Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives.

The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHC), after their cessation, is unknown, but is important to guide clinical practice. Our objective was to conduct a prospective cohort study to define the time until normalization of the estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18-50 years who had decided to stop their CHC, excluding those with a personal history of VTE, current anticoagulation, a recent medical event or pregnancy. The study started prior to cessation of CHC, with 6 visits afterwards (at 1-2-4-6-12 weeks post-cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary endpoint. We also included women without CHC as controls. Among 66 users of CHC, from baseline until 12w, average levels of nAPCsr, nTMsr and SHBG decreased from 4.11 (SD2.06), 2.53 (SD1.03) and 167 nmol/L (SD103) to 1.27 (SD0.82), 1.11 (0.58) and 55.4nmol/L (SD26.7), respectively. On a relative scale, 85.8%, 81.3% and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks, and 86.7%, 85.5% and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to four weeks of cessation prior to planned major surgery, or withdrawal of anticoagulants in VTE patients, appears sufficient for the majority of women.

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