Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing

Cancer J. 2022 May-Jun;28(3):208-223. doi: 10.1097/PPO.0000000000000591.


The totality of evidence indicates menopausal hormone replacement therapy (HRT) effects are determined by timing of initiation according to age and/or time since menopause, underlying health of target tissue, and duration of therapy. Initiated in women at younger than 60 years and/or at or near menopause, HRT significantly reduces all-cause mortality and cardiovascular disease (CVD), whereas other primary CVD prevention therapies such as lipid-lowering fail to do so. The magnitude and type of HRT-associated risks, including breast cancer, stroke, and venous thromboembolism, are rare (<10 events/10,000 women), not unique to HRT, and comparable with other medications. Hormone replacement therapy is a sex-specific and time-dependent primary CVD prevention therapy that concomitantly reduces all-cause mortality, as well as other aging-related diseases with an excellent risk profile. Keeping in mind that prevention strategies must be personalized, health care providers and patients can use cumulated HRT data in making clinical decisions concerning chronic disease prevention including CVD and mortality reduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / prevention & control
  • Estrogen Replacement Therapy*
  • Female
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Menopause
  • Postmenopause