Women are missing out on optimum medical treatment because most pre-clinical drug research is done in male animals, a new study suggests. New drugs must be evaluated in animals before being considered for human trials. Over three-quarters of these studies use only male animals because of concerns that female hormone cycles will affect experiments. It is also widely assumed that what works for males will work for females. However, research by Natasha Karp at the Wellcome Trust Sanger Institute in Cambridge and her colleagues casts doubt on this assumption. They compared 234 physical traits in 14,000 male and female lab mice. Sex differences were identified for 57 per cent of quantifiable traits – like cholesterol level and bone mass – and for 10 per cent of qualitative traits, like head shape. In another 40,000 mice, they found that when they switched off specific genes, the effects varied according to sex. This suggests that genetic diseases may manifest themselves differently in males and females and require different treatments, says Karp. These sex nuances mean that drugs optimised for male animals may be less effective in females, or even cause harm, says Karp. Between 1997 and 2001, 8 of the 10 drugs that were pulled from the market in the US posed greater health risks for women – possibly as a result of male-biased animal research, she says. Moreover, the male bias means that drugs that work better in females could be overlooked and never make it into clinical trials in the first place, because they are only tested in male animals, says Karp. Time to change Karp argues that the fluctuating hormones of female animals is also no longer a good argument. Male animals vary in other ways, and research has shown they are just as variable as female animals, she says. “Unless there’s a really good reason not to, we should be using both sexes in biomedical research,” says Karp. Peter Rogers at the University of Melbourne in Australia agrees. “I think the world is changing,” he says. “I sit on lots of grant review panels, and it’s rare now for research to be funded if the experimental design fails to consider both males and females where relevant.” In human trials, there has been a greater focus on female representation. Since 1994, the US has required all clinical trials funded by the National Institutes of Health (NIH) to include women. As a result, the proportion of women in clinical trials for heart disease prevention, for example, has increased from only 9 per cent in 1970 to 41 per cent in 2006. In 2014, the NIH also announced that it would provide $10 million to fund research on sex differences in a range of medical conditions, such as drug addiction, migraine and stroke. Source
