Artículos de revistas
Emerging Female Contraceptives
Registro en:
Expert Opinion On Emerging Drugs. , v. 16, n. 2, p. 373 - 387, 2011.
14728214
10.1517/14728214.2011.536761
2-s2.0-79957617934
Autor
Bahamondes L.
Bahamondes M.V.
Fernandes A.M.D.S.
Monteiro I.
Institución
Resumen
Introduction: Fifty years after the first contraceptive, the market remains restricted regarding composition, cost and routes of administration, and satisfying the needs of millions of women with different requirements according to their stage in life. Areas covered: Women need contraception for almost 30 years of their life. Currently available contraceptives are highly effective with few side effects. This review provides information on emerging female contraceptives including some registered and others at different stages of development. Research efforts aim to reduce costs, improve acceptability and refine 'forgettable' reversible methods. Although developing and testing a new method is laborious and expensive, many new contraceptives are currently under development including different routes of administration. Expert opinion: New methods should be affordable, simple to use and suitable for many women. Much work remains to be done and new methods that act on the fusion process between both gametes are desirable without affecting the hormonal milieu. © Informa UK, Ltd. 16 2 373 387 (2004) Medical Eligibility Criteria for Contraceptive Use, , World Health Organization 3rd edition. WHO, Geneva Chang, M.C., Development of the oral contraceptives (1978) American Journal of Obstetrics and Gynecology, 132 (2), pp. 217-219 Transitions in world population (2004) Popul Bull, 16 (1), pp. 1-43. , Population Reference Bureau Staff Provides a review about new contraceptive female hormonal methods Merkatz, R.B., Tokay, B., Sitruk-Ware, R.L., Methods for female contraception: A model for innovation in drug delivery systems (2009) Clin Pharmacol Ther, 85 (5), pp. 553-557 Hugon-Rodin, J., Chabbert-Buffet, N., Bouchard, P., The future of women's contraception: Stakes and modalities (2010) Ann NY Acad Sci, 1205, pp. 230-239 Moore, C., Feichtinger, W., Klinger, G., Mellinger, U., Spona, J., Walter, F., Winkler, U.H., Zahradnik, H.P., Clinical findings with the dienogest-containing oral contraceptive Valette (1999) Drugs of Today, 35 (SUPPL. C), pp. 53-68 Huber, J., Foidart, J.M., Wuttke, W., Merki-Feld, G.S., The, H.S., Gerlinger, C., Schellschmidt, I., Heithecker, R., Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone (2000) European Journal of Contraception and Reproductive Health Care, 5 (1), pp. 25-34 Spona, J., Feichtinger, W., Kindermann, C., Moore, C., Mellinger, U., Walter, F., Graser, T., Modulation of ovarian function by an oral contraceptive containing 30 microg ethinyl estradiol in combination with 2.00 mg dienogest (1997) Contraception, 56 (3), pp. 185-191. , DOI 10.1016/S0010-7824(97)00123-6, PII S0010782497001236 Bannemerschult, R., Hanker, J.P., Wunsch, C., Fox, P., Albring, M., Brill, K., A multicenter, uncontrolled clinical investigation of the contraceptive efficacy, cycle control and safety of a new low dose oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel over six treatment cycles (1997) Contraception, 56 (5), pp. 285-290. , DOI 10.1016/S0010-7824(97)00157-1, PII S0010782497001571 Endrikat, J., Jaques, M.A., Mayerhofer, M., 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 (1995) Contraception, 52 (4), pp. 229-235 Astedt, B., Jeppsson, S., Liedholm, P., Clinical trial of a new oral contraceptive pill containing the natural oestrogen 17 beta-oestradiol (1979) Br J Obstet Gynaecol, 86 (9), pp. 732-736. , An excellent