Gender Gap in Autoimmunity.
In 1999, this report from Caroline Whitacre and her fellow members of the Task Force on Gender, Multiple Sclerosis, and Autoimmunity explained what was known at that time about gender differences in autoimmunity and identified areas for future research.
Some of the issues identified in relation to gender and MS include:
- MS is more common in women, but severity of the disease may be worse in men.
- The prevalence of MS and ratio of women to men has increased during the 20th century and continues to increase.
- In studies involving men with MS, male gender was predictive of a shorter time period before an assistive walking device was required. For example, men were quicker to need devices such as canes after diagnosis.
- Men have a higher rate of cerebellar involvement and a higher risk of primary-progressive disease, both of which are factors associated with a poorer prognosis. A study has found that progranulin gene variability increases the risk of PPMS in men.
- The disease in women tends to be more inflammatory with greater number of gadolinium-enhancing lesions. Men tend to develop more “black holes” as seen on MRI scans.
- Some studies have shown gender has no effect on life expectancy in MS. Some studies have shown shorter than expected life expectancies of men with MS, others have shown longer than expected life expectancies. Perhaps MS in men doesn’t make a difference after all in longevity.
What are some reasons that these might be true for men and women who have MS?
Autoimmune diseases in general are more prevalent in women than in men. The ratio of women to men who have rheumatoid arthritis between 2:1 to 3:1, very similar to MS. For lupus the ratio is 9:1 which is roughly the same for fibromyalgia. Little is known exactly why these diseases are more common in women, but research is trying to figure that out.
A study in Norway demonstrated that the prevalence of MS in women vs. men has increased over time. Based on the Oslo MS Registry, patients born from 1910 to 1980 and residing in Oslo when they were diagnosed were studied. Through those seven decades, the female to male ratio increased significantly from 1.48:1 to 2.30:1. Researchers also found that the ratio of initial relapsing-remitting (RRMS) to primary progressive (PPMS) disease course increased significantly from 1.93:1 to 16.00:1. Wow! The proportion of RRMS patients has grown eight-fold.
The question of why men needed assistive devices sooner after diagnosis has many possible answers. Perhaps women seek medical attention earlier and treatment more aggressively. Perhaps the disease does progress more rapidly for men. Men are diagnosed more often around the same time that their testosterone levels begin to decline later in middle-age. The protective roles of testosterone and estriol will be discussed in later posts.
Another study, from the LORSEP (Lorraine Multiple Sclerosis) population, confirms the finding that the ratio of women vs. men who develop MS is increasing. Their study also reinforces the notion that late onset MS is predictive of quicker progression, regardless of gender. A shorter time to the assignment of an EDSS score of 3 or 4 was associated with late onset MS, incomplete recovery from the first relapse and a high number of relapses during the first five years after MS onset. It didn’t matter how much time occurred between the first two relapses.
Researchers are exploring the role that cytokines and vitamin D have in develop autoimmune diseases such as MS. This may support the idea that the disease in women is more inflammatory in nature.
There are still many questions of why MS is increasingly more common in women. As recently as 2000, the ratio has been estimated at 4:1 women to men. The first time I read that ratio was in a recent edition of MS Focus, the magazine of the Multiple Sclerosis Foundation.
In future posts, I will address the question of hormones in the diagnosis and treatment of multiple sclerosis.
Whitacre CC, Reingold SC, O’Looney PA, et at., Task Force on Gender, Multiple Sclerosis and Autoimmunity. A Gender Gap in Autoimmunity, Supplementary Material. Science, 1999 Feb 26;283(5406):1277-8.
Pozzilli C, Tomassini V, Marinelli F, et al. 'Gender gap' in multiple sclerosis: magnetic resonance imaging evidence. European Journal of Neurology, 2003;10(1):95-97.
Fenoglio C, Scalabrini D, Esposito F, et al. Progranulin gene variability increases the risk for primary progressive multiple sclerosis in males. Genes and Immunity, 13 May 2010; doi: 10.1038/gene.2010.18
Celius EG, Smestad C. Change in sex ratio, disease course and age at diagnosis in Oslo MS patients through seven decades. Acta Neurol Scand Suppl, 2009;(189):27-9.
Eikelenboom MJ, Killestein J, Kragt JJ, et al. Gender differences in multiple sclerosis: Cytokines and vitamin D. J Neurol Sci, 2009 Nov;286(1):40-42.
Debouverie M. Gender as a prognostic factor and its impact on the incidence of multiple sclerosis in Lorraine, France. J Neurol Sci, 2009 Nov 15;286(1-2):14-7.
Multiple Sclerosis Prevalence Increasing Faster Among Women Than Men by Caroline Cassels, Medscape Medical News. April 24, 2007.