An overview of the development of combined oral contraceptives containing estradiol: Focus on estradiol valerate/dienogest

Gynecological Endocrinology

Volumn 28, Issue 5, 2012, Pages 400-408

  Fruzzetti, Franca ^a   Trémollieres, Florence ^b   Bitzer, Johannes ^c  

^a UNIVERSITY OF PISA   (Italy)

^b Paul Sabatier University   (France)

^c UNIVERSITY WOMEN S HOSPITAL   (Switzerland)

Author keywords

Contraceptives; Estradiol; Estrogens; Menstruation; Oral

Indexed keywords

CYPROTERONE ACETATE PLUS ESTRADIOL VALERATE; DIENOGEST PLUS ESTRADIOL VALERATE; DROSPIRENONE PLUS ETHINYLESTRADIOL; ESTRADIOL; ESTRADIOL PLUS NOMEGESTROL ACETATE; ESTRADIOL VALERATE; ETHINYLESTRADIOL; ETHINYLESTRADIOL PLUS LEVONORGESTREL; FEMILAR; NORETHISTERONE; UNCLASSIFIED DRUG;

BLEEDING; BLOOD PRESSURE REGULATION; DRUG ACCUMULATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; HEMOSTASIS; HORMONAL CONTRACEPTION; HUMAN; LOW DRUG DOSE; ORAL CONTRACEPTION; OVARY FUNCTION; OVULATION INHIBITION; PRIORITY JOURNAL; REVIEW; RISK FACTOR; RISK REDUCTION; VENOUS THROMBOEMBOLISM;

CONTRACEPTIVES, ORAL, COMBINED; ESTRADIOL; FEMALE; HISTORY, 20TH CENTURY; HUMANS; NANDROLONE;

EID: 84859777313     PISSN: 09513590     EISSN: 14730766     Source Type: Journal    
DOI: 10.3109/09513590.2012.662547     Document Type: Review

References (57)

