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Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Department of Medical Specialist.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
2010 (English)In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, no 7, 2835-2837 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to evaluate whether age of onset of multiple sclerosis is related to use of combined oral contraceptives and/or timing of childbirth. The results showed that use of combined oral contraceptives and childbirth before the first multiple sclerosis symptom was correlated to a higher mean age at the onset of the disease.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2010. Vol. 94, no 7, 2835-2837 p.
Keyword [en]
Multiple sclerosis, estrogen, combined oral contraceptives
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-63156DOI: 10.1016/j.fertnstert.2010.06.045ISI: 000284573700084OAI: oai:DiVA.org:liu-63156DiVA: diva2:376662
Note
Original Publication: Per Holmqvist, Mats Hammar, Anne-Marie Landtblom and Jan Brynhildsen, Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis, 2010, Fertility and Sterility, (94), 7, 2835-2837. http://dx.doi.org/10.1016/j.fertnstert.2010.06.045 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2017-12-11
In thesis
1. Multiple Sclerosis in relation to sex steroid exposure
Open this publication in new window or tab >>Multiple Sclerosis in relation to sex steroid exposure
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Multiple sclerosis (MS) is a potentially severe chronic inflammatory disease of the central nervous system (CNS) and is usually diagnosed between 20 and 40 years of age. The incidence of MS is two to three times higher among women and the type and course of the disease often differ between the sexes. Sex steroids, especially estrogens, have been shown to influence the immunopathology involved in MS and the mouse model experimental allergic encephalomyelitis (EAE), as well as radiological and clinical signs of the disease. The ovarian cycle and hormonal contraception result in fluctuations in sex steroid concentrations that could possibly affect MS. The incidence of MS in women is highest at an age when a reliable contraceptive method is an important matter but the effects of estrogen-containing combined hormonal contraceptives (CHC) on MS have not been thoroughly studied. The general aim of the research for this thesis was to investigate how fluctuations in sex steroid exposure during the menstrual cycle and use of CHC affect MS in a clinical context.

Paper I is based on female MS patients with or without hormonal contraception. Symptoms were reported prospectively in an MS-symptom diary. In contrast with results from previous retrospective studies, 16 women without hormonal contraception reported fewer complaints regarding one out of 13 symptoms during the low estrogen/progesterone phase of the menstrual cycle. Seven women who used CHC experienced three of the symptoms significantly more strongly during the low estrogen/progestogen, pill-free period. In paper II 22 women with MS who used CHC reported higher scores for four out of 10 symptoms during the “pill-free” week, i.e. during the low-estrogen/progestogen phase using a modified symptom diary. Women with MS who did not use hormonal contraception reported no differences in symptom scores between high and low estrogen/progesterone phases. Paper III included 770 women who answered a questionnaire that was designed to investigate whether longer periods of high estrogen concentration such as CHC-use and pregnancies delay the onset of MS. The mean age at MS onset was significantly higher among women who had been using COC before their first MS symptom (26 vs 19 years, p<0.001) and the longer the women had been using COC the higher the mean age at MS onset. The number of children born before the first symptom of MS was positively correlated with age at MS onset (r=0.6; p<0.001). Paper IV aimed to investigate if peripheral blood levels of cytokines, chemokines, and transcription factors for different T helper (Th) cell subsets change in relation to high and low estrogen/progestogen states in women with MS and healthy controls with and without CHC using multiplex bead technology and qPCR. Expression of the B cell-associated chemokine CXCL13 was generally higher in high the estrogen/progestogen phase than in the low estrogen/progestogen phase and the expression of the transcription factors showed a general activation of peripheral blood T cells during high estrogen and progestogen phases in women with MS as well as in healthy women.

The clinical implication of these and other studies is that there is probably no reason for avoiding CHC as a contraceptive method in women with MS. It is also probably beneficial for women with MS to use CHC regimens with longer estrogen periods and fewer pill-free intervals. Future studies should investigate the outcomes of such regimens on relapse rate, MRI lesions, disease activity related cytokines and chemokines in CSF and peripheral blood and the women’s experiences of their symptoms.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 83 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1415
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-108888 (URN)10.3384/diss.diva-108888 (DOI)978-91-7519-257-4 (ISBN)
Public defence
2014-09-11, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
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Supervisors
Available from: 2014-07-10 Created: 2014-07-10 Last updated: 2014-07-11Bibliographically approved

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Holmqvist, PerHammar, MatsLandtblom, Anne-MarieBrynhildsen, Jan

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Department of Clinical and Experimental MedicineFaculty of Health SciencesObstetrics and gynecologyDepartment of Gynecology and Obstetrics in LinköpingNeurologyDepartment of NeurologyDepartment of Medical Specialist
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