New pill options give women choices while changing menstrual bleeding
New extended-regimen pill OK'd, continuous-use pill may soon follow
The Food and Drug Administration (FDA) has just given approval to Seasonique (Duramed Pharmaceuticals; Pomona, NY), an extended-regimen oral contraceptive (OC). The first 84 tablets of each package contain 0.15 mg levonorgestrel and 0.03 mg ethinyl estradiol. They are followed by seven tablets of 0.01 mg ethinyl estradiol, one-third of the dosage found in the first 84 pills.
It is the second extended-regimen contraceptive. It joins Duramed's Seasonale, which is formulated with 84 tablets of 0.15 mg levonorgestrel and 0.03 mg of ethinyl estradiol, plus seven placebo tablets. (Editor's note: Seasonique marks the 74th available OC in the United States. Seventy of those pills are shown in picture format in a wall poster developed by Bridging the Gap Communications.
The FDA also has given tentative approval to Corona, CA-based Watson Pharmaceuticals' request to market a generic version of Duramed's Seasonale extended-regimen OC. Full approval of the product is expected after Duramed's market exclusivity expires on Sept. 5, says Watson spokeswoman Patty Eisenhaur.
As of Contraceptive Technology Update press time, the FDA was scheduled to take action on the first continuous oral contraceptive, Lybrel, developed by Wyeth Pharmaceuticals of Collegeville, PA. Lybrel is formulated with 20 mcg ethinyl estradiol and 90 mcg levonorgestrel. According to Wyeth spokeswoman Candace Steele, the agency could move to approve the drug; issue an "approvable" letter, signaling the need for further information; or deny the drug's application.
Bye-bye placebo week
What do these new drugs mean for your patients? They signal an end of the placebo week, says Carolyn Westhoff, MD, medical director of the family planning clinics at Columbia Presbyterian Hospital and professor of obstetrics and gynecology, and public health at Columbia University, both in New York City.
For women using low-dose OCs, the clearance of estrogen and progestin from the circulation can lead to ovulation if a new cycle of OCs is not started.1 Reducing or eliminating the number of hormone-free days should aid in decreasing the incidence of ovulation and pregnancy that occurs in typical oral contraceptive use when women fail to begin their pill packs on time.
"What does this translate into as far as I'm concerned?" asks Westhoff. "Better contraceptive protection, because all human beings miss some pills from time to time, and if you also have the ovary waking back up every time you have a placebo week, then that is going to be a recipe for those occasional pill failures that we all see."
Providers recently have expanded their OC option list to include two oral contraceptives with a 24-day dosing regimen: Loestrin 24 Fe (Warner Chilcott; Rockaway, NJ), which uses 24 days of active hormonal therapy and four days of iron- containing placebo pills, and Yaz (Berlex, Montville, NJ), which uses 24 days of active hormones and four days of placebo pills.
The classic 21/7 schedule for combination oral contraceptive formulations represents an approach developed more than 40 years ago, says Andrew Kaunitz, MD, professor and assistant chair in the obstetrics and gynecology department at the University of Florida Health Science Center/Jacksonville. Kaunitz says he is enthusiastic about OC formulations that reduce hormone-free days, such as Mircette (Organon; West Orange, NJ), LoEstrin 24, Yaz, and Seasonique, or eliminate them entirely, as is the case with Lybrel, because of their potential to minimize hormone withdrawal symptoms and enhance contraceptive efficacy.
