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Psychopharmacology (Berl). 2008 Jan;195(4):527-36. Epub 2007 Sep 21.

Altered levels of sex and stress steroid hormones assessed daily over a 28-day cycle in early abstinent cocaine-dependent females.

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  • 1Department of Psychiatry, Yale University School of Medicine, Substance Abuse Center, Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06519, USA.



There is growing evidence of alterations in brain stress and reward circuits associated with cocaine dependence. Sex differences are also documented and sex steroid hormones have been linked to cocaine reinforcement.


The current study therefore assessed daily fluctuations in stress and sex hormones in cocaine-dependent females compared with healthy females.


Daily salivary samples of cortisol, progesterone, and estradiol were collected at waking across 28 days from 12 cocaine-dependent females receiving inpatient treatment and 10 healthy females. Participants also completed mood-rating scales each week corresponding to four phases of the menstrual cycle and cocaine craving was monitored in cocaine patients at each phase.


Cocaine-dependent females in their first month of abstinence demonstrated significantly higher levels of both cortisol and progesterone across the menstrual cycle and significantly lower estradiol/progesterone (E2/P) ratios compared to healthy controls. They also showed significantly increased negative mood compared with controls, but no variation in cocaine craving across the menstrual cycle.


Findings indicate altered stress and sex hormones suggestive of an overactive stress system during the first month of cocaine abstinence after chronic cocaine abuse. These increased levels of cortisol and progesterone could impact both abstinence-related symptoms such as negative mood and susceptibility to drug-seeking behavior in cocaine-dependent females.

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