The effect of hormone replacement therapy on the survival of UK women: a retrospective cohort study 1984−2017

Nurunnahar Akter, Elena Kulinskaya, Nicholas Steel, Ilyas Bakbergenuly

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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.
Original languageEnglish
Pages (from-to)994-1003
Number of pages10
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Issue number6
Early online date12 Nov 2021
Publication statusPublished - May 2022


  • Hormone replacement therapy
  • The Health Improvement Network
  • menopause
  • mortality
  • primary care records

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