Review new research
To assess the efficacy and safety of Seasonique, researchers conducted a multicenter, open-label, one-year study of the drug.2 According to their analysis, the method failure rate was 0.78 (Pearl index) and 0.64% (life table analysis). Cycle control and safety of the regimen were similar to that reported for other OCs. According to study results, the drug is effective, safe, and well tolerated for the prevention of pregnancy.2
Scientific abstracts regarding Lybrel research were presented at the May 2006 Annual Meeting of the American College of Obstetricians and Gynecologists.3,4 One abstract reported on the safety and efficacy profile of Lybrel compared with a traditional 21-day cyclic oral contraceptive, while the second paper focused on the return to menstruation after stopping the noncyclic oral contraceptive.3,4
In the safety and efficacy trial, no pregnancies occurred with the continuous regimen, while three occurred with the cyclic regimen, researchers report.3 After pill pack four, women taking the continuous regimen pill experienced a fewer number of median breakthrough bleeding days than women taking the traditional, cyclic pill. After pill pack six, bleeding-related adverse events were not significantly different between those taking the investigational and traditional oral contraceptive regimens. Reported nausea and breast pain were lower with the noncyclic pill during pill packs seven to 13.3
Researchers involved in the analysis of return to menses after stopping the noncyclic pill report that 99% of 187 participants experienced either a return to menses or became pregnant within 90 days after stopping the study drug. Four women became pregnant before returning to menses and two women reported a return to menses more than 90 days after the completion of the study, they note.4
What do women want?
Studies report that approximately 20% of women would prefer not to have a menstrual cycle, while 25% think that a monthly bleeding episode is needed to be "normal."5 The other 50% appear not to have a firm opinion on how much importance to place on a monthly menses, says David Archer, MD, professor of obstetrics and gynecology and director of the Clinical Research Center at the Eastern Virginia Medical Center in Norfolk. This 50% represent the "swing vote" when it comes to extended and continuous regimens, he notes.
"My feeling is that providers will be reluctant to push too hard for continuous use OC because of the intermenstrual bleeding," says Archer. "The acceptance and continuation data from clinical use still is unknown."
Although physicians participate in decisions regarding contraceptive options, the consumer has become more sophisticated due to the internet and direct-to-consumer advertisement, observes Archer. The acceptance of continuous contraception such as Lybrel depends upon the consumer interest, he contends.
Seasonique and Seasonale are available for women who want to experience fewer withdrawal bleeds, while a continuous regimen pill would be for the woman who prefers none, says Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles (UCLA) and medical director of the women's health care programs at Harbor-UCLA Medical Center in Torrance. Which women would not be candidates for such regimens? Only those who really want to have periods, she says.
Withdrawal bleeds from cyclic pills offer no health benefit, says Nelson. If women are going to be concerned that their bodies are not working properly, more focus needs to be given to shortening the pill-free interval in cyclic pills, she states.
"I think today that the seven days of placebo pills is out," states Nelson. "The only question is, do we eliminate them entirely or do we just shorten them and let women choose themselves which ones they want to have?" (Editor's note: Do new pills represent true advancement in contraception? Family planning providers' knowledge banks must now span more than 70 pills on the U.S. market. In an upcoming editorial, Robert Hatcher, MD, MPH, professor of obstetrics and gynecology at Emory University in Atlanta, will review the advantages and disadvantages offered by the latest additions to the OC list.)
References
- Mishell DR. Rationale for decreasing the number of days of the hormone-free interval with use of low-dose oral contraceptive formulations. Contraception 2005; 71:304-305.
- Anderson FD, Gibbons W, Portman D. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception 2006; 73:229-234.
- Teichmann AT, Kluft C, Grubb G, et al. Comparative trial of continuous-use and 21-day cyclic levonorgestrel and ethinyl estradiol oral contraceptive. Obstet Gynecol 2006; 107:12S.
- Davis AR , Kroll R, Soltes B, et al. Return to menses after continuous use of a low-dose oral contraceptive. Obstet Gynecol 2006; 107:113S.
- Den Tonkelaar I, Oddens BJ. Preferred frequency and characteristics of menstrual bleeding in relation to reproductive status, oral contraceptive use, and hormone replacement therapy use. Contraception 1999; 59:357-362.
Resource
Bridging the Gap Communications offers a 2' x 3' color poster of every oral contraceptive option available in 2004/2005 for use in clinic/office settings. It is available in English and Spanish versions. To order on-line, visit www.managingcontraception.com. Costs are as follows: 1-4: $19.95 each; 5-10: $15.95 each; 20-35: $12.95 each; 36-200: $12.95 each. Shipping is 15% of total order, plus a $1 handling charge. For more information, contact Bridging the Gap Communications. Telephone (770) 887-8383. Fax (770) 205-1180. E-mail: [email protected].
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