The use of hormone replacement therapy (HRT) to ease the effects of menopause has been associated with a higher risk of dementia, a new study has found – but the link between the two may not be down to the treatment.
The nationwide study from Denmark, published in the British Medical Journal, appears to contradict some earlier studies that suggested HRT protects against cognitive decline if treatments are started near the onset of menopause.
But it was complicated by the fact that scientists could not distinguish the reasons HRT was prescribed in the first place – to treat changes in sleep, mood, memory, and thinking – from the early symptoms of dementia.
Therefore, in some of the women treated with HRT in the study, symptoms that prompted the therapy may actually have reflected early neurological changes that would have led to a dementia diagnosis anyway.
Dr Sarah-Naomi James of the MRC Unit for Lifelong Health and Ageing at University College London, who was not involved in the Danish research, said the study “has fundamental limitations” in its ability to interpret the link between HRT and dementia, given the similarities between reasons for prescribing HRT and early symptoms of dementia.
“This new study alone should not change practice,” Dr James said in a statement.
For the study, researchers tracked more than 60,000 Danish women, including 5,589 who developed dementia.
Nearly 18,000 had received HRT with a combination of estrogen and progestin, with half starting treatment before age 53 and half stopping within four years. Roughly 90% used oral medications.
Compared with women who never used HRT, those who did had a 24% higher risk of an eventual dementia diagnosis.
The risk increased with the duration of treatment, reaching 74% for people who took HRT for more than 12 years.
About 15% of women aged 45 to 64 in England are currently prescribed HRT, according to Department of Health figures.
HRT’s links to dementia
HRT was widely prescribed before 2003 when a large, randomised, trial found it was linked with a two-fold increase in the risk of dementia in women older than 65.
But subsequent studies found no increase when HRT was started between the ages of 50 and 55, or shortly after menopause.
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But in this new study, the link between HRT use and dementia persisted regardless of when treatment started.
“The observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk” or to help doctors and patients make decisions about using HRT, the authors of the study said.
Study leader Dr Amani Meaidi of the Danish Cancer Society Research Center in Copenhagen said while the study cannot prove HRT contributes to dementia, causality “is biologically plausible,” and further research is needed.
The benefits of HRT
In the meantime, due to well-known adverse effects of HRT, including increased risks of cancer and blood clots, experts in Denmark advise women with menopausal symptoms to first try lifestyle interventions such as exercise, minimising alcohol and caffeine use, not smoking, and maintaining a healthy weight, Dr Meaidi said.
If lifestyle changes do not help and there are no medical reasons to avoid HRT, doctors are advised to prescribe hormone therapy with the shortest duration and the smallest dose possible, she said.
The Menopause Charity says body-identical HRT has already been shown to help reduce the long-term risk for women of osteoporosis, heart disease, and even colon cancer.
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Other research from the US found that “women who took transdermal, body-identical estrogen and progesterone were 73% less likely to get dementia and other brain-degenerating diseases”.
The charity called this an “amazing and heartening figure” because two out of three Alzheimer’s patients are female.