Sex effects across the lifespan in women with multiple sclerosis

Kristen M Krysko¹, Jennifer S Graves², Ruth Dobson³, Ayse Altintas⁴, Maria Pia Amato⁵, Jacqueline Bernard⁶, Simona Bonavita⁷, Riley Bove⁸, Paola Cavalla⁹, Marinella Clerico¹⁰, Teresa Corona¹¹, Anisha Doshi¹², Yara Fragoso¹³, Dina Jacobs¹⁴, Vilija Jokubaitis¹⁵, Doriana Landi¹⁶, Gloria Llamosa¹⁷, Erin E Longbrake¹⁸, Elisabeth Maillart¹⁹, Monica Marta²⁰, Luciana Midaglia²¹, Suma Shah²², Mar Tintore²¹, Anneke van der Walt¹⁵, Rhonda Voskuhl²³, Yujie Wang²⁴, Rana K Zabad²⁵, Burcu Zeydan²⁶, Maria Houtchens²⁷, Kerstin Hellwig²⁸

Affiliations

¹ Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, 675 Nelson Rising Lane, Suite 221, San Francisco, CA 94158, USA.
² Department of Neurosciences, University of California San Diego, UCSD ACTRI, La Jolla, CA, USA.
³ Preventive Neurology Unit, Wolfson Institute of Preventive Neurology, Queen Mary University of London, London, UK.
⁴ Department of Neurology, School of Medicine, Koc University, Istanbul, Turkey.
⁵ Department NEUROFARBA, Section of Neurosciences, University of Florence, Florence, Italy.
⁶ Department of Neurology, Oregon Health Science University, Portland, OR, USA.
⁷ Department of Advanced Medical and Surgical Sciences, University of Campania, "Luigi Vanvitelli", Naples, Italy.
⁸ Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco CA, USA.
⁹ Department of Neuroscience and Mental Health, City of Health and Science University Hospital of Torino, Turin, Italy.
¹⁰ Department of Clinical and Biological Sciences, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
¹¹ Clinical Laboratory of Neurodegenerative Disease, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico.
¹² Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
¹³ Multiple Sclerosis & Headache Research Institute, Santos, SP, Brazil.
¹⁴ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
¹⁵ Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
¹⁶ Department of Systems Medicine, Multiple Sclerosis Center and Research Unit, Tor Vergata University and Hospital, Rome, Italy.
¹⁷ Neurologia Integral, Tlalpan, Mexico City, Mexico.
¹⁸ Department of Neurology, Yale University, New Haven, CT, USA.
¹⁹ Department of Neurology, Pitie Salpetriere Hospital, Paris, France.
²⁰ Neurosciences and Trauma Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²¹ Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain.
²² Department of Neurology, Duke University, Durham, NC, USA.
²³ Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
²⁴ Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
²⁵ Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
²⁶ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
²⁷ Department of Neurology, Partners MS Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁸ Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.

PMID: 32655689
PMCID: PMC7331774
DOI: 10.1177/1756286420936166

Review

Sex effects across the lifespan in women with multiple sclerosis

Kristen M Krysko et al. Ther Adv Neurol Disord. 2020.

. 2020 Jul 1:13:1756286420936166.

doi: 10.1177/1756286420936166. eCollection 2020.

