Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome Susceptibility

Background The incidence of multiple sclerosis (MS) is rising in women. Objective To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content. Methods We conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record. Results We identified 400 women with incident MS/CIS and 3904 matched controls. Forty-percent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95% CI = 1.21-1.91; p< 0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95% CI = 1.29-2.37; p< 0.001) than norethindrone (adjusted OR = 1.57, 95% CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95). Conclusions Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.