Cocaine-induced cerebral vasoconstriction differs as a function of sex and menstrual cycle phase

Background: Chronic cocaine abusing women experience fewer cerebral perfusion defects and less neuronal injury than men with comparable drug use histories. This study assessed whether a basis for this discrepancy is a sex difference in cocaine’s acute cerebrovascular effects. Methods: The subjects in this study were 13 healthy and neurologically normal women, reporting occasional cocaine (mean 13, range 1–40 lifetime cocaine exposures). All subjects were administered cocaine (0.4 mg/kg) intravenously, during both the follicular (days 3–8) and luteal (days 18–24) menstrual cycle phases. Dynamic susceptibility contrast magnetic resonance imaging assessments of relative global cerebral blood volume (CBV) changes were conducted on both study days, 10 min after cocaine administration. Results: Cocaine did not alter CBV in follicular phase women, but reduced luteal phase CBV by 10%, indicative of vasoconstriction (analysis of variance [ANOVA], F = 5.1, p< .05). Postcocaine CBV was lower in men administered the drug via an identical protocol relative to follicular phase women (ANOVA, F = 5.4, p< .04). Postcocaine CBV was also lower in the male referent group relative to luteal phase women, but this difference did not achieve statistical significance. No measurable sex or menstrual cycle phase differences in cocaine’s cardiovascular effects were noted. Conclusions: These findings suggest both menstrual cycle phase and sex differences in cocaine’s acute cerebrovascular effects, which may contribute to sex differences in the severity of brain dysfunction found in chronic cocaine abusers. These findings imply that gonadal steroids or the factors they modulate merit study as possible therapeutic agents for reducing cocaine-induced cerebrovascular disorders.