The role and needs of family doctors in sexual medicine: contributions of a preliminary Portuguese qualitative study for a global action.

Sexual health is fundamental for overall well-being and quality of life, making it the focus of intervention in Sexual Medicine (SM). Within the National Health Services, Primary Care Physicians (PCPs) guarantee comprehensive care in a biopsychosocial action, including in sexual health. This exploratory study aimed to investigate PCPs' perceptions about their role in SM and how to improve it. A cross-sectional online qualitative design was used, and a sample of 73 Portuguese PCPs was collected. Data was analyzed employing a summative content analysis. Three categories were established regarding how PCPs perceive their role in SM: "Protagonist", "Antagonist", and "Circumstantial". Concerning improving PCP's practice, two categories were identified: "Legitimizing Sexual Health" and "Enhancing Professional Development". In relation to SM, PCPs recognize themselves as institutional gatekeepers and comprehensive caregivers, resorting to familiar tasks to practice in a conditioned framework. To improve their role in SM, PCPs highlighted education investment, making specific suggestions for educational content, resource expedition, detailed guidelines creation, and raising provider and patient awareness beyond the biomedical scope. The results stress the need for an institutional effort to uphold PCPs' crucial role in SM to ensure adequate resource use and consistent, comprehensive sexual healthcare provision, enhancing overall patient care and placing sexual health as an essential field in primary care.

Consensos em HPV Masculino da Sociedade Portuguesa de Andrologia, Medicina Sexual e Reprodução: Seguimento.

Patients with genital HPV lesion, as well as partners, usually present higher psychological stress, than the actual medical consequences of the lesion. Follow-up of these patients should be based on education and counseling. HPV molecular tests are not recommended as a follow-up test, or for screening partners. Development and implementation of protocols, by the centers or units, that follow these patients, are recommended.

Inflatable penile prosthesis reservoir placement-Are we ready for a paradigm change?

In 2002, Steve Wilson pioneered new procedures for alternative placement of reservoirs for inflatable prostheses in patients who have suffered damage to the space of Retzius following pelvic surgery or obliteration of the transversalis fascia by mesh hernia repair. Since then, surgical techniques and tools for ectopic reservoir placement have gradually gained acceptance to minimize palpability, and the risk of visceral and vascular lesions for high risk patients has been all but eliminated. Lockout valves and high submuscular placement techniques are now recommended, and reports of vascular, bowel or bladder injuries are uncommonly rare. While surgeons continue their search for safer and more effective placement methods, new skills and instruments are constantly being introduced to make recommendations to minimize complications and provide safety and functionality. Additional studies and comparisons of techniques are needed to achieve a consensus of best practice for reservoir placement solutions.

[Consensus on HPV of the Portuguese Society of Andrology, Sexual Medicine and Reproduction: Treatment]. / Consensos em HPV Masculino da Sociedade Portuguesa de Andrologia, Medicina Sexual e Reprodução: Tratamento.

The treatment of condyloma is generally a challenge in clinical practice. Although the spontaneous resolution rate is high, a significant proportion of patients seek treatment, not because of symptomatology, but mainly for aesthetic issues and concerns related to the transmission or worsening of existing lesions. The available treatments should be applied only for clinically evident macroscopic lesions. Ideally, available therapies should have rapid action onset and clearance, resolve symptoms, reduce recurrence rate and viral load, be effective in treating small lesions, and be well tolerated. However, none of the currently available treatments is clearly more effective than the others and there is no ideal treatment for all patients or for all condyloma. Therefore, the therapeutic decision should be based on the clinician's experience, available resources, lesion morphology, size, number and location, primary or recurrent lesions, disease severity, patient preference and expectations, patient's immune competence, convenience, tolerance, cost of treatment and results of previous therapies. The available treatments are divided into three groups: applied by the patient himself (imiquimod 3.75 or 5%, podophyllotoxin .5%, synecatekines 10% or 15%), applied by the health care provider (bi- and tricloacetic acids 80%-90%, intralesional interferon alpha, cryotherapy, surgical removal, electrofulguration, laser ablation) and experimental or alternative therapies (topical cidofovir, intralesional bleomycin, photodynamic therapy). Treatment methodologies can be further divided into their action - ablative or destructive treatment (cryotherapy, electrofulguration, laser ablation, surgical excision), cytotoxic or proapoptotic treatments (podophyllotoxin .5%, 5-fluoruracil, bleomycin) and immunomodulatory treatments (imiquimod 3.75% or 5%, synecatekines 10% or 15%, intralesional interferon alpha). The overall success rate of the various treatments available ranges from 23% to 94%. Only treatments that include cryotherapy or surgical excision are suitable in condyloma with any anatomical location and that have the highest success rate in monotherapy. Recurrences are common regardless of the treatment received. In contrast, immunomodulatory therapies despite having lower initial clearance rates appear to have higher probabilities of cure in the medium term, with low recurrence rates. Some treatments may be combined with each other and the effectiveness of combined therapies appears to be superior to monotherapy (proactive sequential treatment). The consensuses for the treatment of HPV also consider special situations: immunocompromised patients, meatus and intraurethral lesions and treatment of the partner.

