Erectile dysfunction (ED) may be the early clinical manifestation of a generalized vascular disease and carries an independent risk for cardiovascular events. Low-grade subclinical inflammation affects endothelial function and is involved in all stages of the atherosclerotic process. This review identifies potential pathophysiologic links among low-grade inflammation, ED, metabolic syndrome, and coronary artery disease (CAD) and presents the clinical implications in terms of ED diagnosis, assessment of patient risk, and therapy.
Methods
A comprehensive evaluation was performed for available published data in full-length papers that were identified in MedLine up to July 2007.
Results
Studies support an association between metabolic syndrome, ED, and increased inflammatory state. Increased circulating levels of inflammatory and endothelial-prothrombotic compounds are related to the presence and severity of ED. Specific inflammatory biomarkers and their combination appear to have the potential to aid ED diagnosis or exclusion. ED and CAD may confer a similar unfavorable impact on the inflammatory and prothrombotic state, whereas ED adds an incremental activation on top of CAD; these findings have important implications for cardiovascular risk. Lifestyle and risk factor modification, as well as pharmacologic therapy, are associated with anti-inflammatory effects.
Conclusions
Low-grade systemic inflammation could be an important element of the association between metabolic syndrome, ED, and CAD. Its individualized assessment may be a valuable tool for ED diagnosis, risk assessment, and rationalized therapeutic approach especially in patients with ED who have metabolic syndrome and carry an intermediate risk for future cardiovascular events.
Introduction
Longitudinal population-based studies clearly demonstrate that cardiovascular risk factors such as hypertension, dyslipidemia, central obesity, and insulin resistance are major risk factors for vasculogenic erectile dysfunction (ED) as well [1]. Furthermore, recent data suggest that the clustering of these factors, as occurs in patients with metabolic syndrome, increases the risk for the development of ED even further [2], [3].
ED may be the early clinical manifestation of a generalized vascular disease and carries an independent risk for cardiovascular events [4], [5]. ED is associated with the presence and extent of asymptomatic atherosclerosis, including that of the coronary arteries, and precedes the development of clinically evident coronary artery disease (CAD) by a significant amount of time [6], [7], [8], [9]. In angiographically documented CAD, ED rate varies according to type of clinical presentation (acute or chronic) and related atherosclerotic background (single or multivessel disease) [9].
Low-grade subclinical inflammation affects endothelial function and is involved in all stages of the atherosclerotic process. This review presents available evidence that identifies inflammation as a common pathophysiologic mechanism linking ED, the metabolic syndrome, and CAD. Furthermore the clinical implications in terms of ED diagnosis, risk determination, and therapy are discussed.
Section snippets
Pathophysiologic considerations of vasculogenic ED
Vasculogenic ED results from impairment of endothelial dependent or independent smooth muscle relaxation (functional vascular ED, initial stages), occlusion of the cavernosal arteries by atherosclerosis (structural vascular ED, late stages), or a combination of these [8], [10], [11]. Endothelial dysfunction is the key event in the pathophysiology of ED and, importantly, men with penile vascular dysfunction have endothelial dysfunction in other vascular beds as well [12]. Interestingly, the
Metabolic syndrome and ED
Central obesity together with hypertension, dyslipidemia, and insulin resistance defines the metabolic syndrome. The above-mentioned risk factors appear to carry a threat to the penile endothelium and the smooth muscle tissue leading to functional and structural changes in the cavernous arteries. Indeed, clinical and epidemiologic studies (Table 2) support an association between metabolic syndrome and ED [1], [2], [3], [30], [40], [41], [42], [43], [44], [45]. Metabolic syndrome and increased
CAD and ED
Vasculogenic changes in the penile vascular bed mirror those in the coronary arteries and ED is closely related to CAD at the clinical level. Among patients with established CAD, ED prevalence is reported to range from 33% to 75% [49], [50], [51], [52]. Recently, Montorsi et al reported that ED rate differs significantly in patients with established CAD according to clinical presentation of CAD and atherosclerosis burden. It is low in acute coronary symptoms and single-vessel disease and it is
Evaluation of inflammatory state in patients with ED: clinical implications
Apart from elucidation of pathophysiologic mechanisms, evaluation of inflammatory status has the potential to be useful in the clinical setting. In particular, it can be used in diagnosing patients with possible ED, assessing patient risk, and monitoring therapy of patients with ED.
Conclusions
Recent findings have pointed toward an important role of low-grade inflammation in the pathogenesis of vasculogenic ED in various patient subgroups. ED appears to be a “CAD equivalent” in terms of inflammatory activation and endothelial-prothrombotic activation and confers an incremental unfavorable impact when combined with the latter disorder. Subclinical inflammation may comprise a common pathophysiologic denominator of metabolic syndrome, ED, and CAD; however, because complex
The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease
Arch Intern Med
(2006)
I.M. Thompson et al.
