Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging

Abstract

Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men.

Progesterone selectively increases amygdala reactivity in women

“…Studies with depressed patients suggest that negative mood is generated by increased activity of brain structures that support the identification of the emotional significance of stimuli and the generation of an affective response (for example, the amygdala, insula, ventral striatum and ventral prefrontal cortex), and decreased activity of brain structures supporting emotion regulation (for example, the dorsal prefrontal cortex and hippocampus). 61 The menstrual cycle has been shown to modulate activity in several of these brain regions, [62][63][64][65] suggesting that progesterone and estradiol may influence mood by modulating this emotion circuitry. The results of the present study show that progesterone increases amygdala activity and indicate that it increases functional coupling with the dACC, without affecting the response amplitude in other brain regions.…”

Evolving Knowledge of Sex Differences in Brain Structure, Function, and Chemistry

“…Circulating estrogen has been shown to reduce arousal in women via the hypothalamic-pituitary-adrenal axis (56). However, postmenopausal women had decreased arousal compared to premenopausal women in response to erotic videos which was reversed with the administration of estradiol (57).…”

Estrogen Administration Negatively Alters Mood Following Monoaminergic Depletion and Psychosocial Stress in Postmenopausal Women

“…Pearson and Lewis (2005) demonstrated that women during high estrogen phases of the menstrual cycle were more accurate at assessing fearful facial expressions than low estrogen phases. Recent functional neuroimaging studies in premenopausal women have demonstrated significant differences in cortical activation of emotional stimuli-modulating areas in response to positive and negative emotional stimuli during high-vs low-estrogen periods of the menstrual cycle (Amin et al, 2006a;Goldstein et al, 2005a;Protopopescu et al, 2005). Alterations in cortical activity produced by differing circulating levels of hormones such as E2 may play a role in regulating how the amygdala and other emotion-related structures respond to emotional stimuli and/or stressful events.…”