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

Date of ISAC Approval: 
Lay Summary: 
Background: 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 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 (HRT) can reduce the risk of dementia in women, but studies investigating this have so far been conflicting and inconclusive. Purpose of the study: To clarify whether HRT can reduce the risk of developing dementia or delay onset. Potential importance of the findings: If HRT 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.
Technical Summary: 
The technical summary should provide a succinct overview of the overarching study aim and objectives, primary exposure(s), and outcome(s), if relevant, study design, and methods including the main statistical tests to be used. Objective: The study will investigate risks of incident dementia associated with different types of HRT. Outcome: Incident dementia Exposure: Prescriptions for HRT Methods: This will be a nested case-control study. Cases will be women aged 55 years and over with incident dementia diagnosed between 1998 and 2019, matched with up to 5 controls by age, sex, practice and calendar year. Cases will be selected using GP, ONS mortality and HES data. Analysis: Exposure to different HRTs will be defined as at least one prescription for that HRT excluding three years before the index date (date of diagnosis of dementia or equivalent date in matched controls). Conditional logistic regression will be used to assess the risks associated with different types of oestrogen and progesterone. The effects of duration, length of any gap since the last use, different application routes and the age at which treatment started will be analysed for the most common types of hormones. All analyses will be adjusted by available data for potential confounding variables. A study using this same protocol will also be carried out using data from another primary care database (QResearch). Adjusted odds ratios from the conditional regression analyses of the two datasets will be pooled using a fixed effect model with inverse variance weights.
Health Outcomes to be Measured: 
First record of diagnosis of dementia in general practice, hospital admission data and ONS Mortality data, or treatment for dementia in general practice.

Yana Vinogradova - Chief Investigator - University of Nottingham
Professor Carol Coupland - Collaborator - University of Nottingham
Professor Julia Hippisley-Cox - Collaborator - University of Oxford
Dr Lauren Taylor - Collaborator - University of Nottingham
Dr Michael Moore - Collaborator - University of Southampton
Professor Tom Dening - Collaborator - University of Nottingham
Yana Vinogradova - Corresponding Applicant - University of Nottingham

HES Admitted;ONS;Patient Townsend