Hormone replacement therapy-related changes in the early postmenopausal period (critical window): an in vivo brain proton magnetic resonance spectroscopy study

Findings from clinical studies in postmenopausal women with late initiation of hormone replacement therapy (HRT) that test whether HRT protects cognitive functions in women are inconsistent. The aim of this study was to investigate the effects of HRT on brain metabolite ratios when initiated in the early postmenopausal period (critical window). Proton magnetic resonance spectrometry (1H MRS) was performed in 4 brain regions of 47 healthy postmenopausal women (21 received HRT, 26 did not). The subjects were aged between 45 and 65 years. The duration of HRT ranged from 1 to 12 years (mean: 6.3 years). The duration of menopause was 2-12 years (mean: 6.1 years) for HRT users and 1-20 years (mean: 7.8 years) for non-HRT users. Metabolite ratios [N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr] were evaluated. Cho/Cr ratios were significantly increased and NAA/Cho ratios significantly decreased in all 4 regions in the HRT user group compared to the other group after elimination of the effects of age and menopause duration. Regression analysis revealed an association only between NAA/Cho and duration of menopause. HRT-related changes in metabolite ratios are found in all brain regions. Decreased NAA/Cho and increased Cho/Cr levels do not support the neuroprotective role of HRT in the critical window.