Visceral obesity,androgens and the risks of cardiovascular disease and diabetes mellitus

The sex difference in cardiovascular morbidity is traditionally ascribed to the effects of testosterone on the lipid profile. Epidemiological studies show, however, that men with cardiovascular disease have low rather than high circulating testosterone. The factor responsible for both the higher prevalence of cardiovascular disease and the low testosterone might be visceral obesity. Men and women differ in their pattern of fat distribution. Women have predominantly gluteofemoral fat depots and men preferential abdominal/visceral depots. In puberty testosterone favors abdominal/visceral fat deposition. Visceral fat has a high metabolic turnover and the free fatty acids drain on the portal vein. With a large visceral fat depot the liver is flooded with free fatty acids inducing high levels of triglycerides and low high-density lipoprotein cholesterol, impairment of insulin metabolism and reducing insulin sensitivity. These factors contribute to the development of cardiovascular disease and diabetes type II. High insulin levels suppress sex hormone-binding globulin thus lowering circulating testosterone. The fat cell produces leptin signalling to the brain to reduce food intake and increase energy expenditure. High leptin levels suppress testosterone. Some studies suggest that testosterone supplementation reduces visceral obesity and improves cardiovascular risks but more evidence is needed.     

Aging androgens and the metabolic syndrome

Objective: To assess the responses of a symptom complex related to partial androgen deficiency in the aging male (PADAM) to androgen supplementation. Subjects and methods: Eighty-six men from five hospitals in Beijing aged 50-70 years with symptoms related to PADAM received oral testosterone undecanoate for 2 months, and the effects of the therapy were evaluated. Results: After treatment, the symptom scores were significantly improved (all p < 0.001). Serum levels of luteinizing hormone and follicle stimulating hormone were suppressed, and free testosterone and albuminbound testosterone levels were elevated. However, they were not significantly different from the pretreatment values. Waist/hip ratio and blood pressure were markedly decreased, but no changes were found in serum levels of total cholesterol, triglyceride, albumin and prostate specific antigen. Conclusions: Two months of treatment with oral testosterone undecanoate clearly improved the symptoms related to PADAM. No statistical relationship was found between symptom improvement and androgen levels. Androgen therapy for 2 months was beneficial to the waist/hip ratio and blood pressure, and no harm was done to the prostate gland or lipid metabolism.     

Androgens, apoE, and Alzheimer's disease

Increasing evidence indicates that there are reductions in estrogen and androgen levels in aged men and women. These hormonal reductions might be risk factors for cognitive impairments and the development of Alzheimer's disease (AD). Aged people show improved cognition after treatments with sex steroids. Therefore, ongoing clinical AD trials have been designed to evaluate the potential benefits of estrogen therapy in women and testosterone therapy in men. Apolipoprotein E (apoE) plays an important role in the metabolism and redistribution of lipoproteins and cholesterol. The three major human apoE isoforms, apoE2, apoE3, and apoE4, differ in their effects on AD risk and pathology. Here I review various mechanisms proposed to mediate the differential effects of apoE isoforms on brain function and highlight the potential contribution of detrimental isoform-dependent effects of apoE on androgen- and androgen receptor (AR)-mediated pathways. I also discuss potential interactions of androgens with other AD-related factors.     

Association of vitamin D status and the risk of cardiovascular disease as assessed by various cardiovascular risk scoring systems in patients with type 2 diabetes mellitus

Objective: The aim of the present study was to evaluate the relationship between vitamin D (25[OH]D) status and the risk of cardiovascular disease as assessed by various cardiovascular risk scoring systems such as QRISK2, BNF, ASSING, SCORE, and Framingham in patients with type 2 diabetes mellitus(T2DM).

Methods: The study included 108 patients with vitamin D insufficiency (25[OH]D?≥?10–30?ng/mL) and 100 patients with vitamin D deficiency (25[OH]D?Results: HbA1c levels were significantly higher in patients with vitamin D deficiency. Patients with vitamin D deficiency had significantly higher Framingham risk score (p?p?r?=?0.537) and a weak but statistically significant correlation between 25[OH]D levels and BNF score (r?=?0.295). 25[OH]D levels were significantly higher and HbA1c levels were significantly lower in patients with Framingham cardiovascular risk score ≤10%.

