Hormone-replacement therapy: current thinking

Journal name:
Nature Reviews Endocrinology
Year published:
Published online
Corrected online


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.

At a glance


  1. Adverse effects in women treated with HRT.
    Figure 1: Adverse effects in women treated with HRT.

    Data shown represent lifelong probability of adverse effects in 50-year-old white women; uterus status and progestogen addition have been omitted for simplicity. Effects of oestrogen (blue) versus no treatment (red). Relative risks (RR) and probabilities extracted taken from elsewhere8. HRT, hormone-replacement therapy.

  2. Coronary vessels in atherosclerosis.
    Figure 2: Coronary vessels in atherosclerosis.

    Left panel depicts coronary vessels in a young woman with early atherosclerosis. Right panel depicts coronary vessels in an older (aged >65 years) woman with established atherosclerosis. Various effects of hormone-replacement therapy (HRT) on the vessels in the two stages of atherosclerosis are shown, with benefit in young arteries and altered biology in old arteries. CAMs, cell adhesion molecules; COX2, cyclooxygenase 2; ER, oestrogen receptor; MCP1, monocyte chemoattractant protein 1; MMP, matrix metalloproteinase; TNF, tumour necrosis factor; VSMC, vascular smooth muscle cell. Permission obtained from the American Association for the Advancement of Science © Mendelsohn, M. E. & Karas, R. H. Science 308, 15831587 (2005).

  3. Breast cancer risk.
    Figure 3: Breast cancer risk.

    Relative risks of breast cancer associated with treatment with conjugated equine oestrogens (CEE) alone or with medroxyprogesterone acetate (MPA), occupational exposures and endogenous risks. Data obtained from elsewhere19, 25, 81, 82.

  4. Events and symptoms associated with CEE.
    Figure 4: Events and symptoms associated with CEE.

    Absolute changes in events or symptoms (minus placebo effect) per 1,000 women aged 50–59 years who were treated for 5 years with conjugated equine oestrogens (CEE). Data obtained from elsewhere25, 89.

Change history

Corrected online 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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  1. Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 622 West 168th Street, New York, New York 10032, USA.

    • Roger A. Lobo

Competing interests statement

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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  • Roger A. Lobo

    Roger Lobo obtained his MD in 1974 from Georgetown University, Washington D.C., USA. He is board certified in Obstetrics and Gynecology, Reproductive Endocrinology and Infertility. He has held several teaching positions including Fellowship Director and Chairman of the Department of Obstetrics and Gynecology at Columbia University in New York, where he is Professor at present. He has 480 peer-reviewed publications and several books on reproductive endocrinology and menopause. He serves on several advisory boards and conducts clinical trials in reproductive endocrinology and menopause.

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