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Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation.

Original publication




Journal article


American journal of epidemiology

Publication Date





1394 - 1403


Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, Medical Sciences Division, University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF, United Kingdom.


Humans, Endometrial Neoplasms, Norpregnenes, Estrogen Receptor Modulators, Body Mass Index, Estrogen Replacement Therapy, Incidence, Proportional Hazards Models, Risk Factors, Retrospective Studies, Cohort Studies, Age Factors, Postmenopause, Aged, Middle Aged, Europe, Female