The prevalence of cocaine use disorder has increased over the past 10 years. Cocaine is currently second only to opioids as the leading cause of overdose deaths in the United States, and drug relapse remains the foremost obstacle in the treatment of cocaine dependence. Self-reports in cocaine users suggest  that women transition to cocaine dependence faster and report more intense craving in response to cocaine-associated cues than men; however, experimental studies demonstrating these gender differences in cocaine craving and relapse are scarce. Evidence from preclinical animal studies indicates that females may be more vulnerable to cocaine craving and relapse, in part due to the influence of ovarian hormones (see [1] for review). Unfortunately, there are currently no FDA-approved medications for cocaine use disorders in men or women.

Stress is a significant factor eliciting drug craving in male and female cocaine users, and it interacts with other triggers, such as drug-associated cues and small amounts of the drug, to increase relapse propensity. Animal studies have offered critical insights into the mechanisms by which stress potentiates cocaine relapse [2], operationalized as reinstatement of drug-seeking behavior, but most of these studies did not consider sex as a biological variable. Thus, the neuroendocrine mechanisms for sex and estrous differences in stress-potentiated cocaine relapse have remained poorly understood; even though some studies report sex or ovarian hormone effects on stress-induced reinstatement of cocaine seeking [3] and stress-potentiated cue-induced reinstatement of cocaine seeking [4].

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