Use of estradiol–progestin therapy associates with increased risk for uterine sarcomas

ObjectiveInsufficient data exist on the effect of postmenopausal hormone therapy as the risk factor for uterine sarcomas. We therefore evaluated the association of estradiol–progestin therapy (EPT) with the risk of uterine sarcoma in nation-wide cohort study.MethodsAll Finnish women (> 50 years of age) who had used EPT during the years 1994–2008 for at least 6 months (n = 243,857) were identified from the national Medical Reimbursement Registry. Their incidence of uterine stromal and leiomyosarcoma among the EPT users was compared to that in the background population with the aid of the Finnish Cancer Registry.ResultsA total of 76 uterine sarcomas were encountered in the EPT cohort; 45 (59%) were leiomyosarcomas, 24 (32%) stromal sarcomas and 7 (9%) other sarcomas. The exposure to EPT for less than 5 years did not associate with significant rises in the sarcoma risk but longer exposure was accompanied with significant risk elevations for all uterine sarcomas: the standardized incidence ratio (SIR) for 5–10 years of use was 2.0, 95% confidence interval (CI) 1.4–2.9 and for ≥ 10 years of use 3.0 (1.3–5.9): the SIRs were highest for leiomyosarcoma. The sequential and continuous uses of progestin were associated with similar increased SIRs for uterine sarcoma.ConclusionsThe use of EPT for 5 years or more is associated with an increased risk for uterine sarcomas. This turns to an absolute excess risk of 2–3 extra uterine sarcoma cases per 10,000 long-time EPT users followed for 10 years.

Research highlights
► The use of estradiol–progestin therapy (EPT) for 5+ years is associated with 2-fold increase in the risk for uterine sarcomas.
► The absolute excess risk is 2–3 extra uterine sarcoma cases per 10,000 long-time EPT users followed for 10 years.
► The sequential and continuous uses of progestin in EPT preparations were associated with similar increased risks for uterine sarcoma.