be taken when looking at clinic populations versus the larger community. People with the most severe conditions are the ones who come to tertiary care.

BOX 3-4

Key Points: Multiple Sclerosis (MS) and Neuroinflammation

  • Clear sex differences are evident in the incidence of MS: MS is two to three times more common in women.

    • Onset occurs later in men, and is more likely to be primary progressive MS.

    • Women appear to have a better prognosis, but differences are less apparent after adjusting for age at diagnosis and disease course.

    • Pregnancy decreases disease activity (but the effect of oral contraceptives is unclear).

  • The clinical course of sex differences shows little evidence of sex differences:

    • Despite observations in smaller studies, large magnetic resonance imaging (MRI) studies suggest no effect of sex on MRI measures of either inflammation or tissue injury.

    • Histopathology shows virtually no effect of sex differences.

    • Most clinical trials show no effect of sex differences.

  • There are sex-based immune differences in MS:

    • Females mount a stronger immune response.

    • Males have more severe inflammation.

  • Studies suggest a role for ultraviolet light and vitamin D in the pathogenesis of MS.

  • Clinical observations can lead to potential treatments for MS:

    • Animal studies to elucidate mechanisms of the observed clinical phenotypes and pilot trials of potential products in humans are possible, but funding can be a major obstacle.

    • Preclinical studies should include both sexes.

In the community, there are large sex differences in pain, but within the tertiary care setting there are not many differences between males and females.

OVERARCHING DISCUSSION

Following the disease-specific panel discussions of issues related to sex differences in translational research, the four panel moderators and the workshop cochairs assembled to consider overarching issues across major disease areas.



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