Medroxyprogesterone for arterial blood gases and oxygenation parameters in COPD: a systematic review and meta-analysis

Background Chronic obstructive pulmonary disease (COPD) is a common, progressive pulmonary disorder associated with significant morbidity and mortality rates throughout the world. Although several studies suggest that medroxyprogesterone acetate (MPA), a synthetic progesterone, can safely increase ventilatory drive to manage hypercapnic respiratory failure in patients with COPD, a preliminary search of PROSPERO and the Cochrane Database confirmed that no comprehensive systematic review has evaluated its physiological efficacy in this population. Objective This systematic review and meta-analysis aims to evaluate the efficacy of MPA on arterial blood gases and oxygenation parameters in COPD patients. Methods This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, ClinicalTrials.gov, and Web of Science till 15 October 2025. Eligible studies included randomized clinical trials (including crossover trials) and clinical trials involving patients diagnosed with COPD receiving MPA compared with placebo or standard care. Outcomes were pooled using the generic inverse-variance method to account for both crossover and parallel-group designs, with a random-effects model. Data analysis was performed using R version 4.5.3. The certainty of evidence was assessed for each outcome using the GRADE framework. Results Eight studies were included, comprising 210 randomized participants and 182 analyzed (seven randomized and one non-randomized trial). A significant improvement was observed in the MPA group compared with placebo for arterial partial pressure of carbon dioxide (PaCO₂) (MD − 6.07, 95% CI − 7.61 to − 4.53), partial pressure of oxygen in arterial blood (PaO₂) (MD + 4.40, 95% CI 2.10 to 6.70), and arterial oxygen saturation (SaO₂) during sleep (MD + 1.57, 95% CI 0.41 to 2.72) and wakefulness (MD + 1.98, 95% CI 0.28 to 3.67). No statistically significant difference was found between groups for blood acidity (pH) (MD + 0.018, 95% CI − 0.005 to 0.042). Conclusion This systematic review and meta-analysis indicates that MPA improves gas exchange in patients with COPD, with low certainty of evidence for PaCO₂ and very low certainty for PaO₂, SaO₂, and pH. Given the small number of included studies, the limited analyzed sample, and the reliance on surrogate physiological outcomes, these findings should be regarded as hypothesis-generating and require confirmation in larger, adequately powered randomized controlled trials with patient-important outcomes. Clinical trial number Not applicable.