[Recommendations in Male HPV from the Portuguese Society of Andrology, Sexual Medicine and Reproduction: Prevention]. / Recomendações em HPV Masculino da Sociedade Portuguesa de Andrologia, Medicina Sexual e Reprodução: Prevenção.

The prevention of HPV-related diseases is an important healthcare issue due to its increasing incidence. Primary prevention is most important in males as it avoids initial infection and includes the use of condom, circumcision and vaccination. Primary prevention with vaccination is effective in decreasing HPV-related lesions in women up to 45 years old and the existing data for men comes from the experience from vaccinating women. Although it is the only vaccine that prevents cancer, the worldwide rates of vaccination in males is very low due to lack of information related to efficacy and side effects, lack of recommendation from the treating doctor, price and concern about encouragement of sexual promiscuity.

[The consensus of the Portuguese Society of Andrology, Sexual Medicine and Reproduction on Male HPV: diagnosis]. / Consensos em HPV masculino da Sociedade Portuguesa de Andrologia, Medicina Sexual e Reprodução: diagnóstico.

HPV infection affects about 50% of sexually active individuals at least once in a lifetime. Diagnosis is made on careful inspection of the genital area and can be divided into benign lesions (genital warts or condyloma acuminatum) and pre-malignant lesions (intraepithelial neoplasia) that can lead to cancer (invasive neoplasia). Diagnostic recommendations are reviewed in Male, Female, Couple and in the immunocompromised host. Recent histological concepts are also discussed.

Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPK/SIRT1-PGC-1α-SIRT3 Pathway in the Human Erectile Tissue.

Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1α-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n = 27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing ≤2 CVDRF (group A) and ≥3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with α-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPKα, total AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPX1 was performed by western blotting and of miR-200a, miR-34a, miR-421, and miR-206 by real-time PCR. Phospho-AMPKα and SIRT3 expression was found significantly increased in group B relative to other groups, suggesting a marked influence of CVDRF, additional to DM, in the regulation of these enzymes. NOX1 was also increased in group B relative to controls. Only an increasing tendency was observed in the phospho-AMPKα/total AMPKα ratio, SIRT1, and PGC-1α expression in groups A and B when compared with controls. Concerning antioxidant enzymes, GPX1 expression was found incremented in group A, but SOD2 expression was decreased in groups A and B, comparative with controls. Group B presented significantly diminished levels of miR-421 and miR-200a, but only a decreasing trend on miR-34 and miR-206 expression was observed. Taken together, our findings demonstrated that besides DM, additional CVDRF presented a cumulative effect in the cellular response to oxidative unbalance, contributing to AMPK/SIRT1-PGC-1α-SIRT3 pathway activation. SOD2, a major mitochondrial antioxidant defence, did not follow the same variation.

Long-term patient-reported satisfaction with different inflatable penile prosthesis: Comparison between AMS 700CX and Coloplast Titan.

