Several interesting articles have surfaced in the New York Times on the topic of equal sex representation in clinical research, namely The Drug-Dose Gender Gap 1; A New Women’s Issue: Statins 2 and Labs Are Told to Start Including a Neglected Variable: Females 3. Perhaps, these articles caught my attention in particular since I have been flipping through what some may argue is a proponent of today’s feminist reform, Sheryl Sandberg’s best-seller: Lean In. This association got me wondering why, in 2014 – whether it’s in the office, clinical research or wet lab – are we still talking about gender inequality?
Up until the Revitalization Act 4, clinical trial research and participation predominantly focused on men 5. In 1993, the National Institute of Health (NIH) implemented the Revitalization Act to include women in clinical research 5. However, articles (much like those identified above) continue to emerge and question the validity of clinical research results where women have been ignored.
As long as clinical practice continues to extrapolate male-centric data to women rather than including them in clinical trials, women will continue to be at risk for increased adverse drug reactions. For example, a recent study investigating a new sleeping pill proved a dose-drug gender gap 1,6. While it was a new sleeping pill that uncovered the sex differences in drug metabolism, the active ingredient zolpidem has been used in other sleeping products such as Ambien for two decades. It was only after this new study’s findings 1 that the FDA reduced the recommended doses of Ambien for women 7,despite there being numerous complaints of prolonged drowsiness. Zolpidem is only one of the many marketed drugs that have shown unexpected effects in women; sex differences in drug metabolism to aspirin, anesthesia 1, 8 and antithrombotic agents 8,9 have also been reported.
Furthermore, some cardiologists are now left wondering whether so many women should be taking statins 2. Their uncertainty is valid since the new medical guidelines do not provide sex specification and the results of the controversial JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin) trial show that there was no significant reduction in heart attacks, strokes and deaths among women 2,10.
While researchers are beginning to understand that women and men metabolize drugs differently because of size; percentage of body fat; differences in hormonal fluctuations; the monthly menstrual cycle in women 11; sex differences in liver metabolism, kidney function and certain gastric enzymes 1, preclinical studies continue to focus on male models. In fact, according to Dr Kathryn Sandberg 1, 90 percent of researchers are still studying male animal models of diseases.
Fortunately, the NIH is taking another positive step to sex equality by phasing in new guidelines this coming October 12. The new guidelines will include female cells and animals in preclinical research and will hopefully provide further impetus to include females in the overall drug development process whether it is at the cellular, preclinical or clinical level.
1. Rabin RC (2013, January 28). The Drug-Dose Gender Gap. The New York Times. Retrieved from http://well.blogs.nytimes.com.
2. Rabin RC (2014, May 5). A New Women’s Issue: Statins. The New York Times. Retrieved from http://well.blogs.nytimes.com.
3. Rabin RC (2014, May 14). Labs Are Told to Start Including a Neglected Variable: Females. The New York Times. Retrieved from http://www.nytimes.com.
4. US Food and Drug Administration. (1993). National Institutes of Health Revitalization Act of 1993. Washington, DC: Author. Retrieved from http://orwh.od.nih.gov/about/pdf/NIH-Revitalization-Act-1993.pdf.
5. Sherman LA, Temple R, Merkatz RB. (1995). Women in clinical trials: an FDA perspective. Science, 269, 793-795.
6. US Food and Drug Administration. (2001). Reference ID. Washington, DC: Author. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022328lbl.pdf.
7. Tavernise S. (2013, January 10). Drug Agency Recommends Lower Doses of Sleep Aids for Women. The New York Times. Retrieved from http://www.nytimes.com.
8. Schiebinger L. (2003, October 1). Women’s health and clinical trials. J Clin Invest, 112(12), 973-977.
9. Nechas, E, and Foley, D. (1994). Unequal treatment: what you don’t know about how women are mistreated by the medical community. Simon & Schuster Inc. New York, New York, USA. 272 pp. (Should we add the Amazon link here? http://www.amazon.com/Unequal-Treatment-Mistreated-Medical-Community/dp/0671791869)
10. Ridker, PM et al. (2008). Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med, 359(21), 2195-207.
11. Whitley H, Lindsey W. (2009). Sex-based differences in drug activity. Am Fam Physician, 80(11), 1254-8.
12. Janine CA, Francis CS. (2014, May 14). Policy: NIH to balance sex in cell and animal studies. Nature, 509, 282-283.