Impact of female cyclical reproduction on sex differences. Many endpoints with robust sex differences are not modulated by reproductive cycle stage, and a strategy is to assume this is the case until proven otherwise. A simple comparison of gonadally intact males and females will reveal whether there is greater variability in the females compared with the males. If so, this suggests that reproductive cycle stage might be important. There are various approaches that can be used to either determine the status of naturally cycling females or to provide them with a standard regimen of exogenous hormones. If the variability in females does not differ from that in males, this does not necessarily mean there is no role for the estrous cycle. Variability in males may be increased by unanticipated factors such as dominance status during group housing. Conversely, variability in females may be reduced because of either suppression or synchronization of reproductive cycles within group-housed females. Because assessing the stage of the cycle can be laborious, a simpler strategy may be to first determine which hormone(s) when given exogenously alters the endpoint, and then decide whether further assessing estrous cycle stage is worthwhile.