Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval

Abstract

Purpose: To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI).

Patients and methods: This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs.

Results: There was a 10% increase (OR =1.102; 95% CI: 1.006-1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393-1.683) and 31% (OR =1.307; 95% CI: 1.205-1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle.

Conclusion: Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles.

Keywords: 91-day cycle; combined oral contraception; extended-regimen COC; menstrual cycle.

Figure 1

Percentage of women reporting the occurrence of scheduled bleeding (A) or spotting (B) during each extended-regimen 91-day cycle. Note: Women receiving 91-day extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and EE 10 µg for 7 days showed a 10% increase in the likelihood of reporting no scheduled bleeding (OR =1.102 [95% CI: 1.006–1.206]) and a 9% increase in the likelihood of reporting no scheduled spotting (OR =1.085 [95% CI: 1.005–1.170]) for each additional 91-day cycle completed. Abbreviations: COC, combined oral contraception; EE, ethinyl estradiol; LNG, levonorgestrel.

Figure 2

Percentage of women reporting 0 to ≤6 days or >6 days of unscheduled bleeding during each extended-regimen 91-day cycle. Note: Women receiving 91-day extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and EE 10 µg for 7 days showed a 53% increase in the likelihood of reporting 0 to ≤6 days of unscheduled bleeding per 91-day cycle (OR =1.531 [95% CI: 1.393–1.683]). Abbreviations: COC, combined oral contraception; EE, ethinyl estradiol; LNG, levonorgestrel.

Figure 3

Percentage of women reporting 0 to ≤6 days or >6 days of unscheduled spotting during each extended-regimen 91-day cycle. Note: Women receiving 91-day extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and EE 10 µg for 7 days showed a 31% increase in the odds of reporting 0 to ≤6 days of unscheduled spotting per 91-day cycle (OR =1.307 [95% CI: 1.205–1.418]). Abbreviations: COC, combined oral contraception; EE, ethinyl estradiol; LNG, levonorgestrel.

Figure 4

Percentage of women reporting no unscheduled bleeding during each extended-regimen 91-day cycle by COC use history (A), smoker status (B), BMI (C), and age (D). Note: *Chi-square test, P<0.05. Abbreviations: COC, combined oral contraception; BMI, body mass index.