Dydrogesterone and inflammatory marker regulation: a systematic review and quantitative meta-analysis

Abstract

Objective To evaluate the effects of dydrogesterone on systemic inflammatory biomarkers in women across different reproductive and hormonal clinical contexts compared with placebo or other pharmacological interventions.Methods This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251163959). Searches covered database inception through December 2025. Randomised controlled trials and controlled studies reporting IL-6, IL-10, TNF-α, or C-reactive protein were included. Quantitative synthesis used a random-effects model. Risk of bias and certainty of evidence were assessed using Cochrane and GRADE tools.Results Seven studies were included. No statistically significant effects were found for IL-6 (mean difference [MD], −0.15 pg/mL; 95% CI, −0.67 to 0.38; p = 0.58), IL-10 (MD, 2.39 pg/mL; 95% CI, −2.08 to 6.86; p = 0.29), TNF-α (MD, 0.06 pg/mL; 95% CI, −0.09 to 0.22; p = 0.42), or C-reactive protein (MD, 0.08 mg/L; 95% CI, −0.25 to 0.40; p = 0.65). Heterogeneity was very high for IL-10 and moderate for IL-6 and TNF-α. Most studies had high risk of bias; certainty was very low for all biomarkers.Conclusion Dydrogesterone did not significantly alter systemic inflammatory biomarkers. Evidence does not indicate increased inflammation, but certainty is very low. Larger, well-designed randomised controlled trials are needed to clarify its immunomodulatory effects.