The Pill Leaves Fewer Disability Traces and Holds no Association With Future Multiple Sclerosis Risk: Evidence From a Systematic Review and Meta-analysis
Rana Sameh1, Mohamed I. Mohamed1, Noor M. Elshinawy1, Nasser A. Abdelall2, Mona AF Nada3
1Alexandria University, Faculty of Medicine, Alexandria, Egypt, 2Department of Neurology, Louisiana State University School of Medicine, New Orleans, LA, 3Department of Neurology, Cairo University, Faculty of Medicine, Giza, Egypt
Objective:

To provide the largest-to-date meta-analytic evidence of oral contraceptives’ (OCs) impact on MS relapse and future risk of development.


Background:
Historical evidence from peer-reviewed literature suggests lower MS risk in women consuming OCs. Emerging literature suggests no association. Further, OCs emerged over the years as promising protective medications against MS relapse severity, yet conflicts remain. We purport to settle these debates.
Design/Methods:
A comprehensive MeSH-guided search - with no publication period or linguistic restrictions - across PubMed, Scopus, and Web of Science was attempted. Best adjusted risk ratios (RRs) were pooled using a random-effects model in R software. Sensitivity and subgroup analyses were performed based on OC duration, recency of use, and hormonal composition.
Results:

We identified 20 relevant studies. Ever OC use did not increase the future risk of MS (RR: 1.07, 95% CI: 0.92-1.24, I2: 66.5%). However, upon elimination of an outlier, a modest association was revealed (RR: 1.14, 95% CI: 1.00-1.30, I2: 51.8%). A pooled analysis of individuals with past use of OCs yielded no significant association with MS development. This observation was sustained following a leave-one-out test (RR: 1.23, 95% CI: 0.99-1.52, I2: 0%). Similarly, a current use of OCs did not put women at an increased MS risk. Duration of OC consumption appears not to influence MS risk either (5 years or more: 95% CI: 0.88-1.52, I2: 51.7%; 2 years or less: 95% CI: 0.95-1.25, I2: 0%). Finally, to assess the differential impact of OC types, a meta-analysis of progesterone-only OCs concluded insignificant MS future risk following consumption. A systematic literature review suggests that OCs are associated with lower expanded disability status scale and MS severity scores, though with no unanimous consensus on relapse rate reductions.


Conclusions:

Collectively, these findings challenge historical doubts and support the reassurance of OC safety in women at risk for or living with MS.


10.1212/WNL.0000000000217844
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