The Current Status of Oral Contraceptives: Progress and Recent Innovations

Abstract

Millions of women in the United States and abroad use oral contraceptive pills. These popular contraceptives are the most common reversible birth control method in the United States, and a wide variety of pills are available for prescription. Oral contraceptives provide safe and effective protection against pregnancy and offer several noncontraceptive benefits. Over the years, advances in the laboratory and knowledge gained through epidemiologic data promoted the development of new contraceptive preparations. Generations of oral contraceptives emerged over time, containing lower doses of estrogens and new and novel progestins. The current review discusses the clinical characteristics of oral contraceptives, with emphasis on basic pharmacology and the evolution of various contraceptive formulations and regimens.

Keywords

oral contraception - estrogen - progestin - extended-cycle oral contraceptive - noncontraceptive benefits - oral contraceptive regimen

• References

• 1 Speroff L, Darney PD. Oral contraception. In: A Clinical Guide for Contraception. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011: 19-166
• 2 Meldrum M. Women making contraceptive choices in 20th-century America. Lancet 2012; 380 (9837) 102-103
• 3 Junod SW, Marks L. Women's trials: the approval of the first oral contraceptive pill in the United States and Great Britain. J Hist Med Allied Sci 2002; 57 (2) 117-160
• 4 Jones J, Mosher W, Daniels K. Current contraceptive use in the United States, 2006–2010, and changes in patterns of use since 1995. Natl Health Stats Rep 2012; 60: 6
• 5 Daniels K, Daugherty J, Jones J. Current contraceptive status among women aged 15-44: United States, 2011-2013. NCHS Data Brief 2014; 173 (173) 1-8
• 6 Gerstman BB, Gross TP, Kennedy DL, Bennett RC, Tomita DK, Stadel BV. Trends in the content and use of oral contraceptives in the United States, 1964-88. Am J Public Health 1991; 81 (1) 90-96
• 7 Kiley JW, Shulman LP. Estradiol valerate and dienogest: a new approach to oral contraception. Int J Womens Health 2011; 3: 281-286
• 8 Kiley J, Hammond C. Combined oral contraceptives: a comprehensive review. Clin Obstet Gynecol 2007; 50 (4) 868-877
• 9 Speroff L, DeCherney A ; The Advisory Board for the New Progestins. Evaluation of a new generation of oral contraceptives. Obstet Gynecol 1993; 81 (6) 1034-1047
• 10 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 (1) 57-62
• 11 Nelson AL. Combined oral contraception. In: Hatcher RA, Trussell J, Stewart F, eds. Contraceptive Technology. New York: Ardent Media; 2011: 193-270
• 12 Burkman RT. Venous thromboembolism and oral contraceptives: current status and clinical implications. Treat Endocrinol 2002; 1 (3) 143-147
• 13 Shulman LP, Goldzieher JW, Minkin MJ, Sulak PJ, Thorneycroft I. Oral contraceptives and venous thromboembolic events. J Reprod Med 2003; 48 (4) 306-307
• 14 Krattenmacher R. Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception 2000; 62 (1) 29-38
• 15 Batukan C, Muderris II. Efficacy of a new oral contraceptive containing drospirenone and ethinyl estradiol in the long-term treatment of hirsutism. Fertil Steril 2006; 85 (2) 436-440
• 16 American Congress of Obstetricians and Gynecologists . ACOG Committee Opinion #540. Risk of Venous Thromboembolism Among Users of Drospirenone-Containing Oral Contraceptive Pills, November 2012
• 17 Hoy SM, Scott LJ. Estradiol valerate/dienogest: in oral contraception. Drugs 2009; 69 (12) 1635-1646
• 18 Grimes DA, Schulz KF. Nonspecific side effects of oral contraceptives: nocebo or noise?. Contraception 2011; 83 (1) 5-9
• 19 Kaunitz AM. Noncontraceptive health benefits of oral contraceptives. Rev Endocr Metab Disord 2002; 3 (3) 277-283
• 20 Trussell J. Contraceptive failure in the United States. Contraception 2011; 83 (5) 397-404
• 21 Gallo MF, Nanda K, Grimes DA, Lopez LM, Schulz KF. 20 µg versus >20 µg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev 2013; 8: CD003989
• 22 Hauck BA, Brown V. A primer on the hormone-free interval for combined oral contraceptives. Curr Med Res Opin 2015; 31 (10) 1941-1948
