Complete remission of recurrent multiple insulin-producing neuroendocrine tumors of the pancreas with somatostatin analogs: a case report and literature review.

Hyperinsulinemic hypoglycemia is most commonly caused by a single, sporadic insulinoma. Multicentric insulinoma disease (insulinomatosis) as well as metachronous neuroendocrine tumors of the pancreas, known also as neuroendocrine adenomatosis, represent a very rare condition, if not associated with multiple endocrine neoplasia type 1 syndrome (MEN1) or Von Hippel Lindau disease. We report a 9-year follow-up of a 41-year-old woman, initially presenting with hypoglycemic syndrome caused by two insulin-producing tumors, who underwent subtotal pancreasectomy in 2012, with histology compatible with multiple small neuroendocrine tumors. An approximately 1-cm insulin-producing tumor recurred at subsequent biochemical and radiological follow-up, and was cured with the somatostatin analog octreotide as a single treatment, until remission of symptoms and complete regression of the pancreatic lesion achieved after only 16 months of treatment. The possible mechanisms for these findings are discussed and the literature is briefly reviewed.

The Role of Somatic Symptoms in Sexual Medicine: Somatization as Important Contextual Factor in Male Sexual Dysfunction.

INTRODUCTION: An important feature of somatic symptom disorder is the subjective perception of the physical symptoms and its maladaptive interpretation. Considering that psychological distress is often expressed through somatic symptoms, it is possible that they underlie at least a part of the symptoms in subjects complaining of sexual dysfunction. Nevertheless, studies on the impact of somatoform disorders in sexual dysfunction are scanty. AIM: To define the psychological, relational, and organic correlates of somatic symptoms in a large sample of patients complaining of sexual problems. METHODS: A consecutive series of 2833 men (mean age 50.2 ± 13.5 years) was retrospectively studied. MAIN OUTCOME MEASURES: Somatic symptoms were assessed using the "somatized anxiety symptoms" subscale of the Middlesex Hospital Questionnaire (MHQ-S). Several clinical, biochemical, psychological, and relational parameters were studied. Patients were interviewed with the previously validated Structured Interview on Erectile Dysfunction (SIEDY), and ANDROTEST (a structured interview for the screening of hypogonadism in patients with sexual dysfunction). RESULTS: Among the 2833 patients studied, subjects scoring higher on somatic symptoms were older, more obese, reporting unhealthy lifestyle (current smoking, alcohol consumption), and a lower education (all P < .05). Moreover, they reported a general impairment of their sexuality more often, including erectile problems (spontaneous or sexual-related), low sexual desire, decreased frequency of intercourse, and perceived reduction of ejaculate volume (all P < .005). Interestingly, we observed a significant association between MHQ-S scoring with a reduced testosterone level and hypogonadism symptoms (both P < .05). Finally, we found a significant association between somatic symptoms and both SIEDY Scales 1 (organic domain of ED) and 3 (intrapsychic domain of ED) (both P < .0001). CONCLUSION: The present study demonstrates that the presence of somatic symptoms can represent an important contextual factor in the determination of or in the exacerbation of male sexual dysfunction. High levels of somatic symptoms in subjects with sexual dysfunction can be related to the sexual symptom itself. The consequences of this pattern have great clinical relevance in a sexual medicine setting, considering their severe impact on sexuality.

Conflicts Within the Family and Within the Couple as Contextual Factors in the Determinism of Male Sexual Dysfunction.

INTRODUCTION: The deterioration of a couple's relationship has been previously associated with impairment in male sexual function. Besides a couple's dystonic relationship, other stressors can unfavorably influence dyadic intimacy. A largely neglected etiopathogenetic factor affecting couple sexuality is the frustration caused by conflicts within the family. AIM: To evaluate the possible associations between male sexual dysfunction (SD) and conflictual relationships within the couple or the family. METHODS: A consecutive series of 3,975 men, attending the Outpatient Clinic for SD for the first time, was retrospectively studied. Conflicts within the family and within the couple were assessed using two standard questions: "Are there any conflicts at home," and "Do you have a difficult relationship with your partner?" respectively, rating 0 = normal relationships, 1 = occasional quarrels, and 2 = frequent quarrels or always. MAIN OUTCOME MEASURES: Several clinical, biochemical, and psychological (Middlesex Hospital Questionnaire) parameters were studied. RESULTS: Among the 3,975 patients studied, we observed a high prevalence of conflicts within the family and within the couple (32% vs. 21.2%). When compared with the rest of the sample, subjects reporting both type of conflicts showed a higher prevalence of psychiatric comorbidities. Hence, all data were adjusted for this parameter and for age. Family and couple conflicts were significantly associated with free floating anxiety, depression symptoms, and with a higher risk of subjective (self-reported) and objective (peak systolic velocity at the penile color Doppler ultrasound <35 mm/sec2) erectile dysfunction and hypoactive sexual desire. Female sexual function parameters, as reported by the patient, retained a significant association with both type of conflicts. CONCLUSIONS: This study indicates that the presence of often unexplored issues, like conflicts within the family or within the couple, can represent an important contextual factor in the determinism of male SD.

