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Hormone replacement therapy and dementia risk: nested case-control studies using QResearch and CPRD

Status

Completed

Title

Hormone replacement therapy and dementia risk: nested case-control studies using QResearch and CPRD

What were the objectives of the study?

Dementia is a devastating condition with serious consequences for affected individuals, families, carers and wider society. It is commonest in older people, affecting 1 in 14 over the age of 65. In the UK, there are currently about 850,000 people living with dementia, and the number is expected to increase to over 1 million by 2025.

Some factors, such as smoking, alcohol and obesity, are known to increase the risk of developing dementia, but there is a lack of information about factors which could delay or prevent its development. If taken at around the time of the menopause, there is some evidence that hormone replacement therapy can reduce the risk of dementia in women, but studies investigating this have so far been small and inconclusive.

The proposed study will use the two largest UK databases of anonymised GP treatment records to select all women over 55 with a diagnosis of dementia. For comparison, a second group of women with no diagnosis of dementia will be identified from the same GP surgeries. For both groups, information on previous prescriptions for hormone replacement therapy will then be used to compare the proportions of women with dementia previously prescribed hormone replacement treatments with the proportions in the comparison group of patients with no dementia diagnosis. Other potential factors will be taken into account and details of different hormonal treatments will also be investigated. This will clarify whether hormone replacement therapy can reduce the risk of dementia.

If hormone replacement therapy is found to reduce the risk of developing dementia, this will be a significant step forward for women considering using hormonal therapies for menopausal symptoms. Concern about the prospect of dementia is growing, so a beneficial effect from hormonal treatments on development of dementia would be an important decision factor.

How was the research done?

The proposed study will use the two largest UK databases of anonymised GP treatment records to select all women over 55 with a diagnosis of dementia. For comparison, a second group of women with no diagnosis of dementia will be identified from the same GP surgeries. For both groups, information on previous prescriptions for hormone replacement therapy will then be used to compare the proportions of women with dementia previously prescribed hormone replacement treatments with the proportions in the comparison group of patients with no dementia diagnosis. Other potential factors will be taken into account and details of different hormonal treatments will also be investigated. This will clarify whether hormone replacement therapy can reduce the risk of dementia.

Chief Investigator

Julia Hippisley-Cox

Lead Applicant Organisation Name

Sponsor

University of Oxford

Location of research

University of Oxford

Date on which research approved

03-Feb-2020

Project reference ID

OX66

Generic ethics approval reference

18/EM/0400

Are all data accessed are in anonymised form?

Yes

Brief summary of the dataset to be released (including any sensitive data)

Women with a diagnosis of dementia on GP hospital or mortality records, matched to controls without a diagnosis of dementia. Exposures include HRT prescriptions. Potential confounders include variables which are risk factors for dementia including body mass index, smoking status, alcohol consumption, Townsend deprivation score, ethnic group, co-morbidities, use of other medications. We will also adjust for oophorectomy/hysterectomy and other variables which would be indications for HRT use (menopausal symptoms) and cancer diagnoses (breast, ovarian, cervical and endometrial).

What were the main findings?

Menopause is the stage in a woman’s life when her hormone levels decrease and periods stop. At this time, many women also experience a range of symptoms, such as hot flushes, sleep disturbances, depression, mood swings or memory losses – sometimes so severely that they need treatment to counteract the effects. Some of these symptoms coincide with early warnings of future dementia. Hormone therapy (MHT – also commonly known as HRT) is effective in easing menopausal symptoms, but whether women who use it are at higher or lower risk of developing dementia has been unclear.
Menopausal hormone therapy usually consists of two types of hormones – an oestrogen being the key component and a progestogen added for womb protection. Biological studies have suggested that exposure to an oestrogen may have a protective effect on the aging brain, but that the addition of a progestogen may counteract this effect. Previous investigations on this topic have either been too small to deliver clear results or have investigated only specific treatments. Our study considered all menopausal hormone treatments available in the UK and included a large number of women, representative of the general population.
We used anonymised records from UK general practices contributing to two of the largest primary care databases. From each database, we selected all women over 55 with a diagnosis of dementia (the cases). For comparison, we identified for each case a number of women with no diagnosis of dementia at the case diagnosis date, drawn from the same practice and of the same age as the case (the controls). For all women, we used information from previous prescriptions for MHT and compared this between cases and controls. We took into account details of use (dosage levels and duration of use) for specific hormonal treatments, and allowed for other potential factors that can affect development of dementia, such as smoking, alcohol, obesity, depression, some chronic conditions and other medications.
We found that use of MHT is not associated generally with increased or decreased dementia risk and that this was consistent across all different hormones treatments, doses, durations or ways of using them. However, for women with an early diagnosis of dementia (before 80) who had used oestrogen-only therapy for 10 years or more, we found a very small decreased risk association between MHT and dementia.
We then analysed the subgroup of women diagnosed with Alzheimer’s disease – a specific sub-type of dementia which slowly develops over years – and their controls. For this group, we found a slowly increasing risk of Alzheimer’s disease, which becomes noticeable only after 5 years of oestrogen-progestogen therapy. In absolute terms, this risk represents, in any year, about an extra 5 diagnoses among every 10,000 women who have used an oestrogen-progestogen therapy for between 5 and 10 years and about an extra 7 cases among every 10,000 woman who have used the therapy for 10 years or more.
Our findings show that MHT is not a significant risk factor for dementia overall, having no measurable effect except in the group of women diagnosed with Alzheimer’s disease – and then only for those with long exposure to combined oestrogen-progestogen treatments. This should reassure women who are in need for MHT and help their discussions with doctors about safe treatment choices.

Implications and Impact

Dementia is a devastating condition with serious consequences for affected individuals, families, carers and wider society. It is commonest in older people, affecting 1 in 14 over the age of 65. In the UK, there are currently about 850,000 people living with dementia, and the number is expected to increase to over 1 million by 2025.

If hormone replacement therapy is found to reduce the risk of developing dementia, this will be a significant step forward for women considering using hormonal therapies for menopausal symptoms. Concern about the prospect of dementia is growing, so a beneficial effect from hormonal treatments on development of dementia would be an important decision factor.

Funding Source

NIHR School for Primary Care Research

Public Benefit Statement

Research Team

Julia Hippisley-Cox, Yana Vinogradova, Carol Coupland, Lauren Taylor, Tom Denning, Michael Moore

Publications

  • Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases
    Authors: Yana Vinogradova, Tom Dening, Julia Hippisley-Cox, Lauren Taylor, Michael Moore, Carol Coupland
    Ref:
    https://www.bmj.com/content/bmj/374/bmj.n2182.full.pdf

Press Releases

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Access Type

Trusted Research Environment (TRE)

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