A protocol to assess risk of fractures associated with use of menopausal hormone therapy: nested case-control study using CPRD

AO_SCPLOWBSTRACTC_SCPLOWMenopausal hormone therapy (MHT) is prescribed to women with severe symptoms of menopause. Various studies have demonstrated increased bone density and decreased fracture risk in women using MHT. The randomised controlled trials were, however, run over only relatively short time periods, and there is no reliable or consistent evidence about fracture risk after MHT discontinuation. The proposed nested case-control study aims to fill this gap. We will use CPRD (GOLD and AURUM) and HES data. Every woman 40 years or over with a diagnosis of first fracture between 1998 and 2022 (a case) will be matched by age and general practice to up to 5 female controls with no previous records of fracture at the time of the case diagnosis (index date). MHT exposure will be assessed using prescriptions for the different types of MHT treatment historically available from the NHS. Conditional logistic regression will estimate fracture risk associated with duration of use and gap after discontinuation of MHT. The findings will be adjusted for smoking status, body mass index, family history of dementia, medical conditions and events, other medications and contraceptive drugs. A number of sensitivity analyses will be run to address the limitations of the study.