As more and more women entered the research arena in the mid- to late twentieth century, some of them began to notice that many clinical studies neglected to include two sexes.
The dearth of female participants resulted in part from a reaction to a tragedy: the use of a sedative called thalidomide during pregnancy had been found to cause congenital anomalies. One upshot was that in 1977 the US Food and Drug Administration (FDA) recommended that almost all women who could become pregnant be excluded from early-phase clinical trials — those that test the safety and efficacy of therapies in healthy volunteers. A policy meant to protect women ended up leaving a vacuum of information on how drugs affect them.
It began to dawn on researchers and funders that excluding a large proportion of the population from these studies or blending the sexes for analyses would have clinical consequences. In response, in 1990, the NIH established the ORWH, and three years later began requiring that women be included in clinical research.
When women are included in trials, it is often in proportions that do not tally with the real-life prevalence of certain diseases in that group. A 2020 review published by Clayton and her colleagues found that of the 11 disease categories the authors analysed from 2014 to 2018, women were under-represented in 7, including liver and kidney diseases9.
Despite the bumpy ride, the federal guidelines that were put into place in the early 1990s have led to some important medical discoveries, perhaps a signal that key revelations could emerge from basic research in a few years.
For instance, there are sex-based differences in the heart’s electrical response to several classes of drug, including antidepressants and antibiotics. As a result, sex-based dose adjustments are now recommended for some drugs2.
Source: The fraught quest to account for sex in biology research





