Luisa Petrone

Structured interview on erectile dysfunction (SIEDY © ): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction

The aim of the present study is the definition of a brief structured interview (SI) providing scores useful for identification and quantification of pathogenetic factors of erectile dysfunction (ED). A SI was developed and applied to a consecutive series of 320 ED patients. A 13-item SI, with three-factor analysis-derived scales, was identified and applied for validation to an independent consecutive series of 194 ED patients. PGE1 (10 μg) intracavernosal injection, penile duplex ultrasound (PDU), blood hormones, PSA, glycemia, and lipids were used for the assessment of an organic component (OC), and Middlesex Hospital Questionnaire (MHQ) modified for psychological disturbances. Scale 1, dealing with OC, showed a positive correlation with age, BMI, blood pressure, glycemia, and inverse correlation, with testosterone, PGE1 and several parameters derived from PDU. Scale 2, related to partners relationship, was not correlated with organic parameters. Scale 3, which measures psychopathological traits was correlated with MHQ scales. Scale 1 (>3) had a sensitivity of 67.9% and a specificity of 67.6% for OC. SIEDY© provides information on ED pathogenesis and might assist physicians in diagnostic and therapeutic choices.

Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic.

Patients with diabetes mellitus (DM) were more often hypogonadal than normal fasting glucose subjects. The aim of this investigation is the assessment of characteristics and psychobiological correlates of DM associated with hypogonadism (DMAH). The Structured Interview SIEDY© was used along with several biochemical, psychological and instrumental investigations in a series of more than 1200 patients with erectile dysfunction (ED); 16% of whom with type II DM. Hypogonadism was defined as circulating total testosterone (T) below 10.4 nmol/l. The prevalence of hypogonadism was 24.5% in DM versus 12.6% in the rest of the sample (P<0.0001); differences in the prevalence of hypogonadism retained significance after adjustment for age and BMI. DMAH was associated with typical hypogonadism-related symptoms, such as reduction in sexual desire, leading to a decreased number of sexual attempts, and with higher depressive symptomatology. In DMAH, testis size and LH concentrations were significantly reduced, suggesting a central origin of the disease. At penile Duplex ultrasound examination, diabetic patients and in particular hypogonadal type II diabetic patients showed lower levels of basal and dynamic (after PGE1 injection) peak systolic velocity and acceleration, when compared to the rest of the sample, even after adjustment for age and BMI. Our results show that hypogonadism is frequently associated with type II DM, at least in the 6th decade. DMAH might exacerbate sexual dysfunction by reducing libido and mood and further compromising penile vascular reactivity.

ORIGINAL RESEARCH—ENDOCRINOLOGY: ANDROTEST©: A Structured Interview for the Screening of Hypogonadism in Patients with Sexual Dysfunction

INTRODUCTION Detecting hypogonadism, which is important in the general population, becomes crucial in patients with sexual dysfunctions, because hypogonadism can have a causal role for them and testosterone (T) substitution represents a milestone for the therapy. AIM No inventories are available for the screening of hypogonadism in patients with sexual dysfunction. We wished to set up a brief structured interview providing scores useful for detecting hypogonadism defined as low total T (<10.4 nmol/L, 300 ng/dL) in a symptomatic population (sexual dysfunction). METHODS A minimum set of items was identified within a larger structured interview through iterative receiver-operating characteristic curve analysis, with assessment of sensitivity and specificity for hypogonadism in a sample of 215 patients. MAIN OUTCOME MEASURES Sensitivity and specificity were verified in a further sample of 664 patients. Correlation of test scores with prostate-specific antigen (PSA), testis volume, and others clinical and psychological parameters, was assessed for concurrent validity. RESULTS In the validation sample, the final 12-item version of the interview (ANDROTEST) had a sensitivity and specificity of 68% and 65%, in detecting low total T (<10.4 nmol/L) and of 71% and 65%, in the screening for low free T (<37 pmol/L). Furthermore, patients with a pathological test (i.e., score >8) showed higher prevalence of hypogonadism-related signs, such as lower testis volume and higher depressive symptoms. Finally, when only younger patients (<54 years, which represents the median age of the sample) were considered, Log10 [PSA] levels were significantly lower in those with ANDROTEST score >8. CONCLUSION ANDROTEST is a quick and easy-to-administer interview that provides scores for the screening of male hypogonadism in patients with sexual dysfunction.

