Efficacy and Safety of Oral Traditional Herbal Medicine in the Treatment of Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis

Abstract

Premature ovarian insufficiency (POI) is a condition characterized by impaired ovarian function before the age of 40 years. Oral traditional herbal medicine is used either alone or in combination with hormone replacement therapy (HRT); however, its efficacy and safety remain unclear. This study evaluated traditional herbal medicine versus HRT, and traditional herbal medicine plus HRT versus HRT. Five databases were searched up to 27 July 2026. Randomized controlled trials (RCTs) were analyzed using a random-effects model and stratified by treatment duration of ≤3 months and >3 months. Risk of bias and certainty of evidence were assessed using the Cochrane Risk of Bias 2 (RoB 2) tool and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, respectively. A total of 28 RCTs were included. Traditional herbal medicine alone yielded inconsistent results, whereas traditional herbal medicine combined with HRT showed more pronounced improvements in several biological markers. In the ≤3-month subgroup, the combination of traditional herbal medicine and HRT significantly reduced follicle-stimulating hormone (FSH) levels (SMD = −1.61; 95% CI: −1.96 to −1.26) and increased estradiol (E2) levels (SMD = 1.07; 95% CI: 0.71–1.43), anti-Müllerian hormone (AMH) levels (SMD = 1.35; 95% CI: 0.59–2.11), and antral follicle count (AFC) (MD = 1.17; 95% CI: 0.78–1.56). The clinical effective rate was also higher with traditional herbal medicine plus HRT. No clear differences in adverse events were observed between treatment groups. However, many analyses showed substantial heterogeneity, and the certainty of the evidence was predominantly low or very low. Traditional herbal medicine, particularly when combined with HRT, may improve certain biological markers in patients with POI; nevertheless, further high-quality RCTs with long-term reproductive outcomes are warranted.