Hypersexuality, Paraphilic Behaviors, and Gender Dysphoria in Individuals with Klinefelter's Syndrome.

INTRODUCTION: An increased risk of autistic traits in Klinefelter syndrome (KS) has been reported. In addition, some studies have shown an increased incidence of gender dysphoria (GD) and paraphilia in autism spectrum disorder. AIM: The aim of this study was to evaluate the presence of (i) paraphilic fantasies and behaviors; and (ii) GD symptomatology in KS. METHODS AND MAIN OUTCOMES MEASURES: A sample of 46 KS individuals and 43 healthy male controls (HC) were evaluated. Subjects were studied by means of several psychometric tests, such as Autism Spectrum Quotient (AQ) and Reading the Mind in the Eyes Revised (RME) to measure autistic traits, Gender Identity/GD questionnaire (GIDYQ-AA), and Sexual Addiction Screening Test (SAST). In addition, body uneasiness psychopathological symptoms were assessed using Symptom Checklist 90 Revised (SCL-90-R). The presence and frequency of any paraphilic fantasy and behavior was assessed by means of a clinical interview based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. Finally, all individuals included were assessed by Wechsler Adult Intelligence Scale-Revised to evaluate intelligence quotient (IQ). Data from a subsample of a previous published series of male to female GD individuals, with the battery of psychological measures useful to provide a psychopathological explanation of GD in KS population available, was also considered. RESULTS: When compared with HC, KS reported significantly lower total, verbal and performance IQ scores and higher SCL-90 obsession-compulsive symptoms (all P < 0.001). In line with previously reported findings, KS showed higher autistic traits according with both RME and AQ tests (P < 0.001). With respect to sexuality, KS showed a significant higher frequency of voyeuristic fantasies during masturbation (52.2% vs. 25.6%) and higher SAST scores (P = 0.012). A mediation role of obsessive symptoms on the relationship between Klinefelter and SAST was confirmed (unstandardized estimate b = 2.75, standard error = 0.43 P < 0.001). Finally, KS individuals showed significantly higher gender dysphoric symptoms than HC (P = 0.004), which were mediated by the presence of autistic traits (Sobel's test; P < 0.05). CONCLUSIONS: KS is associated with hypersexuality, paraphilic behaviors, and GD, which were mediated by obsessive-compulsive and autistic traits.

Present and future association between obesity and hypogonadism in Italian males.

OBJECTIVE: Obesity prevalence is increasing worldwide and it is nowadays considered a real public health problem. Obesity is associated with co-morbidities like cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM), furthermore visceral obesity can be related to low testosterone (T) plasma levels. The link between obesity and hypogonadism (HG) is complex and not completely clarified. Current guidelines suggest that screening for HG should be done in subjects with obesity and T2DM. The aim of this evaluation is to assess the estimated actual and future prevalence of obesity and related co-morbidities, in particular HG, in the Italian general population. MATERIALS AND METHODS: The Strategyst Consulting Inc. recently completed an epidemiology forecast model for several countries, looking at HG and CV/Metabolic Disease, based on National Health and Nutrition Examination Survey (NHANES) data collected between 1999-2010. Data from NHANES survey were used to evaluate the Italian estimated prevalence of obesity and HG. RESULTS: Results show that obesity estimated prevalence will increase in 2030 also in Italy. In addition, also the prevalence of obese CVD and T2DM subjects will increase too. Even Italian HG prevalence is estimated to increase in the next two decades, irrespective of T threshold considered (< 8, 10 and 12 nmol/L). In obese CVD subjects the relative risk (RR) of developing HG (T < 8 nmol/L) is four times greater than in not-CVD obese subjects (RR = 4.1, 3.1 and 1.9 accordingly to the aforementioned T thresholds for defining HG). Accordingly, the estimated percentage of hypogonadal obese CVD and T2DM subjects will rise in 2030. CONCLUSIONS: The Strategyst epidemiology forecast model has allowed to assess the current and future prevalence of obesity and its relative co-morbidities like HG in Italy. Data emerged from this evaluation suggest that obesity and HG prevalence will increase in Italian population and confirm the complex link between adipose tissue and male T levels.

Lack of sexual privacy affects psychological and marital domains of male sexual dysfunction.

