Postmenopausal Hormone Treatment Correlates with Increased Dementia Risk

Researchers here report on a large study showing that an increased risk of dementia is correlated with postmenopausal hormone treatment in women. It may well be the case that the people who opt into this form of treatment are doing so because they tend to be more burdened by the processes of aging, and are thus more likely to develop later dementia regardless of the therapy. Under the hood, a range of possibly relevant mechanisms can be used to argue for protective or harmful effects of increased levels of the hormones used in these therapies; the biochemistry is complex and there is a lack of satisfactory answers as to whether long term use is in fact harmful in this way.

Dementia affects more women than men worldwide. Even when controlling for differences in survival rates, the incidence of dementia among women is higher compared with that of men, suggestive of risk factors related to the female sex. Oestrogen is known to have both neuroprotective and neurodamaging properties. Exogenous systemic oestrogen is used in the management of menopausal vasomotor symptoms. The effect of menopausal hormone therapy on the risk of dementia is uncertain.

Recent, large scale observational studies have reported a positive association between use of menopausal hormone therapy and Alzheimer's disease in long term users who initiated treatment before age 60 years. However, the studies were not able to obtain full exposure history of hormone treatment for most of their study population, especially short term use (e.g. up to five years) around the age of menopause. We report a nationwide study on the association between menopausal hormone therapy and development of dementia. 5,589 incident cases of dementia and 55,890 age matched controls were identified between 2000 and 2018 from a population of all Danish women aged 50-60 years in 2000 with no history of dementia or contraindications for use of menopausal hormone therapy.

Compared with people who had never used treatment, people who had received oestrogen-progestin therapy had an increased rate of all cause dementia (hazard ratio 1.24). Increasing durations of use yielded higher hazard ratios, ranging from 1.21 for one year or less of use to 1.74 for more than 12 years of use. Oestrogen-progestin therapy was positively associated with development of dementia for both continuous (hazard ratio 1.31) and cyclic (hazard ratio 1.24) regimens. Associations persisted in women who received treatment at the age 55 years or younger (hazard ratio 1.24). Findings persisted when restricted to late onset dementia (hazard ratio 1.21) and Alzheimer's disease (hazard ratio 1.22).


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