Hyaluronic acid for vaginal health and quality of life in postmenopausal women: A systematic review and meta‐analysis of randomized controlled trials

Abstract Introduction Postmenopausal women often experience genitourinary symptoms that affect the quality of life (QoL), including dryness in vaginal, atrophy and sexual dysfunction. Pharmacists, as frontline healthcare practitioners, are essential in advising on safe and effective non‐hormonal alternatives such as hyaluronic acid (HA); yet, its effects on tolerance and QoL have not been extensively assessed via meta‐analysis. Methods We conducted a prospective systematic review and meta‐analysis of randomized controlled trials (RCTs) to evaluate the efficacy, safety, and tolerability of HA in improving QoL among postmenopausal women. Only prospective, parallel‐group or single‐group RCTs were included; no retrospective, cohort, case–control, or non‐randomized studies were considered. Eleven studies meet the inclusion criteria in two evidence tiers: placebo‐controlled RCTs for primary outcomes and comparative studies. Primary results were vaginal dryness‐related QoL and female sexual function index. Vaginal health index (VHI) and tolerability/safety were designated as secondary outcomes. The risk of bias and GRADE assessments were applied. Results Three placebo‐controlled RCTs showed significant improvements in VHI, vaginal dryness‐related QoL, and FSFI (with standardized mean difference [SMD] = 3.40, 95% confidence interval [CI]: 2.73 to 4.06; P < 0.00001, SMD = −0.98, 95% CI: −1.24 to −0.71; P < 0.00001, and SMD = 0.85, 95% CI: 0.50 to 1.20; P < 0.00001), respectively. In comparative studies, HA was not found to be inferior to active comparators. No serious adverse events were reported (relative risk = 0.35; 95% CI: 0.10 to 1.23; P = 0.10), with moderate heterogeneity ( I 2 = 52%), and treatment discontinuations were minimal. GRADE evaluation rated the evidence as moderate for vaginal dryness and FSFI but low for VHI and safety outcomes due to heterogeneity and publication bias concerns. Conclusion Hyaluronic acid is a safe and effective non‐hormonal treatment for vulvovaginal discomfort in postmenopausal women, with moderate‐quality evidence supporting its benefits for sexual function and QoL. While these findings are encouraging, the variability between research emphasizes the need for more standardized formulations, treatment protocols, and long‐term evaluations.