Estradiol valerate and dienogest: A novel four-phasic oral contraceptive pill effective for pregnancy prevention and treatment of heavy menstrual bleeding

Women's Health

Volumn 7, Issue 5, 2011, Pages 513-524

  Micks, Elizabeth ^a   Jensen, Jeffrey T ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

contraception; dienogest; estradiol valerate; heavy menstrual bleeding; menorrhagia

Indexed keywords

DIENOGEST; DIENOGEST PLUS ESTRADIOL VALERATE; DIENOGEST PLUS ETHINYLESTRADIOL; DRUG METABOLITE; ERYTHROMYCIN; ESTRADIOL; ESTRADIOL VALERATE; ESTRONE; ETHINYLESTRADIOL; ETHINYLESTRADIOL PLUS LEVONORGESTREL; FIBRINOGEN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; KETOCONAZOLE; LOW DENSITY LIPOPROTEIN CHOLESTEROL; NATAZIA; PLACEBO; PROTHROMBIN; QLAIRA; RIFAMPICIN; UNCLASSIFIED DRUG;

ACNE; ACUTE HEART INFARCTION; AREA UNDER THE CURVE; ARTICLE; BREAST TENDERNESS; CEREBROVASCULAR ACCIDENT; CHOLESTEROL BLOOD LEVEL; DEEP VEIN THROMBOSIS; DEPRESSION; DIARRHEA; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG FORMULATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSMENORRHEA; EYE IRRITATION; FURUNCULOSIS; HEAVY MENSTRUAL BLEEDING; HUMAN; HYDROXYLATION; KIDNEY COLIC; LIVER FOCAL NODULAR HYPERPLASIA; MASTALGIA; MAXIMUM PLASMA CONCENTRATION; MENORRHAGIA; MENSTRUAL CYCLE; METRORRHAGIA; MORBIDITY; MULTIPLE CYCLE TREATMENT; OCULAR HISTOPLASMOSIS; ORAL CONTRACEPTION; OVARY CYST; OVULATION INHIBITION; PHARMACODYNAMICS; POSTMARKETING SURVEILLANCE; RHINOPHARYNGITIS; SIDE EFFECT; THROMBOEMBOLISM; TIME TO MAXIMUM PLASMA CONCENTRATION; TONSILLITIS; UTERUS MYOMA; WEIGHT GAIN;

CONTRACEPTIVE AGENTS; CONTRACEPTIVES, ORAL; DRUG COMBINATIONS; DRUG EVALUATION; ESTRADIOL; FEMALE; HUMANS; MENORRHAGIA; NANDROLONE; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 80052459557     PISSN: 17455057     EISSN: 17455065     Source Type: Journal    
DOI: 10.2217/whe.11.49     Document Type: Article

References (48)

