Hemostatic effects of a novel estradiol-based oral contraceptive: An open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel

Drugs in R and D

Volumn 11, Issue 2, 2011, Pages 159-170

  Klipping, Christine ^a   Duijkers, Ingrid ^a   Parke, Susanne ^b   Mellinger, Uwe ^b   Serrani, Marco ^b   Junge, Wolfgang ^c  

^a Dinox BV   (Netherlands)

^b BAYER PHARMA AG   (Germany)

^c Laboratorium fuer Klinische Forschung   (Germany)

Author keywords

Contraceptives; Estradiol valeratedienogest; Ethinylestradiollevonorgestrel; Prothrombin

Indexed keywords

DIENOGEST; DIENOGEST PLUS ESTRADIOL VALERATE; ESTRADIOL VALERATE; ETHINYLESTRADIOL; ETHINYLESTRADIOL PLUS LEVONORGESTREL; LEVONORGESTREL; PLACEBO; PROTHROMBIN;

ADULT; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG EFFECT; DRUG EFFICACY; DYSMENORRHEA; FEMALE; GASTROINTESTINAL DISEASE; HEADACHE; HEMOSTASIS; HUMAN; HUMAN EXPERIMENT; LOW DRUG DOSE; NAUSEA; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS;

ACTIVATED PROTEIN C RESISTANCE; ADOLESCENT; ADULT; ANTIGENS; ANTITHROMBIN III; BLOOD PRESSURE; CONTRACEPTIVES, ORAL, HORMONAL; CROSS-OVER STUDIES; DRUG COMBINATIONS; ESTRADIOL; ETHINYL ESTRADIOL; FACTOR VII; FACTOR VIII; FEMALE; FIBRIN FIBRINOGEN DEGRADATION PRODUCTS; FIBRINOGEN; HEMOSTASIS; HUMANS; LEVONORGESTREL; MIDDLE AGED; NANDROLONE; PATIENT COMPLIANCE; PEPTIDE FRAGMENTS; PROTEIN C; PROTEIN PRECURSORS; PROTEIN S; PROTHROMBIN; SEX HORMONE-BINDING GLOBULIN; YOUNG ADULT;

EID: 79959419295     PISSN: 11745886     EISSN: 11796901     Source Type: Journal    
DOI: 10.2165/11591200-000000000-00000     Document Type: Article

References (47)

