I Should Be Allowed to Leave Men Out of My Studies

For much of scientific history, the study of women’s health has been thought to be complex and wildly unpredictable, as if men’s health issues are stable and static. Indeed, although it is well known that women have monthly hormonal cycles, men’s daily fluctuations in testosterone levels are largely ignored. These biases are baked into research—fewer than 10% of all fundamental research studies look exclusively at female subjects, even though more than 50% of our population is biologically female.

Now, as government funding agencies in North America are starting to understand the importance of including the female sex in research, there has been a movement toward acknowledging how sex differences affect drug efficacy and disease outcomes. In the U.S., the National Institutes of Health (NIH) has called for sex as a biological variable, and anyone who receives its research grants are required to include this in their studies. In Canada, the Canadian Institutes for Health Research (CIHR) has established sex and gender based analyses as part of its criteria.

On the face of it, this seems like progress. Before, men were treated as the default human, which put women’s bodies in danger when they received high medication doses, or when their basic functions—like menstruation or ovulation—weren’t factored into treatments. But the new movement has also resulted in a sort of overcorrection: women’s health researchers are being asked to add men into their studies in order to provide balance, even if it doesn’t make scientific sense. A grant application I recently submitted on a women’s health topic was rejected by the funder, citing a need to include male participants. And this hasn’t just happened to me—a colleague was asked to provide a male group when studying inflammation in the placenta.

Not all studies benefit from looking at both sexes. In fact, there are examples in scientific literature that point to greater success when we study one sex in a disease that only influences that one sex. We don’t use female models in studying prostate cancer, or men to study breast cancer. Yet, we have made great strides in treatment and survival rates in both prostate and breast cancer over the last 35 years. Relative five-year survival rates have increased by 33% in prostate cancer and by 16% in female-only breast cancer in the US; by contrast, the survival rates for lung, bladder or thyroid cancer have only improved by five to eight percent over the same time period.

There is also the intriguing possibility that when a body of research considers only one sex, the improvements for treatment can also improve dramatically for that one sex. For example, we do not need to compare perimenopausal women to men to understand how the menopausal transition influences Alzheimer’s disease or osteoporosis. These are physical phenomena specific to female bodies, and the research needs to focus on that.

Of course, this is not to say we should go back to what we used to do—in fact, funders should be prioritizing women’s health beyond just these basic requirements. Male is still the default in research models and clinical trial participants, and drugs and treatments are designed for them, putting women at risk. For example, women suffer very different symptoms of heart attack symptoms than men do, and as a result are more likely to die after a cardiac event. In 2014, the FDA ruled for the first time that a different dose of the sleep aid, Ambien, was required for women, who retained the drug in their systems much longer than men because of their lower average weight. If only the powers that be had paid attention to data they already had, they would have factored this in earlier.

There’s also a lax understanding of how inclusivity should work. Since 1993, the NIH has mandated that all the clinical trials it funds must include both men and women. This is technically a good thing, but there are no rules as to how many of each sex should be included, nor do researchers always analyse the data by sex. Data indicate that even now, only 26% of papers actually investigated whether sex of subject made a difference; and the rest ignored sex as a variable and mixed subjects together. When data is blended, we obscure important information about how a drug or a disease affects females and males differently.

NOTE since 2010 – the number of articles that have male only has increased (!) while studies with females only "stable and low" plus even the studies that included both sexes NB the % analysing sex was consistently low ~14% https://t.co/flXArb6t3z #SABV #SGBA is not enough /15 pic.twitter.com/vHYX7MjcHR

— Dr. Liisa Galea (@LiisaGalea) July 17, 2019

And asking only how women are different from men does not give us the whole picture of what is contributing to women’s health issues. For example, obsessive compulsive disorder (OCD) is three times more likely to occur in women following childbirth. In other cases, female-specific experiences such as oral contraceptive use, pregnancy, the postpartum period, and menopause have all been implicated in mental health diagnoses. There is an urgent need for more studies focussing on these critical transition periods in women to determine why women are more susceptible to depression during these times.

Our health is affected by our experiences, and men and women have different life experiences. How we are different is not the issue; it is how research addresses these differences that will make a difference in the lives and lifespans of female patients and research participants. After 26 years, we are no further than where we started. Not to mention that NIH only funds around 15% of the clinical trials in the U.S.; their requirements, noble as they are, are not altering the landscape of health research in a meaningful way.

And if this system, in their quest to be inclusive, only blocks more women’s health research, it probably isn’t working.

Dr. Liisa Galea is a Professor in the Department of Psychology and a member Djavad Mowafaghian Centre for Brain Health at the University of British Columbia (UBC). The main goal of her research is to improve brain health for women and men by examining the influence of sex and sex hormones on normal and diseased brain states such as depression and Alzheimer’s disease.

Emily Wight contributed to this piece.