to be bold and assert that male-only studies are not good enough anymore. How many false conclusions have been published as a result of failure to consider sex differences? he asked.

Male Bias in Animal Studies

One argument for the preferential use of males in animal studies, said Rae Silver, Kaplan Professor of Natural and Physical Sciences at Barnard College and Columbia University, is that females are more variable than males, partly because of cyclic reproductive hormones. There is evidence that some behaviors exhibit cycle-related variations, but in most instances there is little or no evidence that such variations make female models inappropriate.

But the arguments persist. One commentary cited by Silver described how a particular rat model of arthritis was more reproducible in male rats and that therefore far fewer males than females were needed to achieve statistically significant results. The researcher asserted, however, that the results were applicable to both sexes.

One argument that is true is that the cyclic nature of female sex hormones necessitates larger samples and more test groups in rodent work. Studying females requires more time, is more labor-intensive, and is more expensive than studying only males. Researchers must often justify the cost, as well as the increased use of animals, to their administration or institutional animal-care-and-use committee.

Silver questioned whether it would be possible to require the animal-research community to include both males and females when appropriate, as has been done for humans. Workshop participant Vivian Pinn, director of ORWH, responded that it takes great effort for NIH to monitor the mandated inclusion of women and minorities in clinical trials, and it could become overwhelming to monitor the sex of animals in studies in the same way. It would be more practical, and probably as effective, if researchers knew that information on the sex of animals was desired or required when submitting the results of studies for publication.

Sex Differences Across the Full Spectrum of Research

Denise Faustman, director of the Immunobiology Laboratory at Massachusetts General Hospital, noted that three large phase 3 clinical trials of type I diabetes products had recently failed; together, they were estimated to have cost over $3 billion to conduct. In two of those trials, she said, enrollment of males and females was fairly well balanced—



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