Selected trials on hormone replacement therapy and risk of VTE in cisgender women
| Study . | Patient demographics . | Study type . | Results . | Interpretation . |
|---|---|---|---|---|
| Weller et al (2023)73 | N = 20 359 | Case control study | For exposures within 60 days, oral HRT VTE risk was almost twice as high as transdermal HT (OR = 1.92; 95% CI, 1.43-2.60); transdermal HRT did not elevate risk compared with no exposure (unopposed OR = 0.70; 95% CI, 0.59-0.83; combined OR = 0.73; 95% CI, 0.56-0.96) | Transdermal HRT did not elevate risk. Oral HRT combinations with estradiol were lower risk than other forms of estrogen. Oral combined hormone contraceptives had much higher risk than oral combined hormonal HRT. |
| Olié et al (2010)19 | Meta-analysis | 2 large cohort studies confirmed that oral but not transdermal estrogens were associated with VTE risk among postmenopAUsal women. Pooled risk ratios for VTE were 1.9 (95% CI, 1.3-2.3) and 1.0 (95% CI 0.9-1.1), respectively. | Transdermal estrogens may substantially improve the benefit/risk ratio of postmenopAUsal hormone therapy and should be considered as a safer option, especially for women at high risk for VTE. | |
| Canonico et al (2007)9 | Meta-analysis | Compared with nonusers of estrogen, the OR for first-time VTE in current users of oral estrogen was 2.5 (95% CI, 1.9-3.4) and in current users of transdermal estrogen was 1.2 (95% CI, 0.9-1.7). | Oral estrogen increases the risk of VTE, especially during the first year of treatment. Transdermal estrogen may be safer with respect to thrombotic risk. | |
| Oger et al (2003)7 | N = 196 | Randomized control trial | Oral HRT induced an ETP-based APC resistance compared with both placebo (P = .006) and transdermal HRT (P < .001), but there was no significant effect of transdermal HRT compared with placebo (P = .191). | The data show that oral, unlike transdermal, estrogen induces APC resistance and activates blood coagulation. These results emphasize the importance of the route of estrogen administration. |
| Hoibraaten et al (2000)13 | N = 140 | Randomized double-blind, placebo-controlled trial | The primary outcome was recurrent DVT or PE. The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial. 8 women in the HRT group and 1 woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the placebo group. In the HRT group, all events happened within 261 days after inclusion. | These data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if possible. |
| Grady et al (1998) (HERS study)74 | N = 2763 | Randomized clinical trial | During an average follow-up of 4.1 years, treatment with oral CEE plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. | CEE plus medroxyprogesterone acetate did not confer a cardiovascular benefit. |
| Study . | Patient demographics . | Study type . | Results . | Interpretation . |
|---|---|---|---|---|
| Weller et al (2023)73 | N = 20 359 | Case control study | For exposures within 60 days, oral HRT VTE risk was almost twice as high as transdermal HT (OR = 1.92; 95% CI, 1.43-2.60); transdermal HRT did not elevate risk compared with no exposure (unopposed OR = 0.70; 95% CI, 0.59-0.83; combined OR = 0.73; 95% CI, 0.56-0.96) | Transdermal HRT did not elevate risk. Oral HRT combinations with estradiol were lower risk than other forms of estrogen. Oral combined hormone contraceptives had much higher risk than oral combined hormonal HRT. |
| Olié et al (2010)19 | Meta-analysis | 2 large cohort studies confirmed that oral but not transdermal estrogens were associated with VTE risk among postmenopAUsal women. Pooled risk ratios for VTE were 1.9 (95% CI, 1.3-2.3) and 1.0 (95% CI 0.9-1.1), respectively. | Transdermal estrogens may substantially improve the benefit/risk ratio of postmenopAUsal hormone therapy and should be considered as a safer option, especially for women at high risk for VTE. | |
| Canonico et al (2007)9 | Meta-analysis | Compared with nonusers of estrogen, the OR for first-time VTE in current users of oral estrogen was 2.5 (95% CI, 1.9-3.4) and in current users of transdermal estrogen was 1.2 (95% CI, 0.9-1.7). | Oral estrogen increases the risk of VTE, especially during the first year of treatment. Transdermal estrogen may be safer with respect to thrombotic risk. | |
| Oger et al (2003)7 | N = 196 | Randomized control trial | Oral HRT induced an ETP-based APC resistance compared with both placebo (P = .006) and transdermal HRT (P < .001), but there was no significant effect of transdermal HRT compared with placebo (P = .191). | The data show that oral, unlike transdermal, estrogen induces APC resistance and activates blood coagulation. These results emphasize the importance of the route of estrogen administration. |
| Hoibraaten et al (2000)13 | N = 140 | Randomized double-blind, placebo-controlled trial | The primary outcome was recurrent DVT or PE. The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial. 8 women in the HRT group and 1 woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the placebo group. In the HRT group, all events happened within 261 days after inclusion. | These data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if possible. |
| Grady et al (1998) (HERS study)74 | N = 2763 | Randomized clinical trial | During an average follow-up of 4.1 years, treatment with oral CEE plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. | CEE plus medroxyprogesterone acetate did not confer a cardiovascular benefit. |
APC, argon plasma coagulation; ETP, endogenous thromobin potential; HT, hormone therapy.