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Breaking the Cycle: Estrous Variation Does Not Require Increased Sample Size in the Study of Female Rats. Hypertension 2016 11;68(5):1139-1144 PMID: 27672030 PMCID: PMC5104284


Despite the striking differences between male and female physiology, female physiology is understudied. In response, the National Institutes of Health is promulgating new policies to increase the use of female organisms in preclinical research. Females are commonly believed to have greater variability than males because of the estrous cycle, but recent studies call this belief into question. Effects of estrous cycling on mean arterial pressure were assessed in female Dahl S rats using telemetry and vaginal cytometry and found that estrous cycling did not affect mean arterial pressure magnitude or variance. Data from the PhysGen arm of the Program for Genomic Applications was used to compare male and female variance and coefficient of variation in 142 heart, lung, vascular, kidney, and blood phenotypes, each measured in hundreds to thousands of individual rats from over 50 inbred strains. Seventy-four of 142 phenotypes from this data set demonstrated a sex difference in variance; however, 59% of these phenotypes exhibited greater variance in male rats rather than female. Remarkably, a retrospective power analysis demonstrated that only 16 of 74 differentially variable phenotypes would be detected when using an experimental cohort large enough to detect a difference in magnitude. No overall difference in coefficient of variation between male and female rats was detected when analyzing these 142 phenotypes. We conclude that variability of 142 traits in male and female rats is similar, suggesting that differential treatment of males and females for the purposes of experimental design is unnecessary until proven otherwise, rather than the other way around.

Author List

Dayton A, Exner EC, Bukowy JD, Stodola TJ, Kurth T, Skelton M, Greene AS, Cowley AW Jr


Allen W. Cowley Jr PhD Chair, Professor in the Physiology department at Medical College of Wisconsin
Andrew S. Greene PhD Interim Vice Chair, Chief, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Pressure
Estrous Cycle
Models, Animal
Rats, Inbred Dahl
Sample Size
Sensitivity and Specificity
Sex Characteristics

View this publication's entry at the Pubmed website PMID: 27672030
jenkins-FCD Prod-169 3190624ff63883a964b0308a7647b09582875180