INTRODUCTION: Sexual dysfunctions (SDs) are dictated by predisposing, precipitating, maintaining, and contextual factors, the latter of which can help sexual problems to emerge. Even if the lack of sexual privacy is one of the most common contextual issues, it has not been extensively studied. AIM: Investigation of sexual privacy in a large sample of men consulting for SD was the aim of this study. METHODS: A consecutive series of 3,736 men, attending the outpatient clinic for SD for the first time, was retrospectively studied. Privacy during sexual intercourse was investigated with the following question, "During the last three months, have you had enough privacy during your sexual activity?" and rated 0 = yes, 1 = sometimes, 2 = rarely, and 3 = never. MAIN OUTCOME MEASURES: Several clinical, biochemical, and psychological (Middlesex Hospital Questionnaire [MHQ]) parameters were studied. RESULTS: Among the 3,736 patients studied, 83.9% reported enough privacy during sexual intercourse, while 8.6%, 5.7%, and 1.7% declared a decrease of sexual privacy of increasing severity. Lack of sexual privacy was associated with ejaculatory dysfunctions and with the inability to maintain an erection during intercourse. Subjects reporting lack of sexual privacy had a higher risk of relational and intrapsychic impairments, as well as psychopathology at MHQ questionnaire, even after adjusting for confounders. Fatherhood was associated with sexual privacy issues only in the lowest quartiles. In subjects without children, the absence of cohabitation with the partner was associated with an increasing risk of not having enough privacy (hazard ratio [HR] = 1.837 [1.269-2.659], P = 0.001); data confirmed, after stratification for age, only in the youngest subjects (I quartile HR = 2.159 [1.211-3.848], P = 0.009). CONCLUSIONS: This study indicates that sexual privacy is often a poorly investigated item, which is important to evaluate in male SD.

Relationship of testis size and LH levels with incidence of major adverse cardiovascular events in older men with sexual dysfunction.

INTRODUCTION: Measurement of testis volume (TV) is a reliable clinical procedure that predicts reproductive fitness. However, the role of TV in overall and cardiovascular (CV) fitness has never been studied. AIM: The study aims to analyze the clinical correlates of TV in patients with sexual dysfunction (SD) and to verify the value of this parameter and its determinants (i.e., luteinizing hormone [LH] levels) in predicting major adverse CV events (MACE). METHODS: A consecutive series of 2,809 subjects without testiculopathy (age 51.2 ± 13.1) consulting for SD was retrospectively studied. A subset of this sample (n=1,395) was enrolled in a longitudinal study. MAIN OUTCOME MEASURES: Several clinical and biochemical parameters were investigated. RESULTS: After adjusting for confounders, TV was negatively associated with both LH (Adj. r=-0.234; P<0.0001) and follicle-stimulating hormone (Adj. r=-0.326; P<0.0001). In addition, overweight/obesity, smoking, and alcohol abuse increased as a function of TV (hazard ratio [HR]=1.041 [1.021-1.061], P<0.0001; 1.024 [1.005-1.044], P=0.012; 1.063 [1.015-1.112], P=0.009, respectively). Furthermore, mean blood pressure was positively related to increased TV (Adj. r=0.157; P<0.0001). The effect of these lifestyle factors on TV were only partially related to changes in gonadotropin levels. In the longitudinal analysis, after adjusting for confounders, TV was associated with a higher incidence of MACE (HR=1.066 [1.013-1.122]; P=0.014), and the stepwise introduction in the Cox model of lifestyle factors, mean blood pressure and body mass index progressively smoothed out the association, which was no longer statistically significant in the fully adjusted model. Conversely, the association of higher LH levels with increased incidence of MACE was not attenuated by the progressive introduction of the aforementioned confounders in the model. CONCLUSIONS: Our data show that in SD subjects, TV and LH are associated with an adverse CV risk profile that mediate the higher TV-associated incidence of MACE. High LH levels are an independent marker of CV risk. Further studies are needed for clarifying determinants and mechanisms of testis enlargement that, beyond gonadotropins, could mediate the increased incidence of MACE.

Impaired masturbation-induced erections: a new cardiovascular risk factor for male subjects with sexual dysfunction.