INTRODUCTION: Erectile dysfunction (ED) is one of the most prevalent male sexual disorders worldwide. When conservative treatment is unsuccessful, contraindicated or causes unacceptable side effects penile prosthesis implantation is a definitive option for the management of ED. Although considered a third-line therapy, it achieves the highest satisfaction rates as compared with non-surgical treatment. Three-piece inflatable penile prothesis (IPP) represents the most sophisticated implantable device, AMS 700CX™ and Coloplast Titan® being the two most commonly used. Although there are several studies evaluating patient satisfaction with either model, there is little published data comparing both models. METHODS: We have compared overall patient satisfaction in 55 patients submitted to either 700CX™ or Titan® implantation. The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire was used to access patient satisfaction. RESULTS: Patient mean age and follow-up time were 59.1 years and 57.9 months respectively. There was no difference in EDITS score between 700CX™ and Titan® IPP (77.2±12.1 versus 77.5±16.6 respectively, p=0.956). CONCLUSION: Overall patient satisfaction as assessed by EDITS questionnaire was not different between 700CX™ and Titan®.

The influence of metabolic profile of obese men on the severity of erectile dysfunction: are metabolically healthy obese individuals protected?

OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) in metabolically healthy obese (MHO) individuals, and to compare ED severity and hypogonadism prevalence in MHO, metabolically unhealthy obese (MUO) and metabolically healthy non-obese individuals. MATERIAL AND METHODS: ED patients (n=460) were evaluated by standardized protocol, that included clinical evaluation, abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire survey, and Penile Duplex Doppler Ultrasound (PDDU) exam. Patients were classified as obese [body mass index (BMI) ≥30.0 kg/m2] and non-obese (BMI <30.0 kg/m2), and metabolic health status was defined by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria. Statistical analysis was performed and statistical significance was considered at p-level <0.05. RESULTS: The mean age of the subjects was 56.2±10.5 years. MHO was present in 40% of obese individuals (n=37). MUO had lower mean peak systolic velocity (mPSV) compared to MHO (28.1 cm/s vs. 36.9 cm/s; p=0.005), and IIEF-5 scores were also lower in MUO compared to MHO patients (10.2 vs. 13.1; p=0.018). No statistical differences in IIEF-5 score, mPSV and hypogonadism prevalence between MHO and metabolically healthy non-obese (MHNO) patients were observed. CONCLUSION: Our results lead us to conclude that healthy metabolic profile protects obese individuals from severity of ED. The strong association between obesity and ED may be otherwise attributed to metabolic abnormalities present in the obese.

Small Intestinal Submucosa Grafting for Peyronie Disease: Outcomes and Patient Satisfaction.

OBJECTIVE: To evaluate surgical outcomes and complications and assess overall patient satisfaction after small intestinal submucosa (SIS) grafting for Peyronie disease. METHODS: Twenty-eight patients were treated with tunical incision and grafting with SIS. Mean age of the patients was 58 (range: 43-71) years. A preoperative protocol was applied to all patients. Patients were also evaluated at follow-up clinic visits. The International Index of Erectile Function, a modified Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, postoperative self-reports, and clinical characteristics were used to measure outcomes. RESULTS: Hypertension, hypercholesterolemia, and type 2 diabetes were reported in 53,6%, 46,4%, and 28,6% of patients, respectively. Previous penile trauma was reported by 10,7%. The mean operative time was 151 ± 23 minutes. Average follow-up was 18 months (range: 3-36). The only surgical complication was 1 case of infected hematoma treated with surgical drainage. Self-reported complete resolution of curvature was 82,1%. Subjective perception of penile shortening was reported by 71,4% of patients. However, only 4 patients objectively showed postoperative penile shortening. Erectile function was completely preserved in 64,2%. Four patients complained of erectile dysfunction despite medication, even though no objective vascular etiology was shown on postoperative penile Doppler ultrasound. Overall, 82,2% of patients reported high levels of satisfaction. CONCLUSION: Surgical treatment of Peyronie disease using SIS grafting is a safe option, with low rate of major complications. It has good surgical outcomes and high patient satisfaction rates.

Effects of Aging and Cardiovascular Disease Risk Factors on the Expression of Sirtuins in the Human Corpus Cavernosum.

