The Influence of Perimenstrual Daily Ovarian Hormones on Anxiety and Cigarette Craving

Estradiol (E2) and progesterone (P) and their fluctuation during the female menstrual cycle have been independently linked to both nicotine reinforcement and anxiety. The fluctuation and withdrawal of E2 and P during perimenstrum (days before and during menses) is a vulnerability window for emotional distress, thus the hormonal influence on anxiety and craving may be amplified during perimenstrum.

Naturalistic daily data were collected from non-treatment-seeking females who endorsed daily cigarette smoking (N = 50). The daily protocol involved morning salivary index of E2 and P and ecological momentary assessments of anxiety and cigarette craving. Days of the menstrual cycle were coded as either occurring during perimenstrum (ie, seven days prior to and first 3 days after menstrual onset) or reference (ie, all other times during cycle). Using multilevel modeling, we tested the main and interactive effects of daily E2, P, and perimenstrum (yes/no) on same-day anxiety and cigarette craving.

Results indicated significant three-way interactions between E2 and P both centered between and within perimenstrum for anxiety and craving. In perimenstrum, anxiety and craving were elevated regardless of hormonal balance. However, the association between P and anxiety varied in the context of E2, such that higher P and lower E2 dampened anxiety outside of perimenstrum. Similarly, higher P and lower E2 was associated with lower craving outside perimenstrum.

These data provide high specificity for understanding hormonal influences on anxiety and craving during the menstrual cycle, which has implications for female-specific models and treatment of the anxiety-smoking comorbidity. Implications: This is the first study to document daily-level associations between salivary E2 and P, and their interaction, with anxiety and cigarette craving, in the context of the female menstrual cycle. Perimenstrum (ie, days before and during menses) appears to confer risk for anxiety and craving regardless of the hormonal balance. However, higher daily P dampened anxiety but only in the context of lower daily E2 on days outside of perimenstrum. For craving, higher P with lower E2 was associated with lower craving outside of perimenstrum. The ovarian hormonal milieu should be considered when understanding the etiology and subsequent treatment of anxiety-smoking comorbidity in females.