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Postmenopausal estradiol–progestagen therapy and risk for uterine cervical cancer

The aim of this study was to evaluate the association of postmenopausal estradiol–progestagen therapy (EPT) with the risk for precancerous lesions, squamous cell carcinoma and adenocarcinoma of the uterine cervix. All Finnish women who had used EPT in 1994–2008 for at least 6 months (n = 243,857) at the age of 50 years or more were identified from the national Medical Reimbursement Registry and linked to the Finnish Cancer Registry. The incidence of cervical precancerous or cancerous lesions among EPT users was compared to that in the background population. There were 210 EPT users with squamous lesions (178 with precancerous and 32 with cancer) and 79 EPT users with glandular lesions (14 precancerous and 65 adenocarcinomas). The ever use of EPT did not associate with the incidence of precancerous lesions, but the risk for squamous cell carcinoma decreased (standardized incidence ratio 0.41; 95% confidence interval 0.28–0.58) and that for adenocarcinoma increased (1.31; 1.01–1.67). After the use of EPT for 5 years, the risk for squamous cell carcinoma decreased (0.34; 0.16–0.65), and the risk for adenocarcinomas increased (1.83; 1.24–2.59). The prolonged use of EPT is associated with the occurrence of cervical malignancies. If the association would be a causal one, the use for 5+ years among 10,000 women followed for 10 years would mean about two to three fewer cases of cervical squamous cell carcinoma but about two extra cases with adenocarcinoma.