Extended Regimens of the Contraceptive Vaginal Ring A Randomized Trial Leslie Miller, MD, Carole H. J. Verhoeven, PhD, and Johanna in’t Hout, MS Objective: To compare the bleeding patterns and tolera- bility of 3 different extended ring regimens with those of the standard 28-day cycle with 21 days of contraceptive vagi- nal ring use followed by 7 ring-free days. Methods: Following a run-in 28-day ring cycle, women were randomized to 1 of 4 regimens: monthly (28-day cycle), every other month (49-day cycle), every third month (91-day cycle), or continuous (364-day cycle). Treatment duration was 1 year. Daily bleeding diary, interval visit questionnaire, and examination data were collected. Results: A total of 561 women were enrolled, 429 were subsequently randomized, and 289 (67.4%) women com- pleted the entire year. All schedules were well tolerated and acceptable to women, but study completion rates were higher for the shorter cycles. Bleeding days were reduced with postponement of the withdrawal bleeding (ring-free) week, but spotting days increased. For example, women using the continuous or 364-day ring cycle reported a median of zero bleeding days but 10 –12 days of spotting during the first 3 months of extended use. Unscheduled bleeding during ring use was the lowest with the traditional 28-day cycle. Adverse events, blood pressure, body weight, and laboratory findings were comparable over the 4 treat- ment groups. Conclusion: The combination vaginal contraceptive ring can be used for extended cycles to alter the bleeding schedule. Women willing to tolerate some spotting might choose the longer extensions to have fewer menstrual periods. (Obstet Gynecol 2005;106:473–482) Level of Evidence: I M ost currently available combined oral contra- ceptives (OCs) are 28-day regimens with 21 hormone-containing pills, followed by either a pill- free week or 7 spacer or placebo pills to induce a regular monthly withdrawal pattern. This bleeding is not necessary for contraceptive efficacy, and shorten- ing the hormone-free week further decreases ovarian activity, 1 whereas extending the hormone-free week increases the risk of ovulation and could lead to method failure. 2 The dogma that women using con- traception must menstruate is changing, 3 and revers- ible amenorrhea is becoming more acceptable to women. 4 Many women using the OC manipulate their withdrawal bleeding, and women are interested in reducing this bleeding. 5 By decreasing the number of hormone-free weeks, cycle-related symptoms such as dysmenorrhea and headaches can be reduced. 6 Recently, an OC was approved with extended use of 84 days of active pill use followed by 7 days of placebo or spacer pill use for a withdrawal week every 3 months. 7 Irregular bleeding was the leading reason for study discontinuation by women using this regi- men. 7 An increase in irregular bleeding is commonly reported with extended use of OCs. 8 –10 A short extension, with just one additional package, or the 49-day regimen may have less irregular bleeding 10 than the longer extension to the 91-day cycle, 7 but there has not been a randomized direct comparison with identical formulation. Paradoxically, as with From the Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington; Clinical Development Department, Contraception, NV Organon, Oss, the Netherlands; and Department of Clinical Trial Operations, Biometrics, NV Organon, Oss, the Netherlands. The authors thank E. Aris and P. J. de Kam for statistical assistance and the 20 study investigators for their clinical contributions to this trial. Corresponding author: Leslie Miller, MD, Department of Obstetrics and Gynecology, Box 359865, 325 9th Avenue, Seattle, WA 98104-2499; e-mail: lmiller@u.washington.edu. Financial Disclosure This study was designed and conducted by Organon, Oss, the Netherlands. Dr. Verhoeven and Ms. Hout are employees of Organon. © 2005 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/05 VOL. 106, NO. 3, SEPTEMBER 2005 OBSTETRICS & GYNECOLOGY 473