Oral Contraceptives Do Not Increase Risk of 2nd Attack, Worse Disease
The use of oral contraceptives does not increase the risk of a second attack of symptoms or the progression of disability in women with clinically isolated syndrome (CIS) or early stage multiple sclerosis, a study demonstrated.
Notably, the researchers also “did not find a protective effect on disability accumulation” from the use of oral birth control, as suggested in other studies. The team said their use of different measures for assessing the impact of oral contraceptives on MS disability enabled what they believe to be “a more robust disability outcome.”
“These findings are relevant for clinical counseling for young women with CIS and/or recent MS diagnosis,” the researchers wrote.
The study, “Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis,” was published in the journal Multiple Sclerosis Journal.
Exposure to hormones has long been suspected of playing a role in MS risk and progression. Estrogen, in particular, has been shown to be protective in animal models of MS and to reduce disease activity in pregnant women.
Yet, how estrogen-based oral contraceptives impact MS development and progression remains uncertain. Studies have suggested protective, neutral, or even negative effects of oral contraceptives on MS risk.
There also is little evidence to indicate whether oral contraceptives affect the transition from CIS to confirmed MS in women. However, as the first exposure to oral contraceptives can overlap with the average age of CIS onset, further understanding of the risks is essential for women undergoing clinical counseling, the researchers said.
To learn more, investigators at the Autonomous University of Barcelona, in Spain, now set out to determine whether oral contraceptive use by women with CIS, or who are in the early stages of MS, increases the risk of transitioning to MS or worsened MS disability.
The study was part of the Barcelona MS & Gender Project — an observational study enrolling CIS patients younger than age 50 whose disease is suggestive of nerve demyelination (loss of myelin).
Of note, CIS is a first episode of neurological symptoms that last at least 24 hours and are suggestive of MS. For an MS diagnosis, patients must experience multiple episodes — the multiple in multiple sclerosis — of neurologic symptoms caused by brain inflammation.
Here, female participants were invited to complete a self-administered survey on reproductive information — such as number of pregnancies, date, and outcome — exposure to hormone therapies, and other environmental risk factors. The team also collected demographics, disease-related information, and data on the use of disease-modifying treatments (DMTs).
Of 1,137 patients enrolled in the Barcelona MS & Gender Project, 764 (67.2%) were female; 495 of them (65%) provided a completed questionnaire. Although respondents had a similar age as non-respondents, more patients who filled out the survey had an abnormal first MRI brain scan (49.4% vs. 34.4%) and more frequently used DMTs (54% vs. 16%). They also had a longer follow-up (9.7 vs. 5.2 years).
Among respondents, a total of 389 women (78.6%) had used oral contraceptives, and 341 (68.9%) had started on their birth control before their CIS diagnosis. Participants who began oral contraceptives before CIS were older at CIS, had a smaller self-reported body size at their first menstrual cycle, and had a shorter follow-up.
A second exacerbation of neurologic symptoms was experienced by 54% of women during their follow-up, and 66 (13%) reached a moderate disability level with no walking impairment, as defined by an expanded disability status scale (EDSS) score of 3.0. Also, at the time of the questionnaire, 28.9% of women did not fulfill the criteria for an MS diagnosis.
Yet, the proportion of participants who used oral contraceptives was similar among those who were and were not diagnosed at the time of the questionnaire (77.3% vs. 81.8%) and between patients who had and had not reached an EDSS score of 3.0 (77.3% vs. 78.8%).
A simple time-dependent analysis calculated from the beginning of hormone exposure showed no association between the use of oral contraceptives and the risk of clinically definite MS diagnosis or reaching an EDSS score of 3.0.
The team then conducted the same analysis after adjusting for factors such as age at CIS, location of CIS damage, presence of MS-related antibodies, number of initial total brain lesions and active disease lesions, and initial DMT use. This calculation also included adjustments for body size at first menstrual cycle and smoking at the time of the CIS.
One factor the researchers took into account was that “women with a milder disease could more likely be engaged in sexual activity and thus exposed to contraceptives as compared to women with a more severe course of the disease.”
Again, no associations were found between oral contraceptive use and progression to clinically definite MS or disability worsening.
Finally, in an analysis that included the entire study group — no oral contraceptive use, oral contraceptive use before the CIS, and oral contraceptive use after the CIS — there was no increased risk of a second symptom attack or an EDSS of 3.0 and use of oral contraceptives.
“Exposure to [oral contraceptives] is not associated … with the risk of second attack or with disability accumulation in CIS patients,” the researchers wrote, adding that the findings might indicate that the “low doses of estrogen … in contemporary [oral contraceptives] might not be high enough to play an anti-inflammatory role in CIS patients.”