1. Speroff L, Darney PD. A Clinical Guide for Contraception (5th Edition).Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, PA, USA (2011).
2. Jensen JT, Speroff L. Health benefits of oral contraceptives. Obstet. Gynecol. Clin. North Am. 27(4), 705-721 (2000).
3. Meade TW. Risks and mechanisms of cardiovascular events in users of oral contraceptives. Am. J. Obstet. Gynecol. 158(6 Pt 2), 1646-1652 (1988).
4. Goebelsmann U, Mashchak CA, Mishell DR Jr. Comparison of hepatic impact of oral and vaginal administration of ethinyl estradiol. Am. J. Obstet. Gynecol. 1151(7), 868-877 (1985). (Pubitemid 15237723)
5. Krishnan S, Kiley J. The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 μg/levonorgestrel 100 μg + ethinyl estradiol 10 μg. Int. J. Womens Health 2, 235-239 (2010).
6. Gallo MF, Nanda K, Grimes DA, Schulz KF. 20 μg versus <20 μg estrogen combined oral contraceptives for contraception. Cochrane Database Syst. Rev. 2, CD003989 (2005).
7. 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. 2861(1), 65-69 (1989). (Pubitemid 19092670)
8. Wiegratz I, Lee JH, Kutschera E, Winkler UH, Kuhl H. Effect of four oral contraceptives on hemostatic parameters. Contraception 70(2), 97-106 (2004). (Pubitemid 38993484)
9. Hoffmann H, Moore C, Zimmermann H et al. Approaches to the replacement of ethinylestradiol by natural 17βestradiol in combined oral contraceptives. Exp. Toxicol. Pathol. 50(4-6), 458-464 (1998).
10. Wenzl R, Bennink HC, van Beek A, Spona J, Huber J. Ovulation inhibition with a combined oral contraceptive containing 1 mg micronized 17 βestradiol. Fertil. Steril. 60(4), 616-619 (1993). (Pubitemid 23298503)
11. Schubert W, Cullberg G. Ovulation inhibition with 17 βestradiol cyclo-octyl acetate and desogestrel. Acta Obstet. Gynecol. Scand. 66(6), 543-547 (1987). (Pubitemid 18014725)
12. Astedt B, Jeppsson S, Liedholm P, Rannevik G, Svanberg L. Clinical trial of a new oral contraceptive pill containing the natural oestrogen 17 βoestradiol. Br. J. Obstet. Gynaecol. 86(9), 732-736 (1979). (Pubitemid 9245029)
13. Hirvonen E, Allonen H, Anttila M et al. Oral contraceptive containing natural estradiol for premenopausal women. Maturitas 21(1), 27-32 (1995).
14. Csemiczky G, Dieben T, Coeling Bennink HJ, Landgren BM. The pharmacodynamic effects of an oral contraceptive containing 3 mg micronized 17 βestradiol and 0150 mg desogestrel for 21 days, followed by 0030 mg desogestrel only for 7 days. Contraception 54(6), 333-338 (1996). (Pubitemid 26412416)
15. Oettel M, Breitbarth H, Elger W et al. The pharmacological profile of dienogest. Eur. J. Contracep. Repr. Health Care 4(1 Suppl. 1), 2-13 (1999).
16. Mosher WD, Martinez GM, Chandra A, Abma JC, Willson SJ. Use of contraception and use of family planning services in the United States: 1982-2002 Adv. Data 10(350), 1-36 (2004).
17. Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J. Fertility, family planning, and reproductive health of US women: data from the 2002 National Survey of Family Growth. Vital Health Stat. (25), 1-160 (2005).
18. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst. Rev. 4, CD000154 (2009).
19. Fraser IS, Romer T, Parke S et al. Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind Phase III trial. Hum. Reprod. doi: 101093/humrep/der224 (2011) (Epub ahead of print).
20. Jensen J, Machlitt A, Mellinger U, Schaefers M, Fraser IS. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial. Obstet. Gynecol. 117(4), 777-787 (2011).
21. Davis A, Godwin A, Lippman J, Olson W, Kafrissen M. Triphasic norgestimate-ethinyl estradiol for treating dysfunctional uterine bleeding. Obstet. Gynecol. 96(6), 913-920 (2000).
22. 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 78(3), 218-225 (2008).
23. Sulak PJ, Kuehl TJ, Ortiz M, Shull BL. Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am. J. Obstet. Gynecol. 186(6), 1142-1149 (2002). (Pubitemid 34665050)
24. Kwiecien M, Edelman A, Nichols MD, Jensen JT. Bleeding patterns and patient acceptability of standard or continuous dosing regimens of a low-dose oral contraceptive: a randomized trial. Contraception 67(1), 9-13 (2003). (Pubitemid 36084281)
