Macronutrient intakes and serum oestrogen, and interaction with polymorphisms in CYP19A1 and HSD17B1 genes: a cross-sectional study in postmenopausal Japanese women.

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.

Predictors and correlates of serum 25-hydroxyvitamin D concentrations in young women: results from the Safe-D study.

Vitamin D deficiency is a global public health concern. Studies of serum 25-hydroxyvitamin D (25(OH)D) determinants in young women are limited and few include objective covariates. Our aims were to define the prevalence of vitamin D deficiency and examine serum 25(OH)D correlates in an exploratory study of women aged 16-25 years. We studied 348 healthy females living in Victoria, Australia, recruited through Facebook. Data collected included serum 25(OH)D assayed by liquid chromatography-tandem MS, relevant serum biochemistry, soft tissue composition by dual-energy X-ray absorptiometry, skin melanin density, Fitzpatrick skin type, sun exposure using UV dosimeters and lifestyle factors. Mean serum 25(OH)D was 68 (sd 27) nmol/l and 26 % were vitamin D deficient (25(OH)D 2 h in the sun in summer daily, holidaying in the most recent summer period, serum Fe levels, height and multivitamin use were positively associated with 25(OH)D. Fat mass and a blood draw in any season except summer was inversely associated with 25(OH)D. Vitamin D deficiency is common in young women. Factors such as hormonal contraception, sun exposure and sun-related attitudes, as well as dietary supplement use are essential to consider when assessing vitamin D status. Further investigation into methods to safely optimise vitamin D status and to improve understanding of the impact of vitamin D status on long-term health outcomes is required.

The association of sex-specific hormones with coronary artery plaque characteristics from Miami Heart (MiHeart) study.

Objective: The association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD). Methods: In this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men. Results: Of the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n = 1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76-0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72-0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07-11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP. Conclusion: Among young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.

Are epigenetic mechanisms and nutrition effective in male and female infertility?

This review discusses epigenetic mechanisms and the relationship of infertility in men and women in relation to parameters pertaining to nutrition. The prevalence of infertility worldwide is 8-12 %, and one out of every eight couples receives medical treatment. Epigenetic mechanisms, aging, environmental factors, dietary energy and nutrients and non-nutrient compounds; more or less energy intake, and methionine come into play in the occurrence of infertility. It also interacts with vitamins B12, D and B6, biotin, choline, selenium, zinc, folic acid, resveratrol, quercetin and similar factors. To understand the molecular mechanisms regulating the expression of genes that affect infertility, the environment, the role of genotype, age, health, nutrition and changes in the individual's epigenotype must first be considered. This will pave the way for the identification of the unknown causes of infertility. Insufficient or excessive intake of energy and certain macro and micronutrients may contribute to the occurrence of infertility as well. In addition, it is reported that 5-10 % of body weight loss, moderate physical activity and nutritional interventions for improvement in insulin sensitivity contribute to the development of fertility. Processes that pertain to epigenetics carry alterations which are inherited yet not encoded via the DNA sequence. Nutrition is believed to have an impact over the epigenetic mechanisms which are effective in the pathogenesis of several diseases like infertility. Epigenetic mechanisms of individuals with infertility are different from healthy individuals. Infertility is associated with epigenetic mechanisms, nutrients, bioactive components and numerous other factors.

Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions.

Cirrhosis predisposes to abnormalities in energy, hormonal, and immunological homeostasis. Disturbances in these metabolic processes create susceptibility to sarcopenia or pathological muscle wasting. Sarcopenia is prevalent in cirrhosis and its presence portends significant adverse outcomes including the length of hospital stay, infectious complications, and mortality. This highlights the importance of identification of at-risk individuals with early nutritional, therapeutic and physical therapy intervention. This manuscript summarizes literature relevant to sarcopenia in cirrhosis, describes current knowledge, and elucidates possible future directions.

Association Between Dietary Inflammatory Index and Sex Hormone Binding Globulin and Sex Hormone in U.S. Adult Females.