study about the replacement of EE by natural estradiol Hoffmann, H., Moore, C., Kovacs, L., Teichmann, A.T., Klinger, G., Graser, T., Oettel, M., Alternatives for the replacement of ethinylestradiol by natural 17beta- Estradiol in dienogest-containing oral contraceptives (1999) Drugs of Today, 35 (SUPPL. C), pp. 105-113 Kivinen, S., Saure, A., Efficacy and tolerability of a combined oral contraceptive containing 17 beta-estradiol and desogestrel (1996) Eur J Contracept Reprod Health Care, 1, p. 183 Samsioe, G., Transdermal hormone therapy: Gels and patches (2004) Climacteric, 7 (4), pp. 347-356. , DOI 10.1080/13697130400012239 Urdl, W., Apter, D., Alperstein, A., Koll, P., Schonian, S., Bringer, J., Fisher, A.C., Germond, M., Contraceptive efficacy, compliance and beyond: Factors related to satisfaction with once-weekly transdermal compared with oral contraception (2005) European Journal of Obstetrics Gynecology and Reproductive Biology, 121 (2), pp. 202-210. , DOI 10.1016/j.ejogrb.2005.01.021, PII S0301211505000540 Abrams, L.S., Skee, D.M., Natarajan, J., Pharmacokinetics of a contraceptive patch (Evra/Ortho Evra) containing norelgestromin and ethinyloestradiol at four application sites (2002) Br J Clin Pharmacol, 53 (2), pp. 141-146 Abrams, L.S., Skee, D.M., Natarajan, J., Multiple-dose pharmacokinetics of a contraceptive patch in healthy women participants (2001) Contraception, 64 (5), pp. 287-294 Abrams, L.S., Skee, D.M., Natarajan, J., Pharmacokinetics of norelgestromin and ethinyl estradiol delivered by a contraceptive patch (Ortho Evra/Evra) under conditions of heat, humidity, and exercise (2001) J Clin Pharmacol, 41 (12), pp. 1301-1309 Sicat, B.L., Evra, O., A new contraceptive patch (2003) Pharmacotherapy, 23 (4), pp. 472-480 Audet, M.-C., Moreau, M., Koltun, W.D., Waldbaum, A.S., Shangold, G., Fisher, A.C., Creasy, G.W., Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: A randomized controlled trial (2001) Journal of the American Medical Association, 285 (18), pp. 2347-2354 Jick, S.S., Hagberg, K.W., Kaye, J.A., Ortho Evra and venous thromboembolism: An update (2010) Contraception, 81 (5), pp. 452-453 Brache, V., Mishell, D.R., Lahteenmaki, P., Alvarez, F., Elomaa, K., Jackanicz, T., Faundes, A., Ovarian function during use of vaginal rings delivering three different doses of Nestorone (2001) Contraception, 63 (5), pp. 257-261. , DOI 10.1016/S0010-7824(01)00199-8, PII S0010782401001998 Guazzelli, C.A., Barreiros, F.A., Barbosa, R., Extended regimens of the vaginal contraceptive ring: Cycle control (2009) Contraception, 80 (5), pp. 430-435 Barreiros, F.A., Guazzelli, C.A., Barbosa, R., Extended regimens of the contraceptive vaginal ring: Evaluation of clinical aspects (2010) Contraception, 81 (3), pp. 223-225 Szarewski, A., High acceptability and satisfaction with NuvaRing use (2002) European Journal of Contraception and Reproductive Health Care, 7 (SUPPL. 2), pp. 31-36 Ahrendt, H.-J., Nisand, I., Bastianelli, C., Gomez, M.A., Gemzell-Danielsson, K., Urdl, W., Karskov, B., Milsom, I., Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone (2006) Contraception, 74 (6), pp. 451-457. , DOI 10.1016/j.contraception.2006.07.004, PII S0010782406003088 Roy, G., Injectable contraception (2010) Semin Reprod Med, 28 (2), pp. 126-132 Luukkainen, T., Levonorgestrel-releasing intrauterine device (1991) Ann NY Acad Sci, 626, pp. 43-49 Luukkainen, T., The levonorgestrel intrauterine system: Therapeutic aspects (2000) Steroids, 65 (10-11), pp. 699-702 Odlind, V., Long-term experience of a levonorgestrel-releasing intrauterine system (1996) European Journal of Contraception and Reproductive Health Care, 1 (4), pp. 