In the growing field of sleep medicine, “We still lack some basic understandings about sex differences and their consequences for disease,” added Roseanne Armitage, Ph.D., professor of psychiatry at the University of Michigan in Ann Arbor.
Jeanne Duffy, Ph.D., director of the Chronobiology Core at Brigham and Women's Hospital, Boston, described profound differences between the sexes in subjective and objective measures of sleep quality. For example, women are more likely to subjectively report not having good sleep even when objective measures would suggest they slept better than men. “We don't understand these differences,” she said.
In other sleep research, men report better daytime functioning after getting less than 7 hours of sleep, though objective measures suggest they're functioning no better than women on the same amount of sleep, said Rachel Manber, Ph.D., director of the Sleep Medicine Clinic at Stanford (Calif.) University.
On a preclinical level, a review of studies in rodents found that 87% either used only male rodents, didn't specify sex, or didn't examine sex differences in the few studies that included males and females, Jeffrey S. Mogil, Ph.D., said (Pain 2005;117:1–5).
There's an assumption among scientists that data from female mice are more variable and thus are harder to work with, but research by Dr. Mogil and his associates found that this is not true. If anything, data are more variable from male mice, although not significantly more so than data from females, said Dr. Mogil, professor of psychology at the center for research on pain at McGill University in Montreal.
Moreover, a once-radical hypothesis has been proved to be true—that males and females have qualitatively different pain processing mechanisms that are genetically and neurochemically distinct from males, Dr. Mogil's mice studies have shown.
All of that could explain why more than 100 promising studies in mice suggesting that dextromethorphan (a common ingredient in cough syrup) potentiates the analgesic effects of morphine resulted in a failed clinical trial in humans of the drug combination, Dr. Mogil said. The mice studies undoubtedly focused on males, and later studies by Dr. Mogil showed that dextromethorphan boosts morphine's effects in males but not in females. The pharmaceutical company that sponsored the human trial and later abandoned the drug combination had not analyzed sex differences.
“That was an example of a flaw in the NIH policy. They included women but didn't do anything with them” in the analysis of results, Dr. Mogil said.
At the basic science level, it's now understood that the three main causes of sex differences are activational and organizational effects of testicular and ovarian hormones and direct sex chromosome effects, Arthur P. Arnold, Ph.D., said.
The differences between these have clinical implications, yet in almost no cases have these “big three” causes of sex differences been studied systematically and comprehensively in preclinical studies, said Dr. Arnold, professor and chair of physiological sciences at the University of California, Los Angeles.
In a discussion at the end of the workshop, more than one participant suggested adopting some kind of mandate to push harder for inclusion of sex differences—perhaps, for instance, requiring that basic scientists or clinicians who do not plan to include female subjects in studies at least provide a rationale for that decision.
Other attendees pushed back against the idea of a mandate, however, and argued instead that making money available for sex difference research would stimulate the desired work.
Dr. Pinn said she'd take back to the NIH the idea of educating program officers who handle grant decisions about sex differences, in hopes of developing some of them into advocates or champions of sex differences research.
She added, “We may think of doing a small pilot program to look at incorporating sex differences in basic research.”
Neuroendocrinologist Jon Levine, Ph.D., argued that scientists and physicians need earlier education on sex differences. “Our brightest and best are going into graduate and medical school programs that don't recognize that there are sex differences in brain function” and other areas, said Dr. Levine, professor of neurobiology and physiology at Northwestern University, Chicago. “At my own institution, there is one day's class within one course on sex differences in brain function and disease. That has to change.”
Disclosures: The speakers included in this article reported having no relevant conflicts of interest.