Testosterone and Cardiovascular Risk in Men

Dm, Kelly; Jones, T. H.

doi:10.1159/000360553

Cited by 41 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While testosterone was previously reported to improve insulin sensitivity, lower visceral adiposity and exert vasodilatory effects ( 51 ), clinical and animal research on the role of testosterone in atherosclerosis and related cardiovascular health remains inconclusive and rather contradictory ( 52 , 53 ). For instance, multiple epidemiological studies suggest that testosterone deficiency may attribute to an increased incidence of adverse cardiovascular events ( 54 – 56 ). Congruently, animal studies using atherosclerotic murine models have shown that testosterone can retard atherogenesis ( 57 , 58 ), possibly via its conversion to cardioprotective estradiol in the vessel wall.…”

Section: Discussionmentioning

confidence: 99%

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice

Gupta

Khanal

Bhavnani

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

IntroductionMetabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression.MethodsMale and female KKAy+/−ApoE–/– (with ectopic agouti gene expression) and age-matched non-agouti KKAy–/–ApoE–/– littermates were placed on a standard laboratory diet from 4 to 24 weeks age followed by blood and tissue harvests for biochemical, molecular, and aortic root morphometric studies.ResultsMetabolic profiling confirmed MetS phenotype of KKAy+/−ApoE–/–; however, only male genotypes were glucose intolerant with elevated VLDL-cholesterol and VLDL-triglyceride levels. Aortic root morphometry demonstrated profound lipid-filled lesions, increased plaque area, and augmented inflammatory and SMC abundance in MetS vs non-MetS males. This increase in lesion burden was accompanied with elevated TSP-1 and attenuated LMOD-1 (SM contractile marker) and SRF (transcriptional activator of SM differentiation) expression in male MetS aortic vessels. In contrast, while lipid burden, plaque area, and TSP-1 expression increased in MetS and non-MetS female mice, there was no significant difference between these genotypes. Increased collagen content was noted in MetS and non-MetS genotypes, specific to female mice. Measurement of plasma testosterone revealed a link between the atherogenic phenotype and abnormally high or low testosterone levels. To interrogate whether TSP-1 plays a direct role in SMC de-differentiation in MetS, we generated KKAy+/− mice with and without global TSP-1 deletion. Immunoblotting showed increased SM contractile markers in male KKAy+/−TSP-1–/– aortic vessels vs male KKAy+/−TSP-1+/ +. In contrast, TSP-1 deletion had no effect on SM contractile marker expression in female genotypes.ConclusionTogether, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice

Gupta

Khanal

Bhavnani

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…When adjusting for age, race/ethnicity, and MESA field site (model 1) we found that total T [percent difference 9% (95% CI, 2, 15)], free T [26% (19, 34)], bio T [19% (12,26)], and E2 [10% (3,17)] all had positive associations with leptin levels, while SHBG [−21% (−26, −17)] had an inverse association. However, after further adjusting for smoking, BMI, education, physical activity, and current use of hormone therapy (model 2a), only the positive association of E2 [7% (1,14)], and the inverse association of SHBG [−6% (−11, 0)], with leptin remained statistically significant.…”

Section: Leptinmentioning

confidence: 97%

“…Total T [6% (2, 11)], SHBG [7% (3,12)], and T/E2 ratio [6% (2, 20)] had a positive relationship with adiponectin, while free T [−7% (−11, −2)] had an inverse relationship in the fully adjusted model (model 3), adjusted for CVD risk factors.…”

Section: Adiponectinmentioning

confidence: 99%

See 1 more Smart Citation

Associations between endogenous sex hormone levels and adipokine levels in the Multi-Ethnic Study of Atherosclerosis

