) (MD = 11.92, 95% CI [8.19, 15.65]; SUCRA = 100%) and Moxibustion combined with acupressure (MD = 3.20, 95% CI [0.16, 6.24]; SUCRA = 81.4%) significantly increased estradiol levels. Moxibustion combined with tuina (Moxi + MT) had the best effect on Kupperman score improvement (MD = 4.63, 95% CI [0.58, 8.68]; SUCRA = 92.1%). Adverse events for all therapies involved in this study were mild and resolved with symptomatic management.Conclusion: AS therapies (especially moxibustion) can safely and effectively improve hormone levels and clinical symptoms in patients with POI, supporting their clinical application as complementary and alternative medicine (CAM).