Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD.

OBJECTIVE:

Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing.

METHODS:

Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale.

RESULTS:

During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala.

CONCLUSION:

COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

Premenstrual disorder (PMDD) affects around 5% of women in childbearing ages. An increased sensitivity in emotion processing areas of the brain to variations in ovarian steroid levels has been suggested as part of the pathophysiology in PMDD, but prior neuroimaging studies of emotion processing are yet inconclusive. Previous behavioral studies of women with PMDD have, however, reported enhanced luteal phase startle responsivity during emotional anticipation. Here we used functional magnetic resonance imaging (fMRI) to investigate central neural circuitry activity during anticipation of, and exposure to, emotional stimuli across the menstrual cycle in women with and without PMDD. As compared to healthy controls, women with PMDD displayed significantly enhanced reactivity in the prefrontal cortex during anticipation of, but not exposure to, negative emotional stimuli during the luteal phase. In PMDD patients, BOLD reactivity during anticipation or viewing of negative emotional stimuli was not dependent on absolute levels of estradiol or progesterone. However, progesterone levels were positively correlated with emotion-induced reactivity in the dorsolateral prefrontal cortex to positive emotional stimuli. These findings suggest that cortical emotional circuitry reactivity during anticipation is altered in PMDD during the luteal phase, which might be part of the pathophysiology behind the emotional symptoms or lack of emotional control reported by women with PMDD.