Authors

Affiliations

¹ Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, 675 Nelson Rising Lane, Suite 221, San Francisco, CA 94158, USA.
² Department of Neurosciences, University of California San Diego, UCSD ACTRI, La Jolla, CA, USA.
³ Preventive Neurology Unit, Wolfson Institute of Preventive Neurology, Queen Mary University of London, London, UK.
⁴ Department of Neurology, School of Medicine, Koc University, Istanbul, Turkey.
⁵ Department NEUROFARBA, Section of Neurosciences, University of Florence, Florence, Italy.
⁶ Department of Neurology, Oregon Health Science University, Portland, OR, USA.
⁷ Department of Advanced Medical and Surgical Sciences, University of Campania, "Luigi Vanvitelli", Naples, Italy.
⁸ Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco CA, USA.
⁹ Department of Neuroscience and Mental Health, City of Health and Science University Hospital of Torino, Turin, Italy.
¹⁰ Department of Clinical and Biological Sciences, University of Torino, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
¹¹ Clinical Laboratory of Neurodegenerative Disease, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico.
¹² Department of Neuroinflammation, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
¹³ Multiple Sclerosis & Headache Research Institute, Santos, SP, Brazil.
¹⁴ Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
¹⁵ Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
¹⁶ Department of Systems Medicine, Multiple Sclerosis Center and Research Unit, Tor Vergata University and Hospital, Rome, Italy.
¹⁷ Neurologia Integral, Tlalpan, Mexico City, Mexico.
¹⁸ Department of Neurology, Yale University, New Haven, CT, USA.
¹⁹ Department of Neurology, Pitie Salpetriere Hospital, Paris, France.
²⁰ Neurosciences and Trauma Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
²¹ Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain.
²² Department of Neurology, Duke University, Durham, NC, USA.
²³ Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA.
²⁴ Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
²⁵ Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
²⁶ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
²⁷ Department of Neurology, Partners MS Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁸ Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.

PMID: 32655689
PMCID: PMC7331774
DOI: 10.1177/1756286420936166

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating central nervous system disorder that is more common in women, with onset often during reproductive years. The female:male sex ratio of MS rose in several regions over the last century, suggesting a possible sex by environmental interaction increasing MS risk in women. Since many with MS are in their childbearing years, family planning, including contraceptive and disease-modifying therapy (DMT) counselling, are important aspects of MS care in women. While some DMTs are likely harmful to the developing fetus, others can be used shortly before or until pregnancy is confirmed. Overall, pregnancy decreases risk of MS relapses, whereas relapse risk may increase postpartum, although pregnancy does not appear to be harmful for long-term prognosis of MS. However, ovarian aging may contribute to disability progression in women with MS. Here, we review sex effects across the lifespan in women with MS, including the effect of sex on MS susceptibility, effects of pregnancy on MS disease activity, and management strategies around pregnancy, including risks associated with DMT use before and during pregnancy, and while breastfeeding. We also review reproductive aging and sexual dysfunction in women with MS.

Keywords: breastfeeding; multiple sclerosis; pregnancy; sex differences; sex hormones; women.

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Conflict of interest statement