1. Lobo RA, Stanczyk FZ. New knowledge in the physiology of hormonal contraceptives. Am J Obstet Gynecol 1994;170:1499-1507.
2. Düsterberg B, Ellman H, Müller U, Rowe E, Mühe B. A three-year clinical investigation into efficacy, cycle control and tolerability of a new low-dose monophasic oral contraceptive containing gestodene. Gynecol Endocrinol 1996;10:33-39.
3. Huber J, Foidart JM, Wuttke W, Merki-Feld GS, The HS, Gerlinger C, Schellschmidt I, Heithecker R. Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone. Eur J Contracept Reprod Health Care 2000;5:25-34.
4. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update 2006;12:169-178.
5. Spona J, Feichtinger W, Kindermann C, Moore C, Mellinger U, Walter F, Gräser T. Modulation of ovarian function by an oral contraceptive containing 30 micrograms ethinyl estradiol in combination with 2.00 mg dienogest. Contraception 1997;56:185-191.
6. Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric 2005;8 Suppl 1:3-63.
7. Inman WH, Vessey MP, Westerholm B, Engelund A. Thromboembolic disease and the steroidal content of oral contraceptives. A report to the Committee on Safety of Drugs. Br Med J 1970;2:203-209.
8. Dinger JC, Heinemann LA, Kühl-Habich D. The safety of a drospirenonecontaining oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 womenyears of observation. Contraception 2007;75:344-354.
9. Gallo MF, Nanda K, Grimes DA, Schulz KF. 20 mcg versus >20 mcg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev 2005:CD003989.
10. 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.
11. 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.
12. Lindberg UB, Crona N, Stigendal L, Teger-Nilsson AC, Silfverstolpe G. A comparison between effects of estradiol valerate and low dose ethinyl estradiol on haemostasis parameters. Thromb Haemost 1989;61: 65-69.
13. Speroff L, Fritz MA. Clinical Gynecologic Endocrinology and Infertility. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.
14. Kuhnz W, Gansau C, Mahler M. Pharmacokinetics of estradiol, free and total estrone, in young women following single intravenous and oral administration of 17 beta-estradiol. Arzneimittelforschung 1993;43: 966-973.
15. Kuhnz W, Blode H, Zimmermann H. Pharmacokinetics of exogenous natural and synthetic estrogens and antiestrogens. In: Oettel M, Schillinger E, editors. Handbook of Experimental Pharmacology, Estrogens and Antiestrogens II. Berlin: Springer Verlag; 1999. p. 261-322.
16. Düsterberg B, Nishino Y. Pharmacokinetic and pharmacological features of oestradiol valerate. Maturitas 1982;4:315-324.
17. Zeun S, Lu M, Uddin A, Zeiler B, Morrison D, Blode H. Pharmacokinetics of an oral contraceptive containing oestradiol valerate and dienogest. Eur J Contracept Reprod Health Care 2009;14:221-232.
18. Endrikat J, Blode H, Gerlinger C, Rosenbaum P, Kuhnz W. A pharmacokinetic study with a low-dose oral contraceptive containing 20 microg ethinylestradiol plus 100 microg levonorgestrel. Eur J Contracept Reprod Health Care 2002;7:79-90.
19. Bostofte E, Hemmingsen L, Møller KJ, Serup J, Weber T. Serum lipids and lipoproteins during treatment with oral contraceptives containing natural and synthetic oestrogens. A controlled double-blind investigation. Acta Endocrinol 1978;87:855-864.
20. Helgason S. Estrogen replacement therapy after the menopause. Estrogenicity and metabolic effects. Acta Obstet Gynecol Scand Suppl 1982;107:1-29.
21. Mashchak CA, Lobo RA, Dozono-Takano R, Eggena P, Nakamura RM, Brenner PF, Mishell DR Jr . Comparison of pharmacodynamicproperties of various estrogen formulations. Am J Obstet Gynecol 1982;144:511-518.
22. Toy JL, Davies JA, Hancock KW, McNicol GP. The comparative effects of a synthetic and a 'natural' oestrogen on the haemostatic mechanism in patients with primary amenorrhoea. Br J Obstet Gynaecol 1978;85: 359-362.
23. Wiegratz I, Lee JH, Kutschera E, Winkler UH, Kuhl H. Effect of four oral contraceptives on hemostatic parameters. Contraception 2004;70:97-106.
24. Ahrendt HJ, Makalová D, Parke S, Mellinger U, Mansour D. 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;80:436-444.
25. Astedt B, Jeppsson S, Liedholm P, Rannevik G, Svanberg L. Clinical trial of a new oral contraceptive pill containing the natural oestrogen 17 beta-oestradiol. Br J Obstet Gynaecol 1979;86:732-736.
26. Bayer Healthcare. Natazia Prescribing Information, 2010. Available from: http://berlex.bayerhealthcare.com/html/products/pi/natazia- pi.pdf [January 7th 2011].
27. Chabbert-Buffet N, Chassard D, Ochsenbein E, Thomas JL, Christin-Maitre S. Inhibition of ovulation by NOMAC/E2, a novel monophasic oral contraceptive combining nomegestrol acetate and 17β-oestradiol: a double-blind, randomised, dose-finding pilot study. Eur J Contracept Reprod Health Care 2011;16:76-84.
28. Christin-Maitre S, Serfaty D, Chabbert-Buffet N, Ochsenbein E, Chassard D, Thomas JL. Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17β-estradiol (NOMAC/E2): a double-blind, randomized study. Hum Reprod 2011;26:1338-1347.
29. Csemiczky G, Dieben T, Coeling Bennink HJ, Landgren BM. The pharmacodynamic effects of an oral contraceptive containing 3 mg micronized 17 beta-estradiol and 0.150 mg desogestrel for 21 days, followed by 0.030 mg desogestrel only for 7 days. Contraception 1996;54:333-338.
