Safety of menopause hormone therapy in postmenopausal women at higher risk of venous thromboembolism: a systematic review

Studies have shown that oral estrogen with or without progestogen increases the risk of venous thromboembolism (VTE). Recent data suggest that transdermal estrogen confers little to no increased risk of VTE. There is no systematic review that examines menopause hormone therapy (MHT) use in women with risk factors for VTE. This systematic review therefore aims to summarize the evidence in this population. The OVID Medline, Embase, PubMed and CENTRAL online databases were searched. A total of 762 studies were screened and 10 were included in the study. Six studies were case-control studies, two were randomized controlled trials (RCTs), one was an RCT that contained a nested case-control study and one was a cohort study. Studies were heterogeneous in their definition of menopause, dose, form and route of administration of MHT, and the underlying VTE risk factor being assessed. In women with risk factors for VTE, transdermal estrogen conferred no increased risk of VTE. Oral estrogen alone has the next safest profile, and oral estrogen plus a progestogen conferred the highest increased risk of VTE. Transdermal MHT appears safe in women with risk factors for VTE. Oral MHT, notably oral estrogen plus a synthetic progestogen, does increase relative risk. More contemporary data are required to confirm these findings.