Conflict of interest statement: Kristen M. Krysko is funded by a Sylvia Lawry Physician Fellowship through the National Multiple Sclerosis Society [FP-1605-08753 (Krysko)]. She also had fellowship funding through Biogen. Jennifer S. Graves has received recent grant and clinical trial support from the National MS Society, Race to Erase MS, UCSF CTSI RAP program, Biogen, and Genentech. She has received honoraria from Biogen and Genzyme for non-promotional trainee education events. She has received personal fees from Novartis and Celgene. Ruth Dobson works within the PNU, which is funded by Barts Charity. She receives grant support from the UK MS Society, Horne Family Charitable Trust, Biogen, Celgene, and Merck. She has received honoraria for Advisory boards and/or educational actives from Biogen, Teva, Sanofi, Merck, and Roche. Ayse Altintas has received speaker honoraria for non-promotional education events and travel grants from Merck, TEVA, and Novartis. Maria Pia Amato has received research grants and honoraria as a speaker and member of advisory boards by Biogen, Merck, Roche, Teva, Sanofi Genzyme, and Novartis. Jacqueline Bernard has served as a Consultant for Biogen. Simona Bonavita has received speaker honoraria and/or Advisory Board fees from Novartis, Teva, Sanofi-Genzyme, Biogen-Idec, and Merck-Serono. Riley Bove is funded by a Harry Weaver Scholarship through the National Multiple Sclerosis Society. She has received recent research support from the National Multiple Sclerosis Society, the California Initiative to Advance Precision Medicine, the Hilton Foundation, the Sherak Foundation, the Weill Innovation Fund, and the UCSF CTSI RAP program. She has received consulting fees from Alexion, Biogen, EMD Serono, Genzyme Sanofi, Novartis, and Roche Genentech. Paola Cavalla has received recent grants and clinical trial support from Biogen and Sanofi-Genzyme. She has received honoraria from Almirall, Biogen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva for non-promotional trainee education events. Marinella Clerico has received personal compensation for speaking/advising/consulting from Merck, Sanofi-Genzyme, Biogen, Novartis, and Teva; was supported in travelling expenses for congresses from Merck, Sanofi-Genzyme, Biogen, Novartis, Teva, and Almirall; has received research grants from Italian MS Foundation (FISM), Italian Ministry of Research, Merck, Sanofi-Genzyme, Biogen, and Novartis. Teresa Corona declares no conflicts of interest. Anisha Doshi declares no conflicts of interest. Yara Fragoso declares no conflicts of interest. Dina Jacobs has clinical research trial support from Genentech/Roche, Biogen, Novartis, and Medimmune, and has received consulting/advisory board honoraria from Celgene, Biogen, Novartis, EMD Serono, and Sanofi Genzyme. Vilija Jokubaitis is funded by an MS Research Australia Fellowship (16-0206). She receives project grant support from the National Health and Medical Research Council (NHMRC) of Australia (GNT1156519) and MS Research Australia (18-0424; 19-0665). She has received honoraria from Biogen and Roche for non-promotional educational activities, and conference travel support from Merck and Roche. Doriana Landi has received travel funding from Roche, Biogen, Merck-Serono, Sanofi-Genzyme, and Teva; speaking or consultations fees from Bayer-Schering, Sanofi-Genzyme, Merck-Serono, Teva, Biogen, Roche, Mylan, and Almirall. Gloria Llamosa declares no conflicts of interest. Erin E. Longbrake has received honoraria from Genentech, Genzyme, Alexion, Biogen, EMD Serono, and Celgene. She has grant support from NIH K23NS107624 and Race to Erase MS. Elisabeth Maillart has received grant support from Biogen, Novartis, and Roche. She has also received consultant honoraria from Biogen, Celgene, Merck-Serono, Novartis, Roche, Sanofi Genzyme, and Teva. Monica Marta has received honoraria and travel costs from Genzyme, AbbVie, Roche, and Novartis. Luciana Midaglia declares no conflicts of interest. Suma Shah has received honoraria from Biogen. Mar Tintoré has received compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merck-Serono, Biogen Idec, Teva Pharmaceuticals, Sanofi-Aventis, Novartis, Almirall, Genzyme, Viela Bio, and Roche. Anneke van der Walt has served on scientific advisory boards, received travel support and speaker’s honoraria from Biogen, Merck, Novartis, and Roche. She is supported by funding from the National Health and Medical Research Council of Australia. Rhonda Voskuhl declares no conflicts of interest. Yujie Wang declares no conflicts of interest. Rana K. Zabad has been a site investigator or site PI for clinical trials funded by Adamas, Biogen, Genentech, Novartis, Sunpharma, and PCORI. In the last 5 years, she has served as a consultant for Bayer, Biogen, Genentech, Celgene, Genzyme, TEVA Neuroscience, and TG therapeutics, and has given unbranded lectures sponsored by TEVA, Novartis, and Genentech. She is a member of the Adjudication Committee for a clinical trial of biotin in primary and secondary progressive multiple sclerosis sponsored by PAREXEL and medDay pharmaceutical. Burcu Zeydan reports funding from NIH (NIA: U54 AG44170). Maria Houtchens has received grant support from Biogen, Serono, Sanofi Genzyme, and Genentech/Roche. She also received consultant honoraria from Biogen, Serono, Sanofi Genzyme, Roche, and Celgene. Kerstin Hellwig receives grant support from the Innovation Fund of the Federal Joint Committee. She has also received consultant and speaker honoraria and grant support from Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, Roche, and Teva.

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Sex effects across the lifespan in women with multiple sclerosis

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Sex effects across the lifespan in women with multiple sclerosis

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Abstract

Conflict of interest statement

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