319-323 Hidalgo, M., Bahamondes, L., Perrotti, M., Diaz, J., Dantas-Monteiro, C., Petta, C., Bleeding patterns and clinical performance of the levonorgestrel- releasing intrauterine system (Mirena) up to two years (2002) Contraception, 65 (2), pp. 129-132. , DOI 10.1016/S0010-7824(01)00302-X, PII S001078240100302X Meirik, O., Fraser, I.S., D'Arcangues, C., Implantable contraceptives for women (2003) Hum Reprod Update, 9 (1), pp. 49-59. , WHO Consultation on Implantable Contraceptives for Women http://www.cecinfo.org/, Available from Accessed 13 July 2009Trussell, J., Rodriguez, G., Ellertson, C., New estimates of the effectiveness of the Yuzpe regimen of emergency contraception (1998) Contraception, 57 (6), pp. 363-369. , DOI 10.1016/S0010-7824(98)00042-0, PII S0010782498000420 Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception (1998) Lancet, 352 (9126), pp. 428-433. , Task Force on Postovulatory Methods of Fertility Regulation The study shows the failure rate with hormonal EC Von Hertzen, H., Piaggio, G., Van Look, P.F., Emergency contraception with levonorgestrel or the Yuzpe regimen (1998) Lancet, 352 (9144), p. 1939 Piaggio, G., Von Hertzen, H., Grimes, D.A., Van Look, P.F.A., Timing of emergency contraception with levonorgestrel or the Yuzpe regimen (1999) Lancet, 353 (9154), p. 721. , DOI 10.1016/S0140-6736(98)05718-3 Von Hertzen, H., Piaggio, G., Ding, J., Chen, J., Song, S., Bartfai, G., Ng, E., Peregoudov, A., Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: A WHO multicentre randomised trial (2002) Lancet, 360 (9348), pp. 1803-1810. , DOI 10.1016/S0140-6736(02)11767-3 Moreau, C., Trussell, J., Bajos, N., The determinants and circumstances of use of emergency contraceptive pills in France in the context of direct pharmacy access (2006) Contraception, 74 (6), pp. 476-482. , DOI 10.1016/j.contraception.2006.07.008, PII S0010782406003131 Woolcock, J.G., Critchley, H.O., Munro, M.G., Review of the confusion in current and historical terminology and definitions for disturbances of menstrual bleeding (2008) Fertil Steril, 90 (6), pp. 2269-2280 Grimes, D.A., Schulz, K.F., Raymond, E.G., Surrogate end points in women's health research: Science, protoscience, and pseudoscience (2010) Fertil Steril, 93 (6), pp. 1731-1734 Oettel, M., Carol, W., Elger, W., Kaufmann, G., Moore, C., Romer, W., Klinger, G., Zimmermann, H., A 19-norprogestin without 17alpha-ethinyl group II: Dienogest from a pharmacodynamic point of view (1995) Drugs of Today, 31 (7), pp. 517-536 Dusterberg, B., Nishino, Y., Pharmacokinetic and pharmacological features of oestradiol valerate (1982) Maturitas, 4 (4), pp. 315-324. , DOI 10.1016/0378-5122(82)90064-0 Zeun, S., Lu, M., Uddin, A., Pharmacokinetics of an oral contraceptive containing oestradiol valerate and dienogest (2009) Eur J Contracept Reprod Health Care, 14 (3), pp. 221-232 Oettel, M., Breitbarth, H., Elger, W., The pharmacological profile of dienogest (1999) Eur J Contracept Reprod Health Care, 4 (1 SUPPL. 1), pp. 2-13 Mueck, A.O., Seeger, H., Buhling, K.J., Why use of dienogest for the first contraceptive pill with estradiol? (2009) Gynecol Endocrinol, 11, pp. 1-5 Ben-Rafaelf, Z., Mastroianni, L., Meloni, F., Total estradiol, free estradiol, sex hormone-binding globulin, and the fraction of estradiol bound to sex hormone-binding globulin in human follicular fluid (1986) J Clin Endocrinol Metab, 63 (5), pp. 1106-1111. , The most important study with the new COC Endrikat, J., Parke, S., Trummer, D., Ovulation inhibition with four variations of a four-phasic estradiol valerate/dienogest combined oral contraceptive: Results of two prospective, randomized, open-label studies (2008) Contraception, 78 (3), pp. 218-225 Palacios, S., Wildt, L., Parke, S., Efficacy and safety of a novel oral contraceptive based on oestradiol (oestradiol valerate/dienogest): A Phase III trial (2010) Eur J Obstet Gynecol Reprod Biol, 149 (1), pp. 57-62 Ahrendt, H.J., Makalova, D., Parke, S., 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 (2009) Contraception, 80 (5), pp. 436-444+54 Parke, S., Nahum, G., Mellinger, U., Junge, W., Metabolic effects of a new four-phasic oral contraceptive containing estradiol valerate and dienogest (2008) Obstet Gynecol, 111 (4 SUPPL.), pp. 12-13 Fraser, I.S., Zeun, S., Machlitt, A., Mellinger, U., A novel oral contraceptive comprising estradiol valerate/dienogest for the treatment of heavy and/or prolonged menstrual bleeding without organic cause: A double-blind, randomised, placebo-controlled trial (2009) Int J Gynecol Obstet, 107 (SUPPL. 2), pp. S183 Jensen, J., Machlitt, A., Mellinger, U., A multicenter, double-blind, randomized, placebo-controlled study of oral estradiol valerate/dienogest for the treatment of heavy and/or prolonged menstrual bleeding (2009) Fertil Steril, 92, pp. S32 Duijkers, I.J.M., Klipping, C., Grob, P., Korver, T., Effects of a unique, monophasic combined oral contraceptive containing nomegestrol acetate/17 beta-estradiol on ovarian function 14 World Congress of Gynecology Endocrinology, Florence, Italy, March, 2010, , Abstract Duijkers, I.J., Klipping, C., Grob, P., Korver, T., Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 beta-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol (2010) Eur J Contracept Reprod Health Care, 15 (5), pp. 314-325 Dinger, J., Assmann, A., Mohner, S., Minh, T.D., Risk of venous thromboembolism and the use of dienogest- and drospirenone-containing oral contraceptives: Results from a German case-control study (2010) J Fam Plann Reprod Health Care, 36 (3), pp. 123-129 Cibula, D., Gompel, A., Mueck, A.O., Hormonal contraception and risk of cancer (2010) Hum Reprod Update, 16 (6), pp. 631-650 Xu, B., Kitawaki, J., Koshiba, H., Ishihara, H., Kiyomizu, M., Teramoto, M., Kitaoka, Y., Honjo, H., Differential effects of progestogens, by type and regimen, on estrogen-metabolizing enzymes in human breast cancer cells (2007) Maturitas, 56 (2), pp. 142-152. , DOI 10.1016/j.maturitas.2006.07.003, PII S0378512206002726 http://www.ClnicalTrials.gov, Available from NCT00464516Creinin, M.D., Schlaff, W., Archer, D.F., Progesterone receptor modulator for emergency contraception: A randomized controlled trial (2006) Obstet Gynecol, 108 (5), pp. 1089-1097. , The most important study in EC with ulipristal Glasier, A.F., Cameron, S.T., Fine, P.M., Ulipristal acetate versus levonorgestrel for emergency contraception: A randomised non-inferiority trial and meta-analysis (2010) Lancet, 375 (9714), pp. 555-562 Fine, P., Mathe, H., Ginde, S., Ulipristal acetate taken 48--120 hours after intercourse for emergency contraception (2010) Obstet Gynecol, 115 (2 PART 1), pp. 257-263 Brache, V., Cochon, L., Jesam, C., Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture (2010) Hum Reprod, 25 (9), pp. 2256-2263 Stratton, P., Levens, E.D., Hartog, B., Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914 (2010) Fertil Steril, 93 (6), pp. 2035-2041 Pall, M.S., Friden, B.E., Brannstrom, M., Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: A randomized double-blind study (2001) Human Reproduction, 16 (7), pp. 1323-1328 Bata, M.S., Al-Ramahi, M., Salhab, A.S., Gharaibeh, M.N., Schwartz, J., Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study (2006) Journal of Clinical Pharmacology, 46 (8), pp. 925-932. , DOI 10.1177/0091270006289483 