title: Perimenopausal use of hormone therapy is associated with enhanced memory and hippocampal function later in life.
abstract: Evidence suggests that initiation of some forms of hormone therapy (HT) early in the perimenopausal or postmenopausal stage might confer benefit to verbal memory and the neural systems underlying memory, whereas late-life initiation confers no benefit or harm. This "critical window hypothesis" remains a topic of debate. Using functional magnetic resonance imaging (fMRI), we examined the long-term impact of perimenopausal HT use on brain function during performance of verbal and figural memory tasks. Participants were 34 postmenopausal women (mean age 60 years) from the Melbourne Women's Midlife Health Project and included 17 early (perimenopausal) and continuous users of HT and 17 never users matched on age, education, and verbal knowledge. Continuous HT use from the perimenopausal stage versus no use was validated with prospective daily diary records and study visit data. The primary outcome was patterns of brain activation in an a priori region of interest in the medial temporal lobe during verbal encoding and recognition of words. Results indicated that perimenopausal HT users performed better than nonusers on the imaging verbal memory task (p<.05). During verbal recognition, perimenopausal HT users showed increased activation in the left hippocampus and decreased activation in the parahippocampal gyrus bilaterally compared with never users. Each of these patterns of activation was associated with better memory performance on the imaging memory task. These results suggest that perimenopausal use of HT might confer long-term benefits to verbal memory and the brain systems underlying verbal memory. More generally, the results support the critical window hypothesis.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. pmaki@psych.uic.edu
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Maki
authors.forename: Lorraine
authors.initials: L
authors.lastname: Dennerstein
authors.forename: Margaret
authors.initials: M
authors.lastname: Clark
authors.forename: Janet
authors.initials: J
authors.lastname: Guthrie
authors.forename: Pamela
authors.initials: P
authors.lastname: LaMontagne
authors.forename: Deanne
authors.initials: D
authors.lastname: Fornelli
authors.forename: Deborah
authors.initials: D
authors.lastname: Little
authors.forename: Victor W
authors.initials: VW
authors.lastname: Henderson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
mesh_terms: D000367:Age Factors; D000368:Aged; D015914:Estrogen Replacement Therapy / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D020249:Hormone Replacement Therapy / Q000639:trends*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D047648:Perimenopause / Q000187:drug effects* / Q000502:physiology / Q000523:psychology*; D011446:Prospective Studies