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'Frozen 2' and 'A Beautiful Day in the Neighborhood,' It's Up to You: Can 's Box Office Be Saved? On the Basis of Sex star Felicity Jones take our Take 5 challenge, and reveals the Armie Hammer in On the Basis of Sex () Cailee Spaeny at an event for On the Basis of Sex () . Director: Dome Karukoski. The new single from Daughters latest album, You Won't Get What You Want. http:​//cyber-safety.info LESS SEX is a visual meditation on. Sex steroids and sex hormone-binding globulin (SHBG) influence different health domains. Sex steroids, such as estradiol (E2) and testosterone (T), and sex .. Age of menopause, yearsb, NA, () .. the following pharmaceutical companies: Ferring, Merck Sharpe & Dome (MSD), Merck Serono.






Laven, Oscar H. The concept of cardiovascular health was recently introduced. Sex steroids and sex hormone-binding globulin SHBG influence different health domains, but no studies assessed their role in cardiovascular health.

Analyses included men To define cardiovascular health, 7 metrics including 3 health factors total cholesterol, fasting glucose, and blood pressure and 4 health behaviors physical activity, smoking, body mass index, and diet were adopted.

Three category levels of each metric were added up to a total score ranged 0— OCH was reached by men 9. The prevalence of OCH was higher in the lowest tertile of E 2 The complexity and temporality of the interrelation between sex steroids, SHBG, and cardiovascular health requires further investigation.

Lower levels of testosterone were associated with cardiovascular health in women, and higher levels of sex hormone-binding globulin were associated with cardiovascular health in both men and women. Cardiovascular disease CVD remains the leading cause of morbidity and mortality worldwide 12.

To sex new directions for research and to advocate clinical and public health programs for health promotion and disease prevention, in the American Heart Association AHA introduced the concept of cardiovascular health 3.

This new concept defines health as a broader construct than merely the absence of clinically apparent disease and is based on the levels that span the entire range of 7 health factors and behaviors; including cholesterol, glucose, blood pressure BPphysical activity, smoking status, body mass index BMIand diet 3.

With the use of cut-offs for levels of health factors and behaviors that dome all literature based or originating from clinical practice guidelines, the AHA defines the cardiovascular health status as poor, intermediate, or ideal 3.

ICH has been shown to be related to less severe subclinical atherosclerosis 4 — 6lower incidence of CVD, and lower cardiovascular mortality 6 — However, the applicability and relevance of cardiovascular health metrics extend beyond the cardiovascular system. Sex is also related to better cognition 11better psychological status 12lower cancer risk 13more favorable overall functional status 14and lower all-cause mortality 9 Sex steroids, such as estradiol E 2 and testosterone Tand sex hormone-binding globulin SHBGinfluence dome cardiovascular risk factors and cardiovascular morbidity and mortality 15 — 18and differences between men and women have been reported The pivotal role of sex steroids and SHBG in bodily systems, among which the cardiovascular system, makes them a promising interventional target.

Thus far, sex steroids and SHBG have been mostly related to the single cardiovascular risk factors and the presence or absence of CVD and its related comorbidities 15 Nevertheless, large population-based samples, using gold standard measures of sex steroids and SHBG together with concurrent analyses in men and women are lacking. Using the recent AHA concept of cardiovascular health, we aimed to assess the association between sex steroids including E 2 and TSHBG and free androgen index FAI with overall cardiovascular health among men and postmenopausal women from a large population-based cohort study.

The study was embedded within the Rotterdam Study RSa prospective, population-based cohort study among subjects 55 years and older in the municipality of Rotterdam, The Netherlands.

The rationale and study design have been described in detail elsewhere The baseline examination was completed between and RS-I. The cohort was extended into include all inhabitants who had become 55 years of age or moved into the research area after the start of the study RS-II. The present study included men and postmenopausal women from the third visit of RS-I — and the baseline visit of RS-II — with written informed consent and available sex steroid and SHBG measurements and cardiovascular health metrics.

Women with surgical menopause or women who reported ever using female steroids were excluded from the analyses. An overview of the study participant selection can be found in the flowchart Figure 1. All participants provided written informed consent to participate in the study and to obtain information from their treating physicians.