Conclusion: We found a close relationship with Framingham cardiovascular risk score in diabetic patients with very low serum vitamin D levels. Cardiovascular risk as assessed by the Framingham’s scale increases with decreasing 25[OH]D levels. BNF score was negatively correlated with 25[OH]D levels.     

Diagnosis,pathogenesis and treatment of erectile dysfunction

Introduction: After middle age, some men show androgen-deficiency symptoms leading to so-called PADAM (partial androgen deficiency in aging males). We tested the oral form of testosterone, testosterone undecanoate (Andriol^®, NV Organon, The Netherlands), in men with PADAM and evaluated its efficacy and safety in Korean male patients. Methods: We included those patients with the clinical symptoms of PADAM who had decreased levels of serum total testosterone (< 2.8 ng/ml) or free testosterone (< 13 pg/ml). We excluded patients with biopsy-confirmed prostrate cancer, abnormal findings in digital rectal examination or prostate specific antigen testing (until prostrate cancer was ruled out), breast cancer, severe voiding symptoms and secondary hypogonadism. At the first visit, the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) and Korean Andropause Questionnaires were administered; complete blood count, the lipid profile, and levels of total and free testosterone, prolactin, luteinizing hormone, follicle stimulating hormone and prostate specific antigen were measured and a digital rectal examination was given. Patients were administered oral testosterone undecanoate 160 mg daily for 3 weeks. The dosage was then decreased to 80 mg daily and changes in symptoms were assessed at every visit. After 3 months, serum tests, including testosterone, were repeated. Results: We evaluated 28 patients who had received testosterone undecanoate for more than 3 months. The patients' mean age was 56.1 (48-68) years. The score of the Korean Andropause Questionnaire changed from 56.2 ± 21.7 at baseline to 52.9 ± 21.3 (p = 0.03) after 3 weeks, to 49.3 ± 19.3 (p = 0.03) after 8 weeks, and to 46.5 ± 25.6 (p = 0.028) after 12 weeks. With respect to sexual function, mean IIEF scores were 37.2 ± 19.6 at baseline and 38.7 ± 19.2 and 40.2 ± 22.0 (p = 0.033) after 3 and 12 weeks, respectively. Serum total testosterone increased from 2.13 ± 1.20 ng/ml at baseline to 6.04 ± 3.08 ng/ml (p = 0.005) after 12 weeks, and free testosterone was marginally significantly changed from 8.60 ± 2.25 pg/ml to 11.40 ± 3.81 pg/ml (p = 0.13). However, there were no significant changes in liver function tests, red blood cell count or lipid profiles. There were no significant adverse reactions that led to the cessation of the administration of oral testosterone. Conclusion: Oral administration of testosterone undecanoate can improve symptoms of PADAM in Koreans. It may, therefore, be an appropriate treatment option with few adverse effects for PADAM patients.     

Age related testosterone level changes and male andropause syndrome

Reproduced with permission     

Work stressors and cardiovascular disease

Over the past 20 years, an extensive body of research evidence has documented that psychosocial work stressors are risk factors for hypertension and cardiovascular disease. These stressors, which appear to be increasing in prevalence, include job strain (the combination of psychological job demands and low job control), imbalance between job efforts and rewards, threat-avoidant vigilant work, and long work hours. This article reviews the evidence linking these stressors with hypertension and CVD, and the physiological and social psychological mechanisms underlying the associations. Also described are methods for measuring work stressors and new, more accurate techniques for measuring blood pressure. Finally, strategies for reducing work stressors and preventing hypertension and CVD are reviewed. These include clinical assessment, worksite health promotion, work organization interventions, legal approaches and work site surveillance.     

Practical consequences of the validation of a mathematical model in assessment of partial androgen deficiency in the aging male using bioavailable testosterone

Partial androgen deficiency or the andropause in the aging male is a complex clinical and biochemical entity that needs to be analyzed at two levels of the constituent structure: the 'deep structure' should come to light with more intensive research, while the 'surface structure' holds the attention of investigators who focus on hormone measurements in the blood to help diagnose the andropause. In this study, it is recognized that bioavailable testosterone decreases progressively during the aging process. This physiological decline may be so important, or so close to castration levels, that aged men may experience numerous symptoms of hypogonadism. The assay for bioavailable testosterone was indirectly validated with a set of equations derived from our knowledge of the law of mass action at equilibrium, as proposed by Vermeulen and colleagues in 1999. With this mathematical model, we have shown that calculated free testosterone was highly correlated with bioavailable testosterone. It is therefore concluded that the evaluation of aged men's androgenicity should rely on at least one of these free testosterone assessments (bioavailable or calculated free testosterone) for the sake of reproducibility in the construction of the 'surface structure' of the andropause in the coming years.     

