Diagnosis and Treatment of Erectile Dysfunction for Reduction of Cardiovascular Risk

PURPOSE: We established erectile dysfunction as an often neglected but valuable marker of cardiovascular risk, particularly in younger men and men with diabetes. We also reviewed evidence that lifestyle change, combined with informed prescribing of pharmacotherapies used to mitigate cardiovascular risk, can improve overall vascular health and sexual functioning in men with erectile dysfunction.

MATERIALS AND METHODS: We performed a PubMed® search for articles and guidelines pertinent to relationships between erectile dysfunction and cardiovascular disease, cardiovascular and all cause mortality, and pharmacotherapies for dyslipidemia and hypertension. The clinical guidance presented incorporates the current literature and the expertise of the multispecialty investigator group.

RESULTS: Numerous cardiovascular risk assessment tools exist but risk stratification remains challenging, particularly in patients at low or intermediate short-term risk. Erectile dysfunction has a predictive value for cardiovascular events that is comparable to or better than that of traditional risk factors. Interventional studies support lifestyle changes as a means of improving overall vascular health as well as sexual functioning. Statins, diuretics, β-blockers and renin-angiotensin system modifiers may positively or negatively affect erectile function. Furthermore, the phosphodiesterase type 5 inhibitors used to treat erectile dysfunction may have systemic vascular benefits.

CONCLUSIONS: Erectile dysfunction treatment should be considered secondary to decreasing cardiovascular risk. However, informed prescribing may prevent worsening sexual function in men receiving pharmacotherapy for dyslipidemia and hypertension. As the first point of medical contact for men with erectile dysfunction symptoms, the primary care physician or urologist has a unique opportunity to identify those who require early intervention to prevent cardiovascular disease.

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology

Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology

BACKGROUND: Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking.

OBJECTIVE: Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model.

DESIGN, SETTING, AND PARTICIPANTS: Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test.

RESULTS AND LIMITATIONS: Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data.

CONCLUSIONS: This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology.

Serum vitamin D and sex hormones levels in men and women

Serum vitamin D and sex hormones levels in men and women

INTRODUCTION: 25-hydroxyvitamin D [25(OH)D] deficiency has been associated with low testosterone levels in men, but there are conflicting reports of its associations with sex hormones in women. Less is known about whether these associations are independent of adiposity and lifestyle factors, and whether they differ by race/ethnicity.

AIM: To examine associations of 25(OH)D concentrations with sex hormone levels.

METHODS: Cross-sectional analysis of 3017 men and 2929 women in a multi-ethnic cohort.

MAIN OUTCOME MEASURES: Testosterone, estradiol, dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and free testosterone.

RESULTS: The mean (SD) levels of 25(OH)D in men and women were 25.7(10.4) and 26.1(12.0)ng/ml, respectively. In men, after adjusting for demographic and lifestyle variables, a 10ng/ml [25nmol/L] decrease in 25(OH)D was associated with an average difference of -0.70nmol/L (95%CI -1.36, -0.05) in SHBG and 0.02 percent (0.01, 0.04) in free testosterone, but was not associated with low total testosterone level (<10.41nmol/L). In women, a 10ng/ml decrease in 25(OH)D levels was associated with an average difference of -0.01nmol/L (-0.01, -0.00) for estradiol, -8.29nmol/L (-10.13, -6.45) for SHBG, 0.06 percent (0.04, 0.07) for free testosterone, and 0.40nmol/L (0.19, 0.62) for DHEA. There was no significant interaction by race/ethnicity.

CONCLUSIONS: Lower 25(OH)D concentrations were associated with lower SHBG levels and higher free testosterone levels in both men and women, and lower estradiol and higher DHEA levels in women, independent of adiposity and lifestyle. We observed no significant association of 25(OH)D with total testosterone in men. Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels.

Vitamin D deficiency is independently associated with greater prevalence of erectile dysfunction: The National Health and Nutrition Examination Survey (NHANES) 2001-2004

Vitamin D deficiency is independently associated with greater prevalence of erectile dysfunction: The National Health and Nutrition Examination Survey (NHANES) 2001-2004

BACKGROUND AND AIMS: Erectile dysfunction (ED) and atherosclerotic cardiovascular disease (ASCVD) share many common risk factors, and vascular ED is a marker for increased ASCVD risk. Low 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with increased ASCVD risk, but less is known regarding the relationship of low 25(OH)D with ED. We determined whether 25(OH)D deficiency is associated with ED independent of ASCVD risk factors.