INTRODUCTION: Erectile dysfunction (ED) is considered an early surrogate marker of silent, or even overt, cardiovascular diseases (CVD). However, epidemiological studies take into account only sexual intercourse-related erections. Although autoeroticism is a very common practice, data on masturbation-induced erections as a possible predictor of major adverse cardiovascular events (MACE) are lacking. AIM: To evaluate the clinical correlates of impaired masturbation-induced erections and to verify the importance of this sexual aspect in predicting MACE. METHODS: A consecutive series of 4,031 male patients attending the Outpatient Clinic for sexual dysfunction for the first time was retrospectively studied. Among these subjects, 64% reported autoeroticism during the last 3 months, and only this subset was considered in the following analyses. In the longitudinal study, 862 subjects reporting autoeroticism were enrolled. MAIN OUTCOME MEASURES: Several clinical, biochemical, and instrumental (Prostaglandin E1 [PGE1 ] test and penile color Doppler ultrasound) parameters were studied. RESULTS: Subjects with an impaired erection during masturbation (46% of those reporting autoeroticism) had more often a positive personal or family history of CVD, a higher risk of reduced intercourse- and sleep-related erections, hypoactive sexual desire and perceived reduced ejaculate volume, and impaired PGE1 test response. Prolactin levels were lower in those having impaired erection during masturbation. In the longitudinal study, unadjusted incidence of MACE was significantly associated with impaired masturbation-induced erections. When dividing the population according to the median age and diagnosis of diabetes, the association between impaired masturbation-induced erections and incidence of MACE was maintained only in the youngest (<55 years old) and in nondiabetic subjects, even after adjusting for confounders (hazard ratio [HR] = 3.348 [1.085-10.335], P = 0.032 and HR = 2.108 [1.002-4.433], P = 0.049; respectively). CONCLUSION: This study indicates that, in subjects with male sexual dysfunction, evaluating an often neglected sexual parameter, such as masturbation-induced erections, can provide further insights on forthcoming MACE in particular in "low risk" subjects.

"It takes two to tango": the relational domain in a cohort of subjects with erectile dysfunction (ED).

INTRODUCTION: The relational domain of erectile dysfunction (ED) is difficult to investigate in a clinical setting. We developed and validated SIEDY, a 13-item structured interview, that evaluates, besides the organic (Scale 1) and intra-psychic (Scale 3) domains, also the relational one (Scale 2). We previously established a pathological threshold for SIEDY Scale 1 and 3. AIM: The aim of this study is to identify a pathological threshold of SIEDY Scale 2. METHOD: A nonselected, consecutive series of 2,992 subjects with ED was retrospectively evaluated. In a first consecutive series of 844 patients (Sample A, studied without systematically applying a psychometric test: Middlesex Hospital Questionnaire), a pathological threshold of SIEDY Scale 2 score was identified through receiver operating characteristic, using, as surrogate marker of impaired couple relationship, at least a positive answer to two standard questions on conflict within the couple and on the presence of extramarital affairs. MAIN OUTCOME MEASURE: Sensitivity and specificity, along with possible associations with biological and psychological correlates were verified in a further sample of 2,148 patients (Sample B). RESULTS: In Sample A, a threshold of Scale 2 score ≥2 predicts couple impairment with a sensitivity of 53% and specificity of 66% and an overall accuracy of 62.0 ± 2.2% (P < 0.0001). When this threshold was verified in sample B, Scale 2 score ≥2 was associated with a higher risk of anxiety and depressive symptoms, higher prevalence of psychopathology, and higher Scale 3 scoring, even after adjusting for confounders. In the same sample, a Scale 2 score ≥2 was associated with a reduced intimacy during sexual intercourse and overall worse sexual functioning. CONCLUSIONS: Until now, no instrument is available to quantify the marital domain of ED. The validation of a threshold of SIEDY Scale 2 score (≥2) represents an easy tool for the identification of ED patients with a relevant marital impairment.

Perceived ejaculate volume reduction in patients with erectile dysfunction: psychobiologic correlates.

The disorders of orgasm/ejaculation encompass a heterogeneous group of dysfunctions including premature ejaculation, delayed ejaculation, and perceived ejaculate volume reduction (PEVR). The aim of this study was to explore specific associations of PEVR in a consecutive series of 3141 patients (mean age, 51.6 ± 13.1 years) seeking consultation for erectile dysfunction (ED). Among these, 71 were excluded because they underwent prostate surgery. Different clinical and biochemical factors were evaluated along with parameters derived from the Structured Interview on Erectile Dysfunction evaluating the contribution of organic, relational, and intrapsychic factors to ED. After adjustment for confounders, PEVR was specifically associated with the use of androgen deprivation therapy as well as with different other medications including α-blockers, serotonergic reuptake inhibitor antidepressants, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. A higher prevalence of diabetes mellitus and hypogonadism was observed in patients with PEVR compared with the rest of the sample (23.0% vs 14.1% and 9.1% vs 5.3% respectively; both P < .05). In addition, different sexual parameters such as severe ED (hazard ratio [HR] = 1.25 [1.11-1.41]; P < .0001) and patient's (HR = 1.53 [1.38-1.70]; P < .0001) and partner's (HR = 1.21 [1.07-1.36]; P < .005) hypoactive sexual desire (HSD) were also significantly related to PEVR. Furthermore, PEVR was associated with an impairment of both the relational and intrapsychic components of ED. In a multivariate model, adjusting for age, body mass index, smoking habits, and medications, hypogonadism, diabetes mellitus, severe ED, and patient's and partner's HSD were all independently associated with PEVR. Our results indicate that PEVR is important not only for couple reproductive purposes but also appears to have a distinct role in the couple's sexual performance.