Richards, J.S., Perspective: The ovarian follicle. A perspective in 2001 Endocrinology 2001, 142 (6), pp. 2184-2193 Jesam, C., Salvatierra, A.M., Schwartz, J.L., Croxatto, H.B., Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: Potential for emergency contraception (2010) Hum Reprod, 25 (2), pp. 368-373 Edelman, A.B., Jensen, J.T., Hennebold, J.D., A nonhormonal model for emergency contraception: Prostaglandin synthesis inhibitor effects on luteal function and lifespan, a pilot study (2010) Contraception, 81 (6), pp. 496-500 Pearce-Pratt, R., Phillips, D.M., Sulfated polysaccharides inhibit lymphocyte-to-epithelial transmission of HIV-1 (1996) Biol Reprod, 54 (1), pp. 173-182. , Provides insight about vaginal gel which has the potential of dual protection Sitruk-Ware, R., Brache, V., Maguire, R., Pharmacokinetic study to compare the absorption and tolerability of two doses of levonorgestrel following single vaginal administration of levonorgestrel in Carraguard gel: A new formulation for "dual protection" contraception (2007) Contraception, 75 (6), pp. 454-460 Elias, C.J., Coggins, C., Alvarez, F., Brache, V., Fraser, I.S., Lacarra, M., Lahteenmaki, P., Salvatierra, A.M., Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan (1997) Contraception, 56 (6), pp. 387-389. , DOI 10.1016/S0010-7824(97)00176-5, PII S0010782497001765 Coggins, C., Blanchard, K., Alvarez, F., Brache, V., Weisberg, E., Kilmarx, P.H., Lacarra, M., Ellertson, C., Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide (2000) Sexually Transmitted Infections, 76 (6), pp. 480-483. , DOI 10.1136/sti.76.6.480 Victor, A., Johansson, E., Plasma levels of d-norgestrel and ovarian function in women using intravaginal rings impregnated with d-norgestrel for several cycles (1976) Contraception, 14 (2), pp. 215-226 Brache, V., Croxatto, H., Sitruk-Ware, R., Effect of a single vaginal administration of levonorgestrel in Carraguard gel on the ovulatory process: A potential candidate for "dual protection" emergency contraception (2007) Contraception, 76 (2), pp. 111-116 Brache, V., Croxatto, H., Kumar, N., Effect of sexual intercourse on the absorption of levonorgestrel after vaginal administration of 0.75 mg in Carraguard gel: A randomized, cross-over, pharmacokinetic study (2009) Contraception, 79 (2), pp. 150-154 http://informa-pipeline.citeline.com, Pharmaprojects. Available fromhttp://informa.citeline.com, Pharmaprojects. Available fromhttp://www.clinicaltrials.gov/NCT01140217, Available from NCT00915915http://www.clinicaltrials.gov/NCT01140217, Available fromHaukkamaa, M., Laurikka-Routti, M., Heikinheimo, O., Transdermal absorption of the progestin ST-1435: Therapeutic serum steroid concentrations and high excretion of the steroid in saliva (1991) Contraception, 44 (3), pp. 269-276 Kumar, N., Koide, S.S., Tsong, Y.Y., Sundaram, K., Nestorone®: A progestin with a unique pharmacological profile (2000) Steroids, 65 (10-11), pp. 629-636. , It is the first study about transdermalcontraceptive spray Fraser, I.S., Weisberg, E., Kumar, N., Kumar, S., Humberstone, A.J., McCrossin, L., Shaw, D., Sitruk-Ware, R., An initial pharmacokinetic study with a Metered Dose Transdermal System® for delivery of the progestogen Nestorone® as a possible future contraceptive (2007) Contraception, 76 (6), pp. 432-438. , DOI 10.1016/j.contraception.2007.08.006, PII S001078240700409X Gilliam, M.L., Neustadt, A., Kozloski, M., Adherence and acceptability of the contraceptive ring compared with the pill among students: A randomized controlled trial (2010) Obstet Gynecol, 115 (3), pp. 503-510 Weisberg, E., Brache, V., Alvarez, F., Massai, R., Mishell