Endogenous sex hormones and cardiometabolic risk factors – population-based studies within the Skaraborg Project

Abstract

Cardiovascular diseases are the major contributors to mortality in Sweden and globally. Men have a higher incidence of cardiovascular diseases compared to women, until women reach the menopause. Levels of sex hormones might explain these sex differences beyond known differences in risk factors. The overall aim of this thesis was to investigate the associations between sex hormones and known cardiometabolic risk factors. Cohort studies in Vara and Skövde, based on a random sample of the population, were conducted. The first visit took place in 2002-2005 including 2,816 participants aged 30-74 years (50% men). The second visit in 2012-2014 included a representative sample of 1,327 participants. Papers I-II are based on this cohort. In 2018 we analyzed eight different sex hormones by a validated high sensitivity liquid chromatography-tandem mass spectrometry in a subset of 240 women who were 50 years old or older at visit 1. Papers III-IV are studying this sub-cohort. Study I showed a significant inverse association between testosterone and insulin resistance in men, both in the cross-sectional analysis and after approximately 10 years’ follow-up. However, no significant association between insulin resistance at visit 1 and testosterone levels at visit 2 was found. Study II found a strong and significant inverse association between levels of sex hormone-binding globulin and insulin resistance in both men and women, also when the female group was stratified for age (50 years old or older) or menopausal status. Study III addressed the association between known cardiometabolic risk factors and sex hormones in postmenopausal women. The waist-tohip ratio was mainly associated with androgens and BMI was associated with estrogens. Study IV showed significant positive associations between estrone, progesterone and testosterone and the revised Framingham stroke risk profile after adjustments were made for confounders. These studies found significant associations between levels of sex hormones and cardiometabolic risk factors. This new knowledge will contribute to the understanding of sex differences in the development of cardiovascular diseases and may contribute to add further precision to the risk stratification of individuals.