title: Impact of oral contraceptive use on APC-resistance: a prospective, randomized clinical trial with three low-dose preparations.
abstract: The evaluation of the study was of the impact of oral contraceptive (OC) use on activated protein C (APC-resistance). Eight hundred eighteen young fertile women were screened for a study designed to compare three different marketed OC preparations. The women could have used either other oral contraceptive preparations before switching to the study medications (switchers) or were not using hormonal contraceptives (new starters) before the study began. Prior to study drug intake and during treatment, APC-resistance was determined with three different tests. Forty-one of 809 women evaluated (5.07%) carried the Factor V Leiden mutation. Twenty-two further participants (2.72%) had a positive screening test, but did not provide samples for the confirmatory mutation test. Two women with homozygous Factor V Leiden mutations and 39 women with heterozygous mutations were identified. The homozygous carriers were identified in all three of the screening tests employed, whereas none of the tests detected all 39 heterozygotes. In the pretreatment screening tests, previous OC users (switchers) had slightly lower APC ratios than the women using non-hormonal birth control methods (starters). During treatment the difference between starters and switchers was no longer apparent, but the APC ratio values of the screening tests slightly increased for both. The homozygous carriers were not treated. Differences in APC-resistance between users of the three different oral contraceptive preparations were not found. In conclusion, laboratory screening for APC-resistance using Coatest APC, ProC Global, or ProC APC-FV-Leiden clearly identifies homozygous mutant carriers. However, with regard to heterozygous mutant carriers, the sensitivity and specificity of the tests, especially during OC intake, is limited. The results of APC screening tests should have, at present, no impact on contraceptive counseling because the predictive value for thromboembolic risk of the test results and even the mutant status is low.
authors.affiliation: Schering AG, Müllerstr. 178, D-13342, Berlin, Germany. jan.endrikat@schering.de
authors.forename: J
authors.initials: J
authors.lastname: Endrikat
authors.forename: M
authors.initials: M
authors.lastname: Noah
authors.forename: C
authors.initials: C
authors.lastname: Gerlinger
authors.forename: R
authors.initials: R
authors.lastname: Bannemerschult
authors.forename: W
authors.initials: W
authors.lastname: Junge
authors.forename: A
authors.initials: A
authors.lastname: Ruebig
authors.forename: W
authors.initials: W
authors.lastname: Schmidt
authors.forename: B
authors.initials: B
authors.lastname: Düsterberg
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D004997:Ethinyl Estradiol / Q000009:adverse effects; D019304:Ethinyl Estradiol-Norgestrel Combination / Q000009:adverse effects; D005165:Factor V / Q000235:genetics; D005260:Female; D006801:Humans; D009154:Mutation; D009640:Norethindrone / Q000009:adverse effects / Q000031:analogs & derivatives; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics
chemical_list: D003277:Contraceptives, Oral, Combined; C451521:EVE 20 TM; D011486:Protein C; C095381:factor V Leiden; D004997:Ethinyl Estradiol; D019304:Ethinyl Estradiol-Norgestrel Combination; D005165:Factor V; D009640:Norethindrone