Journal of the National Cancer Institute (JNCI)Long-acting, Progestin-based Contraceptives and Risk of Breast, Gynecological, and Other Cancers

A large-scale Australian nested case-control study examining 176,601 cancer cases and 882,999 matched controls provides essential data on cancer risks associated with common long-acting, progestin-based contraceptives. The research offers valuable comparative analysis between levonorgestrel intrauterine systems, etonogestrel implants, depot-medroxyprogesterone acetate, and oral contraceptive pills.

Study Design:

• Nested case-control study conducted in Australia between 2004-2013
• Study population included 176,601 cancer cases and 882,999 matched controls
• Evaluated three long-acting contraceptive methods: levonorgestrel IUS, etonogestrel implants, and depot-medroxyprogesterone acetate
• Utilized conditional logistic regression to calculate odds ratios with 95% confidence intervals
• Study acknowledged limitations in adjusting for all potential confounders, though sensitivity analyses suggested minimal impact from parity, smoking, and obesity

Key Findings:

• Breast Cancer Risk:
  • Levonorgestrel IUS: OR = 1.26 (95% CI: 1.21-1.31)
  • Etonogestrel implant: OR = 1.24 (95% CI: 1.17-1.32)
  • Depot-medroxyprogesterone: Only elevated after 5+ years of use (OR = 1.23, 95% CI: 0.95-1.59)
• Protective Effects (≥1 year use):
  • Levonorgestrel IUS reduced risks in:
    • Endometrial cancer: OR = 0.80 (95% CI: 0.65-0.99)
    • Ovarian cancer: OR = 0.71 (95% CI: 0.57-0.88)
    • Cervical cancer: OR = 0.62 (95% CI: 0.51-0.75)
  • Etonogestrel implant reduced risks in:
    • Endometrial cancer: OR = 0.21 (95% CI: 0.13-0.34)
    • Ovarian cancer: OR = 0.76 (95% CI: 0.57-1.02)
  • Depot-medroxyprogesterone reduced risks in:
    • Endometrial cancer: OR = 0.21 (95% CI: 0.13-0.34)

HCN Medical Memo
When counseling patients about contraceptive options, physicians can now provide evidence-based risk assessments showing that long-acting contraceptives carry similar cancer risk profiles to oral contraceptives. This data supports confident prescribing decisions while emphasizing the importance of individualized risk assessment, particularly for patients with personal or family histories of breast cancer.

Contraception/Birth Control Summaries