BACKGROUND AND PURPOSE: 

• The traditional ‘cyclic’ regimen for combined oral contraceptives (COCs) is 21 days on and 7 days off  
• Current low-dose estrogen COC use (≤35 µg ethinyl estradiol) is associated with a 2- to 3-fold higher risk for venous thromboembolism (VTE)  
  • This risk represents a small absolute excess risk which is much less than risk levels seen in pregnancy or postpartum  
• Li et al. (JAMA Internal Medicine, 2018) sought to determine the risk for venous thromboembolism (VTE) when COCs are used with continuous (365/0 days) or extended (84/7 days) regimens

METHODS: 

• Retrospective cohort study  
• US population identified from Sentinel Distributed Database 
  • Administrative medical and prescription drug insurance claims and demographic data 
• Participants 
  • 18 to 50 years old at time of initiating use of COC  
  • Excluded women with medical condition that could impact risk for VTE (e.g., prior VTE or malignancy)  
• Exposure was either 
  • Continuous/extended COCs 
  • Traditional cyclic COCs 
• Initiators defined as  
  • No use of the study COCs that were used to define each cohort during a 6-month lookback period 
• Medication contained ethinyl estradiol or levonorgestrel of any dose 
• Follow-up was index date until  
  • Earliest occurrence of VTE hospitalization | Health plan disenrollment | Cessation of initiated COC | Initiation of a product of the other COC regimen in comparison or a nonstudy hormone contraceptive | Death | Pregnancy or live birth delivery | End of study period 
• Primary outcome: First VTE hospitalization that occurred during the study follow-up 
• Covariates were assessed for confounding including other drug use or medical conditions using propensity scoring

RESULTS: 

• 210,691 initiators of noncyclic COCs
  • 11,504 continuous COC users | 522, 316 initiators of cyclic COCs 
• Mean age 
  • Noncyclic: 30.4 years 
  • Cyclic COCs: 28.8 years 
• Incident VTE cases 
  • Noncyclic COC users: 228  
  • Cyclic COC users: 297  
• Compared to cyclic COCs, continuous/extended cyclic users had 
  • Higher baseline cardiovascular and metabolic conditions (7.2% vs 4.7%) 
  • More gynecological conditions (39.7% vs 32.3%) 
  • Slightly higher health services utilization  
• Adjusting for confounding, there was a higher risk for VTE in the continuous/extended group (progestogen type levonorgestrel) 
  • Hazard ratio 1.32 (95% CI, 1.07-1.64)  
• Adjusting for confounding, the absolute risk difference and the incidence rate difference between the 2 cohorts was low 
  • Absolute risk difference: 0.27 per 1000 persons 
  • Incidence rate difference: 0.35 cases per 1000 person-years 
    • 1.44 vs 1.09 cases per 1000 person-years 

CONCLUSION: 

• Continuous/extended COCs lead to slightly elevated VTE risk, compared to cyclic COCs 
• Authors consider the absolute risk to be small and likely not clinically significant and state 

Accordingly, we do not recommend selective prescribing of COCs based on the cyclic and continuous/extended type. Clinicians should prescribe COCs based on patients’ individual risk factors and preferences. 

Learn More – Primary Sources: 

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

Related ObG Topics:

Hormonal Contraception Benefits – Beyond Pregnancy Prevention

ACOG Practice Advisory: Counseling Patients About Breast Cancer Risk and Hormonal Contraception