What’s in a name…or gender?


From a purely scientific perspective, males and females vary. And sticking with this theme, (aside from the blatantly obvious) the variation is observed across several aspects of physiological and also pathological functions.

I stumbled across an article from earlier this year (01/2015), regarding the sexual dimorphism observed with doxorubicin mediated cardiotoxicity. Doxorubicin is an anthracycline used in the treatment of several different cancers. Whilst it is potent in its ability to reduce tumours, it has been found to be very cardiotoxic. With my research investigating drug induced cardiotoxicity, this particular news is of significance to me. A lot of the models used and indeed clinical trials that take place to investigate novel drug compounds, often only look at males, especially in the early stages. And whilst it is found that the severity of side effects are potentially more apparent in males than females (due to females generally presenting sustained cardiac function); it begs the question that finding a difference in the way we respond to drugs as a gender, should warrant the introduction of a model which can account for these differences. Having a brief glance at the paper, the study shows a remarkable difference in the response to doxorubicin between male and female models, where treated male rats showed 50% mortality and significant changes in cardiac function compared to females who showed no mortality and far less adverse changes with regards to cardiac function (left ventricular ejection fraction). These differences were seen as a result of changes to the signalling pathways which mediate everyday cellular function, such as affecting the mitochondria (the cellular “power” house); where females had fewer alterations in mitochondrial function compared to males.

So what does this mean? It means that there are differences in the way we respond to drug treatments, and that means that “blanket” studies or safety tests can’t truly provide accurate results with regard to clinical safety. Yes, in the case of doxorubicin, females are not affected with the same severity as males, which would provide an overestimate regarding toxicity; however, it is also entirely possible that with some classes of drugs, males may not experience the adverse effects that females would. And these adverse toxicities (particularly cardiac related) are uncovered during the later stages which often mean in the post-marketing phase of drug development.

Cardiac safety profiling and establishing appropriate models is a major issue, especially because so many of us end up with co-morbid conditions and end up having to have a combination of drugs, which again affect the way we respond to drugs. Hopefully, with more studies and with the emerging technologies we have under our vast scientific “tool belt”, we can find the right answers to these questions.

 

Hope this very brief overview is insightful! Check out the paper for an in-depth view of things!

 

 

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