TABLE 3.

Effects of the reproductive cycle and ovarian hormones on drugs of abuse and addiction^a

Drug	Species	Stage of Addiction Cycle
		Binge/Intoxication	Withdrawal/Negative Affect & Preoccupation/Anticipation
Alcohol	Humans	• Premenstrual syndrome-related negative affect increases intake	• Less stress-induced craving during luteal phase
		• Enhanced positive effect in luteal phase
	Rodents	• Intake greatest during diestrus	• Progesterone converted to allopregnanolone modulates withdrawal symptoms
		• Preference lowest during proestrus/estrus
		• Ovariectomy or pregnancy decreases preference
Cocaine	Humans	• Subjective effects greatest during follicular phase	• High progesterone associated with less stress- and cue-induced craving than a low progesterone group
	Rodents	• Ovariectomy attenuates self-administration	• Estradiol enhances cocaine-induced reinstatement and augments cocaine seeking
		• Estradiol enhances intake and motivation	• Females in estrus exhibit greater cocaine-induced responding
		• Motivation for cocaine greater in proestrus/estrus than in diestrus	• Progesterone and allopregnanolone block cocaine-primed reinstatement
Opiates	Humans	• No studies on reinforcing effects of opiates across reproductive cycle	• No studies of withdrawal or relapse across reproductive cycle
	Rodents	• Estradiol enhances intake and motivation	• No studies of withdrawal or relapse across reproductive cycle
Nicotine	Humans	• Reduced craving during luteal phase	• Meta-analysis found greater withdrawal during the luteal phase than during the follicular phase
		• Women with higher progesterone in luteal phase have blunted subjective pleasure from smoking	• Enhanced effect of nicotine cues during follicular phase
	Rodents	• Estradiol is necessary for initiation of nicotine intake in females	• Estradiol is necessary for the effect of stress on relapse in females
Cannabinoids	Humans	• No hormone effect on use or negative affect	• No information available
	Rodents	• No information available	• Ovariectomy attenuates cue-induced reinstatement

^aSummarizing information presented in this article, see text for references.