However, experts who treat and study menopause say the study is unable to draw a direct connection to later-life dementia and that the overall benefits of hormone replacement therapy, or HRT, far outweigh the risks for many patients.

“Understanding whether hormone replacement therapy (HRT) plays a role in dementia risk has been a priority for the research community in recent years. Such studies, however, have so far been inconclusive and contradictory, with some suggesting that HRT reduces risk of dementia, and others suggesting it increases risk.  Reasons for this may be because of differences in age when HRT is given, differences in how HRT is used, and different types of HRT used over the years.

“This large, nationwide Danish study has found an association between both short- and long-term use of HRT and an increased risk of dementia. Unfortunately, it doesn’t provide a conclusive answer on whether HRT contributes to dementia risk, because the study did not consider some of the other factors known to be involved, such as social isolation, smoking or dietary factors like alcohol.

“Further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women in need of these treatments.” 

Objectives To assess the association between use of menopausal hormone therapy and development of dementia according to type of hormone treatment, duration of use, and age at usage.

Design Nationwide, nested case-control study.

Setting Denmark through national registries.

Participants 5589 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.

Main outcome measures Adjusted hazard ratios with 95% confidence intervals for all cause dementia defined by a first time diagnosis or first time use of dementia specific medication.

Results 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 (95% confidence interval 1.17 to 1.33)). Increasing durations of use yielded higher hazard ratios, ranging from 1.21 (1.09 to 1.35) for one year or less of use to 1.74 (1.45 to 2.10) for more than 12 years of use. Oestrogen-progestin therapy was positively associated with development of dementia for both continuous (1.31 (1.18 to 1.46)) and cyclic (1.24 (1.13 to 1.35)) regimens. Associations persisted in women who received treatment at the age 55 years or younger (1.24 (1.11 to 1.40)). Findings persisted when restricted to late onset dementia (1.21 (1.12 to 1.30)) and Alzheimer’s disease (1.22 (1.07 to 1.39)).

Conclusions Menopausal hormone therapy was positively associated with development of all cause dementia and Alzheimer’s disease, even in women who received treatment at the age of 55 years or younger. The increased rate of dementia was similar between continuous and cyclic treatment. Further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women in need of these treatments.