Homocysteine, menopause and cardiovascular disease

A high plasma concentration of total homocysteine (tHcy) and a deficiency of vitamins related to its metabolism, such as vitamin B12 and folate, have been associated with cardiovascular disease. Postmenopausal women have higher concentrations than age-matched premenopausal women, and plasma concentrations of homocysteine in postmenopausal women taking hormone replacement therapy are significantly lower than they are in those who do not take estrogen supplements. Because of the possible mixed effects of HRT on cardiovascular events, surrogate end-points must be evaluated with caution. While measuring homocysteine levels is relatively simple, evidence from well designed trials is awaited before population screening can be advocated. Also, the benefits of reducing homocysteine levels with folic acid and vitamin B6 and B12 supplements are highly debated.     

A paradigm shift: from disease to health orientation

The history of science has been described as ‘paradigm shifts’ of sequential overthrow, each new paradigm replacing the previous one. A paradigm is an overarching view-point which guides the articulation of theories and other activities in a particular field. In the exploration of health, two different types of approach can be identified. The pathogenic view, which has dominated the orientation of medicine over the last hundred years, focuses on disease states and underlying factors that modify the chances of entering into one of those states. The competing salutogenic view appears to be undergoing a renaissance in the new strategies of public health and health promotion, and producing theories of health based on more holistic approaches and diverse methods. The two paradigms exist side by side, and both are in a constant state of flux. The advocates of the health-oriented paradigm say it is difficult to reach a true, in-depth understanding of human health on the basis of a disease-oriented approach or from the traditional vantage-point of risk-factor epidemiology, whereas opponents point out that health does not lend itself to exact measurements or experimentation in keeping with the Galilean natural science ideal. The importance and utility of health orientation need to be explored and ascertained in further research. The approach seems, however, to have a number of crucial assets that might help avoid the limitations of the established disease and risk-factor epidemiology approaches and promote new directions of pursuit, including a better understanding of the complex relationships between aging and health, and other current challenges in creating healthy public policy.

This paper was presented at the Second International Workshop on the Aging Male, Weimar, Germany, November 1999     

Erectile dysfunction,loss of libido and low sexual frequency increase the risk of cardiovascular disease in men with low testosterone

Introduction: Testosterone deficiency increases the cardiovascular disease (CVD) risk.

Aim: To evaluate the effect of erectile dysfunction (ED), sexual frequency and hypogonadal symptoms on CVD risk.

Methods: A total of 395 hypogonadal men aged 45–74 years were surveyed using the Androgen Deficiency in the Aging Male and the International Index of Erectile Function.

Main outcome measures: The 10-year CVD risk was measured with the Framingham Risk Score. Logistic regression was performed to obtain the odds ratios of sexual function and hypogonadal symptoms for a 10-year CVD risk ≥20% (high risk).

Results: The mean age was 56.1?±?6.7 years. The mean 10-year CVD risk of the whole cohort was 18.1%?±?11.4%, while 131 subjects (33.2%) were classified as high risk. Logistic regression revealed that ED severity was associated with CVD risk [OR?=?2.37 (CI 1.24–4.51) for mild-to-moderate ED, OR?=?4.39 (1.78–8.43) for moderate ED and OR?=?12.81 (4.65–26.11) for severe ED]. Compared to sexual frequency <1 per month, sexual frequency?≥4 decreased the risk of high CVD risk [OR?=?0.35 (0.23–0.780)]. Loss of libido [OR?=?2.95 (1.91–4.12)] and less strong erection [OR?=?3.87 (CI 2.11–4.95)] increased the risk of high CVD risk. All remained significant after adjustment for age and testosterone.

Conclusions: ED, decreased sexual frequency and loss of libido predict a high 10-year CVD risk in hypogonadal men.     

