Evaluating the oncologic impact of statin use in gynecologic cancers: a critical review of pre-clinical and clinical evidence.

Statins, potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, have demonstrated anti-neoplastic activity in pre-clinical models; however, their clinical efficacy in gynecologic malignancies remains uncertain. This review evaluates the association between statin use and survival outcomes in cervical, endometrial, and ovarian cancers, and synthesizes emerging pre-clinical and clinical data to clarify their translational potential. A PubMed search identified 44 English-language studies published between January 2005 and August 2025 that reported survival outcomes among gynecologic patients receiving statins, as well as studies assessing statin use in combination with immunotherapy. Across 406,285 patients, evidence in cervical cancer remains limited to a single cohort (n = 76), which showed a markedly reduced risk of mortality among statin users (hazard ratio [HR] 0.098). In endometrial cancer, 5 large observational cohorts (n = 985-295,925) reported post-diagnosis HRs between 0.61 and 0.79. In ovarian cancer, 8 retrospective studies (n = 126-8629) demonstrated HRs ranging from 0.45 to 0.90, and 2 meta-analyses (combined n = 57,564) indicated a survival advantage (HRs 0.74-0.87), particularly for non-serous histologies and among patients initiating statins after diagnosis. Post-hoc analyses of ovarian cancer trials further suggest potential synergy between statins and poly(ADP-ribose) polymerase (PARP) inhibitors. Evidence from non-gynecologic tumors also indicates improved outcomes with concurrent statin use during immunotherapy (overall survival HR 0.76; progression-free survival HR 0.80). Overall, post-diagnosis statin use appears to confer a 10% to 25% improvement in overall survival across gynecologic malignancies, supporting the rationale for prospective, histotype-stratified randomized trials evaluating statins, alone or combined with PARP or immune checkpoint inhibitors, as adjuncts to standard therapy.