Context: It is still unknown whether the dietary inflammatory index (DII) is associated with sex hormones and sex hormone binding globulin (SHBG) in adult women. Objective: This study examined the association between DII and sex hormones and SHBG in U.S. adult women. Design and Participants: This was a cross-sectional study. A total of 2,092 female participants (age ≥ 20) from the 2013-2016 National Health and Nutrition Examination Survey were enrolled. Dietary inflammatory potential was assessed by DII based on 24-h dietary recall. SHBG was assessed using immuno-antibodies and chemo-luminescence, whereas sex hormones were measured by ID-LC-MS/MS. Results: The average DII was 0.21 ± 1.68, ranging from -4.54 (most anti-inflammatory) to 4.28 (most pro-inflammatory). After adjusting all covariates, a per-unit DII increase in DII tertile 3 was related to an 8.05 nmol/L SHBG decrease compared to DII tertile 1 (P = 0.0366). Subgroup analysis stratified by perimenopausal period found that this negative association remained strong but only existed in women before (ß = -3.71, 95% CI: -7.43, -0.12, P = 0.0423) the perimenopausal period. Interaction terms were added to both subgroup analyses and found no significant heterogeneity among different body mass index (BMI) or perimenopausal groups (P > 0.05). Treshold analyses showed that the association of age with SHBG was an inverted U-shaped curve (inflection point: age = 50 yrs). Conclusion: A proinflammatory diet caused decreased SHBG. However, more well-designed studies are still needed to validate and verify the causal relationship between DII and sex hormones and SHBG.

Androgen deprivation therapy and risk of cognitive dysfunction in men with prostate cancer: is there a possible link?

The expansion of the indication to use androgen deprivation therapy (ADT) to treat patients with advanced or metastatic prostate cancer has dramatically increased over the recent decades, resulting in the progress of patients' survival. However, chronic health implications can become more apparent as the number of long-term cancer survivors is expected to be increased along with the adverse effect of ADT. In particular, interest in investigating ADT, especially luteinizing hormone-releasing hormone (LHRH) agonist association with cognitive dysfunction has been growing. Previous studies in animals and humans suggest that the level of androgen decreases with age and that cognitive decline occurs with decreases in androgen. Correspondingly, some of the extensive studies using common neurocognitive tests have shown that LHRH agonists may affect specific domains of cognitive function (e.g., visuospatial abilities and executive function). However, the results from these studies have not consistently demonstrated the association because of its intrinsic limitations. Large-scale studies based on electronic databases have also failed to show consistent results to make decisive conclusions because of its heterogeneity, complexity of covariates, and possible risk of biases. Thus, this review article summarizes key findings and discusses the results of several studies investigating the ADT association with cognitive dysfunction and risk of dementia from various perspectives.

Investigation of Specific Proteins Related to Different Types of Coronary Atherosclerosis.

Objective: Coronary heart disease (CHD) is a complex disease caused by multifaceted interaction between genetic and environmental factors, which makes identification of the most likely disease candidate proteins and their associated risk markers a big challenge. Atherosclerosis is presented by a broad spectrum of heart diseases, including stable coronary artery disease (SCAD) and acute myocardial infarction (AMI), which is the progressive stage of SCAD. As such, the correct and prompt diagnosis of atherosclerosis turns into imperative for precise and prompt disease diagnosis, treatment and prognosis. Methods: The current work aims to look for specific protein markers for differential diagnosis of coronary atherosclerosis. Thirty male patients between 45 and 55 years diagnosed with atherosclerosis were analyzed by tandem mass tag (TMT) mass spectrometry. The study excluded those who were additionally diagnosed with hypertension and type 1 and 2 diabetes. The Mufuzz analysis was applied to select target proteins for precise and prompt diagnosis of atherosclerosis, most of which were most related to high lipid metabolism. The parallel reaction monitoring (PRM) was used to verify the selected target proteins. Finally, The receiver operating characteristic curve (ROC) was calculated by a random forest experiment. Results: One thousand one hundred and forty seven proteins were identified in the TMT mass spectrometry, 907 of which were quantifiable. In the PRM study, six proteins related to lipid metabolism pathway were selected for verification and they were ALB, SHBG, APOC2, APOC3, APOC4, SAA4. Conclusion: Through the detected specific changes in these six proteins, our results provide accuracy in atherosclerosis patients' diagnosis, especially in cases with varying types of the disease.