Jr., D.R., Apter, D., Gale, J., Fraser, I.S., Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen (2005) Contraception, 72 (1), pp. 46-52. , DOI 10.1016/j.contraception.2004.12.014, PII S0010782405000284 Brache, V., Mishell, D.R., Lahteenmaki, P., Alvarez, F., Elomaa, K., Jackanicz, T., Faundes, A., Ovarian function during use of vaginal rings delivering three different doses of Nestorone (2001) Contraception, 63 (5), pp. 257-261. , DOI 10.1016/S0010-7824(01)00199-8, PII S0010782401001998 Sivin, I., Mishell Jr., D.R., Alvarez, F., Brache, V., Elomaa, K., Lahteenmaki, P., Massai, R., Jackanicz, T.M., Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: A 1-year dose-finding trial (2005) Contraception, 71 (2), pp. 122-129. , DOI 10.1016/j.contraception.2004.08.010 Fraser, I.S., Weisberg, E., Brache, V., Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen (2005) Contraception, 72 (1), pp. 40-45. , It is the first final report of a clinical trial with a new combined vaginal ring Sitruk-Ware, R., Merkatz, R., Sussman, H., Variano, B., A one year contraceptive vaginal ring delivering Nestorone® and Ethinyl-Estradiol The 11th Congress of the European Society of Contraception and Reproductive Health. Hague, Holland, May, 2010, , Abstract Merkatz, R., Sussman, H., Sivin, I., Preliminary results from a phase III study of the nestorone®/ethinyl estradiol contraceptive vaginal ring: A new, long acting (one year) user controlled contraceptive method The 11th Congress of the European Society of Contraception and Reproductive Health. Hague, Holland, May, 2010, , Abstract Lahteenmaki, P., Weiner, E., Lahteenmaki, P., Contraception with subcutaneous capsules containing ST-1435. Pituitary and ovarian function and plasma levels of ST-1435 (1981) Contraception, 23 (1), pp. 63-75. , DOI 10.1016/0010-7824(81)90115-3 Diaz, S., Schiappacasse, V., Pavez, M., Clinical trial with NestoroneTM subdermal contraceptive implants (1995) Contraception, 51 (1), pp. 33-38 Brache, V., Massai, R., Mishell Jr., D.R., Ovarian function during use of Nestorone® subdermal implants (2000) Contraception, 61 (3), pp. 199-204. , Shows the final results of the clinical trial on subdermal implants which release NES Sivin, I., Croxatto, H., Bahamondes, L., Brache, V., Alvarez, F., Massai, R., Schechter, J., Moo-Young, A., Two-year performance of a Nestorone-releasing contraceptive implant: A three-center study of 300 women (2004) Contraception, 69 (2), pp. 137-144. , DOI 10.1016/j.contraception.2003.10.003 Bahamondes, L., Hidalgo, M., Petta, C.A., Diaz, J., Espejo-Arce, X., Monteiro-Dantas, C., Enlarged ovarian follicles in users of a levonorgestrel-releasing intrauterine system and contraceptive implant (2003) Journal of Reproductive Medicine for the Obstetrician and Gynecologist, 48 (8), pp. 637-640 www.clinicaltrials.gov, Available from Accessed on 20 July 2010www.clinicaltrial.gov, Available fromGoodman, A.L., Hodgen, G.D., Progesterone receptor antagonists (1996) Reproductive Endocrinology Surgery and Technology, pp. 548-558. , Adashi EY, Rock JA, Rosenwaks Z, editors Chapter 27. Lippincott-Raven Publishers, Philadelphia Provides an insight into SPRM Elger, W., Bartley, J., Schneider, B., Endocrine pharmacological characterization of antiprogestins and progesterone receptor modulators (PRMs) with respect to PR-agonistic and -antagonistic activity (2000) Steroids, 65 (10-11), pp. 713-723 Attardi, B.J., Burgenson, J., Hild, S.A., Reel, J.R., Blye, R.P., CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: In vitro comparison to mifepristone and CDB-2914 (2002) Molecular and Cellular Endocrinology, 188 (1-2), pp. 111-123. , PII S0303720701007432 