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- Osmancevic, Amar, et al.
(author)
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High C-reactive protein is associated with increased risk of biochemical hypogonadism: a population-based cohort study
- 2022
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In: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:7
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Journal article (peer-reviewed)abstract
- Context: Obesity seems to decrease levels of testosterone. It is still unknown what role inflammation plays in the secretion of testosterone in men. Objective: The objective is to study the association between levels of C-reactive protein and testosterone and its role in predicting biochemical hypogonadism in men. Design: This was a longitudinal observational study between 2002 and 2014 in Sweden. Patients or other participants: At the first visit, a random population sample of 1400 men was included, and 645 men fulfilled a similar protocol at a 10-year follow-up visit. After exclusion, 625 men remained to be included in the final analyses. Main outcome measure(s): Serum concentrations of testosterone and C-reactive protein (CRP) were measured at both visits. Bioavailable testosterone was calculated. Biochemical hypogonadism was defined as total testosterone levels <8 nmol/L. Results: At the first visit and in the longitudinal analyses, a strong association was found between high levels of CRP and low levels of calculated bioavailable testosterone even after adjustments for age, waist-hip ratio, hypertension, smoking, type 2 diabetes, and leisuretime physical activity (B = -0.31, 95% CI -0.49 to -0.13, P = 0.001, B = -0.26, 95% CI -0.41 to -0.11, P = 0.001). Similarly, increase with one s. d. in CRP was associated with increased risk of having hypogonadism after adjustment in the final model (odds ratio (OR) 1.76, 95% CI 1.12-2.78, P = 0.015, OR 1.80, 95% CI 1.16-2.78, P =0.008). Conclusions: In this representative cohort of men in southwestern Sweden, high levels of CRP were longitudinally associated with low concentrations of calculated bioavailable testosterone and increased risk of biochemical hypogonadism.
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- Ottarsdottir, Kristin, et al.
(author)
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Cardiometabolic Risk Factors and Endogenous Sex Hormones in Postmenopausal Women: A Cross-Sectional Study
- 2022
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In: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 6:6
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Journal article (peer-reviewed)abstract
- Context: it is uncertain which cardiovascular risk factors are associated with sex hormone levels in postmenopausal women. Objective: This work aimed to investigate the association between cardiometabolic risk factors and sex hormones in a cross-sectional, observational population study. Methods: In this Swedish population study, participants were physically examined from 2002 to 2004, and endogenous sex hormones were analyzed by liquid chromatography-tandem mass spectrometry. Women aged 55 years or older with estradiol levels below 20 pg/mL and not using any hormonal therapy were eligible for inclusion in the study (N = 146). Variable selection and bootstrap stability analyses were performed and linear regression models presented, with each of the 8 hormones as outcome variables. Results: Body mass index (BMI) was positively associated with estradiol (beta = 0.054, P < .001), but negatively associated with 17-alpha-hydroxyprogesterone (beta = -0.023, P = .028). Waist-to-hip ratio (WHR) was negatively associated with dihydrotestosterone (beta = -2.195, P = .002) and testosterone (beta = -1.541, P = .004). The homeostatic model assessment of insulin resistance was positively associated with androstenedione (beta = 0.071, P = .032), estradiol (beta = 0.091, P = .009), estrone (beta = 0.075, P = 0.009), and 17-alpha-hydroxyprogesterone (beta = 0.157 P = .001). Age was positively associated with testosterone (6 = 0.017, P = .042). C-reactive protein showed an inverse association with progesterone (beta = -0.028, P = .037). Lower low-density lipoprotein cholesterol was associated with higher estradiol levels (beta = -0.093, P = .049), whereas lower triglycerides were associated with higher concentrations of dihydrotestosterone (beta = -0.208, P = .016). Conclusion: In postmenopausal women, WHR was strongly inversely associated with androgens, while BMI was positively associated with estrogens.
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3. |
- Ottarsdottir, Kristin
(author)
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Endogenous sex hormones and cardiometabolic risk factors – population-based studies within the Skaraborg Project
- 2023
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Doctoral thesis (other academic/artistic)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.
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4. |
- Ottarsdottir, Kristin, et al.