Low Levels of Androgens in Men with Erectile Dysfunction and Obesity

INTRODUCTION The relationship between obesity and erectile dysfunction (ED) has not been completely clarified. AIM The aim of this study is to investigate the association between different obesity class (the World Health Organization definition) with several hormonal and instrumental parameters, in a large sample of patients with ED. METHODS A consecutive series of 2,435 (mean age 52.1 +/- 13.0 years) male patients with ED was investigated. MAIN OUTCOME MEASURES Several hormonal and biochemical parameters were studied, along with a structured interview on erectile dysfunction (SIEDY), a psychometric questionnaire (Middle Hospital Questionnaire), and penile doppler ultrasound (PDU). RESULTS Among patients studied, 41.5% were normal weight, while 42.4%, 12.1% and 4.0% showed a BMI of 25-29.9, 30-34.9 and 35 kg/m(2 )or higher, respectively. Androgen levels (including sex hormone-binding globuline bound and unbound testosterone) decreased as a function of obesity class, while luteinising hormone levels did not show any significant change. Obesity was significantly associated with a higher organic contribution to ED (as assessed by SIEDY scale 1 score), and worse PDU parameters. At multivariate linear regression analysis, after adjustment for confounders (including metabolic syndrome), low androgens remained associated with BMI, while both basal and dynamic (after prostaglandin E1 [PGE1] stimulation) peak systolic velocity (PSV) at PDU resulted significantly associated with age and elevated blood pressure (Adj. r = -0.179, -0.285 and -0.094, -0.071 for age, hypertension and for basal and dynamic PSV, respectively; all P < 0.05). CONCLUSIONS Obesity is characterized by low levels of androgens in men with ED, after adjustment for comorbidities. Obesity associated comorbidities, particularly hypertension, are the most important determinants of arteriogenic obesity-associated ED.

Different Testosterone Levels Are Associated with Ejaculatory Dysfunction

INTRODUCTION The role of testosterone (T) in pathogenesis of ejaculatory symptoms has not been completely clarified. AIM To evaluate the possible contribution of T and hypogonadism in the control of the ejaculatory reflex, comparing subjects with premature ejaculation (PE) or delayed ejaculation (DE) to those without ejaculatory dysfunction. METHODS A consecutive series of 2,437 (mean age 51.9 +/- 13.0 years) male patients with sexual dysfunction was studied. MAIN OUTCOME MEASURE Several hormonal and biochemical parameters were studied, along with the structured interview on erectile dysfunction (SIEDY) structured interview. Hypogonadism were defined when total testosterone (TT) was lower than 10.4 nmol/L. RESULTS Among the patients studied, 714 (25.9%) and 121 (4.4%) reported PE and DE, respectively. In the youngest age band (25-40 years), subjects with PE reported higher TT and free testosterone (FT) levels when compared to the other groups (subjects with DE or those without PE and DE; P < 0.05 for both). Conversely, in the oldest age band (55-70 years), lower TT and FT levels were observed in DE subjects. Accordingly, patients with PE showed the lowest (12%) and subjects with DE the highest (26%) prevalence of hypogonadism. These differences were confirmed even after adjustment for confounders such as age and libido (HR = 0.75 [0.57-0.99] and 1.83 [1.14-3.94] for PE and DE, respectively; both P < 0.05). CONCLUSIONS Our data seem to suggest that T plays a facilitatory role in the control of ejaculatory reflex. Both central and peripheral mechanisms have been advocated to explain this association. Clinical studies are currently in progress to further establish the role of T in the ejaculatory dysfunction, attempting to revert DE by androgen administration.

