Risk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized trials and observational studies
PubMed 29936403 · doi:10.1016/j.thromres.2018.06.014
What was done
Systematic review of MEDLINE, Cochrane CENTRAL, EMBASE, and ClinicalTrials.gov following PRISMA guidelines to assess venous thromboembolism (VTE) risk in postmenopausal women using non-oral versus oral hormone therapy (HT) compared to non-users or placebo, as well as estrogen alone versus combined estrogen-progestin therapy. The meta-analysis included 22 studies: 9 case-control studies, 9 cohort studies, and 4 randomized controlled trials.
What was found
Compared to controls, non-oral HT was not associated with increased VTE risk overall (OR 0.97 [0.9-1.06]), for non-oral estrogen therapy (ET) alone (OR 0.95 [0.81-1.10]), or for non-oral combined estrogen-progestin (OR 0.92 [0.77-1.09]). In contrast, oral HT significantly increased VTE risk versus controls overall (OR 1.72 [1.47-2.01]), for oral ET alone (OR 1.43 [1.34-1.53]), and for combined oral estrogen-progestin (OR 2.35 [1.9-2.9]). Direct comparison of non-oral versus oral HT showed increased VTE risk with oral HT (OR 1.66 [1.39-1.98]).
Why it matters
This meta-analysis demonstrates that non-oral hormone therapy does not carry the elevated venous thromboembolism risk seen with oral formulations in postmenopausal women.
Limits
The included evidence base is predominantly observational (18 of 22 studies were case-control or cohort studies), resulting in low-to-moderate evidence quality. Total participant count was not reported in the abstract, and data were insufficient to evaluate the impact of specific progestin types, distinct estrogen doses, or varying non-oral delivery methods.
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