25. Sulak P, Scow R, Preece C, Riggs M, Kuehl T. Hormone withdrawal symptoms in oral contraceptive users. Obstet. Gynecol. 95, 261-266 (2000). (Pubitemid 30045651)
26. Rivera R, Yacobson I, Grimes D. The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices. Am. J. Obstet. Gynecol. 181(5 Pt 1), 1263-1269 (1999).
27. Speroff L, Fritz M. Clinical Gynecologic Endocrinology and Infertility (7th Edition).Lippincott Williams & Wilkins, PA, USA (2004).
28. Bitzer J, Parke S, Roemer T, Serrani M. Endometrial safety of an oral contraceptive containing estradiol valerate and dienogest. Int. J. Womens Health 3, 127-132 (2011).
29. Lievertz RW. Pharmacology and pharmacokinetics of estrogens. Am. J. Obstet. Gynecol. 156(5), 1289-1293 (1987). (Pubitemid 17075499)
30. Dusterberg B, Nishino Y. Pharmacokinetic and pharmacological features of oestradiol valerate. Maturitas 4(4), 315-324 (1982). (Pubitemid 13189102)
31. Ben-Rafaelf Z, Mastroianni L, Meloni F, Lee M, Flickinger G. Total estradiol, free estradiol, sex hormone-binding globulin, and the fraction of estradiol bound to sex hormone-binding globulin in human follicular fluid. J. Clin. Endocrinol. Metab. 63(5), 1106-1111 (1986). (Pubitemid 17173045)
32. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT. Characterization of the oxidative metabolites of 17βestradiol and estrone formed by 15 selectively expressed human cytochrome P450 isoforms. Endocrinology 144(8), 3382-3398 (2003). (Pubitemid 36904414)
33. Lobo RA, Cassidenti DL. Pharmacokinetics of oral 17 βestradiol. J. Reprod. Med. 37(1), 77-84 (1992).
34. 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 14(3), 221-232 (2009).
35. Guida M, Bifulco G, Di Spiezio Sardo A, Scala M, Fernandez LM, Nappi C. Review of the safety, efficacy and patient acceptability of the combined dienogest/estradiol valerate contraceptive pill. Int. J. Womens Health 2, 279-290 (2010).
36. 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 RD 11(2), 159-170rfpy1 2011
37. Parke S, Nahum G, Mellinger U, Junge W. Metabolic effects of a new four-phasic oral contraceptive containing estradiol valerate and dienogest. Obstet. Gynecol. 111(4 Suppl.), 12-13 (2008).
38. Klipping C, Duijkers I, Trummer D, Marr J. Suppression of ovarian activity with a drospirenone-containing oral contraceptive in a 24/4 regimen. Contraception 78(1), 16-25 (2008).
39. Nakajima ST, Archer DF, Ellman H. Efficacy and safety of a new 24-day oral contraceptive regimen of norethindrone acetate 1 mg/ ethinyl estradiol 20 μg (Loestrin 24 Fe).Contraception 75(1), 16-22 (2007). (Pubitemid 44854856)
40. Palacios S, Wildt L, Parke S, Machlitt A, Romer 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. 149(1), 57-62 (2010).
41. 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 57th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists. Chicago, IL, USA 2-6 May 2009
42. Ahrendt HJ, Makalova 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 80(5), 436-444 (2009).
43. WHO. A randomized, double-blind study of two combined oral contraceptives containing the same progestogen, but different estrogens. World Health Organization Task Force on Oral Contraception. Contraception 21(5), 445-459 (1980).
44. Hallberg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual blood loss and iron deficiency. Acta Med. Scand. 180(5), 639-650 (1966).
45. Fraser IS, McCarron G. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. Aust. NZJ Obstet. Gynaecol. 31(1), 66-70 (1991).
46. Singh S, Sedgh G, Hussain R. Unintended pregnancy: worldwide levels, trends, and outcomes. Stud. Fam. Plann. 41(4), 241-250 (2010).
47. Mastrup M, Schafer AI, Khan SJ. Predicting fate of the contraceptive pill in wastewater treatment and discharge. Water Sci. Technol. 52(8), 279-286 (2005). (Pubitemid 41723171)
48. Wise A, O'Brien K, Woodruff T. Are oral contraceptives a significant contributor to the estrogenicity of drinking water? Environ. Sci. Technol. 1 45(1), 51-60 (2011).