30. Duijkers IJ, Klipping C, Grob P, Korver T. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 betaoestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol. Eur J Contracept Reprod Health Care 2010;15:314-325.
31. Endrikat J, Parke S, Trummer D, Schmidt W, Duijkers I, Klipping C. 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;78:218-225.
32. Hirvonen E, Allonen H, Anttila M, Kulmala Y, Ranta T, Rautiainen H, SipiläP, Ylöstalo P. Oral contraceptive containing natural estradiol for premenopausal women. Maturitas 1995;21:27-32.
33. Hirvonen E, Stenman UH, Mälkönen M, Rasi V, Vartiainen E, Ylöstalo P. New natural oestradiol/cyproterone acetate oral contraceptive for pre-menopausal women. Maturitas 1988;10:201-213.
34. Hoffmann H, Moore C, Kovacs L, et al. Alternatives of the replacement of ethinylestradiol by natural 17beta-estradiol in dienogest-containing oral contraceptives. Drugs Today 1999;35:105-113.
35. Hoffmann H, Moore C, Zimmermann H, Elger W, Schwarz S, Gräser T, Oettel M. Approaches to the replacement of ethinylestradiol by natural 17beta-estradiol in combined oral contraceptives. Exp Toxicol Pathol 1998;50:458-464.
36. Kivinen S, Saure A. Efficacy and tolerability of a combined oral contraceptive containing 17 beta-estradiol and desogestrel. Eur J Contracept Reprod Health Care 1996;1:183.
37. Palacios S, Wildt L, Parke S, Machlitt A, Römer T, Bitzer J. Efficacy and safety of a novel oral contraceptive based on oestradiol (oestradiol valerate/dienogest): a Phase III trial. Eur J Obstet Gynecol Reprod Biol 2010;149:57-62.
38. Schubert W, Cullberg G. Ovulation inhibition with 17 beta-estradiol cyclo-octyl acetate and desogestrel. Acta Obstet Gynecol Scand 1987;66:543-547.
39. Serup J, Bostofte E, Larsen S, Westergaard J. Effectivity and acceptability of oral contraceptives containing natural and artificial estrogens in combination with a gestagen. A controlled double-blind investigation. Acta Obstet Gynecol Scand 1981;60:203-206.
40. Serup J, Bostofte E, Larsen S, Westergaard J, Lebech PE. Natural oestrogens for oral contraception. Lancet 1979;2:471-472.
41. Wenzl R, Bennink HC, van Beek A, Spona J, Huber J. Ovulation inhibition with a combined oral contraceptive containing 1 mg micronized 17 beta-estradiol. Fertil Steril 1993;60:616-619.
42. World Health Organization Task Force on Oral Contraception. A randomized, double-blind study of two combined oral contraceptives containing the same progestogen, but different estrogens. Contraception 1980;21:445-459.
43. Gaussem P, Alhenc-Gelas M, Thomas JL, Bachelot-Loza C, Remones V, Ali FD, Aiach M, Scarabin PY. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study. Thromb Haemost 2011;105:560-567.
44. 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.
45. Oettel M, Graeser T, Hoffmann H, Moore C, Zimmermann H, Zimmermann T. The preclinical and clinical profile of dienogest. A short overview. Drugs Today 1999;35(Suppl C):3-12.
46. Sasagawa S, Shimizu Y, Kami H, Takeuchi T, Mita S, Imada K, Kato S, Mizuguchi K. Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile. Steroids 2008;73:222-231.
47. Oettel M, Carol W, Elger W, et al. A 19-norprogestin without 17alfaethinyl group II: dienogest from a pharmacodynamic point of view. Drugs Today 1995;31:517-536.
48. Nelson A, Sampson-Landers C, Parke S, Jensen J. Efficacy of estradiol valerate/dienogest OC: Results of 3 large studies in North America and Europe. Presented at the American Congress of Obstetricians and Gynecologists 57th Annual Clinical Meeting, Chicago, May 2-9, 2009.
49. Electronic Medicines Compendium. Qlaira Summary of Product Characteristics, 2011. Available from: http://www.medicines.org.uk/ emc/medicine/21700/SPC/Qlaira/ [12 Apr 2011].
50. Lu M, Uddin A, Foegh M. Pharmacokinetics and pharmacodynamics of a new four-phasic estradiol valerate and dienogest oral contraceptive. Obstet Gynecol 2007;109(4 Suppl):61S (abstract plus poster presentation at the 55th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists: 2007 May 5-9; San Diego, CA, USA).
51. Junge W, Mellinger U, Parke S, Serrani M. Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study. Clin Drug Investig 2011;31:573-584.
52. Klipping C, Duijkers I, Parke S, Mellinger U, Serrani M, Junge W. Hemostatic effects of a novel estradiol based oral contraceptive: An open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel. Drugs R D 2011;11:159-170.
53. Tans G, van Hylckama Vlieg A, Thomassen MC, Curvers J, Bertina RM, Rosing J, Rosendaal FR. Activated protein C resistance determined with a thrombin generation-based test predicts for venous thrombosis in men and women. Br J Haematol 2003;122:465-470.
54. Fraser IS, Parke S, Mellinger U, Machlitt A, Serrani M, Jensen J. Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest. Eur J Contracept Reprod Health Care 2011;16:258-269
55. Sulak PJ, Scow RD, Preece C, Riggs MW, Kuehl TJ. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol 2000;95:261-266.
56. Klipping C, Duijkers I, Trummer D, Marr J. Suppression of ovarian activity with a drospirenone-containing oral contraceptive in a 24/4 regimen. Contraception 2008;78:16-25.
57. Spona J, Elstein M, Feichtinger W, Sullivan H, Lüdicke F, Müller U, Düsterberg B. Shorter pill-free interval in combined oral contraceptives decreases follicular development. Contraception 1996; 54:71-77.