March 06, 2014

Women with multiple sclerosis (MS) or clinically isolated syndrome (CIS) were more likely to have used oral contraceptives in the 3 years before their diagnosis than women who did not have MS or CIS, the results of a new case-control study show.

"Independent of age, smoking status, parity and obesity, there was a link between the use of oral contraceptives and the development of the first symptoms of MS," lead author Kerstin Hellwig, MD, a postdoctoral research fellow at Kaiser Permanente Southern California, commented to Medscape Medical News. "These findings suggest that using hormonal contraceptives may be contributing at least in part to the rise in the rate of MS among women."

The study will be presented at the American Academy of Neurology (AAN) 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.

35% Increased Risk

The researchers investigated such an association in a population-based nested case-control study from the membership of Kaiser Permanente Southern California. They identified 305 women with MS or CIS first diagnosed between 2008 and 2011 who had at least 3 years of continuous membership before symptom onset.

Each case was matched with 10 controls on the basis of age, race/ethnicity, and membership characteristics. Data were obtained from the complete electronic health record and analyzed using conditional logistic regression, adjusted for smoking and live births 3 years before symptom onset.

Results showed that 29.2% of cases and 23.5% of controls had used a hormone contraceptive for at least 3 months within the 3 years before symptom onset. The majority used estrogen/progestin combination preparations.

Women who used any hormonal contraceptive in the 3 years before symptoms onset had a 35% increased risk of developing MS/CIS. Those who had stopped using hormonal contraceptives at least 1 month prior to symptom onset had a 50% increased risk.

Table. Risk for MS/CIS in Women With a History of Hormonal Contraceptive Use vs Nonusers

Group Odds Ratio for MS/CIS (95% Confidence Interval) P Value
Ever users 1.35 (1.01 - 1.80) .04
Not current users 1.50 (1.05 - 2.14) .026


Dr. Hellwig said, "This is a small effect and we cannot make any recommendations based on these observations."

Noting that 2 previous studies have suggested a similar association, she added that "this is just one more small part of the puzzle."

She explained that MS is more common in women, and some studies suggest the incidence is increasing in women but not in men, leading to questions of whether something in the changing lifestyle of women might explain this.

"Hormones play an important role in many diseases, and it is known that pregnancy — which is associated with high estrogen levels — is protective against relapses in women who already have MS, so hormones appear to be involved in some way in this disease."

She noted that one idea is that low estrogen levels may trigger autoimmune disease, but there is no information on possible thresholds necessary for a protective or harmful effect.

The researchers did not measure other factors associated with the lifestyle of modern women, such as diet, activity levels, or how long they spent outside, so several potential confounders were probably not accounted for.

They are now planning to look at lifetime exposure because if the association was causal, the risk would be expected to increase with time of exposure.

This study was supported by the Kaiser Permanente Direct Community Benefit Funds, the National Institutes of Health, and the German Research Foundation.

American Academy of Neurology (AAN) 66th Annual Meeting, Philadelphia, April 26 to May 3, 2014. Abstract 1644.


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