Fifteen Years Later – Does Sex Still Matter?
I had the opportunity to review the section on bone and joint disease before its publication. I thought that the content was outstanding and raised key issues that should be at the forefront of any discussion of human disease. How do differences in sex and gender influence the pathogenesis of disease? How do differences in sex and gender influence the approach to treatment?
My only concern was the title. I did not think that adding the words “Does Sex Matter?” was necessary. Indeed, I thought that the question was not appropriate for a scientific treatise, considering it an easy way to attract attention especially in view of the dual meanings of sex. As a somewhat rigid and stodgy academician, I like rigor and precision in language and would not want to utilize such a rhetorical device even if the purpose was laudable.
Suffice it to say I was wrong. The title was perfect because it got attention. The role of sex and gender are critical to the science and practice of medicine and, if a clever and catchy title is necessary to get someone to look at the table of contents, buy the book and read on, so be it.
Fifteen years have passed since the IOM report and still sex and gender have yet to receive the place they deserve in studies on basic disease mechanisms, treatment paradigms and clinical outcomes. In sports, the game is determined by the X’s and O’s of plays. In medicine, it is the X’s and Y’s of the chromosomes that are often the biggest determinants of outcomes. Nevertheless, while being a male or female may confer the biggest genetic risk for disease-boosting the chance of a disease like lupus 5 to 10 times-a genetic factor with a relative risk of 1.2 may attract far more notice and grant funding.
For the area of bone and joints, the number of instances of male-female differences in disease is striking: osteoporosis, osteoarthritis, rheumatoid arthritis, lupus, scoliosis, anterior cruciate ligament injury and many others. For outcomes, there is interest in differences in the response to therapy for rheumatoid arthritis as well as total joint replacement in osteoarthritis. Even for such basic issues in treatment as drug dosing, the question has not been adequately asked: Should men and women receive the same doses of a drug? Put it another way, should dosing be on the basis of weight and prescribed on the basis of milligrams per kilogram? Another good question is whether being a man or woman affects basic pharmacology.
Pregnancy is always part of any discussion of sex and gender issues in disease in terms of its impact on disease course and vice versa. Does pregnancy change the course of disease and, conversely, does disease affect fertility or the likelihood of a successful pregnancy? The issue of drug safety is paramount in the treatment of diseases such as rheumatoid arthritis and lupus which disproportionately affect young women. As the number of agents being approved increases, we need ways to assess safety more quickly and efficiently. Perhaps the creation of registries will be a solution although I would like to think that laboratory methods can be developed to address safety issues with agents like the biologicals where the in vivo effects may be complex. However, although there is significant impact of sex hormones on disease processes, the effects of sex and gender extend far beyond just those of hormones.
I am very pleased to note that an excellent discussion of the impact of sex and gender on bone and joint disease appears in the BMUS (Burden of Musculoskeletal Diseases in the United States) document on the USBJI website. BMUS, with its many charts and tables, is an invaluable resource and provides one of the most complete datasets available on this and many other issues on musculoskeletal disease for use in research, advocacy and public policy. I would strongly recommend reading the section on Sex and Gender. Dr.Templeton is the lead author while Sylvia Watkins-Castillo, Ph.D. is the supporting author.
As this discussion indicates, Dr. Templeton has done a great job in this important area and I want to commend her leadership in getting USBJI part of the iGIANT initiative from the onset. Sex and gender matter and I look forward to working with our constituent organizations to devise programs that are not only important but are truly downright sexy.
Dr. Pisetsky and Dr. Templeton are developing a Position Paper on this topic and invite your comments. Please email them at firstname.lastname@example.org.