Why you should care
You need to know the safe dose of Ambien. And if aspirin will prevent a heart attack.
The gender divide seems to bisect every corner of life, from wages to diaper duty. And over the past decade, research has revealed that the laboratory is no exception. Although Congress, in 1993, mandated that clinical research include women, the preclinical studies that lead to clinical trials are a different story: Most scientists still use only male cells and animals at the preclinical trial stage.
That worries Janine Clayton, MD, who directs the Office of Research on Women’s Health for the National Institutes of Health (NIH). Women are more likely than men to suffer adverse effects of many medications, and the Ambien incident — in which the FDA halved the recommended dose for women after a study showed that they metabolize the sleep aid more slowly than men — revealed only a sliver of the problem. Knowing how female cells and animals respond differently to active ingredients would allow scientists to fine-tune earlier, before human trials. More broadly, this gap in our understanding of female biology means clinicians lack evidence to make the best treatment decisions for women.
That’s why Dr. Clayton is leading an NIH initiative to require scientists to include female animals and cells in preclinical research. As part of the initiative, the agency provides grant recipients more funding to add subjects, cells or tissues of the sex opposite of the one used in their original studies. Clayton’s edited conversation with OZY follows.
OZY: Why is there a sexual disparity in preclinical research?
Dr. Janine Clayton: Not everyone realizes it’s important to use males and females. They have a blind spot concerning this issue. We now know that the cells of a man respond to drugs differently from those of a woman. One of the other factors is the misconception that the estrous cycle, which corresponds to the menstrual cycle in humans, would cause variability in the data and result in problems with interpreting the data. We now know that that’s not the case. Basically we’re at a tipping point, where it’s clear that sex matters.
OZY: Why consider sexual differences as early as the preclinical stage?
Clayton: We want scientists to collect their data for males and females separately. Otherwise, the research could result in findings that are in error. One area is stroke, in which male cells respond in one way and female cells respond in the exact opposite way. If you put male and female cells together in a petri dish, the results would cancel each other out. You’d move on to the clinical study without knowing if there’s a safety concern or whether the drug would work in only one sex or the other.
OZY: Why women’s health? Why not just broadly tackle health?
Clayton: If we’re not studying female animals and cells, we’re not learning as much about female biology as we are about male biology, which means we don’t have as much evidence on which to base our clinical studies and treatment decisions for women. Eight of the 10 drugs removed from the market in the past 10 years had more serious side effects on women than on men. If we’d known those things earlier, we could have adjusted earlier.
OZY: What are some medical conditions that affect men and women differently?
Clayton: Aspirin can help protect against heart attack, but that’s really only the case for men. Aspirin does help women, but it can help prevent stroke, not heart attack. Nicotine patches work better in men than in women. Women are much more likely to have serious heart rhythm irregularities related to medicines as common as antihistamines and antibiotics. As a clinician, you would design a treatment plan for female patients slightly differently.
OZY: What have been the consequences of the underrepresentation of women of color in clinical research?
Clayton: For example, breast cancer is more common in white women than in women of color. But we see a higher mortality rate in African-American women, who tend to present with what’s called triple negative breast cancer. If there weren’t a lot of African-American women in treatment studies for breast cancer, we wouldn’t know all the drugs available that work for that form of breast cancer.