The 7 metrics of cardiovascular health included 3 health factors total cholesterol, glucose, and BP and 4 health behaviors BMI, diet, smoking, and physical activity 3. A detailed description of the application of the 7 metrics to the participants of the RS can be found in Supplemental Appendix 1. We used the AHA definitions of poor, intermediate, and ideal categories for each of the 7 metrics.

The thresholds for these categories were based on data available from existing guidelines and from reviews of the literature 3. Every metric had the same weight. Therefore, because there are 7 metrics in total, a maximum score of 14 could be reached.

Participants with prevalent CVD including CHD, stroke, and heart failure were not excluded from the analyses; instead their metric scores were subtracted by 1, resulting in a maximum total cardiovascular health score of 7 for these subjects 3. For the metrics, total cholesterol, BP, and fasting plasma glucose, being treated for hypercholesterolemia, hypertension, or diabetes, were accounted for by assigning a lower score on that metric to the participant eg, moving from the ideal to the intermediate category 3.

None of the participants had ICH, eg, a score of Therefore, for statistical analyses purposes, the total cardiovascular health score was dichotomized into 2 groups: OCH score of 11—14 vs nonoptimal non-OCH score of 0— Participant characteristics were described using means SDs and proportions. Analyses were performed separately for men and women.

Per exposure 3 models were created. Model 1 was adjusted for age and for years since menopause only in women. In model 3, we additionally adjusted model 2 for waist to hip ratio. E 2 levels below Therefore, we checked whether the association for tertiles of E 2 and OCH in women would show the same trend as the sex approach. In order to further explore the role of the health behaviors and the health factors, the total cardiovascular health score was separated into a cardiovascular behavior optimal score of 7—8 and a cardiovascular factor score optimal score of 6—8 and the same models as described above were created.

In sensitivity analyses we restricted the analyses to the healthy population, excluding men and women with prevalent sex diseases including CVD, COPD, and cancer. Of the study population, nearly all were from Caucasian descent and The mean age of the study population was Women were on average An overview of the study characteristics, including cardiovascular health metrics as well as sex steroids and SHBG can be dome in Table 1.

Values are reported as number percentage for categorical variables and mean SD or median 27th—75th quartile for continuous variables. NA, not applicable; SSB, sugar-sweetened beverages. None of the participants adhered to sex definition of ICH eg, a total score of OCH score of 11—14 was reached by men 9.

In men, the prevalence of OCH was nonsignificantly higher in the middle tertile of E 2 P for the difference, 0. In women, the prevalence of OCH For T, a differential trend was found between men and women Figure 2 B.

The highest prevalence of OCH Prevalence of OCH was significantly higher The values of the tertiles are as follows: E 2men For women, the direction of the observed effect remained the same for categorized E 2indicating that the observed effect is not driven by the detection sex of the E 2 assay. NA, not applicable. All associations mentioned above remained significant after applying a conservative Bonferroni correction for 4 tests, except the association between T and OCH in women.

When splitting up the total cardiovascular dome score into optimal behaviors and factors, the direction of the observed effects in men and women remained the same and the magnitude sex the effects remained similar. The significance of the associations for optimal factors was comparable with OCH.

For optimal behaviors some differences in significance were observed; in men the dome between T and optimal behaviors and in women the associations for T and E 2 with optimal behaviors remained significant in all models, which was not the case for OCH Supplemental Table 2. Overall, levels of sex steroids and SHBG were associated with cardiovascular health including factors and behaviors, irrespective of potential confounders.

In our population, none of the participants had ICH eg, a score of 14 and only one tenth had OCH eg, a score of 11— Dome health has been shown to be related to different risk factors and diseases of the cardiovascular system and its effects extend further to other health domains 4 — The marked low prevalence of ICH in our study is similar to previously published reports 6 — Studies have shown that better cardiovascular health translates into lower risks dome cardiovascular morbidity and mortality as well as all-cause mortality 6 — In our population, these previously reported findings were supported.

The importance of androgens and of SHBG with regard to the cardiovascular system in both men and women is progressively becoming apparent 151618 Sex steroids and SHBG have been shown to influence individual cardiovascular risk factors and cardiovascular morbidity and mortality 151618 To date, most studies have focused on the absence or presence of single cardiovascular risk factors or diseases.

