Stress, salivary cortisol and periodontitis: A systematic review and meta-analysis of observational studies

•Higher salivary cortisol levels are significantly more associated with aggressive periodontitis•Salivary cortisol levels had no significance in healthy and chronic periodontitis patients.•Larger, well-designed, methodologic improved and more representative studies are needed to confirm this possible association.•Retrospective exposure and baseline cortisol assessment, hormonal variation, oral contraceptives and exercise are major criteria This meta-analysis aims to systematically assess whether periodontitis has a meaningful effect on salivary cortisol, reflecting changes on free blood cortisol levels. The Cochrane Handbook and the PRISMA statement were used as reporting guidelines. The MEDLINE-PubMed, Google Scholar, EMBASE, and CENTRAL databases were searched until September 2017 to identify eligible studies, screened by seven independent authors and verified by an eighth. Studies comparing salivary cortisol level of periodontitis cases to controls were included. Data were extracted using a predefined table and since all papers were non-randomized clinical trials they were appraised using Downs and Black tool. DerSimonian random effects meta-analysis was performed using OpenMetaAnalyst. Six cross-sectional studies were included, with 258 participants with chronic periodontitis and 72 with aggressive periodontitis, in a total of 573 participants. Overall results showed that aggressive periodontitis patients have, on average, 53% higher salivary cortisol levels than healthy controls 1.53 (1.11–2.12). Meta-regression exploring the relationship among salivary cortisol levels and periodontal measures, i.e., periodontitis severity, showed a global neutral effect, although this result requires future confirmation due to the low power of the model. Observational studies results suggest that subjects with aggressive periodontitis have higher salivary cortisol levels than healthy ones or patients with chronic periodontitis. Such salivary cortisol response difference may have a negative impact on the periodontium, contributing to worse the burden of aggressive periodontitis disease. In the future, wide and well-designed longitudinal studies should be carried out in order to extensively confirm this possible effect, considering the complex nature of periodontitis and its many confounders factors that may contribute to this outcome.