Real-world evidence on Hormone Replacement Therapy for menopause: long-term benefits and outcomes (360G-Wellcome-334304_Z_25_Z)

Menopause and perimenopause affect nearly all women, with up to 80% experiencing symptoms such as hot flushes, sleep disturbance, mood changes and urogenital problems. For many, these symptoms are severe and persistent, with substantial impacts on quality of life, relationships, and work. Hormone Replacement Therapy (HRT) is the most effective treatment and is now used by over two million women annually in the UK. Yet key evidence gaps remain. Benefits are rarely quantified beyond symptom relief, long-term outcomes are uncertain for modern regimens, and younger women and women from ethnic minority backgrounds are often underrepresented in existing studies. This fellowship will generate robust, contemporary evidence on HRT benefits and outcomes using population-scale UK electronic health records (EHRs) linked to hospital and cancer registry data. I will combine traditional epidemiology with advanced causal inference and machine learning approaches (e.g. target trial emulation, counterfactual modelling) to: (i) characterise clinical profiles of women approaching menopause, (ii) quantify potential benefits of HRT such as reduced healthcare use and co-medication, (iii) evaluate long-term outcomes including cancer, cardiovascular disease and dementia, and (iv) examine effects in under-researched groups. This will address critical questions about who should receive HRT, when to start and when to stop treatment.