Blithe, D.L., Nieman, L.K., Blye, R.P., Stratton, P., Passaro, M., Development of the selective progesterone receptor modulator CDB-2914 for clinical indications (2003) Steroids, 68 (10-13), pp. 1013-1017. , DOI 10.1016/S0039-128X(03)00118-1 Gainer, E., Ulmann, A., Pharmacologic properties of CDB (VA)-2914 (2003) Steroids, 68 (10-13), pp. 1005-1011 Brenner, R.M., Slayden, O.D., Nath, A., Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques (2010) Contraception, 81 (4), pp. 336-342 Chwalisz, K., Garg, R., Brenner, R., Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs) (2006) Reprod Biol Endocrinol, 4 (SUPPL. 1), pp. S8 Nayak, N.R., Slayden, O.D., Chwalisz, K., Antiprogestin-releasing intrauterine devices: A novel approach to endometrial contraception (2007) Contraception, 75 (6 SUPPL.), pp. S104-S111 Narvekar, N., Cameron, S., Critchley, H.O.D., Lin, S., Cheng, L., Baird, D.T., Low-Dose Mifepristone Inhibits Endometrial Proliferation and Up-Regulates Androgen Receptor (2004) Journal of Clinical Endocrinology and Metabolism, 89 (5), pp. 2491-2497. , DOI 10.1210/jc.2003-031945 Wolf, J.P., Hsiu, J.G., Anderson, T.L., Noncompetitive antiestrogenic effect of RU 486 in blocking the estrogen-stimulated luteinizing hormone surge and the proliferative action of estradiol on endometrium in castrate monkeys (1989) Fertil Steril, 52 (6), pp. 1055-1060. , Offers an explanation about the effect of SPRM on human endometrium Brenner, R.M., Slayden, O.D., Progesterone receptor antagonists and the endometrial antiproliferative effect (2005) Seminars in Reproductive Medicine, 23 (1), pp. 74-81. , DOI 10.1055/s-2005-864035 Brenner, R.M., Slayden, O.D., Nayak, N.R., Baird, D.T., Critchley, H.O.D., A role for the androgen receptor in the endometrial antiproliferative effects of progesterone antagonists (2003) Steroids, 68 (10-13), pp. 1033-1039. , DOI 10.1016/S0039-128X(03)00120-X Brenner, R.M., Slayden, O.D., Critchley, H.O., Anti-proliferative effects of progesterone antagonists in the primate endometrium: A potential role for the androgen receptor (2002) Reproduction, 124 (2), pp. 167-172+106 (2009) World Population Data Sheet of the Population Reference Bureau, , Population Reference Bureau, Washington, DC Ross, J.A., Winfrey, W.L., Unmet need for contraception in the developing world and the former Soviet Union: An updated estimate (2002) Internat Fam Plann Perspect, 28 (3), pp. 138-143 Finer, L.B., Henshaw, S.K., Disparities in rates of unintended pregnancy in the United States, 1994 and 2001 (2006) Perspect Sex Reprod Health, 38 (2), pp. 90-96 Santelli, J.S., Lindberg, L.D., Finer, L.B., Singh, S., Explaining recent declines in adolescent pregnancy in the United States: The contribution of abstinence and improved contraceptive use (2007) American Journal of Public Health, 97 (1), pp. 150-156. , DOI 10.2105/AJPH.2006.089169 Daulaire, N., Leidle, P., Mackin, L., (2002) Promises to Keep: The Toll of Unintended Pregnancies on Women's Lives in the Developing World, pp. 1-48. , Global Health Council, Washingtoon, DC Bongaarts, J., Johansson, E., Future trends in contraceptive prevalence and method mix in the developing world (2002) Studies in Family Planning, 33 (1), pp. 24-36 Grimes, D.A., Forgettable contraception (2009) Contraception, 80 (6), pp. 497-499 Bajos, N., Leridon, H., Goulard, H., Oustry, P., Job-Spira, N., Arduin, P., Bajos, N., Warszawski, J., Contraception: From accessibility to efficiency (2003) Human Reproduction, 18 (5), pp. 994-999. , DOI 10.1093/humrep/deg215 Sitruk-Ware, R., Contraception: An international perspective (2006) Contraception, 73 (3), pp. 215-222. , DOI 10.1016/j.contraception.2005.08.019, PII S0010782405003264