HRT and Mortality Risk in Healthy Women

Pavankumar Kamat


November 21, 2021


  • Combined hormone replacement therapy (HRT), but not oestrogen-only HRT, was associated with a lower risk of all-cause mortality in healthy women (age, 46-65 years) who were followed up for many years.

Why this matters

  • Findings strengthen the emerging consensus that the benefits of long-term HRT balance the harms for most women.

Study design

  • The retrospective matched cohort study included 105,199 HRT users (cases; age, 46-65 years) and 224,643 matched non-users of HRT (controls), identified using data from The Health Improvement Network database (1984-2017).

  • Follow-up duration was 13.5 years per participant.

  • Main outcome: all-cause mortality.

  • Funding: Actuarial Research Centre of the Institute of Faculty of Actuaries.

Key results

  • Among 105,199 HRT users, 17,606 (17%) received oestrogen-only therapy and 87,593 (83%) received combined HRT therapy.

  • Combined HRT (adjusted HR [aHR], 0.91; 95% CI, 0.88-0.94), but not oestrogen-only HRT (aHR, 0.99; 95% CI, 0.93-1.07), was associated with a lower risk of all-cause mortality.

  • Age-specific aHRs (95% CIs) for all-cause mortality in women who received combined HRT and oestrogen-only HRT as first treatment across different age groups were:

    • For combined HRT:

      • 0.98 (0.92-1.04) for age 46-50 years;

      • 0.87 (0.82-0.92) for age 51-55 years;

      • 0.88 (0.82-0.93) for age 56-60 years; and

      • 0.92 (0.85-0.98) for age 61-65 years.

    • For oestrogen-only HRT:

      • 1.01 (0.84-1.21) for age 46-50 years;

      • 1.03 (0.89-1.18) for age 51-55 years;

      • 0.98 (0.86-1.12) for age 56-60 years; and

      • 0.93 (0.81-1.07) for age 61-65 years.


  • Retrospective design.

  • Risk of residual confounding.

Akter N, Kulinskaya E, Steel N, Bakbergenuly I. The effect of hormone replacement therapy on the survival of UK women: a retrospective cohort study 1984-2017. BJOG. 2021 Nov 12 [Epub ahead of print]. doi: 10.1111/1471-0528.17008. PMID: 34773357 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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