Postmenopausal hormone use impact on emotion processing circuitry

Despite considerable evidence for potential effects of estrogen on emotional processing, several studies of postmenopausal women who began hormone therapy (HT) remote from menopause report no effects of HT on emotional measures. As early HT initiation may preserve brain mechanisms, we examined effects of HT on emotional processing in postmenopausal women who started HT early after menopause. We performed a cross-sectional comparison of 52 postmenopausal women 66 ± 5 years old, including 15 users of conjugated equine estrogen, 20 users of conjugated equine estrogen plus medroxyprogesterone acetate, and 17 who never used hormones (NT). All hormone users started therapy within two years of menopause, and received at least 10 years of continuous therapy. Outcomes were fMRI-detected brain activity and behavioral measures during an emotional processing picture rating task. During processing of positive pictures, NT women had greater activation than estrogen treated women in medial prefrontal cortex extending to the anterior cingulate, and more activation than estrogen plus progestin treated women in the insula. During processing of negative pictures, estrogen treated women had higher activation than NT women in the entorhinal cortex. Current compared to past HT users showed greater activation in the hippocampus and higher emotion recognition accuracy of neutral stimuli. Estrogen plus progestin treated women had slower response time than NT women when rating all pictures. In conclusion, hormone use was associated with differences in brain functional responses during emotional processing. These fMRI effects were more prominent than those observed for behavioral measures and involved brain regions implicated in cognitive-emotional integration.

► Long-term early-initiated hormone therapy effects an emotional task in postmenopause.
► Estrogen therapy seemed to preserve brain emotional processing mechanisms.
► Brain differences had no measurable behavioral consequences for the estrogen users.
► Estrogen plus progestin therapy appeared less neuroprotective than estrogen therapy.
► Current compared to past hormone users showed greater activation in the hippocampus.