Resistance to APC and SHBG levels during use of a four-phasic oral contraceptive containing dienogest and estradiol valerate: a randomized controlled trial.

The use of combined oral contraceptives is associated with a 3- to 6-fold increased risk of venous thrombosis. This increased risk depends on the estrogen dose as well as the progestogen type of combined oral contraceptives. Thrombin generation-based activated protein C resistance (APC resistance) and sex hormone-binding globulin (SHBG) levels predict the thrombotic risk of a combined hormonal contraceptive. Recently, a four-phasic oral contraceptive containing dienogest (DNG) and estradiol valerate (E2V) has been marketed. The aim of this study was to evaluate the thrombotic risk of the DNG/E2V oral contraceptive by comparing APC resistance by measuring normalized APC sensitivity ratios (nAPCsr) and SHBG levels in users of oral contraceptives containing dienogest and estradiol valerate (DNG/E2V) and oral contraceptives containing levonorgestrel and ethinyl estradiol (LNG/EE).
We conducted a single-center, randomized, open label, parallel-group study in 74 women using DNG/E2V or LNG/EE, and measured nAPCsr and SHBG levels in every phase of the regimen of DNG/E2V.
During the pill cycle SHBG levels did not differ between DNG/E2V users and LNG/EE users. nAPCsr levels were overall slightly lower in DNG/E2V users than in LNG/EE users, mean difference -0.44 (95% CI, -1.04 to 0.17) for day 2, -0.20 (95% CI, -0.76 to 0.37) for day 7, -0.27 (95% CI, -0.81 to 0.28) for day 24 and -0.34 (95% CI, -0.91 to 0.24) for day 26.
No statistical significant differences in nAPCsr and SHBG levels were found between users of the oral contraceptive containing DNG/E2V and LNG/EE, suggesting a comparable thrombotic risk.
AuthorsM Raps, F Rosendaal, B Ballieux, J Rosing, S Thomassen, F Helmerhorst, H van Vliet
JournalJournal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 11 Issue 5 Pg. 855-61 (May 2013) ISSN: 1538-7836 [Electronic] England
PMID23410231 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright© 2013 International Society on Thrombosis and Haemostasis.
Chemical References
  • Contraceptives, Oral, Combined
  • Sex Hormone-Binding Globulin
  • dienogest
  • Estradiol
  • Nandrolone
  • estradiol valerate
  • Activated Protein C Resistance (blood)
  • Adolescent
  • Adult
  • Contraceptives, Oral, Combined (administration & dosage)
  • Estradiol (administration & dosage, analogs & derivatives)
  • Female
  • Humans
  • Nandrolone (administration & dosage, analogs & derivatives)
  • Sex Hormone-Binding Globulin (metabolism)
  • Young Adult

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