• 23 Archer DF, Nakajima ST, Sawyer AT , et al. Norethindrone acetate 1.0 milligram and ethinyl estradiol 10 micrograms as an ultra low-dose oral contraceptive. Obstet Gynecol 2013; 122 (3) 601-607
• 24 Sulak PJ, Cressman BE, Waldrop E, Holleman S, Kuehl TJ. Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms. Obstet Gynecol 1997; 89 (2) 179-183
• 25 Shulman LP. The use of triphasic oral contraceptives in a continuous use regimen. Contraception 2005; 72 (2) 105-110
• 26 Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG. Continuous use of an oral contraceptive for endometriosis-associated recurrent dysmenorrhea that does not respond to a cyclic pill regimen. Fertil Steril 2003; 80 (3) 560-563
• 27 Miller L, Notter KM. Menstrual reduction with extended use of combination oral contraceptive pills: randomized controlled trial. Obstet Gynecol 2001; 98 (5, Pt 1): 771-778
• 28 Schwartz JL, Creinin MD, Pymar HC. The trimonthly combination oral contraceptive regimen: is it cost effective?. Contraception 1999; 60 (5) 263-267
• 29 Seasonale (Levonorgestrel/Ethinyl Estradiol Tablets). Current US Prescribing Information. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-544_SEASONALE_Prntlbl.pdf . Accessed October 22, 2015
• 30 Anderson FD, Gibbons W, Portman D. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception 2006; 73 (3) 229-234
• 31 Anderson FD, Feldman R, Reape KZ. Endometrial effects of a 91-day extended-regimen oral contraceptive with low-dose estrogen in place of placebo. Contraception 2008; 77 (2) 91-96
• 32 Teichmann A, Apter D, Emerich J , et al. Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial. Contraception 2009; 80 (6) 504-511
• 33 Edelman A, Micks E, Gallo MF, Jensen JT, Grimes DA. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev 2014; 7: CD004695
• 34 Coffee AL, Kuehl TJ, Willis S, Sulak PJ. Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended regimen. Am J Obstet Gynecol 2006; 195 (5) 1311-1319
• 35 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 micro g (Loestrin 24 Fe). Contraception 2007; 75 (1) 16-22
• 36 Anttila L, Bachmann G, Hernádi L, Kunz M, Marr J, Klipping C. Contraceptive efficacy of a combined oral contraceptive containing ethinyloestradiol 20 μg/drospirenone 3mg administered in a 24/4 regimen: a pooled analysis of four open-label studies. Eur J Obstet Gynecol Reprod Biol 2011; 155 (2) 180-182
• 37 Anttila L, Kunz M, Marr J. Bleeding pattern with drospirenone 3 mg+ethinyl estradiol 20 mcg 24/4 combined oral contraceptive compared with desogestrel 150 mcg+ethinyl estradiol 20 mcg 21/7 combined oral contraceptive. Contraception 2009; 80 (5) 445-451
• 38 Berga SL. Metabolic and endocrine effects of the desogestrel-containing oral contraceptive Mircette. Am J Obstet Gynecol 1998; 179 (1) S9-S17
• 39 The Mircette Study Group. An open-label, multicenter, noncomparative safety and efficacy study of Mircette, a low-dose estrogen-progestin oral contraceptive. Am J Obstet Gynecol 1998; 179 (1) S2-S8
• 40 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 2010; 2: 235-239
• 41 Jensen JT, Parke S, Mellinger U, Machlitt A, Fraser IS. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial. Obstet Gynecol 2011; 117 (4) 777-787
• 42 Ebede TL, Arch EL, Berson D. Hormonal treatment of acne in women. J Clin Aesthet Dermatol 2009; 2 (12) 16-22
• 43 Beyaz Prescribing Information . Available at: http://labeling.bayerhealthcare.com/html/products/pi/fhc/Beyaz_PI.pdf . Accessed October 21, 2015
• 44 Yaz Prescribing Information . Available at: http://labeling.bayerhealthcare.com/html/products/pi/fhc/YAZ_PI.pdf . Accessed October 21, 2015
• 45 Nelson AL. Comprehensive evaluation of Safyral(®) 2012. Womens Health (Lond Engl) 2012; 8 (6) 619-633
• 46 Taylor TN, Farkouh RA, Graham JB , et al. Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States. Am J Obstet Gynecol 2011; 205 (5) 460.e1-460.e8
• 47 Archer DF, Ahrendt HJ, Drouin D. Drospirenone-only oral contraceptive: results from a multicenter noncomparative trial of efficacy, safety and tolerability. Contraception 2015; 92 (5) 439-444