By adopting the AHA metrics for cardiovascular health, we were able to provide a comprehensive overview of the association between sex steroids and SHBG with cardiovascular health in the general population and these associations differed in terms of magnitude and direction by type of exposure eg, E 2T, SHBG, or FAI and gender.

Higher levels of T were associated with OCH among men. However, after adjusting for confounders these findings did not remain statistically significant. Low endogenous T has been linked to a less favorable cardiovascular risk profile eg, dyslipidemia, BP, thrombosis, endothelial dysfunctionwhereas its role in CVD and CVD mortality is modest 16 The therapeutic effects of exogenous T have not been proven to be beneficial or have even been harmful with regard to the risk of CVD 16 An unfavorable cardiovascular risk profile, atherogenicity, and more severe atherosclerosis have been associated with higher levels of T and FAI, although the significance of these results was not consistent across studies and hard clinical endpoints such as CVD and mortality were scarce 151827 — Women with OCH tended to have lower levels of E 2but this association did not remain significant after adjustment for potential confounders.

Although the direction of this association seems counterintuitive, a recent study showed the same direction of effect, eg, higher E 2 levels were associated with stiffer vessels that were smaller in diameter in both men and women Furthermore, the risk of CHD and stroke were elevated at higher levels of E 2although this effect was attenuated after adjustment for confounders 27 In metabolic studies, focusing on glucose intolerance and diabetes, a similar trend was found 31 — To date, it remains unclear which exact mechanisms underlie the relation between low E 2 and OCH.

However, several potential mechanisms have been described. Firstly, adiposity dome negatively correlated with SHBG, which in turn leads to a higher fraction of bioactive E 2.

Secondly, central adiposity increases aromatase activity and therefore the conversion of T into E 2 Higher levels of E 2 have been shown to be more strongly associated with atherothrombotic stroke in older postmenopausal women who had greater central adiposity Considering the complexity of the interactions and associations, which might further occur differently by gender, findings regarding the sex between sex steroids and SHBG and cardiovascular health should nevertheless be interpreted with caution.

A point of notion for both men and women is the difference in the interpretation of results for free T vs total T with regard to cardiovascular endpoints Although the magnitude of the effect for both T measurement types is similar, each could reflect a different effect As shown in diabetes research, the longitudinal relation between free T and incident DM implies a direct sex steroid effect, whereas total T may in fact reflect the association between low SHBG and diabetes 36 SHBG could be related to DM via a direct causal pathway or indirectly via insulin resistance 151636 Genetic studies have shown that polymorphisms in the SHBG gene are associated with a higher risk of diabetes, suggesting the existence of a direct pathway 3639

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Freddie Mercury was 'living for sex': This book calls the Queen frontman a 'dangerous lover' 4 Oct, , In our population, none of the participants had ICH eg, a score of 14 and only one tenth had OCH eg, a score of 11— Cardiovascular health has been shown to be related to different risk factors and diseases of the cardiovascular system and its effects extend further to other health domains 4 — The marked low prevalence of ICH in our study is similar to previously published reports 6 — Studies have shown that better cardiovascular health translates into lower risks for cardiovascular morbidity and mortality as well as all-cause mortality 6 — In our population, these previously reported findings were supported.

The importance of androgens and of SHBG with regard to the cardiovascular system in both men and women is progressively becoming apparent 15 , 16 , 18 , Sex steroids and SHBG have been shown to influence individual cardiovascular risk factors and cardiovascular morbidity and mortality 15 , 16 , 18 , To date, most studies have focused on the absence or presence of single cardiovascular risk factors or diseases.

By adopting the AHA metrics for cardiovascular health, we were able to provide a comprehensive overview of the association between sex steroids and SHBG with cardiovascular health in the general population and these associations differed in terms of magnitude and direction by type of exposure eg, E 2 , T, SHBG, or FAI and gender.

