Research supports safety of continuous regimen pill
Research regarding the safety and efficacy of the first continuous regimen oral contraceptive (OC) has just been published, with results indicating a good safety profile and efficacy similar to cyclic OCs.1
Lybrel (20 mcg ethinyl estradiol/90 mcg levonorgestrel tablets) is a low-dose, continuous, noncyclic combination oral contraceptive in development by Wyeth, of Madison, NJ. The drug was given approvable status by the Food and Drug Administration (FDA) in June 2006 and is awaiting a final decision from the regulatory agency. If given the go-ahead from the FDA, Lybrel will be the only combination oral contraceptive approved with this regimen designed to be taken daily, 365 days a year, without a placebo phase or pill-free interval.
If such a pill becomes available, who would be a potential candidate? Look to women who don't want to have menstrual periods and are willing to accept some degree of unanticipated endometrial bleeding or spotting, says David Archer, MD, professor of obstetrics and gynecology at Eastern Virginia Medical School in Richmond and lead author of the current study.
Review the results
To perform the study, researchers at 92 sites in North America enrolled sexually active women ages 18-49. A total of 2,402 women were enrolled in the study; 2,134 took at least one dose of the study drug, and 921 completed the study. The study drug was supplied in 28-day pill packs; women took one pill daily for 12 months with no pill-free intervals.
During the study, which lasted more than 18 months, the median and mean number of bleeding days decreased progressively. Researchers report 79% of women reported an absence of bleeding after one year, while 58.7% reported cessation of menstrual cycles.1
About 85% of the women noted one or more treatment-emergent adverse event, with headache and dysmenorrhea listed as the most common complaints. Discontinuations due to adverse events occurred in 17% of women and included discontinuations due to uterine bleeding.
Nineteen women became pregnant while using the drug, yielding an on-treatment Pearl Index of 1.60 (95% CI=0.96–2.49). Fifteen of these pregnancies were attributed to method failure (Pearl Index=1.26; 95% CI=0.71–2.08), and four were attributed to user failure (Pearl Index=0.34; 95% CI=0.09–0.86).1
While researchers report that the incidence of uterine bleeding decreased with longer use, 21% of women had uterine bleeding by Pill Pack 13, with a median of four days of bleeding and three days of spotting per 28-day pill pack. More than three-quarters (77%) of women who experienced bleeding on Pill Pack 13 reported they were satisfied with the method, with 7% as neutral and 16% as dissatisfied.1
"This suggests that there is a subset of women who may not achieve amenorrhea with prolonged use of continuous OC," researchers note. "The lack of amenorrheic outcome may lead to the discontinuation of OCs in these women."
Counseling is key
If a dedicated continuous regimen pill becomes available, be ready to counsel women about bleeding, says Archer. While a woman may not have a regular withdrawal bleeding episode with a continuous regimen pill, she would have to accept the unanticipated bleeding as a trade-off, he notes.
"Many women may start with the expectation that they will not have any bleeding at all; those women who do not experience any bleeding, or only some inconvenience, will be those who continue this method," notes Archer. "There is no way that we can identify those who will vs. those who will not bleed."
For most women, breakthrough bleeding with continuous dosing improves with increasing duration of use, but for a small number, it may never improve, agrees Alison Edelman, MD, MPH, assistant professor of obstetrics and gynecology at Oregon Health & Science University, who served as lead author of a review of continuous- or extended-cycle OCs.2 "I think future studies will focus on formulations or interventions that will improve the rate of breakthrough bleeding," Edelman notes.
To provide education about the menstrual cycle and the effects of hormonal contraception on cycles, the Association of Reproductive Health Professionals has launched an on-line Menstruation Resource Center (www.arhp.org/menstruationRC), which includes a variety of information, resources, recent headlines, and links to other sources of evidence-based information on menstruation.
A pill that women can take indefinitely has many potential benefits, says Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta. Most important is the fact that women will know they have to do the same thing every day — take one pill, he says.
"The concern I have is that women will only be provided pills in 28-day packages and will have to return to a pharmacist every month for a very expensive pill," observes Hatcher. "If women have to return every month for a new package of pills, it defeats the main purpose of this medication. My hope is that once women find that they can tolerate this medication, they are provided a full year's supply of pills."
For this pill to have any impact in the public sector, it is going to have to be available inexpensively to health departments, hospital-based programs, and Planned Parenthood affiliates, says Hatcher.
- Archer DF, Jensen JT, Johnson JV, et al. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: Phase 3 study results. Contraception 2006; 74:439-445.
- Edelman AB, Gallo MF, Jensen JT, et al. Continuous or extended cycle vs. cyclic use of combined oral contraceptives for contraception. Cochrane Database Syst Rev 2005; CD004695.