Pulse pressure independently predicts major cardiovascular events in younger but not in older subjects with erectile dysfunction.

INTRODUCTION: Pulse pressure (PP; i.e., the arithmetic difference between systolic and diastolic blood pressure) has been suggested to be an independent cardiovascular risk (CV) factor in the general population. We previously also reported a negative association between PP and arteriogenic erectile dysfunction (ED). This finding has recently been questioned. AIM: To verify the association of PP with ED severity and to evaluate its role in predicting forthcoming CV events. METHODS: This is an observational prospective cohort study evaluating a consecutive series of 1,687 patients attending our Andrological Unit for ED. MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters were studied, along with SIEDY structured interviews and penile Doppler ultrasound. RESULTS: Subjects with PP in the lowest quartile (I: 20-45; II: 46-55; III: 56-62; IV: 63-115 mm Hg) had a significant reduction in the risk of severe ED (RR = 0.60[0.47-0.76]; P < 0.0001). When the same analysis was repeated as a function of age quartile (I = 17-44, II = 45-55, III = 56-62, and IV = 63-88 years old), after adjusting for testosterone levels, mean blood pressure, Chronic Disease Score, and body mass index, PP was inversely related to ED only in the youngest age group. During a mean follow up of 4.4 ± 2.6 years, 147 major cardiovascular events (MACE) were observed. In a Cox regression model, after adjusting for possible confounding factors, a lower PP was associated with a lower risk of MACE in the whole sample and in younger subjects, but not in the older ones. CONCLUSIONS: Checking for blood pressure in ED subjects and calculating PP should become a routine practice in sexual medicine. In younger individuals, low PP reflects not only sexual health (better erection) but also cardiovascular health (less prevalence of MACE).

Priapus is happier with Venus than with Bacchus.

INTRODUCTION: The relationship between alcohol consumption and erectile function is still not completely clarified. AIM: Aims of the present study are to explore a number of biological and clinical correlates of alcohol consumption in a sample of men consulting for sexual dysfunction, and to verify possible associations with the incidence of major adverse cardiovascular events (MACEs). METHODS: A consecutive series of 1956 (mean age 55 ± 11.9 years old) attending our outpatient clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N = 1687) was enrolled in a longitudinal study. MAIN OUTCOME MEASURES: Different clinical, biochemical, instrumental (penile Doppler ultrasound [PCDU]), and intrapsychic (Middlesex Hospital Questionnaire [MHQ]) were evaluated. We considered alcohol abuse more than three drinks per day. RESULTS: Among the patients studied 81% reported no or mild (<4 drinks/day) alcohol consumption whereas 14.3% and 3.9% declared a moderate (4-6 drinks/day) or severe (>6 drinks/day) alcohol abuse, respectively. After adjustment for confounders, both moderate or severe alcohol abuse was associated with low perceived partner's sexual desire, worse couple relationship, and smoking abuse. Furthermore, moderate and severe alcohol abuse was associated with low prolactin and thyroid-stimulating hormone levels, as well as an increase in triglycerides and total cholesterol levels. Penile blood flow was reduced in moderate and severe alcohol drinkers even after adjustment for confounders. In the longitudinal study, after adjusting for confounding factors, any kind of alcohol abuse was independently associated with a higher incidence of MACE (hazard ratio = 2.043 [1.059-3.943]; P < 0.0001). CONCLUSIONS: Our findings demonstrate that, in subjects consulting for erectile dysfunction, severe alcohol consumption is associated with a worse sexual function and a higher incidence of MACE.

Severe depressive symptoms and cardiovascular risk in subjects with erectile dysfunction.

