Less Effect of Intranasal Than Oral Hormone Therapy on Factors Associated With Venous Thrombosis Risk in Healthy Postmenopausal Women

Abstract

Objective-To compare the effects of intranasal and oral administration of 17␤-estradiol (E 2 ) and norethisterone (acetate) [NET(A)] in healthy postmenopausal women on activated protein C (APC) resistance and other hemostatic parameters associated with venous thrombosis. Methods and Results-In this 2-center, randomized, double-blind, 1-year trial, 90 postmenopausal women (56.6Ϯ4.7 years of age) received daily either an intranasal spray with 175 g/275 g E 2 /NET (nϭ47) or 1 mg/0.5 mg oral E 2 /NETA (nϭ43). Normalized APC sensitivity ratios (nAPCsr) were determined with a thrombin generation-based APC resistance test. After 1 year, the increase in nAPCsr was smaller in the intranasal than in the oral group: 11% (95% CI, 1% to 22%) versus 53% (95% CI, 37% to 72%). Overall, the decrease in antithrombin and increase in prothrombin fragment 1ϩ2 (F1ϩ2) were smaller and the decrease in free protein S larger in the intranasal compared with the oral group after 1 year. In both groups, the decreases in protein C and prothrombin, and the increase in D-dimer were similar. Conclusion-Compared

Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review

“…Using transdermal HT, one study found a significant increase compared with baseline and placebo for unopposed transdermal E 2 (42) and the other found a nonsignificant decrease for transdermal E 2 plus oral micronized P (91). For intranasal E 2 plus NETA one study found a significant increase from baseline (100). In all studies, the effect of non-oral HT was significantly less when compared with the large increase in the oral HT group.…”

“…One did not find an effect during unopposed transdermal E 2 or during oral HT (42), whereas the other reported a significant decrease from baseline during intranasal as well as oral E 2 plus NETA (100). Both studies found no difference between oral and non-oral therapy.…”

“…Whereas 6 of 10 studies reported a significant decrease in total protein S in the oral groups, none of the 5 did so for free protein S. For protein C, effects in the oral groups were somewhat inconsistent as 6 of 11 oral studies did not find a significant effect, 4 reported a significant decrease from baseline (28,42,65,100) or control (42) and another found a significant increase from baseline (79). The oral group of this latter study was one of the two studies included in this review that used cyproterone acetate as a progestogen (63,79).…”

“…For antithrombin 13 of 16 studies with oral groups found a decrease, which was significant in 10 studies. Only 3 of 17 studies reported a significant difference in the effect on the antithrombotic proteins between oral and non-oral administration (26,42,100); others were nonsignificant.…”

Effect of Estrogen-Progestin Hormonal Replacement Therapy on Blood Coagulation and Fibrinolysis in Postmenopausal Women

“…3 Several case-control studies demonstrated an increased incidence of venous thrombosis among HT users. [4][5][6][7][8] A meta-analysis performed by Meade 9 showed a higher incidence of venous thrombosis with HT, usually at the beginning of treatment. HT-triggered blood clotting modifications that contribute to thrombosis are particularly important to identify in women with other thrombotic risk factors, such as hereditary or acquired thrombophilia.…”