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. 2025 May 1;117(5):1046-1055.
doi: 10.1093/jnci/djae282.

Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers

Karen M Tuesley  1   2 , Katrina Spilsbury  3 , Sallie-Anne Pearson  4   5 , Peter Donovan  6   7 , Andreas Obermair  8   9 , Michael D Coory  10 , Sitwat Ali  1   2 , Nirmala Pandeya  1   2 , Louise Stewart  11 , Susan J Jordan  1   2 , Penelope M Webb  1   2
Affiliations

Long-acting, progestin-based contraceptives and risk of breast, gynecological, and other cancers

Karen M Tuesley et al. J Natl Cancer Inst. .

Abstract

Background: Use of long-acting, reversible contraceptives has increased over the past 20 years, but an understanding of how they could influence cancer risk is limited.

Methods: We conducted a nested case-control study among a national cohort of Australian women (n = 176 601 diagnosed with cancer between 2004 and 2013; 882 999 matched control individuals) to investigate the associations between the levonorgestrel intrauterine system, etonogestrel implants, depot-medroxyprogesterone acetate and cancer risk and compared these results with the oral contraceptive pill. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results: Levonorgestrel intrauterine system and etonogestrel implant use was associated with breast cancer risk (OR = 1.26, 95% CI = 1.21 to 1.31, and OR = 1.24, 95% CI = 1.17 to 1.32, respectively), but depot-medroxyprogesterone acetate was not, except when used for 5 or more years (OR = 1.23, 95% CI = 0.95 to 1.59). Reduced risks were seen for levonorgestrel intrauterine system (≥1 years of use) in endometrial cancer (OR = 0.80, 95% CI = 0.65 to 0.99), ovarian cancer (OR = 0.71, 95% CI = 0.57 to 0.88), and cervical cancer (OR = 0.62, 95% CI = 0.51 to 0.75); for etonogestrel implant in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34) and ovarian cancer (OR = 0.76, 95% CI = 0.57 to 1.02); and for depot-medroxyprogesterone acetate in endometrial cancer (OR = 0.21, 95% CI = 0.13 to 0.34). Although levonorgestrel intrauterine system, etonogestrel implant and depot-medroxyprogesterone acetate were all associated with increased cancer risk overall, for etonogestrel implant, the risk returned to baseline after cessation, similar to the oral contraceptive pill. We were unable to adjust for all potential confounders, but sensitivity analyses suggested that adjusting for parity, smoking, and obesity would not have materially changed our findings.

Conclusion: Long-acting, reversible contraceptives have similar cancer associations to the oral contraceptive pill (reduced endometrial and ovarian cancer risks and short-term increased breast cancer risk). This information may be helpful to women and their physicians when discussing contraception options.

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Conflict of interest statement

P.M.W. received grant funding from AstraZeneca for an unrelated study of ovarian cancer and a speaker’s fee from AstraZeneca (November 2021). All remaining authors have declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Flowchart of the selection of case and control individuals for the study. Abbreviation: PBS = Pharmaceutical Benefits Scheme.
Figure 2.
Figure 2.
Summary of associations between recent and former contraceptive use and risk of cancer. a Possible uncontrolled confounding or detection bias.
See this image and copyright information in PMC

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