Cardiovascular outcomes of menopause hormone therapy initiated in women aged ≥60 years or ≥10 years post-menopause: A systematic review of the literature

Abstract

Introduction

Menopause hormone therapy (MHT) is the most effective treatment for climacteric syndrome. However, its cardiovascular effects remain complex. The ‘timing hypothesis’ suggests these effects depend on the timing of initiation, but this has been increasingly questioned. This study evaluates evidence on cardiovascular risks associated with late MHT initiation in healthy women aged ≥60 years or ≥10 years post-menopause.

Methods

A comprehensive literature search was conducted from the inception of each database until November 2023. The databases searched included PubMed, SciELO, Embase, and Cochrane. RCTs of human studies examining the cardiovascular effects of MHT in healthy women aged ≥60 years or those ≥10 years post-menopause were included. Eligibility screening, data extraction, risk of bias assessment were performed independently and in duplicate.

Results

Nine RCTs comprising 36,051 participants were included. We focus on results from participants aged ≥60 years. The mean follow-up was 7.2 years. Six studies were sub-analyses of the Women’s Health Initiative (WHI) trial, while three studies originated from other trials. Results from the WHI indicated no significant increase in cardiovascular risks with either CEE + MPA or Estrogen-only therapy. Non-WHI studies showed an elevated stroke risk with tibolone and higher doses of combined MHT, but no cardiovascular complications were observed with low doses.

Conclusion

The increased risk of cardiovascular events in our target population is not statistically significant. There is a lack of high-quality evidence to suggest an increased risk of adverse cardiovascular outcomes in healthy women who initiate MHT at age ≥60 years or ≥10 years post-menopause.