Erectile dysfunction and subsequent cardiovascular disease
JAMA
(2005)
P. Montorsi et al.
Association between erectile dysfunction and coronary artery disease. Role of coronary clinical presentation and extent of coronary vessels involvement: the COBRA trial
PURPOSE: Neutrophil-to-lymphocyte ratio (NLR), a marker for subclinical inflammation, has been previously shown to be associated with erectile dysfunction (ED). We studied the potential predictive value of the NLR on ED after prostate brachytherapy (PB) for PCa.
METHODS AND MATERIALS: Between July 2005 and January 2021, 842 patients were included in this retrospective study of a prospectively maintained database. ED was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) physician-reported scale. ED was defined as a Grade 2 or 3 function. NLR count was determined 1–2 months before PB and separated into values PB <2 and ≥2. Patient characteristics and erectile function at last follow-up were compared for patients with a Univariate and multivariate analyses were performed to evaluate the predictive value of baseline NLR ≥2 on post-PB ED.
RESULTS: Baseline NLR ≥2 was found to be a statistically significant predictor of post-PB ED on both univariate (p = 0.002) and multivariate analyses (p = 0.008). Furthermore, the difference in ED prevalence between the NLR <2 and NLR ≥2 groups became more pronounced with longer follow-up after PB. The ED rate at 5 years post-PB was 43% for the NLR ≥2 groups, compared to 29% for the NLR <2 groups.
CONCLUSIONS: Subclinical systemic inflammation is a potentially important factor for predicting sexual toxicity after pelvic radiotherapy. NLR may be used as a proxy for predicting post-PB ED.
Gout is the most prevalent inflammatory crystal arthropathy worldwide and is a chronic disease requiring strict, lifelong adherence to drug therapy and healthy lifestyles. Gout has a heavy burden on the patient's sexual health, owing to the associated inflammatory status, long-term complications, and chronic pain; however, the effects of gout also extend to the partner's sexual health.
We aimed to investigate how the presence of a partner could influence the complex interaction between risk factors for sexual dysfunctions in gout in order to define novel strategies to improve sexual health and disease management.
Clinical and experimental data on the role of the couple in chronic diseases, as well as on the association between gout and sexual health, were searched through Pubmed.
Evidence from studies describing how the presence of a couple and leveraging sexual health can improve management and clinical outcomes for chronic diseases.
Treatment adherence can improve the sexual health of gout patients and their partners; likewise, by leveraging sexual health, it would be possible to promote better health-seeking behaviors, ultimately improving gout management.
Promoting awareness of the sexual health relevance of gout can potentially be a pivotal strategy to improve disease management and prevent the progression of sexual dysfunctions from subclinical to overt forms.
Identifying a bidirectional association between sexual health and disease management paves the way for improved disease control and can potentially prevent the development of sexual dysfunctions in couples affected by gout. However, the relevance of the couple has not been adequately addressed in gout management, and most evidence comes from other chronic diseases.
Improving gout management results in better sexual health, and vice-versa promoting better sexual health can improve disease control for gout. The presence of a partner improves the behavioral well-being of gout patients, with beneficial effects on both sexual health and gout management.
Sansone A, Reisman Y, Meto S, et al. The Role of the “Anti-Inflammatory” Couple for the Management of Hyperuricemia With Deposition. Sex Med 2022;10:100562.
Platelet Rich Plasma (PRP) is a novel therapy rich in growth factors and cytokines used to target the underlying causes of erectile dysfunction (ED). It is not known, however, if the composition of growth factors in PRP varies between men.
To evaluate PRP growth factor variability among men with ED.
Whole blood was collected from 8 participants with at least a 6-month history of ED. Seven men with Peyronie's disease and 1 healthy male (without sexual dysfunction) were used as the control group. PRP was extracted from whole blood using the Arthrex Angel system. A Human Growth Factor Antibody Array for 41 proteins was performed using 3 participants and the healthy control. Using all 16 samples, quantitative detection of factors from the array that were decreased by 1.5-fold were validated with western blot.
From the growth factor array, 2 growth factors—granulocyte-macrophage colony stimulating factor and transforming growth factor-β were identified as having a 1.5-fold decrease between the participants and the control. Vascular endothelial growth factor (VEGF) was selected because androgens can upregulate VEGF production. Other than a weak negative correlation between VEGF expression and age, we found no correlation between growth factor expression for granulocyte-macrophage colony stimulating factor or transforming growth factor-β and age, body mass index, or comorbidities.
PRP growth factor concentration appears to vary among men with ED. PRP treatment for ED may need to be personalized for patients, depending on individual growth factor concentration.
This study demonstrates the variability in PRP growth factors among men with ED. This is an important finding in the investigation of PRP as a restorative treatment option for men with ED. Our study, however, was limited by a small sample size.
PRP growth factors vary among men with ED.
Khodamoradi K, Dullea A, Golan R, et al. Platelet Rich Plasma (PRP) Growth Factor Concentration Varies in Men With Erectile Dysfunction. J Sex Med 2022;19:1488–1493.