INTRODUCTION: Sirtuin (SIRT)1 was recently identified in human corpus cavernosum (CC). We hypothesized that other sirtuins could also be expressed in the CC. Expression of these enzymes in tissues is affected by aging, the main independent risk factor for erectile dysfunction besides other cardiovascular disease risk factors (CVDRF), such as diabetes or obesity. AIM: The aim of this study was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC relatively to age and CVDRF. METHODS: Samples of CC collected from patients submitted to programmed surgeries or organ donors were divided in three groups according to age and presence of CVDRF. Expression of SIRT1-3 and SIRT5-7 mRNAs was assessed by real-time polymerase chain reaction. Cellular localization and semi-quantification of sirtuins proteins were performed by immunofluorescence and Western blotting (WB), respectively. Nuclear factor kappa B (NFkB)-p65, inducible (iNOS) and endothelial nitric oxide synthase (eNOS) levels were also assayed by WB. MAIN OUTCOME MEASURES: The main outcome measure was to characterize the expression of SIRT1-3 and SIRT5-7 in human CC. RESULTS: SIRT1-3 and SIRT5-7 mRNAs were detected in all individuals, without statistical differences among groups, excepting SIRT7 that decreased four times in aged groups relatively to young (P = 0.013). WB analysis demonstrated that aged individuals with CVDRF presented higher levels of SIRT7 protein relatively to young (P = 0.0495) and lower levels of SIRT3 protein relatively to healthy aged (P = 0.0077). Expression of NFkB-p65 and iNOS were higher in aged than in young individuals (P = 0.0185; P = 0.004, respectively). No differences in other sirtuins or total eNOS were seen among groups although phospho eNOS Ser(1177) levels decreased in groups of aged men relatively to young (P = 0.0043; P = 0.0099). CONCLUSIONS: Our results demonstrate for the first time expression of SIRT2-3 and SIRT5-7 in the human CC. Aged individuals with CVDRF presented an increase in SIRT7 protein levels and a decrease in mitochondrial SIRT3. This finding suggests that CVDRF induces the loss of antioxidant defense mechanisms leading to endothelial injury.

Effect of aging and cardiovascular risk factors on receptor Tie1 expression in human erectile tissue.

INTRODUCTION: Erectile dysfunction is highly prevalent in patients with advanced age or cardiovascular disease risk factors (CVDRFs). These conditions interfere on expression of vascular growth factors and respective receptors causing disturbance in endothelial function. AIM: This study aims to assess the effect of aging and CVDRF on the expression of tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie) 1 in human corpus cavernosum (CC). METHODS: CC fragments obtained from programmed surgeries or organ donors were divided into three groups: young, healthy aged, and aged with CVDRF. Angiopoietin (Ang) 1, Ang2, Tie1, and Tie2 mRNA and protein levels were assessed by real-time polymerase chain reaction and Western blotting, respectively. Dual-immunolabeling of Tie1 with specific markers of endothelium and smooth muscle and Ang1 and Ang2 was performed. MAIN OUTCOME MEASURES: To characterize the expression of Tie1 in human CC and elucidate its potential inhibitory effect in Ang-Tie2 system. RESULTS: Analysis of mRNAs demonstrated a decrease in Tie1 expression in CVDRF individuals compared with aged or young healthy individuals. No variation for Tie2, Ang1, or Ang2 expression was observed among the studied groups. In all analyzed CC fragments, a 125 kDa band, Tie1, was detected. This protein presented a significant age-related decrease, specially in individuals with CVDRF. Immunofluorescence study revealed Tie1 expression in the endothelium of samples of all experimental groups. CONCLUSIONS: Employing different methodological approaches, we show for the first time that Tie1 is expressed in human CC endothelium, and its level of expression diminishes in aged individuals, particularly those with CVDRF. This finding reinforces the view that delivery of Ang1 to the CC of erectile dysfunction affected CVDRF patients is able to activate a beneficial Tie2 response.

Penile corporoplasty with Yachia's technique for Peyronie's disease: Single center experience with 117 patients.

