Background: Use of long-acting, reversible contraceptives (LARCs) has increased substantially over the last 20 years, however there is limited understanding on how these might influence cancer risk.
Methods: We conducted a nested case-control study among a national cohort of Australian women (176,601 women with a first cancer diagnosis 2004-2013 and 882,999 matched controls) to investigate the associations between the levonorgestrel intrauterine system (LNG-IUS), etonogestrel implants (ENG-IMP) and depot-medroxyprogesterone acetate (DMPA) and cancer risk and compared these results to the oral contraceptive pill (OCP). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI).
Results: Compared to never users, use of LNG-IUS, ENG-IMP and DMPA was associated with increased cancer risk. For LNG-IUS and DMPA this persisted among former users, while for ENG-IMP the risk returned to baseline after cessation, similar to the oral contraceptive pill (OCP). LNG-IUS and ENG-IMP use was associated with increased breast cancer risk (OR=1·26, 95%CI:1·21-1·31 and OR=1·24, 95%CI:1·17-1·32, respectively), but not DMPA except when used for five or more years (OR=1·23, 95%CI:0·95-1·59). Use of LNG-IUS (1+ years) was associated with reduced risks of endometrial (OR=0·80, 95%CI:0·65-0·99), ovarian (OR=0·71, 95%CI:0·57-0·88) and cervical cancers (OR=0·62, 95%CI:0·51-0·75). ENG-IMP and DMPA were associated with reduced risk of endometrial (OR=0·21, 95%CI:0·13-0·34; OR=0·52, 95%CI:0·32-0·84) and, less strongly, ovarian cancer (OR=0·76, 95%CI:0·57-1·02; OR=0·82, 95%CI:0·54-1·25).
Conclusion: LARCs have similar cancer associations to the OCP (reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk). Women should be advised of this when choosing a form of contraception.