Why women are getting the rough end of the therapy stick

If you are sick, you go to your doctor. Your doctor may examine you. They may prescribe you some medication. You, most likely, get better.

So far, so usual. But what if you have heart disease and your doctor misses it because they are looking for the wrong symptoms? Or the treatment prescribed to treat your cancer is not the most suitable or at the optimal dosage? What if the life-saving treatment that you need was at one point sat on a lab bench, only to be discarded at the earliest stage of drug development?

This may sound preposterous, or incredible, or perhaps just unlucky. But this is the reality facing 50% of the population. The female half.

When scientists are looking to test drug candidates in the lab, they have a choice. Male mouse, or female mouse. Over 75% of the time, they pick the male mouse. Why? Because there are concerns that the cycling of female hormones may skew the data. Some also assume that the difference between the sexes at the cellular level is negligible enough that it doesn’t really matter which one you pick.

It is somewhat understandable given the time and money spent in this research that corners will be cut, for want of a better phrase. But there are legitimate worries that women are not receiving as personalised a diagnosis and treatment as men. A new report out in Nature Communications may have edged the medical world one step closer to fixing this issue by stating that there are considerable differences between male and female mice in terms of both physical traits and the effect of gene knock-outs. 

What this means is that it can no longer be assumed that what works well in males will work equally well in females. Women may be receiving sub-optimal drugs or the incorrect dosage. Drugs that may work well in women could be failing to make it to clinical trials if they show no significant response in male mice.

Scientists now need to ensure that the sex of their mice is always reported, that there is a balance between males and females and that any difference in response to drug candidates is noted. It is not enough to simply take an average of a mixed population as then you risk neither sex receiving the best treatment possible. The effect of fluctuating hormone levels is something that needs to be investigated, not ignored; women cannot be expected to only take medication at certain times of their cycle. There is an increase in the use of female volunteers in human drug trials but this is not enough on its own. The imbalance needs to be acknowledged and addressed at the start of the process. 

Full articles:

Prevalence of sexual dimorphism in mammalian phenotypic traits, Karp et al., Nature Comms.

Sex bias exists in basic science and translational surgical research, Yoon et al., Surgery.

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