Differential Effects of Oral and Transdermal Estrogen/Progesterone Regimens on Sensitivity to Activated Protein C Among Postmenopausal Women
- 1 September 2003
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 23 (9), 1671-1676
- https://doi.org/10.1161/01.atv.0000087141.05044.1f
Abstract
Objective— Activated protein C (APC) resistance not related to the factor V Leiden mutation is a risk factor for venous thrombosis. Oral estrogen replacement therapy (ERT) has been reported to induce APC resistance. Little is known about the effect of transdermal estrogen. Methods and Results— We enrolled 196 postmenopausal women who were randomly allocated to receive either 1 mg 17β-estradiol orally (n=63) or 50 μg 17β-estradiol transdermally per day (n=68), both associated with 100 mg progesterone daily or placebo (n=65) for 6 months. An activated partial thromboplastin time (APTT)–based test and the effect of APC on thrombin potential (ETP) were used. Oral ERT induced an ETP-based APC resistance compared with both placebo ( P =0.006) and transdermal ERT ( P P =0.191). There was no significant effect of ERT on the APTT-based APC sensitivity ratio. Prothrombin fragment 1+2 plasma levels were significantly higher after 6 months of treatment in women allocated to oral ERT compared with those on placebo and transdermal ERT and were positively and significantly correlated with changes in ETP-based APC sensitivity ratio. Conclusions— Our 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.Keywords
This publication has 26 references indexed in Scilit:
- Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled TrialJama-Journal Of The American Medical Association, 2002
- Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factorsJournal of Internal Medicine, 2001
- The Effects of Hormone Replacement Therapy on Hemostatic Variables in Women with Angiographically Verified Coronary Artery Disease: Results from the Estrogen in Women with Atherosclerosis StudyThrombosis Research, 2000
- Acquired APC resistance and oral contraceptives: differences between two functional testsBritish Journal of Haematology, 1999
- The effects of oestrogen replacement therapy on haemostatic variables in postmenopausal women with non-insulin-dependent diabetes mellitusBlood Coagulation & Fibrinolysis, 1999
- Effect of activated protein C on thrombin generation and on the thrombin potential in plasma of normal and APC-resistant individualsBlood Coagulation & Fibrinolysis, 1997
- Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogensThe Lancet, 1996
- Risk of venous thromboembolism in users of hormone replacement therapyThe Lancet, 1996
- Prospective study of exogenous hormones and risk of pulmonary embolism in womenThe Lancet, 1996
- Mutation in blood coagulation factor V associated with resistance to activated protein CNature, 1994