INTRODUCTION: Erectile dysfunction (ED) and mood depression are often associated and both are correlated with an increased risk of cardiovascular morbidity and mortality. AIM: The aim of the present study is to explore biological and clinical correlates of depressive symptomatology in a sample of men consulting for sexual dysfunction and to verify possible associations between depressive symptoms and incidence of major cardiovascular events (MACE). METHODS: A consecutive series of 2,303 male patients attending the Outpatient Clinic for sexual dysfunction was retrospectively studied. A subset of the previous sample (N= 1,687) was enrolled in a longitudinal study. All patients were investigated using a Structured Interview on Erectile Dysfunction (SIEDY), composed of 3 scales which explore organic, relational and intra-psychic components of ED. MHQ-D scoring from Middlesex Hospital Questionnaire (MHQ) was used as a putative marker of depressive symptoms. MAIN OUTCOME MEASURES: Information on MACE was obtained through the City of Florence Registry Office. RESULTS: We found a positive relationship between MHQ-D score and a progressive impairment in obtaining an erection hard enough for penetration, even after adjusting for confounding factors. Moreover, we observed positive relationships between MHQ-D score and the three pathogenetic domains underlying ED. When the longitudinal subset was evaluated, during a mean follow-up of 4.3±2.6 years, 139 MACE, 15 of which were fatal, were observed. Unadjusted incidence of MACE was significantly associated with baseline depressive symptoms. When the presence of severe depressive symptoms were introduced in a Cox regression model, along with the arteriogenic ED and partner's hypoactive sexual desire, after adjusting for age, Chronic Diseases Score, and ΣMHQ (a broader index of psychopathology), severe depressive symptomatology was independently associated with a higher incidence of MACE. CONCLUSION: Depressive symptomatology constitutes an independent risk factor for cardiac morbidity and mortality in men with ED.

Is obesity a further cardiovascular risk factor in patients with erectile dysfunction?

INTRODUCTION: Erectile dysfunction (ED) and, in particular, arteriogenic ED have been proposed as new markers of risk for incident major adverse cardiovascular events (MACE). Reduced penile blood flow is more common in obese people than in leaner ED subjects. AIM: To explore the interaction of overweight/obesity and penile blood flow in the prediction of incident MACE. METHODS: This is an observational prospective cohort study evaluating a consecutive series of 1,687 patients attending our andrological unit for ED. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound: PCDU) parameters were evaluated. MAIN OUTCOMES MEASURES: According to body mass index (BMI), subjects were divided into three groups: normal weight (BMI = 18.5-24.9 kg/m(2)), overweight (BMI = 25.0-29.9 kg/m(2)), and obese (BMI >or= 30.0 kg/m(2)). Information on MACE was obtained through the City of Florence Registry Office. RESULTS: Among patients studied, 39.8% were normal weight, while 44.1% and 16.1% showed BMI 25-29.9 and 30 kg/m(2) or higher, respectively. During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression model, after adjusting for age and Chronic Diseases Score, showed that obesity classes along with the presence of arteriogenic ED (peak systolic velocity at PCDU <25 cm/second) were significantly and independently associated with incident MACE (hazard ratio = 1.47 [1.1-1.95], P < 0.05 and 2.58 [1.28-5.09], P < 0.001, respectively). When a separate analysis was performed for classes of obesity, reduced peak systolic velocity at PCDU (<25 cm/second) was significantly associated with incident MACE in obese (BMI >or= 30 kg/m(2)), but not in leaner, subjects. CONCLUSIONS: In obese subjects, more than in leaner ED subjects, impaired penile blood flow is associated with an increased risk of incident cardiovascular disease. The interaction with concomitant risk factors, such as obesity, should be taken into account when assessing the predictive value of penile blood flow for cardiovascular diseases.

Psychobiological correlates of women's sexual interest as perceived by patients with erectile dysfunction.

INTRODUCTION: We have recently reported that the perceived loss of a partner's sexual desire is independently associated with an increased incidence of major cardiovascular events in patients with erectile dysfunction (ED). No study has ever evaluated the specific impact of men's perception of women's sexual desire on male sexual function and lifestyle attitudes in ED subjects. AIM: To evaluate the clinical correlates of the perception of a partner's sexual desire [hypoactive sexual desire (HSD)] in a consecutive series of subjects seeking medical care for ED. METHODS: A consecutive series of 2,303 heterosexual male patients (mean age 58.1 ± 10.5) was studied. MAIN OUTCOME MEASURES: Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) structured interview. They also completed the Middlesex Hospital Questionnaire, a brief questionnaire for the screening of the symptoms of mental disorders. RESULTS: Among the patients studied, 458 (19.9%) reported a mild loss of their partner's desire, 302 (13.1%) a moderate reduction of libido, while 118 (5.1%) complained of a complete absence of sexual interest on the part of their partner. After adjustment for confounding factors, the perceived women's HSD was associated with different sexual, lifestyle, and relational factors. In particular, more extra-marital affairs, a longer and more hostile couple relationship, as well as a stressful job and both alcohol and smoking abuse were all significantly associated with perceived women's HSD. In addition, the perceived women's moderate to severe HSD was significantly associated with severe ED and less frequent sexual intercourse. Finally, partner HSD was significantly associated with a stepwise increase of free-floating anxiety and depressive symptoms (adj. r = 0.081, P < 0.05 and 0.158, P < 0.0001, respectively). CONCLUSIONS: Perceived sexual interest (éros) on the part of the woman can be seen for men not only as a fun and enjoyable behavior, but also a safe strategy for improving a man's overall health and life expectancy.

