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Patches, rings, implants, and gels are in research
What can American women expect to see as new contraceptive options in the next five years? While novel forms of hormonal delivery might not yet be approved, family planning experts say there will be new forms of birth control available for use in the form of contraceptive patches and rings.
Several strides already have been made this year with the U.S. introduction of the monthly contraceptive injectable Lunelle, marketed by Pharmacia Corp. of Peapack, NJ, and the Mirena levonorgestrel-releasing intrauterine system (IUS), marketed by Berlex Laboratories of Montville, NJ, says Daniel Mishell Jr., MD, professor in the department of obstetrics and gynecology at the University of Southern California School of Medi-cine in Los Angeles. (More information on Lunelle is contained in a special news bulletin inserted in Contraceptive Technology Update, November 2000. The U.S. introduction of the Mirena is the focus of an article in the February 2001 issue, p. 13.)
The Evra contraceptive patch, developed by the R.W. Johnson Pharmaceutical Research Institute in Raritan, NJ, is under review by the Food and Drug Administration (FDA). The transdermal patch serves as a carrier for the progestin/estrogen combination of norelgestromin and ethinyl estradiol. It is worn for one week at a time and is changed on the same day of the week three times a month, with the fourth week patch-free. (See CTU, March 2001, p. 29, for further information on Evra.)
Mishell also points to the U.S. introduction of the Nuvaring contraceptive vaginal ring from Organon USA of West Orange, NJ. The ring, which carries
a combination of the progestin etonogestrel and ethinyl estradiol, is nearing the end of clinical development. (Learn more about ring delivery systems in CTU, May 1998, p. 57.) A just-published study shows that the ring — worn three weeks, then removed for one week — offered good cycle control with favorable patient compliance.1
The New York City-based Center for Biomedical Research, the research arm of
the Population Council, also is investigating contraceptive patch and ring delivery systems, reports Regine Sitruk-Ware, MD, the council’s executive director of contraceptive development. By the end of 2001, Phase III testing is scheduled to begin on a vaginal ring containing two hormones: Nestorone, a progestin developed by the council, and the synthetic estrogen ethinyl estradiol. The ring is inserted for three weeks, removed for one week to allow menstruation, then returned, for a total of 13 consecutive cycles.
Nestorone is ideally suited for transdermal drug delivery systems since it is readily absorbed through the skin into the bloodstream, and its high efficacy can be maintained at low, stable daily doses, according to the Population Council. Its use also is being evaluated in patch form, as well as in gel form, says Sitruk-Ware. (Informa-tion on Nestorone is included in CTU, October 1997, p. 121, and the May 1998 issue, p. 57.)
Implants offer options
Several European markets have seen the introduction of the single-rod contraceptive implant Implanon, marketed by Organon USA’s parent company, NV Organon, in Oss, the Netherlands. Intended for three years of use, the progestin-only implant offers an excellent contraceptive action and an acceptable safety profile, according to research.2 In a comparison study that evaluated the contraceptive efficacy, tolerability, and bleeding patterns of Implanon vs. the six-rod Norplant implant (marketed in the United States by Wyeth-Ayerst Pharmaceuticals of Philadelphia), researchers found less frequent bleeding, a higher incidence of infrequent bleeding, and amenorrhea in the single-rod system.3
The Population Council’s two-rod levonorgestrel implant, marketed internationally as Jadelle, offers a similar side effect profile and contraceptive efficacy as its sister six-rod implant, Norplant.4 Jadelle has been found to be equally as effective and acceptable as Norplant and provides safe, highly-effective reversible contraception, according to research. Because it consists of only two rods, insertion and removal of Jadelle is easier and takes less time than that of Norplant, studies show.4
Family planners may recognize Jadelle as Norplant II, which was approved by the FDA in 1996. Wyeth-Ayerst Pharmaceuticals, which holds the U.S. marketing rights to the device, has not introduced it for sale and has chosen to further research the two-rod implant.
New OCs under review
New oral contraceptives (OCs) are now in the research pipeline, says Mishell. One candidate includes a four periods-per-year pill called Seasonale. Manufacturer Barr Laboratories of Pomona, NY, has signed an exclusive rights agreement with Eastern Virginia Medical School of Norfolk, the original developers of the product, to bring the OC to market. Clinical trials are now under way. If successful — and the FDA approves — Seasonale could reach the shelves of U.S. pharmacies by 2003. (See CTU, May 1999, p. 51, for more information on Seasonale.)
Wyeth-Ayerst is investigating a new oral contraceptive using the novel progestin trimegestone with the established estrogen ethinyl estradiol. The formulation is in Phase II studies in the research pipeline.
The next five years will bring to American women more new choices in contraception than the previous 30 years combined, predicts Philip Darney, MD, MSc, professor at the University of California, San Francisco, and chief of the department of OB/GYN at San Francisco General Hospital Medical Center.
"Providers will have increased responsibility to help their patients understand the positive and negative aspects of these new methods," observes Darney. "The big question is whether new methods will mean greater individual and collective success in avoiding unintended pregnancy."
More choices may not mean increased access, says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville. Even with the debut of the Lunelle injectable and the Mirena IUS, many women may not be able afford such methods because their insurance policies do not offer contraceptive coverage.
"The promise offered by these new methods will not be met unless U.S. insurance plans begin to more routinely cover contraception," states Kaunitz. "That many plans continue not to cover reversible control remains a national disgrace."
1. Roumen FJ, Apter D, Mulders TM, et al. Efficacy, tolerability, and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Hum Reprod 2001; 16:469-475.
2. Croxatto HB, Urbancsek J, Massai R, et al. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod 1999; 14:976-981.
3. Zheng SR, Zheng HM, Qian SZ, et al. A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant. Contraception 1999; 60:1-8.
4. Sivin I, Campodonico I, Kiriwat O, et al. The performance of levonorgestrel rod and Norplant contraceptive implants: a five-year randomized study. Hum Reprod 1998; 13:3,371-3,378.
• Philip Darney, MD, MSc, San Francisco General Hospital,1001 Potrero Ave., Ward 6D, San Fran-cisco, CA 94110. Telephone: (415) 206-8358. Fax: (415) 206-3112. E-mail: Darney@ob.ucsf.edu.
• Daniel Mishell Jr., MD, Women’s and Children’s Hospital, 1240 N. Mission Road,
Room L1009, Los Angeles, CA 90033.
• Regine Sitruk-Ware, MD, The Population Council, One Dag Hammarskjold Plaza, New York, NY 10017.