Long and short-term use of HRT linked to an increased risk of dementia

Both long and short-term use of menopausal hormone therapy, or HRT, is linked to an increased risk of dementia, according to a large study published in The BMJ.

The study found that 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 (oestrogen and progestin taken daily) and cyclic (daily oestrogen with progestin taken 10-14 days a month) treatment regimens.

Although the study was only observational, the authors are now calling for more research into whether a causal link can be discerned.

Risk increases with higher duration of HRT use

The study is based on data from a population of all Danish women aged 50-60 years. Drawing on national registry data, they identified 5,589 cases of dementia and 55,890 age matched dementia-free controls between 2000 and 2018.

The researchers only included women who had no history of dementia and no underlying reason preventing them from using menopausal hormone therapy.

Other relevant factors including education, income, hypertension, diabetes, and thyroid disease were also taken into account.

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. The average duration of use was 3.8 years for cases and 3.6 years for controls.

The results highlight a link between HRT and dementia, with increasing durations of use yielding higher hazard ratios.

However, since short term use was also found to be linked to an increased risk, the authors of the study are calling for more research into whether there is a causal link between HRT and dementia.

This is an area which remains to be fully explored, with most existing studies focusing on the effects of taking HRT on an extended period of time.

Women who take HRT may have a predisposition to dementia

The authors of the study say they cannot rule out the possibility that women using hormone therapy have a predisposition to both menopausal vasomotor symptoms (e.g. hot flushes, night sweats) and dementia.

Nevertheless, they note the study was based on high-quality treatment data with long follow-up time, and by analysing cyclic and continuous hormone formulations separately, they were able to investigate an important aspect which is often overlooked.

As such, 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.”