Contraceptives and conditioning: Different profiles of fear and expectancy ratings during fear conditioning and extinction according to menstrual cycle phase and hormonal contraceptive use

Hormonal contraceptives (HC) such as the oral contraceptive pill (OC) and the hormonal intrauterine device (IUD) have been associated with depressed mood, but research on their role in anxiety is scarce and inconsistent. In a fear acquisition and extinction paradigm, self-report fear, expectancy, and skin conductance responses (SCR) were assessed, along with sex hormone levels. Naturally cycling (NC) participants were measured during the mid-follicular and mid-luteal phases (within subjects, n = 26) and compared with OC (n = 36) and IUD (n = 25) users. IUD users and -participants in the luteal phase showed overall reduced self-reported CS+ vs CS- differentiation compared to the follicular phase and OC use (which both reflect relatively low levels of endogenous gonadal hormones). This overall reduced differentiation in self-reported fear in the luteal phase was attributed to a generalization of fear from CS+ to CS-. NC-individuals with high premenstrual syndrome (PMS) ratings had higher overall fear ratings regardless of cycle phase. For SCR, hormonal status effects were restricted to specific experimental phases during acquisition. SCR to the CS+ was higher at the end of acquisition in the luteal phase compared to the follicular phase, and in OC users during early acquisition (compared to the follicular phase) and mid acquisition (compared to the IUD group). There were no direct associations with sex hormone levels. These findings demonstrate the impact of menstrual cycle and HC use on fear learning and highlight the need for further research that considers different outcome measures across a wide array of menstrual cycle and HC-related characteristics.