Sex Matters: Medical Research Overlooks Women

We are sharing this article, originally published by The Fuller Project, as part of our collaboration with the Spark News Towards Equality Initiative for International Women’s Day. 

Women in the United States are twice as likely as men to die from heart attacks.

When a nonsmoker dies of lung cancer, it’s twice as likely to be a woman as a man.

And women suffer more than men from Alzheimer’s and autoimmune disease.

Yet research into these conditions, and many more, generally fails to examine women separately.

It’s been 30 years since the U.S. Congress ordered the U.S. National Institutes of Health (NIH), the largest funder of medical research in the world, to make sure women were included equally in clinical trials. But research on women still lags, and there’s growing evidence that women and girls are paying the price.

“Research on women’s health has been underfunded for decades, and many conditions that mostly or only affect women, or affect women differently, have received little to no attention,” first lady Jill Biden said in announcing a new White House Initiative on Women’s Health Research late in 2023.

Not only do researchers fail to include enough women in clinical trials, they often don’t look for differences between how men and women respond to treatments.

The new initiative acknowledges that Congress’s earlier directive fell short.

“What most people don’t recognize is that it was advisory. It was a recommendation,” said Dr. Nanette Wenger, a top U.S. cardiologist whose work helped propel the NIH legislation. “It had no teeth.”

Officials at the NIH have urged researchers to include more women in the clinical trials used to study potential treatments. But the drug development process is long and complex and crosses over agencies ranging from NIH to the U.S Food and Drug Administration (FDA), which assesses and approves new treatments. Efforts to increase diversity run up against overburdened investigators, overwhelmed physicians and an FDA pulled between a demanding public clamoring for new drugs and a pharmaceutical industry driven by profits. So questions about gender differences fall through the cracks — and no one can even hazard a guess as to all the consequences.

“We know less about female biology and we are struggling to catch up,” said Dr. Janine Clayton, director of the NIH’s Office of Research on Women's Health.

The effects show up in almost every aspect of human health.

While women are about as likely as men to have heart attacks, they are more likely to die from them, according to the NIH’s Office of Research on Women’s Health. Women given chemotherapy for cancer have a nearly 50% higher rate of adverse events than men, the ORWH says in its latest report.

The U.S. has by far the worst maternal mortality rate of any comparable country. These deaths cannot all be prevented by better research. But the lack of attention to how women respond differently to drugs, how medical providers treat women and how the system still provides women less-than-adequate care is costing lives, experts and advocates say.“Because of research, we know that sex matters,” Clayton said.

Nonetheless, many researchers overlook those differences.

“We still have the same problem that we had 30 years ago,” said Dr. Stephanie Faubion, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida. “We still don’t know if these drugs work the same, better or worse in women than in men.”

A series of studies called the STEP trials, published in 2021 and 2022, are the latest example.

They have shown that the diabetes drug semaglutide, sold under the brand names Wegovy, Ozempic and Rybelsus, can help obese people lose up to 15% or more of body weight in just over a year. They’ve also demonstrated that the injectable drug can treat heart disease.

Faubion was researching whether the drugs have different effects among women taking certain medications for breast cancer. “We think estrogen has something to do with the weight loss,” Faubion said. But none of the trials break out separate data on men and women. “We can’t do it if we can’t get the data. It’s stunning.”

Some efforts have been made. The NIH and FDA both have offices dedicated to ensuring equity for women as well as for ethnic and racial minorities. However, neither agency fully enforces its regulations and policies on sex differences in research, advocates said. “All you have to say is, ‘Oh, yes. We considered it,’” said Katie Schubert, president of the Society for Women’s Health Research. “You don’t have to actually do anything about it.”

Fewer than a third of the results from the most advanced clinical trials, known as Phase III trials, are reported by sex in medical journals, Clayton said. Doctors rely on the journals to inform their practices, so if there’s no data to justify changing how they treat women, they don’t.

Perhaps as a result, emergency room staff take longer to treat women with heart attack symptoms. And doctors and patients alike often miss stroke symptoms among women, even though they have a higher risk than men.

Lung cancer, the biggest cancer killer by far, mostly affects smokers. But every year, it kills 20,000 to 40,000 nonsmokers in the U.S., according to the Centers for Disease Control and Prevention. Two-thirds are women.

Yet only 15% of lung cancer research centers on women, according to a 2022 report by the advocacy group Women's Health Access Matters and the Rand Corporation. Likewise, only 12% of Alzheimer's research and 4.5% of the money for coronary artery disease research goes to projects that focus on women.

It’s difficult to get companies to look at sex differences, said Dr. Janet Woodcock, FDA’s former principal deputy commissioner. “They are going to do the minimum it takes to get on the market,” Woodcock said. “Companies try very hard to dose everybody at the same dose. It is very unpopular to put out a drug and say, ‘these folks need a different dose.’”

Congress may need to step in, said Dr. JoAnn Manson, an epidemiologist at Harvard Medical School who led the biggest-ever study into women’s health, the Women’s Health Initiative. It was specifically written into the federal budget.

“When the Women’s Health Initiative was started in 1992, it was a line item in the congressional budget,” Manson said. She has not been able to get another such study paid for since then.

“We are trying, others are trying, too, to get the research funded,” she said.

*This is an edited version of a longer article available here on The Fuller Project’s website