No one said it’s easy being a woman. 

Compared with men, women are more likely to suffer from autoimmune diseases, may face a higher risk of developing lung cancer and are more likely to suffer depression. They may experience heart attacks differently, they wake up from anesthesia more quickly, and they are not as likely to experience the benefits of painkillers such as ibuprofen and acetaminophen. 

It’s a simple fact of science: men and women aren’t equal – at least not when it comes to medicine. But for years basic scientific research in the U.S. has largely ignored this fact.

“There’s a lot of research out there showing that certain drugs are metabolized differently among the sexes,” said Dr. Melina Kibbe, professor of surgical research at Northwestern University’s Feinberg School of Medicine. “But it never gets translated to the actual care of the patient.”

The Women’s Health Research Institute at Feinberg wants the National Institutes of Health to help change that. 

In a letter sent to NIH director Dr. Francis Collins Friday, Teresa Woodruff, the director of the Northwestern institute, called on the NIH to implement mandatory sex-specific requirements for research undertaken by their grantees. 

“We’ve known for decades that women have not been included in clinical studies,” Woodruff said. “There’s not been the motivation based on the NIH or the [Food and Drug Administration] or the [National Science Foundation], requiring that this be a part of the studies. 

A group of 20 Northwestern doctors and scientists support Woodruff in her initiative. They want all NIH-funded research to require scientists to report the sex of subjects at every level of scientific research from preclinical studies on cells and animals through to clinical studies with human subjects. 

“It’s just bad medicine that we’re not looking at sex as one of the variables,” Woodruff said. “There’s no other time in science when you don’t report the variables.”

A spokeswoman for the NIH Wednesday evening confirmed that that Dr. Collins and Dr. Janine Clayton, director of the NIH’s Office of Research on Women’s Health, had received the letter and would be responding to it. 

Sex differences matter 

In 2013, The FDA changed the recommended dose for women taking Ambien after tests found women metabolize the drug much more slowly than men. Up to 45 percent more Ambien was found in the blood of women who had taken the pill compared with men who took similar doses, making some women dangerously drowsy the morning after taking the pill. Though the FDA did not find why women metabolize the drug differently, Ambien is now the first and only drug on the market to have a different recommended doses for men and women.

“Women have been harmed by FDA-approved drugs that for example, have not been tested in males and females and therefore neither males [or] females get the right dose,” Woodruff said.

Determining sex differences at the basic science or preclinical level of research would not only save money on failed clinical trials, but also “reduce the risk of adverse events and improve the efficacy of drugs,” Woodruff and her colleagues said in the letter. According to a 2001 report published by the U.S. Government Accountability Office, eight of the 10 prescription drugs withdrawn from the market between 1997 and 2001 “posed greater health risks for women than for men.”

This February, the NIH launched a five-year collaboration with industry and non-profits to study Alzheimer’s, type 2 diabetes, rheumatoid arthritis and lupus. Of the four diseases, all but diabetes are more common in women than men. Woodruff sees this collaboration as a prime opportunity to have Collins update sex and gender research guidelines.

“If he doesn’t do this then he’s going to be studying diseases where the vast majority of the patients won’t have the kind of basic science necessary to improve their health,” Woodruff said. 

U.S. vs. the world 

The U.S. is lagging behind Canada and Europe in requiring sex to be considered from the very beginning of the research process. The Canadian Institutes of Health Research added mandatory questions about sex and gender to their funding applications in 2010. According to a spokeswoman for the European Commission’s Office for Research, Innovation and Science, the commission will include a similar question in the application for its €80 billion Horizon 2020. (Horizon 2020 is the body’s seven-year plan for science research funding.)

NIH provides approximately $30 billion a year in grants for health research. In 2012 federal bodies like the NIH provided 31.5 percent of the $130 billion the nation spent on health research. Industry provided 53 percent and other funders including universities and philanthropic organizations such as the Gates Foundation provided the remaining 15.5 percent.

Currently, the NIH is mandated to include women in clinical research and requires that grantees report the sex of human subjects. However, the organization only requires that different sex-based outcomes of studies be analyzed and reported on during Phase III clinical trials involving human subjects.

American women’s mortality rates on the rise 

The Institute of Medicine reported last year that despite spending more than any other nation on health care, Americans are sicker than citizens of most other high-income countries. Women are particularly at risk.

Researchers at the University of Wisconsin-Madison last year reported in the journal Health Affairs, American women’s mortality rates are rising. Researchers found that between 1992-1996 and 2002-2006 female mortality rates rose in 41.9 percent of the 3,140 counties examined. Male mortality rates only rose in 3.3 percent of counties.

Is the lack of female test subjects in the vast majority of medical studies done in the U.S. behind this?

Gender gap in the research 

“When I looked at my own research and found that there was a big difference in how male animals and female animals responded to my therapy, that was my eye-opening event,” said Kibbe, who is a vascular surgeon.

She conducted a review of over 2,000 articles published in the five top surgical journals, finding that the majority studied only males. Only 3 percent of the articles that stated the sex of subjects studied both males and females. Kibbe asked the editors to consider requiring authors to state the sex of the animals and the source of cells involved in their research. 

She hopes to see similar requirements applied by all journal editors, an approach that could complement NIH’s actions.

Catherine Woolley, a professor of neurobiology, is Kibbe’s Northwestern colleague and also a member of the Women’s Health Research Institute leadership council. In her research, Woolley has discovered sex differences in the way brain synapses are modulated at a molecular level, even when sex hormones are taken out of the equation.

“Most psychiatric conditions differ in either incidence or age of onset or symptoms between males and females,” she said. “The basic science that is being done to try and figure out the mechanism of those psychiatric conditions [is] very rarely in both sexes.”

Woolley undertook a similar study to Kibbe’s. In a review of five neuroscience journals, Woolley found that fewer than 4 percent of papers – 45 out of 1,244—studied both males and females and analyzed the data by sex.

“Anxiety and depression are diagnosed at a rate of 3-1 more often in women than men,” said Woolley. “If anything, we should be studying those mechanisms in females more than males because females are more vulnerable to that disorder.”

Knowledge is power

According to Woodruff, the Women’s Health Research Institute at Northwestern is one of a few such organizations in the country. “It seems like there should be centers for women’s health in many places and there aren’t,” she said. Centers specializing in women’s health prevalent a decade ago were slowly phased out due to lack of funding, she added.

So what can the average woman do to protect herself while medical research plays catch up?

“That’s the big question,” said Woodruff. “We’re so shocked that these drugs that we’re taking may not be right for us and the answer is you just have to be as educated as possible.”

She calls for women to find authoritative resources to turn to for information and take more control of their own health.

“Every time [we] go to the doctor [we]’re going to have to say well ‘When you’re prescribing me that medicine, do you know if that dose is right for a woman of my age?’ We’re going to have to really not just ask once but as twice and make doctors start thinking about it.”

MAR 13, 2014

View original article here: Medill Reports Chicago