The association between prescribed hormonal contraception and the risk of MS in England.

Research question: Is exposure to hormonal contraception (HC) associated with the risk of developing multiple sclerosis (MS)? Background: MS is a disabling neurological disease characterised by central nervous system inflammatory demyelination leading to neurodegeneration. In the UK, the median age at diagnosis is 30 years and MS is the leading cause of neurological disability in young adults. After puberty, MS becomes more frequent in females, reaching a 2-3:1 female:male ratio in adults. Female sex hormones are thought to play a part in disease pathogenesis. HC is used by a quarter of women in the UK as a contraceptive method. It is also used by some young women to treat acne and a few other conditions. Our recent systematic review of previous studies on the association of HC and MS identified three groups showing: a) an association between HC and MS, b) a protective effect of HC, and c) no association. Methodological limitations of previous studies include small sample size and recall bias. The inconclusive results of previous studies make it impossible to support women in making informed decisions about HC and the risk of MS, highlighting a research gap in the field. Our patient and public partners emphasised how this research is relevant not only to women at higher risk of developing MS (i.e., biological relatives of those affected), but also to young women in general, given the overlap between the age of use of HC and the age at highest risk of MS (20-40 years). Electronic healthcare records from the Clinical Practice Research Datalink (CPRD) provide an opportunity to conduct a large population-based study, representative of people with MS in England, to assess exposure to HC. Aim: To determine if there is an association between HC exposure and MS risk in England. The objectives are: i. To determine whether women who take HC are at higher or lower risk of developing MS than those who do not take HC. ii. To identify if different types of HC are associated with different risks of developing MS, giving women alternative treatment options if an association exists. iii. To explore the effect of HC duration on MS risk. Methods: A population-based nested case-control study using the CPRD to determine associations between identified HC and MS in England. Cases will be matched (on age and GP practice) to up to 4 controls using incidence density sampling. Exposure: HC commonly prescribed for women in the years leading up to diagnosis (0-6, 7-12, 13-24, 25-60, >60 months). Outcome measures: the odds of MS per HC type (oestrogen/progestogen combined, progestogen-only; oral or parenteral) versus non-use. Analysis: multivariable conditional logistic regression adjusted for a priori confounders such as smoking, body mass index and ethnicity. Timelines for delivery: 1/3/26 to 31/3/27 Anticipated impact: women making a more informed decision about taking HC. Dissemination: We will publish our work and target prescribing, primary care, and neurology committees. We will engage with MS support groups, discussion forums (e.g.Mumsnet) and social media (e.g.LinkedIn/Facebook) to share details with healthcare professionals and patients.