Increase in the prevalence of metabolic syndrome among workers according to age

Androgen levels decline over a man's lifetime. In a proportion of men (increasing with age), levels fall below values that have been established by conventional laboratory criteria as indicative of hypogonadism. Testosterone has a wide range of non-reproductive actions: it preserves bone and muscle mass, it acts on non-sexual mental functioning and it stimulates red blood cell formation. Long-term androgen deficiency has a great impact on quality of life. The first intervention studies provide indications that androgen treatment of men with true androgen deficiency is helpful. Obviously, only men who are testosterone-deficient will benefit from androgen supplementation. The diag nosis of testosterone deficiency in old age is not unambiguous. Signs and symptoms of aging sometimes clinically overlap with those of testosterone deficiency. The groups that are at higher risk of testosterone deficiency are those men with disease (pulmonary disease, gastrointestinal disease, rheumatoid disease, etc.). Usually, sex hormone binding globulin levels increase with aging, leading to lower levels of free, biologically available testosterone. For the time being, arbitrary criteria for testosterone deficiency in aging men have to be adopted. The best practical approach is to calculate the free testosterone level. The calculation can be found at www.issam.ch under 'Tools'.     

Diagnosis of cardiovascular disease in women

Cardiovascular disease (CVD, comprising coronary heart disease and stroke) is the leading cause of death in both sexes in developed countries. Although women are nine times more likely to die from CVD than they are from breast cancer, there is a general public belief that the most common cause of death is cancer. The symptoms of acute myocardial infarction and acute coronary syndromes differ between the sexes. Women are less likely to experience chest pain and may have non-specific symptoms. Normal or non-obstructive coronary disease, as detected by angiography, is more common in women. Scintigraphy improves the detection of coronary disease in women. There is an urgent need to increase awareness of both coronary heart disease in women and the limitations of commonly used diagnostic tools.     

Rural-urban differences in college students’ cardiovascular risk perceptions

Abstract

Objective: To examine rural-urban differences in college students’ cardiovascular risk perceptions. Participants: College students in rural (n?=?61) and urban (n?=?57) Kentucky counties were recruited from November 2012 to May 2014. Methods: This was a secondary data analysis of a cross-sectional study examining rural-urban differences in cardiovascular risk factors. Students rated their risk for developing high blood pressure, diabetes, high cholesterol, heart disease, having a stroke, and gaining excess weight. Chi-square and logistic regression were used for data analysis. Results: Rural students had lower odds of perceived high risk for developing high blood pressure compared to urban students (odds ratio (OR): 0.32, 95% CI: 0.11–0.96) after adjusting for race, sex, and body mass index. This association was not observed after adjusting for healthcare access variables. No other significant differences were observed. Conclusions: Efforts to raise perceived risk for developing hypertension among rural college students may be warranted.     

Heart checks in college-aged students link poor sleep to cardiovascular risk

Objective: To describe the relationships between the cardiovascular health, lifestyle behaviors, and lifestyle beliefs among college-aged students.

Participants: Seven hundred and twenty-nine college-aged students participated between October 2016 and April 2017.

Methods: Heart checks, consisting of a cross-sectional survey and biometric screening, were conducted on a large Midwestern university campus.

Results: A small proportion of students (24.5%) engaged in the recommended 150+ minutes of physical activity per week and 7.9% consumed 5+ servings of fruit/vegetables daily. Half (49.6%) slept 7 hours or less per night. Biometric screenings found that 26.4% of the students had high stress, 31.9% were overweight or obese, and 17.3% had prehypertension or hypertension. Less sleep was significantly associated with higher risks of being stressed, being overweight/obese, and having elevated blood pressure.

Conclusions: Early detection, treatment, and education is critical to identify individuals at risk for cardiovascular disease and to promote healthy lifestyle changes before heart disease develops or progresses.     

Sexual Function in Postmenopausal Women and Serum Androgens: A Review Article

Abstract

Objectives: This study aimed to narratively summarize the effects of serum androgens on sexual function of postmenopausal women and the impact of administration of various types of androgens in improving the sexual function of these women. Methods: After searching for articles indexed in various databases, a total of 59 studies were selected. Results: There appears to be a great deal of controversy regarding the relationship between androgens and sexual function and the beneficiary effect of androgens therapy. Conclusions: Androgens may affect sexual function; however, androgen therapy, as an option for improving sexual function in menopause, needs further research.