Takaisin Tulosta

Continuous or extended cycle use of combined oral contraceptives

Evidence summaries
Heidi Alenius
Last reviewed as up-to-date 19.1.2024Latest change 19.1.2024

Level of evidence: A

Combined oral contraceptives taken continuously for more than 28 days are similar to traditional cyclic oral contraceptives as judged by bleeding, discontinuation rates, and reported satisfaction.

A Cochrane review «Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception»1 «Edelman A, Micks E, Gallo MF et al. Continuous or ...»1 included 12 studies with a total of 3 628 subjects.

Study findings for combined oral contraceptives (COC) were similar between 28-day and extended cycles in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended cycles was found. Participants reported high satisfaction with both dosing regimens.

The few studies that reported menstrual symptoms found that the extended cycle group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. However, breast tenderness was increased in continuous dosing of the contraceptive patch. 11/12 studies found that bleeding patterns were either equivalent between groups or improved with extended or continuous cycles. Endometrial lining assessments by ultrasound were done in a small number of participants and were all normal.The studies were too small to address efficacy, rare adverse events, and safety.

A safety study «Li J, Panucci G, Moeny D et al. Association of Ris...»2 using the sentinel distributed database of United States assessed the association of continuous/extended use of COC (84/7 or 365/0 days cycles) and venous thromboembolism (VTE). 210 691 initiators of continuous/extended COC and 522 316 initiators of cyclic COC were included. Baseline cardiovascular and metabolic conditions (7.2% vs 4.7%), gynecological conditions (39.7% vs 32.3%), and health services utilization were slightly higher among continuous/extended cyclic than cyclic COC users. Propensity score matching decreased the hazard ratio estimates from 1.84 (95% CI, 1.53 to 2.21) to 1.32 (95% CI, 1.07 to 1.64) for continuous/extended use compared with cyclic COC use. The absolute risk difference (0.27 per 1000 persons) and the incidence rate difference (0.35 cases per 1000 person-years [1.44 vs 1.09 cases per 1000 person-years]) remained low, which may not translate into a clinically significant risk differences between cyclic and noncyclic use.

A survey «Nappi RE, Lete I, Lee LK et al. Real-world experie...»3 compared extended-cycle use of COC (3 months between periods, n= 260) with women using monthly-cycle COC (n=3616). Women using extended-cycle COC reported significantly higher treatment satisfaction (P = 0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029). A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using extended-cycle vs monthly-cycle COC.

A post hoc analysis «Nappi RE, Lobo Abascal P, Hsieh J et al. Cycle con...»4 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 women. There was a 10% increase in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed (OR 1.10, 95% CI 1.01 to 1.21). From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23%; fourth cycle =22%). There were increases in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting (OR 1.53, 95% CI 1.39 to 1.68 and OR 1.31, 95% CI 1.21 to 1.42; 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.

A randomized, active controlled, open, prospective, parallel-group trial «...»5 including 1314 women was conducted in 48 German gynecological centers. With an unadjusted PI of 0.483 (upper 95% CI 1.237), the extended-cycle regimen containing ethinylestradiol and levonorgestrel fulfilled the contraceptive efficacy.The mean total number of bleeding days per year was significantly lower in the extended-cycle vs. the conventional-cycle regimen. Both regimens were well accepted and the adverse effects were comparable in both groups.

References

  1. Edelman A, Micks E, Gallo MF et al. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev 2014;(7):CD004695. «PMID: 25072731»PubMed
  2. Li J, Panucci G, Moeny D et al. Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel Distributed Database. JAMA Intern Med 2018;178(11):1482-1488. «PMID: 30285041»PubMed
  3. Nappi RE, Lete I, Lee LK et al. Real-world experience of women using extended-cycle vs monthly-cycle combined oral contraception in the United States: the National Health and Wellness Survey. BMC Womens Health 2018;18(1):22. «PMID: 29347935»PubMed
  4. Nappi RE, Lobo Abascal P, Hsieh J et al. 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. Int J Womens Health 2017;(9):739-747. «PMID: 29042818»PubMed
  5. Hadji P, Neulen J, Schaudig K, et al. Extended-cycle versus conventional treatment with a combined oral contraceptive containing ethinylestradiol (30 μg) and levonorgestrel (150 μg) in a randomized controlled trial. Gynecol Endocrinol 2020;36(6):513-520 «PMID: 32064971»PubMed