INTRODUCTION: Peyronie's disease is an acquired penile deformity with a variety of presentations, caused by the formation of fibrous plaques within the tunica albuginea, leading to bio-mechanical and vascular abnormalities. The objective is to investigate the 18 years outcome of patients with Peyronie's disease treated with penile corporoplasty (Yachia technique) in our department. MATERIALS AND METHODS: One hundred and seventeen patients underwent surgical treatment for PD between 1991 and 2009 and were retrospectively evaluated. We used the Levine and Lenting's algorithm for surgical treatment. Data was obtained from medical records, clinical evaluation, and telephone interview. Post-operative follow-up was at 6 weeks and 12 months. The mean time of follow-up was 14 months (12-19 months). MAIN OUTCOME MEASURES: Patient demographic, co-morbidities, erectile function, penile curvature, and surgical intervention were documented. The main outcome measures of this study are postoperative complications, surgical purpose, and patients and partner's satisfaction rates. RESULTS: Surgical aim was obtained in 106 patients (success rate of 94.6%). Complications occurred in 4.5% of patients, but most of these were mild. At 6 weeks, complete straightening of the penis was achieved in 57 patients (50.9%), and partial straightening which allow sexual intercourse in 49 patients (43.7%). Nine patients report gland hypoesthesia and almost all report subjective perception of penis shortening (0.5 cm to 5 cm). Twenty-two patients developed recurrent deformity at 12 months follow-up, with compromise of sexual intercourse in 7 patients. Patients' responses to our questionnaire showed that overall 88.4% of the patients and partners were satisfied with the surgical results. CONCLUSION: According to the results of this long-term, retrospective study, surgical correction, using the Yachia technique, is an excellent option for patients with functional impairment from their Peyronie's disease, especially.

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1-eNOS axis.

Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD(+)-dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

Hormonal modulation in aging patients with erectile dysfunction and metabolic syndrome.

Erectile dysfunction (ED), metabolic syndrome (MetS), and hypogonadism are closely related, often coexisting in the aging male. Obesity was shown to raise the risk of ED and hypogonadism, as well as other endocrinological disturbances with impact on erectile function. We selected 179 patients referred for ED to our andrology unit, aiming to evaluate gonadotropins and estradiol interplay in context of ED, MetS, and hypogonadism. Patients were stratified into groups in accordance with the presence (or not) of MetS and/or hypogonadism. Noticeable differences in total testosterone (TT) and free testosterone (FT) levels were found between patients with and without MetS. Men with MetS evidenced lower TT circulating levels with an increasing number of MetS parameters, for which hypertriglyceridemia and waist circumference strongly contributed. Regarding the hypothalamic-pituitary-gonadal axis, patients with hypogonadism did not exhibit raised LH levels. Interestingly, among those with higher LH levels, estradiol values were also increased. Possible explanations for this unexpected profile of estradiol may be the age-related adiposity, other estrogen-raising pathways, or even unknown mechanisms. Estradiol is possibly a molecule with further interactions beyond the currently described. Our results further enlighten this still unclear multidisciplinary and complex subject, raising new investigational opportunities.

Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats.

The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) 1 and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed ad libitum with an HF diet for 8 or 16 weeks. After 8 weeks of the HF diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays (VEGF, VEGF receptor (VEGFR) 1 and 2, Ang1, Ang2 and Tie2) and semiquantification of VEGF, VEGFR1, VEGFR2, Ang1, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.

Real-time PCR study of Ang1, Ang2, Tie-2, VEGF, and KDR expression in human erectile tissue during aging.

INTRODUCTION: Aging is a recognized risk factor for erectile dysfunction (ED), contributing independently to vascular damage of penile tissue. Vascular maintenance depends on angiogenic balance in tissues. Vascular endothelial growth factor (VEGF) is a modulator of endothelial cells functions, after engagement to specific receptor kinase domain region (KDR). Other factors, such as angiopoietins, cross talk with VEGF, modulating its effects. Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) compete for binding to Tie-2 and, while Ang1 promotes vascular stabilization, Ang2 acts as a partial agonist or antagonist of Ang1 signaling, depending on VEGF bioavailability. AIMS: To quantify the expression of Ang1, Ang2, Tie-2, VEGF, and KDR by real-time polymerase chain reaction (PCR) in human corpus cavernosum (CC) from young and aged healthy individuals. METHODS: Human CC fragments were obtained from organ donors without known risk factors to ED and divided in two groups: young (16-35 years) and aged (59-74 years). RNA was extracted and converted to cDNA. Real-time PCR reactions employed appropriate primers. KDR, Tie-2, Akt, and phospho-Akt protein levels were also assessed by Western blotting (WB). Computer-assisted evaluation of vascular areas was performed. MAIN OUTCOME MEASURES: Study of angiopoietins-Tie-2 and VEGF-KDR systems in human CC during aging by real-time PCR and WB. The ratios Ang1/Tie-2 and VEGF/KDR and Akt levels were also determined. RESULTS: Real-time PCR results showed a sixfold significant reduction in the Ang1/Tie-2 ratio during aging. Ang2, VEGF, and KDR expression results were highly variable. Nevertheless, the ratio VEGF/KDR was significantly higher in the aged individuals. Akt and phospho-Akt levels were similar in both groups. Immunohistological evaluation revealed a significant decrease in vascular areas and endothelial surface in CC with aging, despite no differences found in vessel number. CONCLUSIONS: The obtained results suggest an aging-associated downregulation of angiopoietins/Tie-2 system and an apparent compensatory upregulation of the VEGF/KDR system.

