This retrospective multinational cohort study (TriNetX) evaluated whether initiating estrogen-based hormone therapy (HT) within 1 year of chemoradiotherapy was associated with better long-term metabolic, skeletal, cardiovascular, oncologic, and survival outcomes in women <45 years with FIGO 2018 stage IIB–IVA cervical cancer; median follow-up ~11–12 years.
After propensity score matching (n=4,656), HT was associated with lower risk of type 2 diabetes (5.3% vs. 9.8%; HR 0.59), cerebrovascular events (5.1% vs. 8.9%; HR 0.71), and compression fractures (3.1% vs. 7.4%; HR 0.69), improved overall survival (HR 0.81), and no increased risk of thromboembolism, breast cancer, or colorectal cancer.
- Retrospective EHR-based design limits causal inference; cumulative HT dose, formulation, and discontinuation rates were not quantifiable. - Crossover contamination: 4.8% of non-HT patients later received HT, likely biasing results toward the null. - Residual confounding cannot be excluded despite propensity score matching.
Clinicians treating young patients with locally advanced cervical cancer should strongly consider offering estrogen-based HT after chemoradiotherapy, as it appears safe oncologically and may meaningfully reduce metabolic, skeletal, and cerebrovascular morbidity while improving survival. Persistent hesitation based on cancer-recurrence fears is not supported by this large, long-term dataset.
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