This month’s edition of the science journal Nature has three articles in its op-ed section regarding sex bias against women as the subjects in clinical research trials, and how this lack of adequate testing of treatments’ effects on female physiology leads to diagnostic and therapeutic regimes that are either ineffective for women or actively harmful. The full articles are behind a paywall, but the press release below gives a summary.
The editorial – Sex Bias in Research Trials and Treatment Must End – lays out the big picture, the second article – Pregnant women deserve better – asks why pregnant women are routinely excluded from clinical trials despite many pregnant women being willing to act as subjects, while the third article shows how sex bias begins in the lab with the animal tests that underpin the development of treatments (male animal studies outnumber female animal studies 5 to 1).
Press Release: CHICAGO — Women remain vastly underrepresented in biomedical research despite significant differences in the way they experience many diseases, medications and therapies compared to men. Despite federal mandates to include women in studies, there is much that still needs to be done, says Teresa Woodruff, a leading women’s health scientist at Northwestern University Feinberg School of Medicine, in a June 9 commentary in the journal Nature.
“It’s time for the sex bias in basic research and clinical medicine to end,” writes senior author Woodruff, executive director of the Institute for Women’s Health Research and the Thomas J. Watkins Professor of Obstetrics and Gynecology at Feinberg. This bias, she says, has an enormous effect on women’s health, resulting, for example, in delayed diagnosis of cardiovascular disease, the leading killer of women, and in adverse reactions to medication. Alison Kim and Candace Tingen, post-doctoral fellows at Feinberg, are coauthors on the paper.
Women need to be adequately represented in studies, and results need to be specifically designed and analyzed to determine sex differences, the authors note, in order for both men and women to receive more tailored care. Understanding sex as a determinant of disease and care is the first step towards personalized care for every patient. Sex differences in the incidence, prevalence, symptoms and severity of disease have already been shown in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis; in psychological disorders including depression, autism, eating disorders and schizophrenia; and in asthma and several types of cancer.
“Differences are particularly acute in cardiovascular disease, the leading cause of death for both men and women,” Woodruff writes. Women in the early stages of cardiovascular disease may experience fatigue, abdominal discomfort and back, jaw or neck pain, all of which are considered atypical because diagnostics were mainly established from research conducted primarily on men. “As a result, women can be subject to potentially life-threatening delays before crucial diagnostic tests are administered,” she said. And some of those tests, like exercise electrocardiography, can’t detect cardiovascular disease as well in women as in men.
Northwestern is a good example of making significant strides in treating women with heart disease and in sex-balanced health research, Woodruff noted. She pointed to Feinberg’s Institute for Women’s Health Research, which supports clinical research trials that focus on women’s health and sex-balanced research, and the institute’s Illinois Women’s Health Registry, a growing database of 4,500 potential study subjects, that has encouraged Northwestern researchers to do more research in sex differences. About 1,000 of these women have participated in trials.
In addition, the Center for Women’s Cardiovascular Health at the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital has a unique clinical program focusing on women’s heart health. Women also respond differently to medication than men, yet drugs are rarely prescribed accordingly, according the Nature article. “This may be part of the reason why women are 1.5 times more likely to develop an adverse reaction to prescription drugs than men,” Woodruff notes. For example, a 2005 study of new drug applications found that even the drugs that had substantial differences in how they were metabolized by women and men did not have sex-specific dosage recommendations on the labels.
How to fix the void? Among the authors’ suggestions:
* Journals should indicate if results are in male or female animal models.
* Regulatory and funding agencies should require appropriate representation of both sexes in human and animal trials and require researchers to consider sex differences when they analyze data.
* Educate doctors in the clinical importance of sex differences. The Food and Drug Administration also should mandate that medication dosages be sex-specific based on clinical studies.