OBJECTIVE: To assess the efficacy, safety, and tolerability of an extended-duration, combined hormonal oral contraceptive pill (OCP) that reduces the estrogen exposure by almost half compared with other OCPs.
METHODS: This open-label, uncontrolled, multicenter study used an ultra low-dose OCP (1.0 mg norethindrone acetate and 10 micrograms ethinyl E2). The OCP was administered in a regimen of 24 days of a 28-day cycle followed by 10 micrograms ethinyl E2 for 2 days and an inactive tablet for 2 days. The study included healthy, heterosexually active women aged 18–45 years who were at risk of pregnancy.
RESULTS: The discontinuation rate was 41.7% (692/1,660 patients). Twenty-six pregnancies occurred in 1,555 participants during 15,596 at-risk cycles, resulting in a Pearl Index of 2.2 and a cumulative pregnancy rate of 2.1 for the overall population. Participants experienced an average of 2.6 days of intracyclic (unscheduled) bleeding or spotting per cycle over treatment cycles 213. Intracyclic bleeding was more common in users new to OCPs than in users switching from another OCP and in women aged 18–35 years compared with those aged 36 years or older. The frequency of bleeding episodes decreased after cycle 2 and throughout treatment in all subpopulations.
CONCLUSION: The findings of this study demonstrate that this ultra low-dose OCP regimen is effective in preventing pregnancy with a safety and tolerability profile that is comparable with that reported for other low-dose OCPs.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00391807.
LEVEL OF EVIDENCE: III
Ultra low-dose norethindrone acetate and ethinyl estradiol is effective in preventing pregnancy, with a similar tolerability profile to that reported for other low-dose combined oral contraceptive pills.
Department of Obstetrics and Gynecology, Eastern Virginia Medical School, and the Group for Women, Norfolk, Virginia; the Department of Obstetrics, Gynecology & Women's Health, University of Louisville, Louisville, Kentucky; HOPE Research Institute LLC, Phoenix, Arizona; the Women's Health Practice, Champaign, Illinois; the Medical Center for Clinical Research, San Diego, California; and TKL Research Inc, Rochelle Park, and Warner Chilcott, Rockaway, New Jersey.
Corresponding author: David F. Archer, MD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, 601 Colley Avenue, Norfolk, VA 23507; e-mail: email@example.com.
Financial Disclosure Dr. Archer is a consultant to Warner Chilcott and has received research grants from Warner Chilcott. Dr. Nakajima is a consultant for Warner Chilcott. Dr. Trupin is a principal investigator for Merck Sharp & Dohme Corporation and is a speaker for Warner Chilcott. Dr. Gilbert's work on the study was funded by Warner Chilcott. Dr. Ellman is an employee of Warner Chilcott. The other authors did not report any potential conflicts of interest.
Funded by Warner Chilcott (U.S.) LLC. Warner Chilcott participated in the design, conduct, and analysis of the study. Editorial and writing support was funded by Warner Chilcott (U.S.) LLC.
The authors thank Tam Vo, PhD, from Excerpta Medica for providing editorial and writing assistance in the preparation of the manuscript.