Possible interactions between sex steroids and plasma lipoprotein metabolism in multiple sclerosis

Abstract

Introduction: Sex hormones may modulate the clinical course of multiple sclerosis (MS) [1]. Sex steroids interact with cholesterol metabolism and the serum lipid profile has been associated with progression of disability in MS patients [2]. We hypothesized that the putative associations between lipoprotein metabolism and severity of MS could be modulated by sex steroids exposure. The aim of this study was to investigate whether oral contraceptives (OC) use changes the lipoprotein profile associated with disability in patients with MS.

Materials and methods: Clinical data was collected from 133 women with the diagnosis of relapsing-remitting MS prior to the start of disease-modifying therapies. Patients who were using OC after disease onset (DO) (OC+, n = 57) were compared to those who never used OC or discontinued its intake before DO (OC−, n = 76). In both cohorts of subjects, the associations between the apolipoprotein E (ApoE) polymorphism and plasma lipid levels and the Expanded Disability Status Score (EDSS) and the Multiple Sclerosis Severity Score (MSSS) were evaluated using a hierarchic multiple regression analysis after adjustment for confounders. Approval for the study by the local Ethical Committee was obtained and all participants signed a written informed consent.

Results: In patients carrying the E3/E3 phenotype of ApoE (73.7%), EDSS and MSSS were lower in OC + in comparison with OC- subgroup of patients (p < 0.01). In this population, LDL and total cholesterol were associated with EDSS (p = 0.005 and p = 0.041, respectively), and LDL and the triglyceride/high density lipoprotein ratio with MSSS (p = 0.029 and p = 0.016, respectively) in OC + patients. ApoE levels were associated with EDSS (p = 0.012) and MSSS (p = 0.025) in OC- subgroup of patients.

Discussion and conclusions: OC use changes the serum lipoprotein profile associated with disability in patients with MS. These results suggest that lipoprotein metabolism could be involved in the modulatory effects of sex steroids in the disease.

Acknowledgements

The authors acknowledge funding from Merck, Bayer Health Care and Teva, in Portugal (Projects PPAR/2007, Lilericop/2004 and Pillbeta-Lipesbeta/2003-2005) and are grateful to nurse Cristina Araújo for help in research and to Maria de Lurdes Andrade, Maria Adalgisa Tavares and Firmina Lebre for technical assistance.