Abstract Background Sex hormones can influence susceptibility to multiple sclerosis (MS). Around 400 million women worldwide use hormonal contraceptives (HC), which contain synthetic versions of female sex hormones. Evidence on HC use and MS risk is inconclusive. The aim of this study was to synthesise studies on the association between prescribed HC and the risk of MS. Methods Medline, Embase, Cochrane library and grey literature were systematically searched on 7th November 2024. Two reviewers independently screened, extracted data and appraised each study’s quality using the Joanna Briggs Institute critical appraisal tool. Pre-determined criteria were used to differentiate between high- and low-quality studies. Random-effects meta-analysis was conducted for studies providing the same effect measure; heterogeneity was assessed. Sensitivity analyses included only high-quality studies. Results Eleven studies were included, six of these were cohort and five were case-control. Three studies were deemed high-quality. Five of the studies found no significant association between HC use and MS risk, four found a decreased risk, and two found an increased risk. Meta-analysis of the unadjusted odds ratio (OR) showed a significantly increased risk of MS with HC use of 1.28 (95% CI 1.08–1.52). However meta-analysis of adjusted ORs and sensitivity analyses showed no significant association. Heterogeneity was high. Conclusion No statistically significant association between HC use and MS risk was observed. The meta-analyses indicate a possible increased risk warranting further investigation. Given that heterogeneity was high and only three of the included studies were classed as high-quality, a well-designed study is needed to clarify this association.
McDonald et al. (Fri,) studied this question.