What do male rodents and human females have in common?

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Drug Development Conducted mostly in Male Rodents

According to most researchers, male rodents share enough in common with human females to extrapolate findings about the mechanisms and treatment of pain. A review of research in the journal Pain (2007) found that over a ten year period, fully 79% of all animal studies published, performed drug testing on male animals only. Only 8% of the published research included female animals and a mere 4% investigated the possible differences between males and females.

The preponderance of male rodents in animal research is in stark contrast to the higher prevalence of women suffering from pain related disorders. I find it difficult to justify using male rodents for drug research that will be translated to the female population, especially when the estrus and menstrual cycles influence so many pharmacokinetic variables.

What do you think? How do the numbers stack up in other areas of research?

Greenspan et al. Pain. 2007 Nov;132 Suppl 1:S26-45. Epub 2007 Oct 25.
To read the full article click here.

Chandler Marrs MS, MA, PhD spent the last dozen years in women’s health research with a focus on steroid neuroendocrinology and mental health. She has published and presented several articles on her findings. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas.

2 Comments

  1. I agree that there’s not enough neuroscience research involving female animal models. As someone who has tried to conduct such research, I can tell you there are some very simple, practical reasons that more scientists don’t work with female animals. It’s difficult and expensive. A female rat’s estrus cycle lasts 4-5 days. Let’s say you’re running a sub-chronic pain treatment study in which the rats get one week of treatment and are then tested for pain sensitivity. You have to take vaginal epithelium samples from every rat every day to determine which phase she’s in. If you’re really being rigorous, you should do two weeks of sampling before the treatment begins to make sure everyone’s cycling normally. When it comes time to test, you have a dilemma. Many behaviors, including responses to pain, vary over different phases of the cycle. So, if you test all your rats at the same time point relative to the end of treatment (say one day after the last drug administration), some rats will be in estrous, some in diestrous, etc. Your data will be all over the place. You can include cycle phase as a variable in your analysis, but you have to use more rats to get adequate power. Alternatively, you can do the pre-treatment estrus tracking and plan your experiment so that every rat starts treatment on the same day of her cycle. That way, most rats will be on the same day of their cycles on the testing day. However, this means you have to stagger your treatment and testing over 4-5 days. Animal care costs vary considerably, but at our facility, it’s $0.70/day/rat. It doesn’t sound like much, but if you have 100 rats in a study, it could cost you $350 more to run the experiment this way.
    Unlike its policy regarding clinical research, NIH does not require inclusion of female animals in the studies it funds, nor does it incentivize the use of females with extra funding. I’m more than happy to go to the extra effort associated with using female rats if someone’s going to pay for it.

  2. Excellent point! In a recent review by Beery and Zucker, Sex bias in neuroscience and biomedical research, Neuroscience and Biobehavioral Reviews 35 (2011) 565–572, Figure 1 shows the distribution of studies by sex and field in 2009. Some fields, like immunology, tend not to even specify whether males or females were used; others like pharmacology use mostly males. But in many cases, even if males and females are used, the studies are not analyzed by sex, so they do not explore the huge differences that can exist between the sexes. It’s not just animal studies, though; many clinical trials fail to analyze results by sex, an unfortunate problem, since the differences in e.g., response to drugs applies to humans, as well as other animals.

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