Continuous reference intervals for pediatric testosterone, sex hormone binding globulin and free testosterone using quantile regression.

Testosterone (T), sex hormone binding globulin (SHBG), free testosterone (FT) and bioavailable testosterone (BAT) are commonly employed tests in pediatric endocrinology and all require age-dependent reference intervals for interpretation. The common methods used to derive these reference intervals require decisions about data shape and/or age partition thresholds, which can result in sharp differences between age groups, particularly for pubescent children. Partitioning also results in a form of data loss, where data from one age-bin is completed disconnected from the adjacent age-bins. Non-parametric continuous reference intervals methods have previously been developed to avoid some of these drawbacks. These strategies use all the available data and smooth transitions between ages avoiding partitioning. However, the fitting process involves selection and adjustment of many parameters and it can be difficult to maintain a reproducible approach. Here we provide a workflow for non-parametric continuous reference intervals applied to T, FT, BAT, and SHBG using the R language quantregGrowth package. T measurements were determined by LC-MS/MS, FT and BAT were calculated, and SHBG was measured on the Roche Cobas e601. The continuous interval methodology is described in detail with code examples and illustrations for reproducibility.

Raloxifene augmentation in men and women with a schizophrenia spectrum disorder: A study protocol.

Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.

Systematic review of hormone replacement therapy in the infertile man.

OBJECTIVES: To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve their fertility potential, as testosterone replacement therapy (TRT) inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age. MATERIALS AND METHODS: We performed a comprehensive literature review for the years 1978-2017 via PubMed. Also abstracts from major urological/surgical conferences were reviewed. Review was consistent with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) criteria. We used Medical Subject Heading terms for the search including 'testosterone replacement therapy' or 'TRT' and 'male infertility'. RESULTS: In all, 91 manuscripts were screened and the final number used for the review was 56. All studies included were performed in adults, were written in English and had an abstract available. CONCLUSIONS: Exogenous testosterone inhibits spermatogenesis. Hypogonadal men wanting to preserve their fertility and at the same time benefiting from TRT effects can be prescribed selective oestrogen receptor modulators or testosterone plus low-dose human chorionic gonadotrophin (hCG). Patients treated for infertility with hypogonadotrophic hypogonadism can be prescribed hCG alone at first followed by or in combination from the start with follicle-stimulating hormone preparations.

Influence of peroxisome proliferator-activated receptor-γ exon 2 and exon 6 and insulin receptor substrate (IRS)-1 Gly972Arg polymorphisms on insulin resistance and beta-cell function in southern mediterranean women with polycystic ovary syndrome.

BACKGROUND AND OBJECTIVE: The Pro12Ala (exon 2) and His447His (exon 6) polymorphisms of PPAR-γ, and Gly972Arg polymorphism of IRS-1 have been implicated in insulin resistance (IR) and adiposity. Our aim was to investigate the influence of these polymorphisms on metabolic features of polycystic ovary syndrome (PCOS). METHODS: Fifty-three PCOS women and 26 control women underwent a clinical and biochemical evaluation, including a 75-g oral glucose tolerance test. Insulin secretion and insulin sensitivity indices were calculated. RESULTS: Frequencies of PPAR-γ polymorphisms did not differ from those predicted by the Hardy-Weinberg equilibrium. Instead, the IRS-1 Gly972Arg allele was significantly more frequent in the PCOS group compared to controls. The most frequent allelic combinations were IRS1+/exon2-/exon6- (which prevailed in PCOS) and IRS-1-/exon2-/exon6- (which prevailed in controls). Among PCOS women, compared with the wild type patients, carriers of the Gly972Arg IRS-1 allele had lower E2 levels, while carriers of the Pro12Ala PPAR-γ (exon 2) allele had lower free testosterone levels. No other significant relationships were noted. When compared with the wild type, in PCOS group IR and beta-cell function were: (i) trendwise greater in carriers of the variant IRS-1 allele; (ii) trendwise lower in carriers of the variant PPAR-γ exon 6 allele; (iii) significantly lower in carriers of the variant PPAR-γ exon 2 allele. CONCLUSIONS: Our data support the protective influence of PPAR-γ-exon 2 and exon 6 variants on IR and beta cell function, whereas IRS-1 polymorphism is associated with an unfavorable metabolic profile. However, these associations do not fully explain the high metabolic risk associated with PCOS.