Male sexuality and cardiovascular risk. A cohort study in patients with erectile dysfunction.

INTRODUCTION: Although penile blood flow (PBF) has been recommended as an additional diagnostic test in identifying erectile dysfunction (ED) patients at risk for latent cardiovascular disease, no study has ever assessed the possible association of PBF and the relational component of sexual function with incident major cardiovascular events (MACE). AIM: The aim of this study is to investigate whether severity of ED, PBF, and other factors related to a couple's relationship predict incident MACE. METHODS: A consecutive series of 1,687 patients was studied. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound) parameters were evaluated. MAIN OUTCOME MEASURES: Information on MACE was obtained through the City of Florence Registry Office. RESULTS: During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression analysis, after adjustment for age and Chronic Disease Score, showed that severe ED predicted MACE (hazard ratio [HR] 1.75; 95% confidence interval 1.10-2.78; P < 0.05). In addition, lower PBF, evaluated both in flaccid (before) and dynamic (after prostaglandin-E1 stimulation) conditions, was associated with an increased risk of MACE (HR = 2.67 [1.42-5.04] and 1.57 [1.01-2.47], respectively, for flaccid [<13 cm/second] and dynamic [<25 cm/second] peak systolic velocity; both P < 0.05). Reported high sexual interest in the partner and low sexual interest in the patient proved to have a protective effect against MACE. CONCLUSIONS: The investigation of male sexuality, and in particular PBF, and sexual desire, could provide insights not only into present cardiovascular status but also into prospective risk.

The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction.

INTRODUCTION: Previous clinical studies on effect of statins treatment on testosterone (T) levels have produced mixed results. AIM: The aim of the present study is to evaluate the association between statin therapy and hormonal parameters in a large series of subjects seeking medical care at our unit for erectile dysfunction (ED). METHODS: A consecutive series of 3,484 (mean age 51.6 + or - 13.1 years) patients with ED was studied. MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters were investigated, along with ANDROTEST structured interview measuring hypogonadism-related symptoms. RESULTS: Among the patients studied, 244 (7%) patients were being treated with statins. After adjustment for confounding factors (including body mass index and Progetto Cuore cardiovascular (CV) risk engine score), both total and calculated free testosterone levels were significantly lower in subjects taking statins, when compared to the rest of the sample (hazard ratio [HR] = 0.93 [0.90; 0.96] and 0.26 [0.01; 0.18] for each decrement of total T and calculated free T, respectively; both P < 0.0001). The use of statins was also associated with a reduced testis volume and a higher prevalence of hypogonadism-related symptoms and signs, as assessed by higher ANDROTEST score (HR = 1.12 [1.03; 1.21]; P < 0.01 after adjustment for confounders). Follicle-stimulating hormone levels were significantly higher in subjects treated with statins when compared to the rest of the sample, while there was a trend toward higher luteinizing hormone levels, but this did not reach statistical significance. The lower levels of total and calculated free T observed in subjects treated with statins were also confirmed comparing them with age-waist circumference and CV risk score matched controls. Finally, subjects being treated with statins showed lower prolactin levels when compared to the rest of the sample. CONCLUSIONS: Our data demonstrated that statin therapy might induce an overt primary hypogonadism and should be considered as a possible confounding factor for the evaluation of testosterone levels in patients with ED.

Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction.

INTRODUCTION: Although testosterone (T) has been suggested to play a protective role against the development of atherosclerosis, studies demonstrating an association between low T and incident major adverse cardiovascular events (MACE) are scanty in the general population and absent in subjects with erectile dysfunction (ED). AIM: To investigate whether low T in subjects with ED predict incident fatal or nonfatal MACE. METHODS: This is an observational prospective cohort study evaluating a consecutive series of 1687 patients attending our andrological unit for ED. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY) and ANDROTEST structured interviews measuring components relative to ED and hypogonadal-related symptoms, respectively. MAIN OUTCOME MEASURES: Total T was evaluated at baseline. Information on MACE was obtained through the City of Florence Registry Office. RESULTS: Among the patients studied, 5.2, 13.8, and 22.4% were hypogonadal according to different thresholds (T < 8, 10.4 and 12 nmol/L or 230, 300 and 350 ng/dL, respectively). During a mean follow-up of 4.3 + or - 2.6 years, 139 MACE, 15 of which were fatal, were observed. Unadjusted incidence of MACE was not associated with T levels. Conversely, the proportion of lethal events among MACE was significantly higher in hypogonadal patients, using either 10.4 nmol/L (300 ng/dL) or 8 nmol/L (230 ng/dL) thresholds. However, after adjustment for age and Chronic Diseases Score in a Cox regression model, only the association between incident fatal MACE and T < 8 nmol/L (230 ng/dL) was confirmed (HR = 7.1 [1.8-28.6]; P < 0.001). Interestingly, measuring hypogonadal-related symptoms and signs through ANDROTEST, only fatal MACE were also associated with a higher score (HR = 1.2 [1.0-1.5] for each ANDROTEST score increment; P = 0.05 after adjustment for age and Chronic Diseases Score). CONCLUSIONS: T levels are associated with a higher mortality of MACE. The identification of low T levels should alert the clinician thus identifying subjects with an increased cardiovascular risk.