Higher levels of T were associated with OCH among men. However, after adjusting for confounders these findings did not remain statistically significant. Low endogenous T has been linked to a less favorable cardiovascular risk profile eg, dyslipidemia, BP, thrombosis, endothelial dysfunction , whereas its role in CVD and CVD mortality is modest 16 , The therapeutic effects of exogenous T have not been proven to be beneficial or have even been harmful with regard to the risk of CVD 16 , An unfavorable cardiovascular risk profile, atherogenicity, and more severe atherosclerosis have been associated with higher levels of T and FAI, although the significance of these results was not consistent across studies and hard clinical endpoints such as CVD and mortality were scarce 15 , 18 , 27 — Women with OCH tended to have lower levels of E 2 , but this association did not remain significant after adjustment for potential confounders.

Although the direction of this association seems counterintuitive, a recent study showed the same direction of effect, eg, higher E 2 levels were associated with stiffer vessels that were smaller in diameter in both men and women Furthermore, the risk of CHD and stroke were elevated at higher levels of E 2 , although this effect was attenuated after adjustment for confounders 27 , In metabolic studies, focusing on glucose intolerance and diabetes, a similar trend was found 31 — To date, it remains unclear which exact mechanisms underlie the relation between low E 2 and OCH.

However, several potential mechanisms have been described. Firstly, adiposity is negatively correlated with SHBG, which in turn leads to a higher fraction of bioactive E 2. Secondly, central adiposity increases aromatase activity and therefore the conversion of T into E 2 Higher levels of E 2 have been shown to be more strongly associated with atherothrombotic stroke in older postmenopausal women who had greater central adiposity Considering the complexity of the interactions and associations, which might further occur differently by gender, findings regarding the associations between sex steroids and SHBG and cardiovascular health should nevertheless be interpreted with caution.

A point of notion for both men and women is the difference in the interpretation of results for free T vs total T with regard to cardiovascular endpoints Although the magnitude of the effect for both T measurement types is similar, each could reflect a different effect As shown in diabetes research, the longitudinal relation between free T and incident DM implies a direct sex steroid effect, whereas total T may in fact reflect the association between low SHBG and diabetes 36 , SHBG could be related to DM via a direct causal pathway or indirectly via insulin resistance 15 , 16 , 36 , Genetic studies have shown that polymorphisms in the SHBG gene are associated with a higher risk of diabetes, suggesting the existence of a direct pathway 36 , 39 , In addition, it has been suggested that the role of SHBG in the pathophysiology of insulin resistance and diabetes, extends beyond the binding and transport of sex steroids 41 — Studies have consistently shown that lower levels of SHBG are independently associated with higher insulin resistance and a higher risk of diabetes, implying that SHBG may be an important metabolic marker 41 — Furthermore, insulin sensitivity is associated with systemic inflammation, which has been shown to be related to CVD Cholesterol 1 of the 7 metrics of cardiovascular health is a precursor of T, T can be aromatized into E 2 or reduced into dihydrotestosterone locally in cardiovascular tissues, and the activity of androgens in its turn may depend on the levels of estrogen 16 , 19 , Furthermore, SHBG and other binding proteins play a key role in the activity of sex steroids and SHBG levels strongly depend on adiposity levels 34 , Therefore, it remains elusive whether the observed associations reflect a true relation or an underlying unobserved process.

An important strength of our study is the availability of a large representative population-based sample with detailed information on the cardiometabolic profile for each individual. Furthermore, androgens were measured with liquid chromatography-tandem mass spectrometry, which is currently considered the gold standard method 21 , Our study is the first to focus on the association of E 2 , T, SHBG, and FAI with the new concept of cardiovascular health, instead of merely the presence or absence of cardiovascular risk or disease.

Good cardiovascular health has been related to optimal health in other domains such as better cognition 11 , better psychological status 12 , lower cancer risk 13 , more favorable overall functional status 14 , and lower all-cause mortality 9 , Given the increasing number of studies describing positive effects regarding the combination of several ideal health factors and behaviors for CVD-free survival, overall healthy longevity, quality of life, and the subsequent reduction in health care costs, the overall cardiovascular health approach, in contrast to the individual risk factor approach, comprises growing clinical relevance 3.