Sex hormones and quantitative ultrasound parameters at the heel in men and women from the general population.

PURPOSE/INTRODUCTION: The present study investigates potential associations between liquid chromatography-mass spectrometry (LC-MS) measured sex hormones, dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG) and bone ultrasound parameters at the heel in men and women from the general population. METHODS: Data from 502 women and 425 men from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Cross-sectional associations of sex hormones including testosterone (TT), calculated free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), androstenedione (ASD), estrone (E1) and SHBG with quantitative ultrasound (QUS) parameters at the heel, including broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were examined by analysis of variance (ANOVA) and multivariable quantile regression models. RESULTS: Multivariable regression analysis showed a sex-specific inverse association of DHEAS with SI in men (Beta per SI unit = - 3.08, standard error (SE) = 0.88), but not in women (Beta = - 0.01, SE = 2.09). Furthermore, FT was positively associated with BUA in men (Beta per BUA unit = 29.0, SE = 10.1). None of the other sex hormones (ASD, E1) or SHBG was associated with QUS parameters after multivariable adjustment. CONCLUSIONS: This cross-sectional population-based study revealed independent associations of DHEAS and FT with QUS parameters in men, suggesting a potential influence on male bone metabolism. The predictive role of DHEAS and FT as a marker for osteoporosis in men warrants further investigation in clinical trials and large-scale observational studies.

Up-regulation of selenoprotein P and HIP/PAP mRNAs in hepatocytes by intermittent hypoxia via down-regulation of miR-203.

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for insulin resistance/type 2 diabetes. However, the mechanisms linking IH stress and insulin resistance remain elusive. We exposed human hepatocytes (JHH5, JHH7, and HepG2) to experimental IH or normoxia for 24 h, measured mRNA levels by real-time reverse transcription polymerase chain reaction (RT-PCR), and found that IH significantly increased the mRNA levels of selenoprotein P (SELENOP) - a hepatokine - and hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) - one of REG (Regenerating gene) family. We next investigated promoter activities of both genes and discovered that they were not increased by IH. On the other hand, a target mRNA search of micro RNA (miRNA) revealed that both mRNAs have a potential target sequence for miR-203. The miR-203 level of IH-treated cells was significantly lower than that of normoxia-treated cells. Thus, we introduced miR-203 inhibitor and a non-specific control RNA (miR-203 inhibitor NC) into HepG2 cells and measured the mRNA levels of SELENOP and HIP/PAP. The IH-induced expression of SELENOP and HIP/PAP was abolished by the introduction of miR-203 inhibitor but not by miR-203 inhibitor NC. These results demonstrate that IH stress up-regulates the levels of SELENOP in human hepatocytes to accelerate insulin resistance and up-regulates the levels of HIP/PAP mRNAs to proliferate such hepatocytes, via the miR-203 mediated mechanism.

Normal menstrual cycle steroid hormones variation does not affect the blood levels of total adiponectin and its multimer forms.

