Many clinical trials are done on men, because those running them fear women's hormonal cycles will confuse the results. Yet findings are taken as being valid for women on the assumption that such effects will not be large enough to make the drugs useless or unsafe. But some findings are increasingly challenging these somewhat contradictory beliefs, particularly the second part, and questioning whether there are dangers in ignoring the influence of sex chromosomes on medication.

"Right now, when you go to the doctor and you are given a prescription, it might not ever have been specifically tested in females," said Professor Deborah J. Clegg of Cedars-Sinai Hospital, California, in a statement. "Almost all basic research – regardless of whether it involves rodent models, dogs, or humans – is predominately done in males. The majority of research is done with the assumption that men and women are biologically the same."

The problem has been recognized for some time. Canada has adopted policies to encourage research that uses both male and female animals in research, leading to at least one scientific breakthrough that would probably not have occurred had they not. Nevertheless, it may be more serious than previously realized.

Clegg is senior author of a paper in Cell Metabolism exploring the ways failure to account for sex can distort scientific results. “While the sex of the subject in clinical studies is obviously important, so too is the sex of the cell, or the hormonal context in which in vitro studies incorporate sex in the model, important,” the paper argues. “Cells may exhibit differential variations upon exposure to sex hormones. Female and male cells respond differently to chemical and microbial stressors.”

Despite this, the authors observe: “The sex of cell lines studied in vitro is mostly ignored and rarely reported.”

Clegg and her co-authors also raise the problem of neglect of the influence of X and Y chromosomes on matters other than sex. “Divergence from the normal number of X and Y chromosomes, called sex chromosome aneuploidy (SCA), accounts for approximately half of all chromosomal anomalies in humans,” they write.

Studies on people with three or one sex chromosomes have demonstrated that they have an influence other than through hormones, including on disease risk. Clegg said that little is known about whether drugs interact differently with two X chromosomes compared to an X and a Y, but there are reasons to think this is a possibility. The effects of medication on transsexuals undergoing hormone therapy are even more poorly studied.

These factors are seldom taken into account in medical trials. Astonishingly, two-thirds of genome-wide association studies (GWAS) looking for genes associated with traits and medical conditions ignore the X chromosome entirely.

The paper seeks to change this, noting: “Researchers are encouraged to critically think of the impact that their experimental design has on the hormonal profile and to accurately analyze the data focusing on the impact of sex.... It is no longer acceptable to be blind to the influence of sex and gender.”