ORIGINAL RESEARCH—ENDOCRINOLOGY: A Comparison of NCEP‐ATPIII and IDF Metabolic Syndrome Definitions with Relation to Metabolic Syndrome‐Associated Sexual Dysfunction

INTRODUCTION Metabolic syndrome (MetS) is a clustering of cardiovascular and metabolic risk factors, often associated with erectile dysfunction (ED) and hypogonadism. Recently, the International Diabetes Federation (IDF) proposed a substantial revision of the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) MetS criteria, essentially lowering the diagnostic cutoff values. Aim. To investigate the associations between these two recently proposed definitions of MetS with the relative risk of arteriogenic ED and hypogonadism in a large cohort of patients with male sexual dysfunction. METHODS A consecutive series of 1086 patients with sexual dysfunction (mean age 51.9 +/- 12.8 years) was studied. MAIN OUTCOME MEASURES Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with ANDROTEST, a 12-item validated structured interview, specifically designed for the screening hypogonadism in a sexual dysfunction population. In particular, a score >8 is predictive of low testosterone (<10.4 nmol/L) with a sensitivity and specificity of about 70%. RESULTS The prevalence of MetS was 32.0% and 44.7% according to NCEP-ATPIII and IDF criteria, respectively. After adjustment for confounding factors, only NCEP-ATPIII was significantly associated with dynamic prostaglandin E(1)-stimulated penile flow (Vpmax, B = -7.7 +/- 3.8; P < 0.05). Patients with MetS defined according to both criteria reported lower total and free testosterone levels, higher prevalence of hypogonadism, and higher ANDROTEST score. However, when IDF, but not NCEP-ATPIII, criteria were fulfilled, the prevalence of hypogonadism was significantly lower than that observed in patients fulfilling both criteria (15.6% vs. 34.8%, respectively; P < 0.00001). Conversely, patients fulfilling NCEP-ATPIII, but not IDF, criteria did not show a significant different prevalence of hypogonadism than those positive for both sets of criteria (30.8% vs. 34.8%; P = NS). CONCLUSIONS In patients with ED, NCEP-ATPIII criteria seem to be a better predictor of hypogonadism and impaired penile blood flow than IDF ones.

ORIGINAL RESEARCH—ENDOCRINOLOGYORIGINAL RESEARCH—ENDOCRINOLOGY: ANDROTEST©: A Structured Interview for the Screening of Hypogonadism in Patients with Sexual Dysfunction

INTRODUCTION Detecting hypogonadism, which is important in the general population, becomes crucial in patients with sexual dysfunctions, because hypogonadism can have a causal role for them and testosterone (T) substitution represents a milestone for the therapy. AIM No inventories are available for the screening of hypogonadism in patients with sexual dysfunction. We wished to set up a brief structured interview providing scores useful for detecting hypogonadism defined as low total T (<10.4 nmol/L, 300 ng/dL) in a symptomatic population (sexual dysfunction). METHODS A minimum set of items was identified within a larger structured interview through iterative receiver-operating characteristic curve analysis, with assessment of sensitivity and specificity for hypogonadism in a sample of 215 patients. MAIN OUTCOME MEASURES Sensitivity and specificity were verified in a further sample of 664 patients. Correlation of test scores with prostate-specific antigen (PSA), testis volume, and others clinical and psychological parameters, was assessed for concurrent validity. RESULTS In the validation sample, the final 12-item version of the interview (ANDROTEST) had a sensitivity and specificity of 68% and 65%, in detecting low total T (<10.4 nmol/L) and of 71% and 65%, in the screening for low free T (<37 pmol/L). Furthermore, patients with a pathological test (i.e., score >8) showed higher prevalence of hypogonadism-related signs, such as lower testis volume and higher depressive symptoms. Finally, when only younger patients (<54 years, which represents the median age of the sample) were considered, Log10 [PSA] levels were significantly lower in those with ANDROTEST score >8. CONCLUSION ANDROTEST is a quick and easy-to-administer interview that provides scores for the screening of male hypogonadism in patients with sexual dysfunction.

Sexual dysfunction in subjects with Klinefelter's syndrome.

