The effects of smoked nicotine on measures of subjective states and hypothalamic-pituitary-adrenal axis hormones in women during the follicular and luteal phases of the menstrual cycle

Abstract

Objectives: To determine the acute effects of cigarette smoking on hypothalamic-pituitary-adrenal (HPA) axis hormones and subjective states as a function of the menstrual cycle in nicotine-dependent women.

Methods: Seventeen healthy nicotine-dependent women were studied during the follicular and/or luteal phase of the menstrual cycle. Because of observation of a possible bimodal distribution of progesterone levels within the luteal phase group, we performed a set of a posteriori analyses. Therefore, we divided the luteal group into a low progesterone and a high progesterone groups.

Results: Smoked nicotine activated HPA, measured by adrenocorticotropin hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA) response and affected subjective states in both follicular and luteal phases, with increased "High," "Rush," and decreased "Craving." The HPA stimulation revealed a blunting of ACTH response. There was only modest evidence for a blunting of subjective state responses in the luteal phase. However, upon post hoc analyses, the high progesterone luteal group showed a marked blunting of measures of subjective states and a blunted ACTH response. Examining the association between hormone and measures of subjective states revealed tentative associations of ACTH stimulation with increased "Rush" and "Craving," and DHEA stimulation with increased "Craving."

Conclusions: This pilot study suggests that menstrual cycle phase differences in progesterone levels may attenuate nicotine's addictive effects via diminution of its reinforcing properties and augmentation of its aversive effects interfering with the pleasure associated with cigarette smoking.

Figure 1

Mean (± SE) nicotine levels after smoking high-nicotine cigarettes during the follicular and luteal phases of the menstrual cycle. The graph on left depicts the follicular phase in comparison with the luteal phase; the graph on the right depicts the follicular phase in comparison with the two luteal phase subgroups (high progesterone and low progesterone). The 12-min cigarette smoking period is indicated by a gray rectangle. Significant changes (p < 0.05) from the presmoking baseline in follicular phase group are indicated by #; in luteal phase group by ^; in the high progesterone luteal phase subgroup by ‡; and in the low progesterone luteal phase subgroup by ¶.

Figure 2

Mean (± SE) ACTH, cortisol, and DHEA levels after smoking high-nicotine cigarettes during the follicular and luteal phases of the menstrual cycle. The three graphs above depict the follicular phase in comparison with the luteal phase; the three graphs below depict the follicular phase in comparison with the two luteal phase subgroups (high progesterone and low progesterone). The 12-min cigarette smoking period is indicated by a gray rectangle. Significant changes (p < 0.05) from the presmoking baseline in follicular phase group are indicated by #; in luteal phase group by ^; in the high progesterone luteal phase subgroup by ‡; and in the low progesterone luteal phase subgroup by ¶.

Figure 3

Mean (± SE) ratings of High, Rush, and Craving for Nicotine after smoking high-nicotine cigarettes during the follicular and luteal phases of the menstrual cycle. The three graphs above depict the follicular phase in comparison with the luteal phase; the three graphs below depict the follicular phase in comparison with the two luteal phase subgroups (high progesterone and low progesterone). The 12-min cigarette smoking period is indicated by a gray rectangle. Significant changes (p < 0.05) from the presmoking baseline in follicular phase group are indicated by #; in luteal phase group by ^; in the high progesterone luteal phase subgroup by ‡; and in the low progesterone luteal phase subgroup by ¶.