Endocrine Society: Consider sex differences in biomedical research
Researchers must account for biological differences between females and males in all areas of biomedical research to effectively prevent and treat medical conditions, according to a new scientific statement from the Endocrine Society.
“In 2014, the NIH stated their intent for researchers to consider sex as a biological variable in clinical and basic research,” Aditi Bhargava, PhD, professor in the department of obstetrics and gynecology at the Center for Reproductive Sciences at the University of California, San Francisco, told Healio. “That was more than 6 years ago, but we have not really seen much come out of that intent. While these funding agencies recognize the importance of sex as a biological variable, one of the main reasons you do not see much research addressing that is a lot of scientists and reviewers are not completely clear about what that actually entails. We wanted to clarify what sex differences in research design means.”
Women and men differ in many physiologic and psychological variables, and it is important to establish the mechanisms causing such differences in health and disease, Bhargava and colleagues wrote in the statement.
“If you have to reach a destination, there are multiple ways to reach it,” said Bhargava, also chair of the writing group that wrote the scientific statement. “If you only look at the outcome — the final destination — that can be misleading. In that same respect, men and women can reach the same destination but often have different signaling pathways.”
Bhargava said research that does not consider sex differences can lead to the failure of promising drug candidates; many phase 1 drug trials rely predominantly on male animals or cell lines without reporting their sex. Many published studies that use animal models either do not report the breakdown of animals by sex or do not aggregate results by the sex, she said.
“Since changes in hormone levels and gene expression are dynamic, can be localized, and are spatiotemporally distinct, no one study design or condition can be used as a gold standard,” the researchers wrote. “Animal housing and handling conditions can also create sex differences, and thus any experimental design and data interpretation should take these variables into account. If sex-segregated data does not differ for the aspects under study, then data can be pooled from the two sexes and reported accordingly.”
Clinical studies similarly fail to consider sex as a variable and instead often report it as a confounding factor, Bhargava said.
The statement explores three areas of biological differences between females and males. Imaging has found anatomical and volume differences in the brains of women and men, but these differences do not reveal any functional differences between the sexes. Cardiovascular and kidney diseases present differently in women and men, and although twice as many women as men report stress-related diseases, few studies are designed to explore mechanisms that highlight similarities and difference between sexes.
“The first concrete step is to understand what is happening at baseline,” Bhargava said. “It is imperative that we look at and analyze data separating the two sexes. If you do not find differences, you point that out. Once differences are identified, these could be due to changes in gonadal steroids, differential expression from sex chromosomes, environmental, or all of the above.”
For more information:
Aditi Bhargava, PhD, can be reached at aditi.bhargava@ucsf.edu.
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