Progestin-only implant and breast cancer risk in adolescents and premenopausal women: A systematic review and meta-analysis.
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Long-acting reversible contraception with progestin-only subdermal implants is widely adopted. However, the breast cancer (BC) risk signal attributable to implants remains under-characterized, limiting evidence-based counseling. We systematically searched PubMed/MEDLINE, Embase, and Scopus,and screened references for observational cohort and case-control studies evaluating progestin-only implant versus non-use hormonal contraception in adolescents and premenopausal women without prior BC. The primary endpoint was incident BC (invasive with/without in situ, per study definition). Maximally adjusted effect estimates were extracted; measures were harmonized to odds ratios (ORs). Risk of bias was assessed with ROBINS-E. Pooled estimates used inverse-variance random-effects meta-analysis; heterogeneity was quantified with I² and Tau². Five studies met inclusion criteria (3 nationwide cohorts from Denmark/Sweden and 2 nested case-control studies from the UK and Australia). Across cohort studies, implant exposure accounted for 1659,309 person-years with 510 BC events. The largest case-control dataset included 67,470 BC cases. Study-specific adjusted estimates were: Morch 2017 RR 0.93 (95% CI 0.48-1.80), Fitzpatrick 2023 OR 1.22 (0.93-1.60), Hadizadeh 2025 HR 1.22 (1.11-1.35), Hultstrand 2022 IRR 1.22 (0.98-1.52), and Tuesley 2025 OR 1.24 (1.17-1.32). The pooled effect showed higher incident BC risk with implant exposure (OR 1.23, 95% CI 1.19-1.27, p < 0.0001) with no observed heterogeneity (I²=0%; Tau²=0). In contemporary population-based data, progestin-only subdermal implant use is associated with a modest but statistically increase (∼23%) in incident BC risk versus non-use. Given low baseline incidence in younger women, absolute risk impact is likely small, but the signal is decision-relevant for shared contraceptive counseling, particularly in patients with elevated baseline BC risk.