Sex hormones and cardiometabolic risk

Abstract

In this thesis, we set out to investigate the complex relationship between endogenous sex hormones and cardiometabolic risk in men and women. The first part of this thesis is devoted to studies in women, and the second part describes the association between sex hormones and cardiometabolic risk in men. In Chapter 2 we report on the relationship between menopausal age, reproductive lifespan and type 2 diabetes risk. We studied this association in the InterAct study, a case-cohort study nested in the European Prospective Investigation in Cancer and Nutrition (EPIC). In Chapter 3 we examined whether metabolic risk accelerates menopausal onset. Here, we investigated the impact of diabetes and age at diagnosis on timing of natural menopause in the EPIC cohort. As smoking is clearly associated with menopausal age and risk of cardiometabolic disease, we studied the association between smoking habits and sex hormone concentrations in postmenopausal women in Chapter 4. After reviewing the literature on testosterone, SHBG and cardiovascular health in women (Chapter 5), we report on the results of a meta-analysis investigating the association of endogenous testosterone and SHBG with the metabolic syndrome in Chapter 6. In this literature-based meta-analysis, a significant amount of between-study heterogeneity was observed. Therefore, in Chapter 7 we conducted an individual participant data (IPD) meta-analysis to identify sources of this heterogeneity. Chapter 8 describes the association between testosterone, SHBG and glycated haemoglobin in men and Chapter 9 reports on the association with total and differential white blood cell count, a non-traditional CVD risk factor. Both studies have a cross-sectional design and were conducted in the EPIC-Norfolk cohort. Chapter 10 describes the association between endogenous sex hormones and markers of subclinical atherosclerosis in men. In Chapter 11, the main findings are discussed with recommendations for further research, and Chapter 12 summarizes the results reported in this thesis.