Objective: To estimate the effect of estrogen-only and combined hormone replacement therapy (HRT) on the hazards of overall and age-specific all-cause mortality in healthy women aged 46-65 at first prescription.
Design: Matched cohort study.
Setting: Electronic primary care records from The Health Improvement Network (THIN) database, UK (1984-2017).
Population: 105 199 HRT users (cases) and 224 643 non-users (controls) matched on age and general practice.
Methods: Weibull-Double-Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy, hysterectomy, body mass index, smoking and deprivation status.
Main outcome measures: All-cause mortality.
Results: A total of 21 751 women died over an average of 13.5 years follow-up per participant, of whom 6329 were users and 15 422 non-users. The adjusted hazard ratio (HR) of overall all-cause mortality in combined HRT users was 0.91 (95% CI 0.88-0.94), and in estrogen-only users was 0.99 (0.93-1.07), compared with non-users. Age-specific adjusted HRs for participants aged 46-50, 51-55, 56-60 and 61-65 years at first treatment were 0.98 (0.92-1.04), 0.87 (0.82-0.92), 0.88 (0.82-0.93) and 0.92 (0.85-0.98) for combined HRT users compared with non-users, and 1.01 (0.84-1.21), 1.03 (0.89-1.18), 0.98 (0.86-1.12) and 0.93 (0.81-1.07) for estrogen-only users, respectively.
Conclusions: Combined HRT was associated with a 9% lower risk of all-cause mortality and estrogen-only formulation was not associated with any significant changes.
Tweetable abstract: Estrogen-only HRT is not associated with all-cause mortality and combined HRT reduces the risks.
Keywords: Hormone replacement therapy; The Health Improvement Network; menopause; mortality; primary care records.
© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.