Use of oral contraceptives before an MS diagnosis was linked with a lower risk of progression independent of relapse activity (PIRA) in a retrospective study.
Contraceptive use delayed a PIRA event by 2.5 years.
There was no association between duration of contraceptive use and PIRA risk.
The use of oral contraceptives before a multiple sclerosis (MS) diagnosis was tied to a lower risk of progression independent of relapse activity (PIRA), a retrospective cohort study suggested.
Over a mean follow-up of 17 years, women who used oral contraceptives before MS was diagnosed had a 26% lower risk of PIRA (HR 0.74, 95% CI 0.61-0.89, P=0.0018), reported Federica Esposito, MD, PhD, of IRCCS Ospedale San Raffaele in Milan, Italy, and colleagues.
Median time to a PIRA event was delayed by approximately 2.5 years for these women compared with those who had not used oral contraceptives (9.94 vs 7.5 years, P=0.0018), the researchers wrote in the Journal of Neurology, Neurosurgery, and Psychiatry.
There was no association between the duration of contraceptive use before MS diagnosis and PIRA risk. Women who reported pregnancy before diagnosis also showed a shorter time to first PIRA event (HR 1.22, 95% CI 1.006-1.47, P=0.043).
Preventing disability accumulation that occurs independent of relapses "remains the biggest challenge for clinicians and people living with MS," Esposito and co-authors pointed out.
Lifestyle interventions may be a key strategy, given the lack of pharmacological options against MS disease progression, they noted. "Particularly, the use of early oral contraceptives appears to offer a protective long-term effect against disability progression, prompting future -- and possibly interventional -- large prospective studies on women with MS," they wrote.
The findings need to be confirmed with further research, observed Patricia Coyle, MD, of Stony Brook University Hospital in New York, who was not involved with the study.
The researchers suggested "there might be a relationship to oral contraceptive use maybe being a little bit protective if it's used before you develop MS," Coyle said. "That's a huge leap, and it's only based on 1,210 patients."
No previous reports have shown this relationship, she noted. "This [study] obviously looked at even before you had the diagnosis of MS, perhaps in the pre-diagnosis prodromal state, so it raises very interesting questions. You would really want further studies to probe and see if this really stands up," she added.
Esposito and co-authors followed 1,210 MS patients from the San Raffaele MS Center for a mean duration of 16.7 years. Hormone-related data were taken from a questionnaire given to patients between 2019 and 2023.
The cohort included female patients who had a diagnosis of MS based on 2017 McDonald criteria. Patients were excluded if they had a secondary or primary progressive MS course at the start of follow-up, or had less than three assessments on the Extended Disability Status Scale (EDSS).
Mean age at MS onset was 30.1 years. Participants had a mean EDSS score of 2.0 at their last follow-up visit.
PIRA was defined as 12-week confirmed disability progression independent of recent (less than 30 days) relapses. Overall, PIRA occurred in 40% of participants throughout the follow-up period.
Menopause at the time of diagnosis was associated with a shorter time to a PIRA event (HR 1.82, 95% CI 1.24-2.67, P=0.0022), which likely reflected "the established effect of older age, which increases the risk of PIRA," the authors noted.
No difference in the time to first PIRA event was seen in patients who reported an abortion, menstrual irregularity, or the use of fertility therapy.
The findings "support a complex interplay between hormonal changes, age, inflammation and MS progression, as suggested by an expanding body of evidence," the researchers wrote. "Among the factors examined, the use of oral contraceptives warrants special attention, as a modifiable and potentially actionable intervention."
Limitations included the study's single-center and retrospective design, which may limit generalizability or introduce recall bias, Esposito and colleagues acknowledged. The analysis did not account for treatment effects, but current evidence suggests available therapies have limited efficacy in reducing PIRA, they added.
Disclosures
The study is part of the FindingMS Project, supported by ERA PerMed-JTC2018 (cofunded by the European Commission).
The researchers reported no conflicts of interest.
Primary Source
Journal of Neurology, Neurosurgery and Psychiatry
Source Reference: Giordano A, et al "Sex hormone-related factors and the risk of PIRA in women with multiple sclerosis" J Neurol Neurosurg Psychiatry 2025; DOI: 10.1136/jnnp-2024-335547.