(038) Cardiovascular Risk of Hormone Replacement Therapy in Menopausal Women with Diabetes: A Systematic Review and Meta-Analysis of Clinical Trials and Observational Studies

Background: Studies have shown the relative cardiovascular safety of hormone replacement therapy (HRT) for women in the general population, especially during the early years of menopause. Evidence of HRT-associated cardiovascular (CV) risk in the diabetes population remains scarce.

Objectives: To investigate the risk of cardiovascular outcomes in menopausal women with diabetes who use HRT compared to non-users.

Methods: A comprehensive literature search across Medline, Embase, Web of Sciences, and Cochrane Trial databases up to November 2023 was conducted. We combined keywords of menopause, diabetes, HRT, and various CV outcomes. References from prior reviews on this topic were used to identify studies reporting subgroup analyses in the diabetes population. Published papers that were not in English, observational studies other than cohort and case-control, reviews, and conference abstracts were excluded. Individual studies in this review were checked for bias using the ROBINS-I tool for observational studies. We used a random-effects model to calculate summary odds ratios (OR) for studies with similar outcomes. Adherence to the PRISMA guidelines was observed for reporting.

Results: Out of 7625 identified titles, 19 reports (6 clinical trials and 13 observational studies) were included, primarily from Europe and the USA. Most studies exhibited a moderate risk of bias. Pre-specified outcomes identified from the search included chronic heart disease, myocardial infarction (MI), stroke, peripheral arterial disease, and atrial fibrillation. Meta-analysis of MI risk from 7 observational studies (n=~23,254) showed a pooled OR of 0.85 (95% CI, 0.56-1.28). 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 before incorporating them into clinical practice.