Are all metabolic syndrome components responsible for penile hemodynamics impairment in patients with erectile dysfunction? The role of body fat mass assessment.

INTRODUCTION: Erectile dysfunction (ED) is a common disease that is mostly vasculogenic in nature. ED correlates with cardiovascular risk factors, with endothelial dysfunction being the common link. Hypertension (HTA) and insulin resistance are the most important determinants of arteriogenic ED, and are also components of the metabolic syndrome (MetS), which supports a strong association between MetS and ED. However, MetS and, specifically, obesity interference on penile hemodynamics is still controversial. AIM: To evaluate the impact of independent MetS criteria and obesity on penile duplex Doppler ultrasound (PDDU) parameters in men with ED. METHODS: Consecutive patients (n = 212) referred to a unit of PDDU were evaluated for cardiovascular risk factors and MetS (ATP III criteria). Body mass index and body fat percentage (BF%) were calculated. Each patient underwent a PDDU by the same investigator. Data are expressed as mean ± standard deviation, and statistical significance was considered at P level < 0.05. Statistical analysis of clinical, laboratory, and PDDU parameters was performed with SPSS® software. MAIN OUTCOME MEASURES: To evaluate the individual power of MetS clusters and obesity as predictive factors for penile hemodynamic changes namely mean peak systolic velocity (mPSV). RESULTS: MetS was present in 24.8% of men, and 80.8% of them presented penile hemodynamics alterations, with mPSV significantly lower comparatively to no MetS patients (29.0 vs. 35.4 cm/s, P = 0.004). Multivariate analysis demonstrated that, considering all MetS parameters, only HTA was significantly associated with diminished mPSV. However, after further adjustment for all cardiovascular risk factors, BF% remained the sole independent clinical factor for penile hemodynamics impairment. CONCLUSIONS: There is a strong association between MetS and ED, but within MetS criteria, only HTA was independently associated with the deterioration of penile hemodynamics parameters. Although the classical methods of evaluating obesity in MetS were not individually associated with PDDU impairment, BF% represented by itself an excellent predictor of vascular ED.

Characterization of VEGF and angiopoietins expression in human corpus cavernosum during aging.

INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is a highly prevalent and age-related disease, caused by endothelial dysfunction and impaired cavernous angiogenesis. However, cellular and molecular changes involved in erectile pathophysiology in aging male remain to be elucidated. AIM: To characterize the vascular organization, concomitantly with analysis of the expression of vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2) in young and aged human corpus cavernosum. METHODS: Human penile fragments were removed from patients submitted to penile deviation surgery (11 cases; 58-70 years) and from potential organ donors (four cases; 18-28 years) without ED or risk factors for ED. Smooth muscle and connective tissue were assessed by Masson's trichrome staining and computer-assisted histomorphometry. Dual immunostaining for specific markers of endothelium (von Willebrand factor) and smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence microscopy. Semi-quantification of expression of angiogenic factors was performed by Western blotting. MAIN OUTCOME MEASURES: Expression of VEGF and Angiopoietins in human corpus cavernosum, using a combination of histologic stainings, and molecular biology tools in order to achieve a better understanding of cavernosal tissue remodeling with aging. RESULTS: Aged human corpus cavernosum presented wider sinusoidal spaces, loss of muscle cell bundles, and increased connective tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle cell cytoplasm with identical localization in both studied groups. VEGF expression was abundant in smooth muscle cell and its expression markedly decreased in aged tissue, contrasting with the expression of angiopoietins that increased in the aged corpus cavernosum. CONCLUSIONS: Immunoflourescent studies of cellular markers and growth factors help clarifying vascular organization and angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the organization pattern of vascular endothelium and smooth muscle components of cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged penile tissue suggest a VEGF-independent vascular remodeling mechanism.