by Kimberly Templeton and Janice Werbinski
It has been 36 years since the publication of the “Physicians’ Health Study,” which showed that low dose aspirin decreased the risk of a first heart attack in the 50,000 male physicians studied.1 This study became more infamous for its backlash from women than its epidemiological findings, since it gave no information on whether women would respond similarly. When the New England Journal of Medicine finally published a similar study, 18 years later, using 40,000 women in the “Nurses’ Health Study”, the effects were found to be very different.2 Aspirin was not found to be helpful in preventing heart attacks in women under age 65, and, in fact, these women had more haemorrhagic strokes than those on placebo.3 Studies such as these have led to an outcry against gender bias in medicine, and the medical community is slowly taking steps to make research more inclusive.
Sex and gender specific healthcare is important for all patients. When sex differences are not considered, healthcare needs are often not met. Only a small percentage of providers incorporate sex and gender differentiation into their clinical practices. Although the US National Institutes of Health have mandated the inclusion of women in all funded studies since 1993,4 only a minority of outcomes data are analysed by sex/gender, and a minimal number of clinical trials report results by sex/gender. Additionally, 80% of all animal studies use only male animals, and most studies on stem cells do not record the sex of the cells studied. As noted by the Institute of Medicine, “every cell has a sex,”5 and identification of the sex of cells in research, as well as animal or human subjects, needs to be included in evaluation and reporting of results.
As with the Physicians’ Health Study, trials of drugs intended to be prescribed to both men and women have historically not included sufficient numbers of women, due to concerns about the impact of fluctuations of sex hormones or the potential impact on foetuses. This has led to several drugs being removed from the market because of issues of unanticipated side effects in women.6 These side effects often reflect sex-based differences in pharmacokinetics and pharmacodynamics.
While the term “women’s health” was often thought to refer only to reproductive issues, a more accurate, expansive definition of this term is: “any condition for which there are differences noted between men and women in aetiology, prevention, incidence, presentation, or response to treatment.”7 These differences cannot solely be attributed to the impact of sex hormones.
Sex- and gender-based differences have been identified in all health conditions,7,8,9 especially musculoskeletal health. While there can be impact from sex hormones, differences in musculoskeletal anatomy, physiology, and neuromuscular control also contribute to these differences. For example, women are significantly more likely to sustain anterior cruciate ligament injuries while playing sports. Women are more likely to develop osteoporosis and related fractures, but men are significantly less likely to undergo evaluation of their bone health once they sustain a low impact fracture. Women are more likely to develop osteoarthritis of the knee and do not experience as significant functional improvement after arthroplasty, as do men.
Sex- and gender-based differences have also been identified in spine issues. There is a higher incidence of idiopathic scoliosis among females with even higher incidences reported from those countries, especially those in northern latitudes, whose girls have later age at menarche.10 Women, especially those who are post-menopausal, are more likely to complain of low back pain, and to be diagnosed with degenerative disc disease.11 During and after pregnancy, women frequently complain of chronic pelvic and back pain. While the incidence of spinal stenosis increases with age for both sexes, it tends to plateau at about age 70 for men, yet continues to increase for women.12 Women are four to five times more likely than men to be diagnosed with degenerative spondylolisthesis.13 Whilst these results come from studies based around the world, understanding the influence of sex and gender on patient outcomes is likely confounded by a lack of reporting of race and ethnicity within research; another area which needs better consideration in research.
While it is important to continue to identify conditions for which there is differing incidence or risk between men and women, improving the health of all patients requires more than that. We need to continue to study these conditions to identify why women or men are more likely to develop certain conditions, and how to best approach prevention or treatment in light of this. While it is easy to blame the hormones, the answers are likely to be more complicated than that, reflecting the multifactorial aetiology of most health conditions.
It is imperative that medical science make the effort to study males and females separately. Although many areas of difference have been identified, much more needs to be done. The “One size fits all” model of today’s healthcare needs to change. It is not about men and women being equal—it is about evidence that increasingly shows the differences between the sexes. Bringing a sex and gender perspective to education and practice assures a comprehensive understanding that will ultimately improve medical care for all.
- Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989; 321(3):129-35
- Ridker, et al. N Engl J Med 2005; 352: 1293-1304
- Iso H, et al. Stroke 1999; 30(9): 1764-71
- NIH Revitalization Act 1993, PL 103-43
- Institute of Medicine, Board on Health Sciences Policy, Committee on Understanding the Biology of Sex and Gender Differences. Every Cell Has a Sex. In: TM Wizemann and ML Pardue (eds). Exploring the Biological Contributions to Human Health: Does Sex Matter? Washington DC. The National Academies Press. 2001
- Heinrich J. (Director Health Care—Public Health Issues, United States General Accounting Office). Letter to: Harkin T, Snowe OJ, Mikulski BA, United States Senate and Waxman HA, House of Representatives. 19 January 2001. 8 leaf. Located at: United States General Accounting Office, Washington, DC, 20548
- AMA Council on Science and Public Health (A-16). Report 5. An Expanded Definition of Women’s Health (Resolution 604-A-15). 2016
- National Institutes of Health Office of Research on Women’s Health. How SEX and GENDER Influence Health and Disease. http://bit.ly/2mwBh9m [Accessed 7 March 2017]
- Johnson P. When does medicine leave women behind? http://n.pr/2mwFM3S [Accessed 7 March 2017]
- Grivas TB et al. Scoliosis 2006; 1:9
- Lou C, et al. Climacteric 2014; 17(6): 700-704
- Ishimoto Y, et al. Osteoarthritis Cartilage 2012; 20: 103-1108
- Andersen T, et al. BioMed Research International 2013; Article ID 123847
Janice Werbinski is associate clinical professor emerita in Obstetrics and Gynaecology at Western Michigan University Homer R Stryker MD School of Medicine, Kalamazoo, USA. Kimberly Templeton is professor of Orthopedic Surgery at the University of Kansas Medical Center, Kansas City, USA and president of the American Medical Women’s Association