Research emerges on continuous regimen OC
When using contraception to delay or stop menstrual periods, return to fertility is important to patients. Results of a national survey indicate 58% of women worry that menstrual suppression will affect their ability to have children.1 New research on a continuous-regimen oral contraceptive (OC) under review at the Food and Drug Administration (FDA) suggests that the drug's return to fertility is comparable to rates observed with cyclic combined pills.2
The research was presented at the annual meeting of the American Society for Reproductive Medicine.
Lybrel (20 mcg ethinyl estradiol/90 mcg levonorgestrel tablets) is a low dose, continuous, noncyclic combination oral contraceptive under development by Wyeth. The drug was given approvable status by the FDA in June 2006. The company is submitting additional manufacturing stability data and further analyses of submitted clinical data to gain full regulatory approval of the drug. If given final approval, 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.
Women are now familiar with extended-regimen contraception due to dedicated products such as Seasonale (0.03 mg ethinyl estradiol/0.15 mg levonorgestrel tablets) and Seasonique (0.03 mg ethinyl estradiol tablets /0.15 mg levonorgestrel and 0.01 mg ethinyl estradiol tablets), both marketed by Duramed, a subsidiary of Barr Pharmaceuticals. Lybrel is in a slightly new paradigm, says Kurt Barnhart, MD, director of clinical research and associate professor of OB/GYN at the University of Pennsylvania Medical Center in Philadelphia. Barnhart served as lead author on the recently presented Lybrel research.
"The fact that you can use oral contraceptive pills continuously for up to a year is relatively new, and therefore, whenever a product is launched that is new, you want to have very good reassurance of its function and safety," Barnhart says. "One of the theoretical concerns was a delayed return to fertility, and I think the data that we presented can reassure clinicians that that is not an issue, that there will be no delay of fertility."
To evaluate the return to fertility among women planning to become pregnant after the use of Lybrel, researchers followed 21 women for up to 12 months following their last dose of treatment. Average duration of treatment with the drug was 197 days within the study group. The pregnancy rate was 57% (12/21) at three months and 81% (17/21) at 12 months after discontinuation, the scientists report. After the 12-month post-study follow-up, information was sought for the remaining four women who had not become pregnant. One woman conceived within 14 months of the last treatment for a total pregnancy rate of 86% (18/21). In the remaining three women who did not conceive, one woman ceased trying to become pregnant by 12 months, and the other two were lost to follow-up after 12 months, note the researchers.2 Eighteen pregnancies resulted in 17 live births and one spontaneous abortion. Data were obtained from 10 of the 17 newborns; all were uncomplicated term deliveries.2
Research explores safety issues
Is extended menstrual suppression safe? Research findings are encouraging. Both the one-year investigation of Seasonale and a six-month trial of continuous use of a 20 mg ethinyl estradiol/100 mg levonorgestrel OC indicate no untoward effects on the endometrium.3,4
What are the potential disadvantages? Patient counseling should include the following5:
- Breakthrough bleeding initially is more common than with conventional OCs.
- It often takes a few months before the desired effect of reduced bleeding is achieved.
- With no monthly withdrawal bleed, it may be more difficult for patients to determine pregnancy. Breast tenderness, nausea, and fatigue may signal pregnancy in women using extended regimens.
In addition to eliminating the monthly withdrawal bleed, a continuous regimen pill may offer other noncontraceptive benefits as well. Results of a 2005 study indicate that Lybrel significantly alleviates cycle-related symptoms.6 During the three-month, open-label substudy, participants with a history of cycle-related symptoms or premenstrual syndrome (PMS) reported a decrease in symptoms compared to baseline by the first pill pack, and continued to report a decrease in symptoms during the two subsequent pill packs.5
Both mood and physical symptoms of PMS improved with daily continuous levonorgestrel, says Ellen Freeman, PhD, professor of obstetrics and gynecology at the University of Pennsylvania in Philadelphia and lead author of the study. "This may be an appropriate option for cycle-related symptom relief, particularly for women who also want contraception," Freeman says.
- Greenberg Quinlan Rosner Research. Association of Reproductive Health Professionals (ARHP) — Continuous Regimen Frequency Questionnaire. Accessed at: www.arhp.org/2005menstruationsurvey.
- Barnhart K, Mirkin S, Grubb G, et al. Return of fertility after cessation of a continuous oral contraceptive. Presented at the 62nd annual meeting of the American Society for Reproductive Medicine. New Orleans; Oct. 21-25, 2006.
- Anderson FD, Hait H, Seasonale-301 Study Group. A multicenter, randomized study of an extended cycle oral contraceptive. Contraception 2003; 68:89-96.
- Kwiecien M, Edelman A, Nichols MD, et al. Bleeding patterns and patient acceptability of standard or continuous dosing regimens of a low-dose oral contraceptive: A randomized trial. Contraception 2003; 67:9-13.
- Association of Reproductive Health Professionals. Extended and Continuous Use of Contraceptives to Reduce Menstruation. Clinical Proceedings 2004;18.
- Freeman EW, Borisute H, Deal L, et al. A continuous-use regimen of levonorgestrel/ethinyl estradiol significantly alleviates cycle-related symptoms: Results of a phase 3 study. Fertil Steril 2005; 84(Sup1):S25.
Get more information on extended/continuous regimens of contraception. Visit the Menstruation Resource Center portion of the web site for the Association of Reproductive Health Professionals (ARHP), www.arhp.org. Click on "Resources" and then "Menstruation Resource Center" to access articles on the subject as well as patient information, such as an interactive tool on menstrual suppression developed by the organization.