Postmenopausal hormone therapy and cognition: effects of timing and treatment type

Hormone therapy used for the management of postmenopausal symptoms in older women appears to result in variable effects on cognitive function, depending on study design, subjects, tests used, and types of therapy.

To determine the effects of estrogen-only and estrogen plus progestogen preparations on cognitive performance (cognitive status, general and working memory) when taken 'early' and 'late' from the onset of menopause.

The study consisted of 410 women who were participants in a longitudinal study, first recruited at age 40-80 years. They were tested for change over 5 years as an observational cohort by the Mini-Mental State Examination, National Adult Reading Test and the Wechsler Memory Scale Version 3. Cognitive decline, measured by age-adjusted scores, was defined as >or=10% negative change in each individual woman.

Controlling for age and lifestyle factors, and using the criterion of decrease in score >or=10% over 5 years for 'cognitive decline', 'early start' of hormone therapy (<3 years from menopause) was strongly associated with reduction in risk by the Mini-Mental State Examination (estrogen-only preparation, p = 0.005) but with increase in risk for general memory (with estrogen plus progestogen preparation, p = 0.02). Overall, there were no major effects on subgroups with type/timing of hormone therapy in relation to testing for a negative change in cognitive function.

'Early start' of estrogen-only hormone therapy was associated with reduced risk of global cognitive decline, and 'early start' estrogen-only and estrogen/progestogen hormone therapies showed increased risks of general memory decline. Even though this study did not have the power to discriminate between minor and mixed effects, it suggests that cognitive effects of hormone therapies may be mixed, depending on cognitive domain and timing of use/type of preparation.