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Dydrogesterone and inflammatory marker regulation: a systematic review and quantitative meta-analysis
Peter Chedraui1, Vitor E Valenti2, Rafaela P Martineli2
1Escuela de Postgrado en Salud, Universidad Espíritu Santo, Samborondón, Ecuador.
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.