1. Gestodene Study Group 322 The safety and contraceptive efficacy of a 24-day low-dose oral contraceptive regimen containing gestodene 60 microg and ethinylestradiol 15 microg. Eur J Contracept Reprod Health Care 1999; 4 Suppl. 2: 9-15
2. Bannemerschult R, Hanker JP, Wunsch C, et al. A multicenter, uncontrolled clinical investigation of the contraceptive efficacy, cycle control, and safety of a new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel over six treatment cycles. Contraception 1997; 56 (5): 285-90 (Pubitemid 28022880)
3. Endrikat J, Jaques MA,Mayerhofer M, et al. A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 20 micrograms ethinylestradiol/150 micrograms desogestrel, with respect to efficacy, cycle control and tolerance. Contraception 1995; 52 (4): 229-35
4. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update 2006; 12 (2): 169-78 (Pubitemid 43231449)
5. Combined oral contraceptives: a statement by the committee on safety of drugs. Br Med J 1970; 2 (5703): 231-2
6. Bottiger LE, Boman G, Eklund G, et al. Oral contraceptives and thromboembolic disease: effects of lowering oestrogen content. Lancet 1980; I (8178): 1097-101 (Pubitemid 10100362)
7. Blickstein I. Thrombophilia and women' health: an overview. Obstet Gynecol Clin North Am 2006; 33 (3): 347-56
8. Lowe GD. Common risk factors for both arterial and venous thrombosis. Br J Haematol 2008; 140 (5): 488-95 (Pubitemid 351230085)
9. Astedt B, Jeppsson S, Liedholm P, et al. Clinical trial of a new oral contraceptive pill containing the natural oestrogen 17 beta-oestradiol. Br J Obstet Gynaecol 1979; 86 (9): 732-6 (Pubitemid 9245029)
10. Astedt B, Svanberg L, Jeppsson S, et al. The natural oestrogenic hormone oestradiol as a new component of combined oral contraceptives. Br Med J 1977; 1 (6056): 269 (Pubitemid 8021359)
11. Csemiczky G, Dieben T, Coeling Bennink HJ, et al. The pharmacodynamic effects of an oral contraceptive containing 3 mg micronized 17 beta-estradiol and 0150 mg desogestrel for 21 days, followed by 0030 mg desogestrel only for 7 days. Contraception 1996; 54 (6): 333-8 (Pubitemid 26412416)
12. Hirvonen E, Allonen H, Anttila M, et al. Oral contraceptive containing natural estradiol for premenopausal women. Maturitas 1995; 21 (1): 27-32
13. Hirvonen E, Stenman UH, MalkonenM, et al. New natural oestradiol/cyproterone acetate oral contraceptive for premenopausal women. Maturitas 1988; 10 (3): 201-13
14. Hoffmann H, Moore C, Zimmermann H, et al. Approaches to the replacement of ethinylestradiol by natural 17betaestradiol in combined oral contraceptives. Exp Toxicol Pathol 1998; 50 (4-6): 458-64
15. Kovacs L, Hoffmann H. A new low-dose oral contraceptive containing ethinylestradiol, estradiol and dienogest: first experience of its clinical use. In: Elstein M, editor. Extragenital effects of contraceptives. 4th Congress of the European Society of Contraception, Barcelona, Spain, June 1996 Pearl River (NY): The Parthenon Publishing Group Inc., 1997: 39-44
16. Schubert W, Cullberg G. Ovulation inhibition with 17 betaestradiol cyclo-octyl acetate and desogestrel. Acta Obstet Gynecol Scand 1987; 66 (6): 543-7 (Pubitemid 18014725)
17. Serup J, Bostofte E, Larsen S, et al. Natural oestrogens for oral contraception. Lancet 1979; II (8140): 471-2 (Pubitemid 9250419)
18. Hirvonen E, Vartiainen E, Kulmala Y. A multicenter trial with a new OC using natural estradiol and cyproterone acetate for women over 35 [abstract]. Adv Contracept 1990; 6 (4): 248
19. Kivinen S, Saure A. Efficacy and tolerability of a combined oral contraceptive containing 17 b-estradiol and desogestrel [abstract]. Eur J Contracept Reprod Health Care 1996; 1: 183
20. Hoffmann H,Moore C, Kovacs L, et al. Alternatives for the replacement of ethinylestradiol by natural 17b-estradiol in dienogest-containing oral contraceptives. Drugs Today 1999; 35 (Suppl. C): 105-13 (Pubitemid 29355101)
21. Wenzl R, Bennink HC, van Beek A, et al. Ovulation inhibition with a combined oral contraceptive containing 1mg micronized 17 beta-estradiol. Fertil Steril 1993; 60 (4): 616-9 (Pubitemid 23298503)
22. Endrikat J, Parke S, Trummer D, et al. Ovulation inhibition with four variations of a four-phasic estradiol valerate/ dienogest combined oral contraceptive: results of two prospective, randomized, open-label studies. Contraception 2008; 78 (3): 218-25
23. Palacios S, Wildt L, Parke S, et al. Efficacy and safety of a novel oral contraceptive based on oestradiol (oestradiol valerate/dienogest): a phase III trial. Eur J Obstet Gynecol Reprod Biol 2009; 149 (1): 57-62
24. Ahrendt HJ, Makalova D, Parke S, et al. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. Contraception 2009; 80 (5): 436-44
