Cortisol and periodontitis: Prospective observational and Mendelian randomization studies.

Purpose: Cortisol has obesogenic, hyperglycemic and immunomodulating effects. Preclinical and observational research suggested that it is associated with periodontitis but the evidence for potential causality in humans is sparse. We triangulated results from prospective observational and Mendelian randomization (MR) analyses to further explore this. Methods: Using pooled data from 3,388 participants of two population cohort studies embedded in the Study of Health in Pomerania (SHIP) project, we associated serum cortisol levels with periodontal outcomes measured after a median follow-up time of 6.9 years, adjusting for confounding and selection bias using propensity score weighting and multiple imputation. We further examined the effect of genetically proxied plasma morning cortisol levels on periodontitis using two-sample MR of 17,353 cases and 28,210 controls. Results: In SHIP, we found that cortisol levels were positively associated with follow-up levels of mean clinical attachment level (CAL), deep interdental CAL and bleeding on probing but were unrelated to mean probing pocket depth and deep periodontal pockets. In MR analysis, cortisol was not associated with periodontitis. Conclusion: The observational study revealed a prospective association of spot cortisol with makers of periodontitis. Contrary to observational studies, genetically instrumented, long-term cortisol was unrelated to periodontitis. Our results find no univocal evidence that cortisol plays a role in periodontitis pathology, casting doubt on cortisol-related pathways.