OBJECTIVE: Plasma total adiponectin reveals a sexual dimorphism indicating that gonadal steroids may be involved in its secretion and/or metabolism. However, results from previous reports are conflicting and data regarding the influence of ovarian steroids on adiponectin's multimer forms are scarce. The objective of the study was to assess if total adiponectin and its isoforms are affected by the changes of estradiol and progesterone during the normal menstrual cycle and the association of total adiponectin and its isoforms with the gonadal steroid levels. MATERIALS/METHODS: Quantitative determination of plasma adiponectin and its multimers was conducted in the three phases of an ovulatory cycle in 13 premenopausal women, in the follicular phase of 10 more premenopausal women, in 20 postmenopausal women and in 21 men. Moreover, serum levels of FSH, LH, prolactin, estradiol, progesterone, and testosterone, sex hormone binding globulin, glucose, and insulin were measured. RESULTS: The circulating levels of total adiponectin and its multimers were not affected by the normal variation of estradiol and progesterone across the ovulatory menstrual cycle. In the whole number of participants, the total adiponectin and high molecular weight adiponectin levels were significantly different between genders and associated positively with age and sex hormone binding globulin levels, and negatively with testosterone and progesterone levels and the waist/hip ratio. In the multiple logistic regression analysis, after adjustment for age, gender, and sex hormone binding globulin and progesterone levels, significant predictors of total adiponectin levels were the waist/hip ratio and testosterone levels, and of high molecular weight adiponectin the testosterone levels. CONCLUSIONS: Normal menstrual cycle ovarian steroids are not involved directly in the regulation of secretion and/or metabolism of total adiponectin and its multimers. Testosterone seems to be responsible for the adiponectin's sexual dimorphism.

Is there a relationship between the severity of erectile dysfunction and the comorbidity profile in men with late onset hypogonadism?

OBJECTIVE: To determine whether the severity of erectile dysfunction (ED) in a man diagnosed with late-onset hypogonadism (LOH) gives information about his metabolic syndrome state, as patients with LOH often have sexual symptoms and associated cardiovascular and metabolic comorbidities, but the role of ED in predicting the prevalence of comorbid disease in men with low levels of testosterone is currently unknown. PATIENTS AND METHODS: Men (130) diagnosed with LOH and fulfilling the criteria of a total testosterone level of <3.5 ng/mL (<12 nmol/L), and with an erectile function domain score of <21 on the International Index of Erectile Function questionnaire (IIEF, questions 1-5), were enrolled for a subsequent trial of supplementation with testosterone undecanoate. Demographic data were recorded at baseline. The men completed three standardised questionnaires to assess sexual health, including the International Prostate Symptom Score, Ageing Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by the severity of ED, with SHIM scores of 1-7 considered severe, 8-11 moderate, and 12-16 mild to moderate. Levels of serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density and low-density lipoprotein) were assessed, along with plasma fasting glucose and glycated haemoglobin (HbA1c) levels. Body weight, body mass index and waist circumference were also recorded. RESULTS: There was a significant association between the severity of ED and mean weight (P < 0.001), waist circumference (P < 0.001), triglycerides (P = 0.009), total cholesterol (P = 0.027), HbA1c (P < 0.001), fasting glucose (P = 0.003) and AMS scores (P = 0.043). There were no significant differences in testosterone fractions and SHBG levels between the ED subgroups. There was a positive correlation between the prevalence of diabetes mellitus (type 1 and type 2) and the severity of ED in these men (P = 0.018). CONCLUSIONS: The descriptive data showed that a greater severity of ED in men with LOH correlated with an increased waist circumference, hyperglycaemia, hypertriglyceridaemia, hyperlipidaemia, and a history of diabetes mellitus. Severe ED is a prognostic indicator of comorbidities in men with LOH.

The role of the urologist in the prevention and early detection of cardiovascular disease.

In this review we identify whether problems encountered in urology, such as erectile dysfunction, have a bearing on general health, in particular cardiovascular health. Testosterone, traditionally regarded as the hormone subserving male reproductive and sexual functioning, appears to have a much wider role. Recent findings show that testosterone is involved in the metabolic control of glucose and lipids, of strength of bone and muscle, and psychological aspects such as mood and energy. Serum testosterone levels decline with ageing, free testosterone levels more so than total testosterone. At least 10 publications have shown that low testosterone levels are associated with an increased risk of death. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. There is a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin levels predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavourable risk profile for the development of diabetes and atherosclerosis, thus also improving risk factors for erectile dysfunction. We conclude that urologists diagnosing and treating erectile problems are in a unique position to include general aspects of men's health in their work, and thus contribute to general health and to cardiovascular health in particular.