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Hormone-replacement therapy: current thinking

This article has been updated

Key Points

  • The use of hormone-replacement therapy (HRT) has been vigorously debated

  • Earlier observational data showed many benefits of HRT, which include reduced coronary heart disease (CHD) and mortality

  • Randomized trials in older women (aged >60 years) have shown no benefit and increased harm

  • Reassessment of clinical trials in women initiating treatment close to the onset of menopause and newer studies and meta-analyses now show benefit and rare risks

  • More studies show benefit with oestrogen alone than with oestrogen plus progestogen

  • The effects of reduced CHD and mortality in women initiating therapy around menopause suggest a possible role for HRT in primary prevention

Abstract

For several decades, the role of hormone-replacement therapy (HRT) has been debated. Early observational data on HRT showed many benefits, including a reduction in coronary heart disease (CHD) and mortality. More recently, randomized trials, including the Women's Health Initiative (WHI), studying mostly women many years after the the onset of menopause, showed no such benefit and, indeed, an increased risk of CHD and breast cancer, which led to an abrupt decrease in the use of HRT. Subsequent reanalyzes of data from the WHI with age stratification, newer randomized and observational data and several meta-analyses now consistently show reductions in CHD and mortality when HRT is initiated soon after menopause. HRT also significantly decreases the incidence of various symptoms of menopause and the risk of osteoporotic fractures, and improves quality of life. In younger healthy women (aged 50–60 years), the risk–benefit balance is positive for using HRT, with risks considered rare. As no validated primary prevention strategies are available for younger women (<60 years of age), other than lifestyle management, some consideration might be given to HRT as a prevention strategy as treatment can reduce CHD and all-cause mortality. Although HRT should be primarily oestrogen-based, no particular HRT regimen can be advocated.

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Figure 1: Adverse effects in women treated with HRT.
Figure 2: Coronary vessels in atherosclerosis.
Figure 3: Breast cancer risk.
Figure 4: Events and symptoms associated with CEE.

Change history

  • 03 November 2016

    In the original published article, reference 41 was incorrect. The correct reference is Carrasquilla, G. D. et al. The association between menopausal hormone therapy and coronary heart disease depends on timing of initiation in relation to menopause onset: results based on pooled individual participant data from the Combined Cohorts of Menopausal Women — Studies of Register Based Health Outcomes in Relation to Hormonal Drugs (COMPREHEND) study [abstract S17]. Menopause 22, 1373 (2015). This error has been corrected in the HTML and PDF versions of the article.

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Correspondence to Roger A. Lobo.

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R.A.L. declares that in the past 3 years he has consulted for Allergan, Pfizer and Teva, and has participated in clinical trials for TherapeuticsMD, with funds paid to Columbia University.

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Lobo, R. Hormone-replacement therapy: current thinking. Nat Rev Endocrinol 13, 220–231 (2017). https://doi.org/10.1038/nrendo.2016.164

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