Source: Neuroimaging Clin N Am  |  Posted 6 years ago

By Amanda Strong

MONTREAL, QC -- October 19, 2005 -- A daily continuous regimen of levonorgestrel plus ethinyl estradiol (LNG/EE) over a 12-month period without a hormone-free interval has been shown to effectively inhibit menses and incrementally induce amenorrhea, according to findings from a multicenter, phase 3, open-label trial.

The study, presented in a poster session here on October 17[^]th[] at the annual meeting of the American Society of Reproductive Medicine (ASRM), involved 2402 women aged 18 to 49 years treated at 92 sites across the United States and Canada. The women all reported regular menses (21 to 35 days) during the 3 months prior to study entry.

Treatment involved 90 mcg levonorgestrel plus 20 mcg ethinyl estradiol daily for 12-months, without interruption. Main efficacy measures were number of unwanted pregnancies as well as percentage of subjects reporting amenorrhea, defined as an absence of bleeding or spotting.

Over the course of the study, 19 women (0.8%) who took at least one dose of the study drug became pregnant, resulting in a Pearl index analysis of 1.60 (95% CI, 0.96, 2.49). By pill pack 7, 44.8% of women reported amenorrhea with no spotting and 70.8% reported amenorrhea with or without spotting, said presenter Jeffrey Jensen, MD, MPH, Associate Professor and Director, Women's Health Research Unit, Oregon Health and Science University, Portland, Oregon, United States.

The median number of bleeding and spotting days per pill pack decreased over time, Dr. Jensen said. By pill pack 3, the median number of bleeding days was 0, while the median number of bleeding and/or spotting days was 6. By pill pack 8, median reported bleeding and/or spotting days also decreased to 0.

"Although there is a lot of problems with bleeding early on with continuous use, if you stick with it longer you tend to improve bleeding patterns," Dr. Jensen said in an interview.

"Because you are taking active hormones every day, bleeding patterns are inconsistent and non-predictable," Dr. Jensen continued. "The acceptability of that is highly individual. Some women much prefer to have heavier bleeding that is controlled and regimented. What's important, I think, to recognize is that over continuing use there are a greater number of individuals who experience no bleeding. So counselling is key."

Except for treatment-emergent adverse events related to vaginal bleeding, the overall incidence of adverse events was similar to those seen with the 21-day cyclic regimen that includes a 7-day hormone free interval. Dysmenorrhea was the most common urogenital adverse event, reported in 19.6% of women. About 17% of women in the study discontinued due to adverse events.

No clinically important changes in weight, blood pressure, or metabolic measures were observed. Changes in lipid profile were typical of an oral contraceptive containing LNG/EE.

The study was supported by Wyeth Research, Collegeville, Pennsylvania, United States,, manufacturers of levonorgestrel/ethinyl estradiol under the tradename Lybrel(R). A new drug application (NDA) for Lybrel has been submitted to the U.S. Food and Drug Administration (FDA) and is currently under review.

[Poster title: Efficacy and Safety of a Continuous-Use Regimen of Levonorgestrel/Ethinyl Estradiol: North American Phase 3 Study Results. O-59]