(author)
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Longitudinal associations between sex hormone-binding globulin and insulin resistance
- 2020
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In: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 9:5, s. 418-425
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Journal article (peer-reviewed)abstract
- Purpose: We aimed to investigate the association between SHBG and the homeostatic model assessment of insulin resistance (HOMA-Ir) in men and women in a prospective observational study. Methods: The Vara-Skovde cohort is a random population of 2816 participants living in southwestern Sweden, aged 30-74. It was recruited between 2002 and 2005, and followed up in 2012-2014. After excluding participants on insulin therapy or hormone replacement therapy, 1193 individuals (649 men, 544 women) were included in the present study. Fasting blood samples were collected at both visits and stored in biobank. All participants were physically examined by a trained nurse. SHBG was measured with immunoassay technique. Linear regressions were computed to investigate the association between SHBG and HOMA-Ir both in cross-sectional and longitudinal analyses, adjusting for confounding factors. Results: The mean follow-up time was 9.7 +/- 1.4 years. Concentrations of SHBG were significantly inversely associated with log transformed HOMA-Ir in all groups with estimated standardized slopes (95% CI): men: -0.20 (-0.3;-0.1), premenopausal women: -0.26 (-0.4;-0.2), postmenopausal women: -0.13 (-0.3;-0.0) at visit 1. At visit 2 the results were similar. When comparing the groups, a statistically significant difference was found between men and post-menopausal women (0.12 (0.0;0.2) P value = 0.04). In the fully adjusted model, SHBG at visit 1 was also associated with HOMA-Ir at visit 2, and the estimated slopes were -0.16 (-0.2;-0.1), -0.16 (-0.3;-0.1) and -0.07 (-0.2;0.0) for men, premenopausal and postmenopausal women, respectively. Main conclusion: Levels of SHBG predicted the development of insulin resistance in both men and women, regardless of menopausal state.
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5. |
- Ottarsdottir, Kristin, et al.
(author)
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The association between serum testosterone and insulin resistance: a longitudinal study
- 2018
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In: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:12, s. 1491-1500
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Journal article (peer-reviewed)abstract
- The objective of this study was to investigate whether there is a bidirectional association between testosterone concentrations and insulin resistance, in a prospective population study. A random population sample of 1400 men, aged 30-74, was examined in 2002-2005 in southwestern Sweden and followed up in 2012-2014 (N=657). After excluding subjects without information on sex hormones and insulin resistance, 1282 men were included in the baseline study. Fasting measurements of plasma glucose, insulin and hormones were performed. Insulin resistance was defined using HOMA-Ir. Mean age at baseline was 47.3 +/- 11.4 years. From the follow-up survey 546 men were included, mean age 57.7 +/- 11.6 years. Low concentrations of total testosterone at baseline were significantly associated with high IogHOMA-Ir at follow-up in a multivariable model including age, waist-hip ratio, physical activity, alcohol intake, smoking, LDL, CRP, hypertension, diabetes and logHOMA-Ir at baseline as covariates (beta = -0.096, P = 0.006). Similar results were observed for bioavailable testosterone. Men within the lowest quartile of total testosterone at baseline had significantly higher IogHOMA-Ir at follow-up than other quartiles (Q1 vs Q2 P = 0.008, Q1 vs Q3 P = 0.001, Q1 vs Q4 P = 0.052). Multivariable analysis of the impact of insulin resistance at baseline on testosterone levels at follow-up revealed no significant associations regarding testosterone concentrations (beta = -0.003, P = 0.928) or bioavailable testosterone (beta = -0.006, P = 0.873), when adjusting for baseline concentrations of total testosterone, age, waist-hip-ratio, LDL, CRP, physical activity, alcohol intake, smoking, hypertension and diabetes. Low testosterone concentrations at baseline predicted higher insulin resistance at follow-up, but high insulin resistance at baseline could not predict low testosterone at follow-up.
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7. |
- Watz, Michel, 1990, et al.
(author)
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Sex hormone-binding globulin levels and development of hypertension in middle-aged men and women
- 2023
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In: Journal of hypertension. - 0263-6352 .- 1473-5598. ; 41:10, s. 1565-1570
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Journal article (peer-reviewed)abstract
- Objective:To investigate the association between sex hormone-binding globulin (SHBG) levels, change in blood pressure and development of hypertension.Methods:In a community-based study, we examined 2816 middle-aged participants with focus on cardiometabolic risk factors in 2002-2005. A representative sample of 1954 men and women was invited to follow-up in 2012-2014 and 1327 were included in a second study visit. Mean follow-up time was 9.7 years. Blood pressure was measured according to the guidelines from the seventh Joint National Committee of Hypertension, and new cases of hypertension were recorded. SHBG was measured at baseline. The association between SHBG, blood pressure and new cases of hypertension was investigated using linear regression analyses and logistic regression analyses after excluding individuals treated with blood pressure-lowering drugs.Results:Mean SBP and DBP at follow-up was 123 and 72 mmHg, respectively, and mean increase from baseline was 5.8 and 2.9 mmHg. During the follow-up time, 167 new cases of hypertension (16.1%) were identified. One standard deviation (SD) increase in SHBG at baseline was inversely associated with the risk to develop hypertension at follow-up (OR = 0.74, 95% CI 0.58-0.95) in the fully adjusted model. Moreover, one SD increase in SHBG was associated with a decrease in mean SBP (delta = -1.5 mmHg, 95% CI - 2.2 to -0.8) and DBP (delta = - 1.0 mmHg, 95% CI - 1.5 to -0.4), after adjusting for covariates.Conclusion:SHBG levels are inversely associated with development of hypertension and change in blood pressure levels independent of major risk factors.
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