Historically, understanding a woman’s unique biology and developing optimal interventions for women has been somewhat of a blind spot for medical research.

For much of the 20th century, scientists favored enrolling men in large clinical trials. Men were considered easier and safer to study because of the risk of women becoming pregnant mid-trial, among other reasons. Findings from studies in men were considered applicable to women, despite the fact that even beyond the reproductive system, a woman’s body differs significantly from a man’s, with variations in organ function, immune responses, and metabolism.

Recognizing these differences, the National Institutes of Health (NIH) and other government agencies have worked to increase women’s participation in clinical trials. Today, on the whole, nearly equal numbers of men and women participate in clinical trials, though women still may comprise only a minority of participants in certain trials — including some cardiovascular disease studies.

Moreover, too often research fails to take sex and gender into account, which may obscure key findings unique to women that could inform future research and even clinical practice. Ultimately, failure to consider potential sex differences may lead to poorer health outcomes for women.

Two Areas Where More Attention To Sex Differences Is Needed: Heart Disease And HIV

Heart disease and HIV lead the list of medical research fields long overdue for a substantial re-focus on women’s health. Heart disease, originally thought to be a man’s disease, is actually the number one cause of death for women worldwide. Heart disease is often a quiet killer when it targets women. In women, heart attacks can cause nausea, backache, fatigue, or shortness of breath; the dramatic, crushing chest pain classically associated with heart attacks in men may not characterize the clinical picture in women. Tragically, these less distinctive symptoms in women often are ignored or misdiagnosed until it is too late for adequate care.

HIV/AIDS is also often considered a man’s disease. Although AIDS originally presented as a disease afflicting gay men, it was quickly found to affect a broader population, including women, heterosexual men, infants, blood transfusion recipients, and injection drug users. Today, women account for half of all adults living with HIV worldwide. In the United States, African-American women have double the risk of HIV infection as compared to the general population. Despite this burden, gaps in knowledge regarding the appropriate antiretroviral treatment regimens for women infected with HIV still persist. While antiretroviral dosing is currently the same for men and women, sex-specific research may be able to optimize treatment plans for each sex.

Heart disease and HIV converge in the most unfortunate way for women. The risk of heart disease triples for HIV-positive women, even for those receiving treatment, compared with their uninfected counterparts. Heart disease and HIV each exact a substantial toll on women, and they all too frequently occur together. The need for comprehensive research and better care in this area is undeniable.

The REPRIEVE Trial: A Model For Further Research

Science can address that need. An ambitious new clinical trial funded by the NIH called REPRIEVE was launched in 2015 to investigate whether a cholesterol-controlling statin drug can lower the elevated cardiovascular disease risk of people living with HIV. Trial investigators are working to alleviate disparities affecting women in clinical research, enrolling a racially and ethnically diverse group of women alongside men across the United States and internationally. REPRIEVE is unique because it prioritizes the analysis of sex differences in the onset, severity, and course of HIV and heart disease, as well as in the response of participants to statins. Beyond focusing on the physiological issues unique to women, the study will also assess the best ways to recruit and retain women as trial participants, thus informing the design of future studies.

Well-designed studies such as REPRIEVE should be the norm, not the exception. We need studies powered to find breakthroughs for women as well as men. We need to ensure that we can recruit women into clinical trials by identifying and eliminating barriers to their participation. We need scientists to look for differences between men and women in responses to medical interventions to determine how to create more personalized methods of prevention and treatment.

While efforts to fill our historical gaps in knowledge are commendable, we must do more to address the many medical questions that have long gone unanswered for half of the world’s population. Understanding the biologically important differences between men and women will open the door to innovations in preventing disease, providing care, saving lives, and even reducing health care costs. Let us embrace inclusive medical research that acknowledges the inherent differences between the sexes and recognizes women’s and men’s health as equally important.

Editor’s note: For more information on the subjects discussed above, visit the websites for the REPRIEVE trial, the National Institute of Allergy and Infectious Diseases, and the Women’s Heart Alliance.