ABSTRACT

Sitruk-Ware, Régine, Geneviève Plu-Bureau, Joel Menard, Jacqueline Conard, Sushma Kumar, Jean-Christophe Thalaband, Barbara Tokay and Philippe Bouchard. 2007. "Effects of oral and trans-vaginal ethinyl estradiol on hemostatic factors and hepatic proteins in a randomized, cross-over study," Journal of Clinical Endocrinology and Metabolism 92(6): 2074–2079. 

Context
The use of combined hormonal contraceptives with ethinyl estradiol (EE) and a progestin results in alterations in potential biomarkers of venous thromboembolism risk. Evaluation of the impact of delivery route on these changes is difficult due to an interaction between EE and the progestin component.

Objective
The aim of the study was to compare the impact of oral and vaginal administration of EE alone on hemostatic variables and estrogen-sensitive liver proteins.

Design
This was a single-center, randomized, crossover study with two treatment cycles separated by a washout cycle.

Setting
The study was conducted in an academic outpatient center.

Participants
Fourteen healthy postmenopausal women were enrolled; 13 completed the study and were included in the analyses.

Intervention
Participants were randomized to receive EE (15 µg/d) delivered by oral tablet or vaginal ring for 21 days in one of two treatment sequences.

Main outcome measures
Changes in plasma concentration or activity of ten hemostatic variables and six estrogen-sensitive liver proteins between baseline and day 21 of treatment were the primary outcomes.

Results
Prothrombin fragment 1 + 2 plasma level was unaffected by treatment or delivery route. Angiotensinogen (expressed as plasma level of angiotensin I) increased similarly with oral and vaginal delivery; mean (SD) increases were 2,757 (1,033) and 2,864 (893) ng/ml, respectively (P = 0.0002). Alterations in other study variables, except total cholesterol, were similar with oral and vaginal administration.

Conclusion
Our results provide evidence that the customary effects of combined hormonal contraceptives on hemostatic variables and estrogen-sensitive liver proteins are largely related to EE and independent of delivery route during short-term treatment.

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