Impact of Sex Hormones, Postmenopausal Hormone Therapy and Risk Factors on Development of Abdominal Aortic Aneurysm in Women: A Population-based Prospective Study in Norway: A Hunt Study

Abstract

Introduction - Women develop abdominal aortic aneurysms (AAA) five to ten years later than men (1,2). The delay in AAA development may be secondary to a protection from estrogens (3,4). The aim of the present study was to evaluate the impact of risk factors associated with AAA development in women, including postmenopausal hormone therapy. This has previously been investigated in small cohorts with limited information. Methods - In a total cohort of 106,000 individuals from the Norwegian Nord-Trøndelag Health Study (HUNT), 20,024 postmenopausal women were identified, of which 201 developed AAAs during a median follow-up of 18 years (1995-2014, i.e. 295,554 person-years). The data is based on questionnaires, physical measurements, medical records and blood samples. A multivariable Cox regression model was constructed, where the final adjusted model included the following variables: smoking (current, past, never), body mass index, coronary heart disease, diabetes, hypertension and postmenopausal hormone therapy. Multiple imputation was performed for missing data (n=50 data sets). Serum estradiol concentrations were compared between women who later did or did not develop AAAs. Median time from blood sample collection to AAA diagnosis was seven years. Results - Mean age at AAA diagnosis was 77 (59 -100) years. 28% of the cohort reported ever use of postmenopausal hormone therapy. In the multivariable analysis, a notable Hazard ratio (HR) of 0.58 was observed for current use of hormone therapy, but the result was not statistically significant (95% CI 0.29-1.16, p=0.12). Women who reported current smoking had a more than ten-fold risk for developing AAA during follow-up (HR 10.9 (7.4-16.1)). Positive associations were also found for hypertension (HR 2.0 (1.4-3.0)) and coronary heart disease (HR 2.2 (1.6-3.2)). There was no substantial difference in estradiol concentrations between women with and without AAA (p=0.06). Conclusion - Postmenopausal hormone therapy is of less clinical importance compared to the strong associations observed between smoking, hypertension coronary heart disease and AAA development in women. These findings were supported by measured estradiol concentrations.