During menopause, all women experience a drop in their hormone levels. Particularly in older women, one hormone, oestrogen, is linked to osteoporosis – a weakening in bone structure which increases the risk of bone fractures. Statistics show that, after the age of 50, every second woman will experience bone fracture – a burden for the patients, their families and society. The protective role of menopausal hormone therapy (MHT) [also commonly known as hormone replacement therapy (HRT)] has been confirmed by many past studies, and current use of MHT is known to decrease the rate of fractures.
MHT is, however, also associated with some serious side-effects, including increased risk of developing breast cancer and blood clots. In particular, long-term exposure to MHT treatments among older women is not recommended, so it is important to know how long the protective effects may last after treatment is stopped. Information from previous studies on this aspect is conflicting and partial, not covering many different treatments.
This study will produce detailed information on how much risk of fractures are reduced for specific treatments (different hormonal combinations). For each specific treatment commonly prescribed in the UK, it will determine differences in the beneficial effects on fracture risk– how long the beneficial effects last after the treatment stops, the pattern of decline in effects after stopping, and whether dosage differences are important. The information generated will help women and their doctors to manage MHT treatments for countering osteoporosis and improve treatment safety.
Aim: To estimate the risk of fractures associated with current and previous use of the different types of MHT treatment historically available through the NHS.
Methods:
• The proposed study will use CPRD (both GOLD and AURUM). Where practices contribute to both parts only data from GOLD will be used.
• This will be a nested case-control study. Every woman 40 years or over with a diagnosis of first fracture between 1998 and 2022 (case) will be matched by age and practice to up to 5 female controls with no diagnosis of fracture at the time of the case diagnosis (index date). Cases will be selected using GP, ONS mortality and HES data.
• Associations between different uses of MHT (types, applications, different hormones, doses, durations of use, gap after the last use) will be assessed using conditional logistic regression.
• Other potential factors (body mass index, smoking, alcohol consumption, ethnicity, deprivation, medical conditions and other medications associated with osteoporosis risk) will be included into analyses.
• Multiple imputations will be used for missing information on smoking, ethnicity, body-mass index and alcohol consumption.
• A number of sensitivity analyses will be run to address the limitations of the study.
First record of diagnosis of any fracture(s) in general practice, hospital admission data or ONS Mortality data, during the study period. In three subgroup analyses the outcomes will be three most common types of fracture (hip, spine, wrist) and in sensitivity analysis the outcome will be a record of any fragility fracture(s) (hip, spine, rib, humerus, radius/ulna or pelvis), if these are the first records of fracture(s) during the study period.
Yana Vinogradova - Chief Investigator - University of Nottingham
Yana Vinogradova - Corresponding Applicant - University of Nottingham
Barbara Iyen - Collaborator - University of Nottingham
Joe Kai - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Townsend Index;Practice Level Townsend Index