Equal but biologically different

It starts in the laboratory with male cells under the microscope. Traditionally, animal studies have relied mostly on male mice or other creatures. For decades, in human clinical trials focused on diseases, drug safety and treatment effectiveness, women were often excluded or heavily outnumbered. But ignoring biological differences between sexes is bad science. “Without the inclusion of women, all the way through from basic research to clinical research, we can’t be sure we really have the right answers for 51 percent of the population,” says Dr. Kathryn Rexrode, chief of the division of women’s health at Brigham and Women’s Hospital in Boston. Here are just some unanswered questions.

Why do more women face stroke first?

Men and women differ when it comes to their first episode of cardiovascular disease. In a long-term study of nearly 8,500 participants in the Netherlands, stroke or heart failure were more likely first events among women, while men were more likely to have heart attacks or hardening of the arteries. The study was published November 2014 in the journal BMJ, and follow-up research could investigate why cardiovascular disease occurs differently in women and how to better treat it, Rexrode says. According to the American Stroke Association, 55,000 more women than men have a stroke each year. That’s only partially explained by women living longer in general — which is another puzzling disparity for researchers to tease out.

What specific risks do drugs pose for women?

In 2013, the Food and Drug Administration required drug manufacturers to lower recommended doses for women in sleeping medications containing zolpidem, the active ingredient in Ambien and other brands. Women taking these drugs were more vulnerable to impaired alertness the next day, including while driving. Lower body weight in women and the difference in distribution of body fat between sexes can change how drugs are absorbed and broken down in the body. Hormonal and other biological differences also may influence the impact of drugs, their effectiveness and their side effects. More rigor and evaluation of sex differences are needed in clinical trials of both medications and medical devices, Rexrode says.

How do health-research gaps affect men?

Men have been underrepresented in research, too. With conditions such as rheumatoid arthritis, multiple sclerosis and lupus, women are disproportionately affected — but men get them as well. “In those cases, there are more studies that are just done on females, because they’re female-prevalent diseases,” says Teresa Woodruff, director of the Women’s Health Research Institute at Northwestern University in Chicago. “But if you include males in the biology [studies], you often learn more about why there is this impact. That’s why we’re advocating for inclusion at the basic science level.” Transparent, inclusive studies that publish the gender breakdown of participants and provide results stratified by sex would make new scientific discoveries more likely, she says.

Among nonsmokers, why do more women get lung cancer?

Lung cancer is the leading cause of cancer death in women, according to the Centers for Disease Control and Prevention. Twenty percent of people diagnosed with the disease have never smoked. Among nonsmokers, women are three times as likely to have lung cancer. Even so, women are less likely to enroll in lung cancer clinical trials, although the number has risen, according to a 2014 report from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital. However, even when women are included, researchers frequently fail to analyze data by sex, hormone status or other gender-specific factors. That makes it harder to discover differences in how women are affected or should be treated.

Which fertility options exist for women with cancer?

Clearly, preserving fertility is a significant consideration for young men and women undergoing cancer treatment. Yet, until fairly recently, sperm-banking for men before chemotherapy was the only option offered in the field now known as oncofertility. “Women with the same hope for survival were being told: ‘Don’t worry about your fertility; just focus on the cancer,'” Woodruff says. “There really was a complete discordance between options for males and females.” Today, fertility specialists are using in vitro fertilization and other technologies to help women who are cancer survivors. Researchers like Woodruff are now conducting next-generation fertility research to grow individual ovarian follicles and mature human eggs.

How do antidepressants affect women?

Fewer than 45 percent of animal studies on anxiety and depression use any female lab animals, according to the Connors Center report. However, twice as many U.S. women suffer from depression than men. The hormone-based phases of women’s lives, such as starting puberty, becoming pregnant and going through menopause, are directly linked to higher depression risk. More research is needed to uncover differences in the effects of antidepressant drugs in women, and to determine the safety of psychiatric drugs during pregnancy.

How can research close the cardiac gender gap?

Only one-third of participants in cardiovascular clinical trials are female, according to the Connors Center report. Less than one-third of trials including women report their findings by sex. Gaps like these aren’t OK, says Carolyn Thomas, founder of the Heart Sisters blog and author of “A Woman’s Guide to Living With Heart Disease.” Although causes, symptoms and outcomes of women’s heart attacks are different than men’s, that fact has been overlooked by the scientific community until quite recently, she says. In January 2016, the European Heart Journal published a comprehensive overview of the cardiac gender gap. In February 2016, an article in Mayo Clinic Proceedings called for focused care in specialized women’s heart clinics.

Change is coming.

Slowly but surely, women’s health research keeps gaining ground. In 2016, the National Institutes of Health implemented a new policy requiring federally funded scientists to consider sex as a biological factor in their research. “That’s a real watershed for us,” Woodruff says. “Five or 10 years from now, there will be a whole new way we look at health and disease through the prism of sex as a fundamental variable.” Inclusive research benefits everyone, Rexrode says. “I really believe that studying sex differences has the potential to improve the care for both men and women and unlock potential new biologic mechanisms,” she says.

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7 Major Gaps in Women’s Health Research originally appeared on usnews.com