Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on APC resistance and SHBG: A cross-over study

Introduction: The transdermal patch (20 µg ethinylestradiol+150 µg norelgestromin daily) and the vaginal ring (15 µg ethinylestradiol+120 µg etonogestrel daily) are new contraceptives, designed to deliver a low dose of hormones, suggesting a low exposure. However, few data are available about their risk of venous thrombosis. The objective was to investigate the effect of the patch, the ring, and an oral contraceptive (30 µg ethinylestradiol+150 µg levonorgestrel daily) on activated protein C sensitivity ratio (APC-sr) and on sex hormone-binding globulin (SHBG) levels in plasma. Materials and methods: After a two month wash-out, 13 volunteers were randomly assigned to either the patch followed by the oral contraceptive or vice versa, or the ring followed by the oral contraceptive or vice versa. All treatments lasted two cycles and were separated by a wash-out of two cycles. APC-sr and SHBG levels were determined on day 18–21 of the second cycle of the wash-out and of each treatment period. Results Compared to the oral contraceptive, both the patch and the ring led to higher APC resistance (mean difference APC-sr 1.1; 95% CI 0.67–1.52 and 0.55; 95% CI 0.11–1.00, respectively) and higher SHBG levels (mean difference 210 nmol/l; 95% CI 134–286 and 148 nmol/l; 95% CI 48–248, respectively). Conclusion The activity of the protein C system in plasma was impaired more by contraceptive patch and vaginal ring than by an oral contraceptive containing the second generation progestagen levonorgestrel.