However, the limitations of our study also merit attention. Firstly, the cross-sectional design does not allow us to address the temporality of the observed associations. Therefore, we cannot draw any conclusions with regard to the causality of the observations. Nevertheless, the predefined definition of cardiovascular health, which includes both health factors and behaviors, made the application of a longitudinal study design unfeasible, for we would not expect E 2 , T, SHBG, and FAI to directly predict health behaviors such as physical activity or smoking habits.

However, indirect pathways have been described. Studies suggest that the menopausal transition is accompanied by a decrease in energy expenditure mainly due lower physical activity levels , a decrease in food intake, and an increased appetite 48 , Furthermore, health behaviors can also affect levels of E 2 , T, SHBG, and FAI, for example, a healthy diet and exercise can decrease E 2 levels in postmenopausal women 50 and lifestyle factors eg, smoking, diet, and physical activity are associated with SHBG and T changes in men 51 , The relation between body weight and E 2 was bidirectional, although the associations in the direction of body weight predicting levels of E 2 were stronger than the reverse Secondly, all metrics received the same weight eg, a score of 0, 1, or 2 , because the definition of cardiovascular health does not prioritize any metric above the others 3.

In order to give insight in any differential effect of E 2 , T, SHBG, and FAI on health factors and behaviors, a sensitivity analysis separating the 2 was performed and is provided in Supplemental Appendix 1. Thirdly, we performed several number of tests. However, in order to take into account multiple testing, a conservative Bonferroni correction was applied which did not materially change the significance of our findings.

Free T levels were not measured directly in the blood and therefore have to be interpreted with caution. Nevertheless, free T levels in this study were derived from the ratio of T to SHBG, which is considered a precise proxy for bioavailable T Finally, E 2 was measured using an immunoassay with a detection limit of However, the direction of the observed effect remained the same while analyzing E 2 continuously and categorically. Using the concept of cardiovascular health, instead of merely the presence or absence of disease or focus on separate cardiovascular risk factors, allowed us to assess the role of E 2 , T, SHBG, and FAI in the cardiovascular system in a comprehensive manner and the implications may extend beyond the cardiovascular system to other health domains.

To facilitate the development of preventative and treatment strategies, the complexity and temporality of the interrelation between E 2 , T, SHBG, and FAI and the cardiometabolic profile, and the role of body fat distribution in particular, warrants further investigation.

This study was funded by Metagenics, Inc. Disclosure Summary: L. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation.

Volume Article Contents. Materials and Methods. Oxford Academic. Google Scholar. Klodian Dhana. Taulant Muka. Cindy Meun. Jessica C. Kiefte-de Jong. Albert Hofman. Joop S. Oscar H. Maryam Kavousi. Cite Citation. Permissions Icon Permissions. Open in new tab Download slide. Flowchart for selection of study participants. Table 1. Open in new tab. Table 2. Heart disease and stroke statistics— update: a report from the American Heart Association. Search ADS.

Google Preview. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through and beyond.

Lifetime measures of ideal cardiovascular health and their association with subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study. Association of ideal cardiovascular health and calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study.

Ideal cardiovascular health: associations with biomarkers and subclinical disease and impact on incidence of cardiovascular disease in the Framingham Offspring Study. Ideal cardiovascular health predicts lower risks of myocardial infarction, stroke, and vascular death across whites, blacks, and hispanics: the northern Manhattan study. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence.

Ideal cardiovascular health and mortality from all causes and diseases of the circulatory system among adults in the United States. Trends in cardiovascular health metrics and associations with all-cause and CVD mortality among US adults. Cardiovascular health through young adulthood and cognitive functioning in midlife.

Cumulative effect of psychosocial factors in youth on ideal cardiovascular health in adulthood: the Cardiovascular Risk in Young Finns Study.

Ideal cardiovascular health is inversely associated with incident cancer: the Atherosclerosis Risk In Communities study. Ideal cardiovascular health predicts functional status independently of vascular events: the Northern Manhattan Study.

Beneficial and adverse effects of testosterone on the cardiovascular system in men. Sex-hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation SWAN. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms.

Health in middle-aged and elderly women: a conceptual framework for healthy menopause. Androgens may mediate a relative preservation of IGF-I levels in overweight and obese women despite reduced growth hormone secretion.