Cardiovascular risk of hormone replacement therapy in menopausal women with diabetes: a systematic review and meta-analysis of clinical trials and observational studies.

Introduction: Studies have shown the relative cardiovascular safety of hormone replacement therapy (HRT) for women in the general population. Evidence on women with diabetes remains scarce. We aimed to investigate the risk of cardiovascular disease (CVD) in menopausal women with diabetes who use HRT compared to non-users.

Methods: Search across Medline, Embase, Web of Sciences, and Cochrane databases up to November 2023 was conducted. We combined keywords of menopause, diabetes, HRT, and various CVD outcomes. Non-English studies, observational studies other than cohort and case-control, reviews, and conference abstracts were excluded. Bias was checked using validated risk-of-bias tools. Random-effects model was used to calculate pooled relative risks (RR) for similar outcomes.

Results: Out of 7625 identified articles, 19 (6 clinical trials and 13 observational studies) were included, primarily from Europe and the U.S.A. Most studies had moderate risk of bias. Meta-analysis of myocardial infarction (MI) risk from nine observational studies (n =  ~34,626) showed a pooled RR of 0.83 (95% CI 0.62-1.12). Limited data precluded meta-analysis for the clinical trials and other outcomes from observational studies.

Conclusions: Observational studies do not suggest an increased risk of MI in menopausal women with diabetes prescribed HRT. Further research with a more robust method is warranted to validate this finding.

Prospero registration number: CRD42023479335.