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OBJECTIVE: The objective was to develop an individualized risk-benefit model quantifying the impact of combined use of estrogen and progestogen on chronic diseases. DESIGN: The study population consisted of women, aged 40+, prescribed postmenopausal hormone therapy (HT) in the UK General Practice Research Database (N > 200,000). Individualized risks of fracture, colorectal cancer, diabetes mellitus, myocardial infarction, deep venous thrombosis/pulmonary embolism, breast cancer, and stroke were estimated using Cox regression. Relative rates from the Women's Health Initiative trial were used to estimate attributable risks (ie, excess risks) in a risk-benefit simulation model. RESULTS: Risks and benefits increased with age and length of HT use. HT use for 5 years initiated at age 45 increased the absolute risk of myocardial infarction by 0.04% and breast cancer by 0.3% and reduced the risk of hip fracture by 0.03%. Comparably, 5-year HT use started at age 75 led to increases in the risks of myocardial infarction and breast cancer (+0.4% and +0.2%, respectively) and reduced that of hip fracture (-0.9%). There was considerable heterogeneity in the risks and benefits of HT. In most of the younger HT users, the frequency of risks exceeded that of the benefits, although the absolute excess risks were small. In HT users aged 70+, 62.4% experienced more benefits than risks, whereas 37.6% experienced more risks than benefits. CONCLUSIONS: The frequency of beneficial and adverse effects of HT on chronic diseases was low in younger women, whereas the ratio of these risks and benefits varied substantially among the older users. However, the study could not asses the effects of HT on menopausal symptoms and quality of life, benefits more likely to be observed among younger women.

Original publication




Journal article



Publication Date





374 - 381


Adult, Age Factors, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Colorectal Neoplasms, Database Management Systems, Estrogen Replacement Therapy, Female, Hip Fractures, Humans, Middle Aged, Postmenopause, Proportional Hazards Models, Risk Assessment, United Kingdom