Investigating Sex Differences in Systolic Blood Pressure Reductions Across Intervention Types: A Systematic Umbrella Review and Meta-Analysis

Background: 
Hypertension is the leading risk factor for mortality worldwide. However, our understanding of how treatment effects differ by sex remains limited, resulting in a lack of sex-specific recommendations for hypertension management. Specifically, it is unclear whether certain treatment types perform better in men or women for reducing systolic blood pressure (SBP). 

Objective: 
This umbrella review aims to systematically investigate sex differences in the effectiveness of SBP-lowering interventions, and to examine whether the treatment type can explain the magnitude and direction of any observed differences. 

Methods:
The Cochrane Database for Systematic Reviews and MEDLINE were searched up to August 2024 for eligible reviews published in English within the last ten years. All systematic reviews and meta-analyses of randomised controlled trials (RCTs) that investigated SBP-lowering interventions in adults and reported separate effect estimates for men and women were included. The tool "AMSTAR2" was used for critical appraisal. Within-review sex differences were synthesised in a random-effects meta-analysis. Pre-defined subgroup analyses were conducted to investigate sex differences across treatment categories, and a post hoc meta-regression was used to explore heterogeneity. 

Results:

Seventeen reviews summarizing 533 RCTs were pooled for analysis. Three categories of interventions were identified: Diet, sports, and supplementation. Of note, there were no reviews on pharmaceutical interventions that could be included in the analysis. No sex differences were observed overall (weighted mean sex difference = 0.30; CI -0.61, 1.21; p = 0.52) or within any intervention category. There was no variation between intervention categories (p = 0.92). The overall quality of reviews was low, with none specifically designed to investigate sex differences. 

Conclusion: 
While this umbrella review demonstrates the feasibility of quantitatively synthesising evidence across various interventions types, it does not provide any evidence of systematic sex differences in the SBP-lowering efficacy of dietary, sports and supplementation interventions, thereby reinforcing existing guidelines that recommend uniform treatment strategies for men and women. Further high-quality research is required to confirm these findings and to enhance our understanding of sex differences in antihypertensive pharmaceuticals and long-term outcomes.