The relationship of testosterone to prostate-specific antigen in men with sexual dysfunction.

INTRODUCTION: Concern about a testosterone (T)-induced prostate-specific antigen (PSA) increase is often perceived as one of the main limitations in treating hypogonadism even when it is symptomatic, such as in subjects with sexual dysfunction (SD). AIM: The aim of this study was to evaluate the relationship between T and PSA levels in subjects with SD. Methods. We retrospectively evaluated the relationship between T and PSA in 2,291 subjects seeking medical care at our outpatient clinic for SD (sample A). The analysis was then repeated in a selected subpopulation of 1,421 subjects apparently free from prostatic diseases (sample B). MAIN OUTCOME MEASURES: The specific association between PSA levels, circulating androgens, and different clinical signs and symptoms of hypogonadism, as assessed by ANDROTEST structured interview, was evaluated. RESULTS: In both samples A and B, subjects with higher PSA levels reported a lower prevalence of hypogonadism-related symptoms and signs, as well as higher total testosterone (TT), and analogue and calculated free T. However, when the association between PSA and T was evaluated as a function of T deciles, the upper nine groups had similar PSA values, with the lowest demonstrated a significantly reduced PSA (the lowest vs. the rest of the sample: 0.61[0.38-1.23] ng/mL vs. 0.86[0.57-1.44] ng/mL, and 0.51[0.30-0.94] ng/mL vs. 0.73[0.52-1.10] ng/mL, respectively, for samples A and B; both P < 0.0001). Furthermore, when the relationship between hypogonadism (TT < 8 nmol/L) and PSA levels was evaluated according to age, it was significant only in younger subjects, but not in the older ones. CONCLUSIONS: Our data demonstrated that PSA is unrelated to T concentration across most of the T range, except for the most severely T deficient, and that a significant relationship between T and PSA is seen in younger but not in older men.

Autoeroticism, mental health, and organic disturbances in patients with erectile dysfunction.

INTRODUCTION: Masturbation is a common, but often neglected, male sexual behavior. AIM: To investigate the psychobiological correlates of self-reported masturbation in the last 3 months. METHODS: A consecutive series of 2,786 heterosexual male patients (mean age 48.4 +/- 13.2) consulting an outpatient clinic for erectile dysfunction (ED) was studied. MAIN OUTCOME MEASURES: Several hormonal, biochemical and instrumental parameters (penile Doppler ultrasound [PDU]) were investigated. Patients were interviewed, prior to the beginning of any treatment, with Structured Interview on Erectile Dysfunction (SIEDY) and ANDROTEST structured interviews. They also completed the Middlesex Hospital Questionnaire, a brief self-reported questionnaire for the screening of the symptoms of mental disorders in a nonpsychiatric setting. RESULTS: Among the patients studied, 1,781 (61.9%) reported they had masturbated at least once per month in the preceding 3 months. The frequency of masturbation was inversely related to age (r = -0.329; P < 0.0001) and directly associated with education level (adj r = 0.052, P < 0.05 after adjustment for age). A feeling of guilt during masturbation was reported by 274 (15.4%) patients. After adjusting for age, masturbation was positively associated with testosterone levels, stressful conditions, and both unstable and long-lasting couple relationship. Urogenital problems such as varicocele and prostate abnormalities also increased the chance of masturbation. Reported guiltiness during autoeroticism was associated with psychological disturbances, low prolactin, low testosterone, and increased relational problems. An erection not normal during masturbation was declared by 1,361 (76.4%) patients and associated with a prevalent organic component of ED, because of lower peak systolic velocity PDU and higher SIEDY Scale 1 scores. CONCLUSIONS: This study indicates that masturbation is a relatively frequent behavior in male subjects with ED. Inquiring about this sexual behavior is an important issue for understanding overall patients' sexual attitudes and behavior.