Table 2.
Venous thromboembolism risk: features of studies comparing oral and transdermal hormone replacement therapy
| Author, year | Study type | Compared groups | Results |
|---|---|---|---|
| Daly et al. 1996 | Case–control study |
Group 1: HRT Oral Transdermal Implant Tibolone Group 2: never-use HRT |
O-E2: OR of 4.6 (2.1–10.1) T-E2: OR of 2.0 (0.5–7.6) No significant difference between o-E2 and t-E2 No significant difference between high- and low-dose therapy No significant difference between non-opposing estrogens and combined estrogen–progesterone therapy |
| Perez Gutthann S et al. 1997 | Case–control study |
Group 1: HRT Oral Transdermal No HRT Group 2: never-use HRT |
O-E2: OR 2.1 (1.3–3-6) T-E2: OR 2.1 (0.9–4.6) No significant difference between o-E2 and t-E2 No significant difference between high- and low-dose therapy |
| Scarabin PY et al. 2003 | Case–control study |
Group 1: HRT Oral Transdermal No HRT Group 2: never-use HRT |
O-E2: RR 3.5 (95% CI 1.8–6.8) T-E2:RR 0.9 (95% 0.5–1.6) Transdermal administration is safer than oral route (RR 4.0, 95% CI 1.9–8.3) |
| Canonico M et al. 2007 | Case–control study |
Group 1: HRT Oral Transdermal Group 2: never-use HRT |
O-E2: OR 4.2 (95% CI 1.5–11.6) T-E2:OR 0.9 (95% CI 0.4–2.1) Oral not transdermal estrogens were associated with increased thrombotic risk Micronized progesterone and pregnane not associated with an increased risk for VTE (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI 0.4 to 2.3, respectively) Norpregnan: OR 3.9 (95% CI 1.5 to 10.0) Combination of transdermal estrogens and micronized progesterone is the safest choice |
| Canonico M et al. 2010 | Cohort study |
Group 1: HRT Oral Transdermal Group 2: never-use HRT |
O-E2: HR 1.7 (95% CI 1.1–2.8) T-E2: HR 1.1(95% CI 0.8–1.8) Oral estrogens were associated with increased thrombotic risk Norpregnan had an increased risk for VTE, while other progesterone preparations did not show this effect |
| Renoux S et al. 2010 | Case–control study |
Group 1: HRT Oral Transdermal Group 2: never-use HRT |
T-E2: RR 1.01 (95% CI 0.89–1.16)* T-E2 + progestogen: RR 0.96 (95% CI 0.77–1.20) O-E2: RR 1.49 (95% CI 1.37–1.63)** O-E2 + Progestogen: RR 1.54 (95% CI 1.44–1.65) *High dose did not increase the risk for VTE **High dose increased the risk for VTE |
| Sweetland S et al. 2012 | Cohort study |
Group 1: HRT Oral Transdermal Group 2: never-use HRT |
O-E2: RR 1.42 (95% CI, 1.22–1.66) O-E2 + progestins: RR 2.07 (95% CI, 1.86 -2.32) T-E2: RR 0.82 (95% CI, 0.64–1.06) |
| Vinogradova et al. 2019 | Case–control study |
Group 1: cases of VTE Group 2: controls |
E2 with MPA had the highest risk (OR 2.10, 1.92 to 2.31) E2 with dydrogesterone had the lowest risk (OR 1.18, 0.98 to 1.42) Estradiol lower risk than o-CEET-E2: OR 0.93 (95%-CI 0.87 to 1.01) |
| Bergendal et al. 2016 | Case–control study |
Group 1: HRT Group 2: never-use HRT |
Current hormone therapy: OR 1.72 (95% CI 1.34–2.20) Estrogen + progestogen: OR 2.85 (95% CI 2.08–3.90) Estrogen only: OR 1.31 (95% CI 0.78–2.21) T-E2 + progestogen is not associated with higher risk |
| Simon et al. 2016 | Cohort study |
Group 1: HRT O-E2 (N = 316) T-E2 (N = 274) Group 2: never-use HRT |
T-E2 users have significantly lower incidence of VTE events compared to o-E2cohort (RR 0.81; 95% CI 0.67–0.99) |
HRT hormone replacement therapy, VTE venous thromboembolism, RR relative risk, CI confidence interval, HR hazard ratio; o-CEE conjugated equine estrogens