METHODS: We performed cross-sectional analyses of 3390 men aged ≥20 years free of ASCVD who participated in NHANES 2001-2004. Serum 25(OH)D was measured by the DiaSorin radioimmunoassay; deficiency was defined as levels

RESULTS: After accounting for NHANES sampling, the weighted prevalence of 25(OH)D deficiency and of ED were 30% and 15.2%, respectively. 25(OH)D levels were lower in men with vs. those without ED (mean 22.8 vs 24.3 ng/mL, respectively; p = 0.0005). After adjusting for lifestyle variables, comorbidities, and medication use, men with 25(OH)D deficiency had a higher prevalence of ED compared to those with levels ≥30 ng/ml (Prevalence Ratio 1.30, 95% CI 1.08-1.57).

CONCLUSION: In this cross-sectional analysis of a representative sample of U.S. men, vitamin D deficiency was associated with an increased prevalence of ED independent of ASCVD risk factors. Additional research is needed to evaluate whether treating vitamin D deficiency improves erectile function.

Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The Multiethnic Study of Atherosclerosis (MESA)

Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The Multiethnic Study of Atherosclerosis (MESA)

BACKGROUND: The association between subclinical cardiovascular disease and subsequent development of erectile dysfunction (ED) remains poorly described.

HYPOTHESIS: Among multiple subclinical atherosclerosis and vascular dysfunction measurements, coronary artery calcium (CAC) score best predicts ED.

METHODS: After excluding participants taking ED medications at baseline, we studied 1862 men age 45 to 84 years free of known cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) with comprehensive baseline subclinical vascular disease phenotyping and ED status assessed at MESA visit 5 (9.4 ± 0.5 years after baseline) using a standardized question on ED symptoms. Multivariable logistic regression was used to assess the associations between baseline measures of vascular disease (atherosclerosis domain: CAC, carotid intima-media thickness, carotid plaque, ankle-brachial index; vascular stiffness/function domain: aortic stiffness, carotid stiffness, brachial flow-mediated dilation) and ED symptoms at follow-up.

RESULTS: Mean baseline age was 59.5 ± 9 years, and 839 participants (45%) reported ED symptoms at follow-up. Compared with symptom-free individuals, participants with ED had higher baseline prevalence of CAC score >100 (36.4% vs 17.2%), carotid intima-media thickness Z score >75th percentile (35.3% vs 16.6%), carotid plaque score ≥2 (39% vs 21.1%), carotid distensibility 100 (odds ratio: 1.43, 95% confidence interval: 1.09-1.88) and carotid plaque score ≥2 (odds ratio: 1.33, 95% confidence interval: 1.02-1.73) were significantly associated with ED.

CONCLUSIONS: Subclinical vascular disease is common in men who later self-report ED. Early detection of subclinical atherosclerosis, particularly advanced CAC and carotid plaque, may provide opportunities for predicting the onset of subsequent vascular ED.

Cardiovascular Disease Prevention in Men with Vascular Erectile Dysfunction – The View of the Preventive Cardiologist

Cardiovascular Disease Prevention in Men with Vascular Erectile Dysfunction – The View of the Preventive Cardiologist

Vascular erectile dysfunction is a powerful marker of increased cardiovascular risk. However, current guidelines lack specific recommendations on the role that the evaluation of vascular erectile dysfunction should play in cardiovascular risk assessment, as well on the risk stratification strategy that men with vascular erectile dysfunction should undergo. In the last 3 years, erectile dysfunction experts have made a call for more specific guidance and have proposed the selective use of several prognostic tests for further cardiovascular risk assessment in these patients. Among them, stress testing has been prioritized, whereas other tests are considered second-line tools. In this review, we provide additional perspective from the viewpoint of the preventive cardiologist. We discuss the limitations of current risk scores and the potential interplay between erectile dysfunction assessment and the use of personalized prognostic tools, such as the coronary artery calcium score, in the cardiovascular risk stratification and management of men with vascular erectile dysfunction. Finally, we present an algorithm for primary care physicians, urologists, and cardiologists to aid clinical decision-making.