25. Lu M, Uddin A, Foegh M, et al. Pharmacokinetics and pharmacodynamics of a new four-phasic estradiol valerate and dienogest oral contraceptive [abstract]. Obstet Gynecol 2007; 109 (4 Suppl.): 61S
26. Helgason S. Estrogen replacement therapy after the menopause: estrogenicity and metabolic effects. Acta Obstet Gynecol Scand Suppl 1982; 107: 1-29
27. Lindberg UB, Crona N, Stigendal L, et al. A comparison between effects of estradiol valerate and low dose ethinyl estradiol on haemostasis parameters. Thromb Haemost 1989; 61 (1): 65-9 (Pubitemid 19092670)
28. Mashchak CA, Lobo RA, Dozono-Takano R, et al. Comparison of pharmacodynamic properties of various estrogen formulations. Am J Obstet Gynecol 1982; 144 (5): 511-8 (Pubitemid 12002825)
29. Wiegratz I, Lee JH, Kutschera E, et al. Effect of four oral contraceptives on hemostatic parameters. Contraception 2004; 70 (2): 97-106 (Pubitemid 38993484)
30. BayerHealthCare Pharmaceuticals. Impact of SHT00658ID as compared to a monophasic contraceptive containing ethinylestradiol and levonorgestrel (SH D01155E) on hemostatic parameters [ClinicalTrials.gov identifier NCT00318799]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Apr 5]
31. European Medicines Agency (EMEA)Committee for Medicinal Products for Human Use (CHMP): guideline on clinical investigation of steroid contraceptives inwomen, 2005 [online]. Available from URL: pdfs/human/ewp/051998en.pdf [Accessed 2010 Jun 22]
32. Rosing J, Tans G, Nicolaes GA, et al. Oral contraceptives and venous thrombosis: different sensitivities to activatedprotein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997; 97 (1): 233-8 (Pubitemid 27179593)
33. Oettel M, Breitbarth H, Elger W, et al. The pharmacological profile of dienogest. Eur J Contracept Reprod Health Care 1999; 4 (Suppl. 1): 2-13
34. Oettel M, Carol W, Elger W, et al. A 19-norprogestin without 17alfa-ethinyl group II: dienogest from a pharmacodynamic point of view. Drugs Today 1995; 31 (7): 517-36 (Pubitemid 26031142)
35. Parke S,NahumGG, Mellinger U, et al. Metabolic effects of a new 4-phasic oral contraceptive containing estradiol valerate and dienogest [abstract]. Obstet Gynecol 2008; 111 (4 Suppl.): 12S
36. Fleming TR. Surrogate endpoints and FDA' accelerated approval process. Health Aff (Millwood) 2005; 24 (1): 67-78 (Pubitemid 40173935)
37. Grimes DA, Schulz KF, Raymond EG. Surrogate end points in women' health research: science, protoscience, and pseudoscience. Fertil Steril 2010; 93 (6): 1731-4
38. Pabinger I, Ay C. Biomarkers and venous thromboembolism. Arterioscler Thromb Vasc Biol 2009; 29 (3): 332-6
39. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996; 125 (7): 605-13 (Pubitemid 126450094)
40. Gaussem P, Alhenc-Gelas M, Thomas JL, et al. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17beta-estradiol, compared with those of levonorgestrel/ethinyl estradiol: a double-blind, randomized study. Thromb Haemost 2011; 105 (3): 560-7
41. Tans G, van Hylckama Vlieg A, Thomassen MC, et al. Activated protein C resistance determined with a thrombin generation-based test predicts for venous thrombosis in men and women. Br J Haematol 2003; 122 (3): 465-70 (Pubitemid 36951632)
42. Endrikat J, Klipping C, Gerlinger C, et al. A double-blind comparative study of the effects of a 23-day oral contraceptive regimen with 20 microg ethinyl estradiol and 75 microg gestodene and a 21-day regimen with 30 microg ethinyl estradiol and 75 microg gestodene on hemostatic variables, lipids, and carbohydrate metabolism. Contraception 2001; 64 (4): 235-41 (Pubitemid 34020818)
43. Kluft C, Endrikat J, Mulder SM, et al. A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol. Contraception 2006; 73 (4): 336-43 (Pubitemid 43375090)
44. Winkler UH, Holscher T, Schulte H, et al. Ethinylestradiol 20 versus 30 micrograms combined with 150 micrograms desogestrel: a large comparative study of the effects of two low-dose oral contraceptives on the hemostatic system. Gynecol Endocrinol 1996; 10 (4): 265-71 (Pubitemid 26343487)
45. Winkler UH, Schindler AE, Endrikat J, et al. A comparative study of the effects of the hemostatic system of two monophasic gestodene oral contraceptives containing 20 micrograms and 30 micrograms ethinylestradiol. Contraception 1996; 53 (2): 75-84 (Pubitemid 26055430)
46. van der Mooren MJ, Klipping C, van Aken B, et al. A comparative study of the effects of gestodene 60 microg/ ethinylestradiol 15 microg and desogestrel 150 microg/ ethinylestradiol 20 microg on hemostatic balance, blood lipid levels and carbohydrate metabolism. Eur J Contracept Reprod Health Care 1999; 4 (Suppl. 2): 27-35
47. Gestodene Study Group 324 Cycle control, safety and efficacy of a 24-day regimen of gestodene 60 microg/ ethinylestradiol 15 microg and a 21-day regimen of desogestrel 150 microg/ethinylestradiol 20 microg. Eur J Contracept Reprod Health Care 1999; 4 Suppl. 2: 17-25