Varma¹,

Ogunmoroti²,

Ndumele³

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundDifferences in sex hormone levels contribute to differences in cardiovascular disease (CVD) risk. Adipokines play a role in cardiometabolic pathways and have differing associations with CVD. Adipokine levels differ by sex; however, the association between sex hormone profiles and adipokines is not well established. We hypothesized that a more androgenic sex hormone profile would be associated with higher leptin and resistin and lower adiponectin levels among postmenopausal women, with the opposite associations in men.MethodsWe performed an analysis of 1,811 adults in the Multi-Ethnic Study of Atherosclerosis who had both sex hormones and adipokines measured an average of 2.6 years apart. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone (DHEA)] were measured at exam 1; free T was estimated. Serum adipokines (leptin, resistin, adiponectin) were measured at exams 2 or 3. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines.ResultsThe mean (SD) age was 63 (10) years, 48% were women; 59% non-White participants. For leptin, after adjusting for demographics only, higher free T and lower SHBG, were associated with higher leptin in women; this association was attenuated after further covariate adjustment. However in men, higher free T and lower SHBG were associated with greater leptin levels in fully adjusted models. For adiponectin, lower free T and higher SHBG were associated with greater adiponectin in both women and men after adjustment for CVD risk factors. For resistin, no significant association was found women, but an inverse association with total T and bioT was seen in men.ConclusionOverall, these results further suggest a more androgenic sex profile (higher free T and lower SHBG) is associated with a less favorable adipokine pattern. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines, and CVD risk.

show abstract

“…Likewise, low T levels have been associated with arterial calcifications, cardiovascular risk and mortality both in the general population and in men with CKD (Travison et al, 2016;Yilmaz et al, 2011). Although the connection between TRT and cardiovascular risk remains a controversial topic, adequately treating hypogonadal men achieving mid-normal range levels of T does not seem to increase cardiovascular risk or mortality (Gagliano-Jucá & Basaria, 2019;Kelly & Jones, 2014). Taken together, these findings suggest a possible link between androgens and the bonevascular axis in men with CKD.…”

Section: Introductionmentioning

confidence: 98%

Androgen therapy does not prevent bone loss and arterial calcifications in male rats with chronic kidney disease

David

Dubois

Verhulst

et al. 2023

Journal of Endocrinology

View full text Add to dashboard Cite

Patients suffering from chronic kidney disease (CKD) often experience bone loss and arterial calcifications. It is unclear if hypogonadism contributes to the development of these complications, and whether androgen therapy might prevent them. Male adult rats were randomized into 4 groups. The first group received standard chow (Control), while three other groups were fed a 0.25% adenine/low vitamin K diet (CKD). Two CKD groups were treated with testosterone (T) or dihydrotestosterone (DHT), whereas the control group and one CKD group received vehicle (VEH). CKD animals had 10-fold higher serum creatinine and more than 15-fold higher PTH-levels compared to controls. Serum T levels were more than 2-fold lower in the CKD-VEH group compared to Control-VEH and CKD-T groups. Seminal vesicle weight was reduced by 50% in CKD-VEH animals, and restored by T and DHT. CKD animals showed a low bone mass phenotype with decreased trabecular bone volume fraction and increased cortical porosity, which was not rescued by androgen treatment. Aortic calcification was much more prominent in CKD animals and not unequivocally prevented by androgens. Messenger RNA expression of the androgen receptor-responsive genes Acta1 and Col1a1 was reduced by CKD and stimulated by androgen treatment in levator ani muscle, but not in bone or aortic tissue. We conclude that adenine-induced CKD results in the development of hypogonadism in male rats. Androgen therapy is effective in restoring serum T levels and androgen-sensitive organ weights, but does not prevent bone loss or arterial calcifications, at least not in the presence of severe hyperparathyroidism.

show abstract

Testosterone and Cardiovascular Risk in Men

Cited by 41 publications

References 26 publications

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice

Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice

Associations between endogenous sex hormone levels and adipokine levels in the Multi-Ethnic Study of Atherosclerosis

Androgen therapy does not prevent bone loss and arterial calcifications in male rats with chronic kidney disease

Contact Info

Product

Resources

About