Oestrogen plays a crucial role as a female hormone, regulating reproductive function and neurological processes. Changes in oestrogen levels throughout the reproductive lifespan are associated with alterations in cognitive function, and the loss of oestradiol (E₂) at menopause can accelerate cognitive decline. Interest in the potential therapeutic benefits of hormone replacement therapy (HRT) to supplement E₂ levels has grown. However, there is limited evidence on how HRT affects brain chemistry, structure, and cognitive decline trajectories in postmenopausal women.

This thesis offers a comprehensive examination of HRT's impact on human neurochemistry, neuroanatomy, and memory decline post-menopause through the use of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) in a sample of 52 women. Additionally, memory changes over a 10-year period are evaluated in a large UK cohort (N = 2610).

The results of the neuroimaging study show that increased blood E₂ levels caused by HRT intake impact brain metabolites involved in glutamatergic signalling in the posterior cingulate cortex and phospholipid metabolism in the inferior parietal lobule. HRT use is also associated with increased hippocampal CA1 volume and a slowdown in age-related cortical thickness decline in frontal and parietal brain regions. However, the secondary data analysis suggests that HRT use may be linked to lower memory function after menopause without altering the age-related decline in memory.

Overall, these findings highlight the significant role of hormone levels in brain chemistry, structure, and memory in ageing women, with potential modulation through HRT. While there may be benefits to brain health in a confined sample, the effectiveness of HRT is likely influenced by various factors such as the timing of initiation, dosage, formulation, frequency, and duration of treatment, as well as factors associated with general health, lifestyle, and genetic characteristics. A comprehensive assessment of these variables in a larger, more diverse cohort is essential to establish the impact of HRT on memory preservation. Still, the work presented in this thesis provides a first insight to some of the key physiological and cognitive factors that change as a consequence of ageing and that might be further influenced by HRT.