Taking some types of HRT is associated with an increased rate of dementia, especially Alzheimer’s disease, a large Danish observational study has reported.
Research, led by Copenhagen University Hospital, found an increase was identified in long-term users of oestrogen and progestin HRT as well as in short-term users.
Writing in today’s edition of the BMJ, the authors say their findings align with the largest clinical trial carried out on this subject. They call for further studies “to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect”.
Large observational studies have shown that long term use of HRT is associated with development of dementia, but the effect of short-term use around the age of menopause, as is currently recommended, has not been fully explored.
For this study, the Danish team drew on national registry data, identifying 5,589 cases of dementia and 55,890 age-matched dementia-free controls between 2000 and 2018. The data is from a population of all Danish women aged 50-60 years in 2000, none of whom had a history of dementia and no underlying reason preventing them from using HRT.
The average age at diagnosis was 70 years. Before a diagnosis, 1,782 (32%) cases and 16,154 (29%) controls had received oestrogen-progestin therapy from an average age of 53 years, with the average duration of use being 3.8 years for cases and 3.6 years for controls.
Compared with people who had never used treatment, people who had received oestrogen-progestin therapy had a 24% increased rate of developing all cause dementia and Alzheimer’s disease, even in women who received treatment at the age of 55 years or younger.
Rates were higher with longer use, ranging from 21% for one year or less to 74% for more than 12 years of use.
The increased rate of dementia was similar between continuous and cyclic treatment regimens, but there was no such association among women who took progestin only therapy and vaginal oestrogen only.
It was an observational study, so the team cannot establish the cause, and the researchers were not able to isolate vascular dementia from other types of dementia or distinguish between tablets and other ways to take hormone therapy, such as patches.
They also said they could not rule out the possibility that women using hormone therapy have a predisposition to both menopausal vasomotor symptoms and dementia.
Nevertheless, they say theirs was a large study based on high quality treatment data with long follow-up time. They investigated cyclic and continuous hormone formulations separately, as well as age of starting menopausal hormone therapy and length of treatment, allowing them to analyse an important overlooked aspect of this topic.
They conclude: “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.”
Pourhadi N, Mørch LS, Holm EA et al. Menopausal hormone therapy and dementia: nationwide, nested case-control study. BMJ 29 June 2023; doi: 10.1136/bmj-2022-072770
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