Substantial evidence now documents sex-related influences on the neurobiology of emotional memory. Robust sex influences exist, for example, on the amygdala’s role in emotional memory formation, as well as on retention of central information (gist) and detail for an emotional event. Evidence also suggests that the well-documented effects of stress hormones on memory depend upon sex hormone levels. Since hormonal contraception alters sex hormone levels, and must by extension alter sex/stress hormone interactions in memory, we examined whether the use of hormonal contraception also alters memory for an emotional story. Two groups of healthy female subjects—one naturally cycling, one using hormonal contraception—viewed either a brief, emotionally arousing story, or a closely matched, but more emotionally neutral story. Each subject’s eye movements and pupil dilation changes were recorded as they viewed the story. Additionally, saliva samples were taken throughout the experimental session to examine salivary alpha-amylase, a biomarker for norepinephrine. A surprise free recall test one week later measured story memory in all subjects. Naturally cycling women exhibited enhanced memory of story details, but not of central information (gist), in the emotional compared with neutral story conditions. In contrast, women using hormonal contraception exhibited enhanced memory of gist, but not story details, in the emotional compared with neutral story conditions. Analysis of eye movements made while watching the stories indicated that the differences in memory could not be attributed either to a differential attention focus or to the degree of arousal induced by the stories in the two groups. These findings suggest that the use of hormonal contraception alters memory for an emotional event, perhaps by altering sex/stress hormone interactions in memory formation. They also suggest that further investigation of the mnemonic effects of these very widely used treatments is warranted.

Emotionally arousing material is typically better remembered than neutral material. Since norepinephrine and cortisol interact to modulate emotional memory, sex-related influences on stress responses may be related to sex differences in emotional memory. Two groups of healthy women – one naturally cycling (NC women, N = 42) and one using hormonal contraceptives (HC women, N = 36) – viewed emotionally arousing and neutral images. Immediately after, they were assigned to Cold Pressor Stress (CPS) or a control procedure. One week later, participants received a surprise free recall test. Saliva samples were collected and later assayed for salivary alpha-amylase (biomarker for norepinephrine) and cortisol. Compared to NC women, HC women exhibited significantly blunted stress hormone responses to the images and CPS. Recall of emotional images differed between HC and NC women depending on noradrenergic and cortisol responses. These findings may have important implications for understanding the neurobiology of emotional memory disorders, especially those that disproportionately affect women.

Sex influences on emotional memory have received increasing interest over the past decade. However, only a subset of this previous work explored the influence of sex on memory for central information (gist) and peripheral detail in emotional versus neutral contexts. Here we examined the influence of sex and menstrual cycle phase at encoding on memory for either an emotional or neutral story, specifically with respect to the retention of gist and peripheral detail. Healthy naturally cycling women and men viewed a brief, narrated, three-phase story containing neutral or emotionally arousing elements. One week later, participants received a surprise free recall test for story elements. The results indicate that naturally cycling women in the luteal (high hormone) phase of the menstrual cycle at encoding show enhanced memory for peripheral details, but not gist, when in the emotional compared with neutral stories (p<.05). In contrast, naturally cycling women in the follicular (low hormone) phase of the menstrual cycle at encoding did not show enhanced memory for gist or peripheral details in the emotional compared with neutral stories. Men show enhanced memory for gist, but not peripheral details, in the emotional versus neutral stories (p<.05). In addition, these sex influences on memory cannot be attributed to differences in attention or arousal; luteal women, follicular women, and men performed similarly on measures of attention (fixation time percentage) and arousal (pupil diameter changes) during the most arousing phase of the emotional story. These findings suggest that sex and menstrual cycle phase at encoding influence long term memory for different types of emotional information.

Studies with animals of both sexes show that the adrenal glands release progesterone in addition to cortisol in response to stress. However, little is known about the progesterone response to stress in naturally cycling women. We investigated the effect of stress on estradiol, progesterone, and cortisol levels in women during the follicular phase of the menstrual cycle. We found that physical stress (the cold pressor test) had no effect on estradiol levels, but increased progesterone and cortisol. We also found positive correlations between baseline progesterone and cortisol levels, as well as between the change in progesterone and cortisol before and after water exposure in both the stress and control sessions. Mediation analyses revealed during the stress session, the change in progesterone from baseline to 42-min post-stress onset was mediated by the magnitude of change in cortisol levels across the same time span. Overall, these findings reveal that progesterone released in response to stress as observed in animals and men extends to women during the low ovarian output follicular phase of the menstrual cycle, and that the mechanism of release may be similar to the mechanism of cortisol release.

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