While the association of Klinefelters Syndrome (KS) with infertility is well-known, very few investigations have evaluated the prevalence of sexual dysfunction in KS. The aim of the present study was to systematically analyse the prevalence of KS in a consecutive series of adult male patients consulting for sexual problems and to investigate its specific correlates. Among a consecutive series of 1386 men (mean age 48.9 +/- 12.7 years old), 23 (1.7%) subjects with KS were found. Patients with KS were younger and more often hypogonadal when compared with the rest of the sample. Among patients with KS, five (22.7%) subjects reported severe erectile dysfunction, 14 (60.9%) hypoactive sexual desire (HSD), two (9.5%) premature and two (9.5%) delayed ejaculation. Only the association between KS and HSD was confirmed after adjustment for age [HR = 3.2 (1.37-7.5)], however, when patients with KS were compared with age, smoking habit, and testosterone matched controls, even the association between KS with HSD disappeared. In comparison to matched hypogonadal controls, subjects with KS had lower levels of education, a higher frequency of cryptorchidism and poorer pubertal progression. In conclusion, our results indicate that sexual dysfunction present in KS is not specifically associated with the syndrome but is caused by the underlying hypogonadal state. Further studies are needed to evaluate the efficacy of testosterone substitution in ameliorating the hypoactive sexual desire often reported in subjects with KS.

Circulating BRAFV600E in the Diagnosis and Follow-Up of Differentiated Papillary Thyroid Carcinoma

CONTEXT Cell-free nucleic acids circulating in plasma are considered a promising noninvasive tool for cancer monitoring. BRAF(V600E) mutation in cell-free DNA (cfDNA) could represent an appropriate marker for papillary thyroid carcinoma (PTC). OBJECTIVE Our aim is to investigate the role of BRAF(V600E)-mutated allele in cfDNA as a marker for the diagnosis and follow-up of PTC. STUDY DESIGN BRAF(V600E) allele was detected and quantified by an allele-specific real-time quantitative PCR assay in plasma from 103 patients affected by nodular goiter. As control populations, we enrolled 49 healthy subjects and 16 patients with non-nodular thyroid diseases. RESULTS The percentage of circulating BRAF(V600E) was significantly different between patients and controls and throughout different cytological categories of ultrasound-assisted fine-needle aspiration. Patients with a histopathological diagnosis of PTC showed a higher percentage of circulating BRAF(V600E) (P = .035) compared to those with benign histology. In 19 patients, a second blood draw, taken 3-6 months after surgery, showed a lower percentage of BRAF(V600E) in cfDNA than the presurgical sample (P < .001). The diagnostic performance of circulating BRAF(V600E) was assessed by receiver operating characteristic curve analysis resulting in an area under the curve of 0.797. A cutoff value was chosen corresponding to maximum specificity (65%) and sensitivity (80%). On this basis, we evaluated the predictive value of BRAF(V600E) in Thy 3 patients with a resulting positive predictive value of 33% and a negative predictive value of 80%. CONCLUSIONS The results of the present study provide encouraging data supporting the possibility to take advantage of circulating BRAF(V600E) in the management of PTC.

Psychobiological correlates of smoking in patients with erectile dysfunction

Although it is clear that cigarette abuse is closely linked to sexual dysfunction, it is still unclear which are the psychobiological correlates of smoking among individuals with sexual dysfunction. The aim of the present study is the assessment of the organic, psychogenic and relational correlates of erectile dysfunction (ED) in outpatients with different smoking habits. We studied the psychobiological correlates of smoking behaviour in a consecutive series of 1150 male patients, seeking medical care for ED. All patients were investigated using a Structured Interview (SIEDY©), which explores the organic, relational and intra-psychic components of ED, and a self-administered questionnaire for general psychopathology (MHQ). In addition, several biochemical and instrumental parameters were studied, to clarify the biological components underlying ED. Current smokers (CS) showed a higher activation of the hypothalamus–pituitary–testis axis (higher LH, testosterone and right testicular volume) and lower levels of both prolactin and TSH. Hormonal changes were reverted after smoking cessation. CS showed a higher degree of somatized anxiety and were more often unsatisfied of their occupational and domestic lifestyle. Smoking, as part of a risky behaviour, was significantly associated with abuse of alcohol and cannabis. Both CS and past smokers (PS) showed an impairment of subjective and objective (dynamic peak systolic velocity at penile duplex ultrasound) erectile parameters. This might be due to a direct atherogenic effect of smoking, a cigarette-induced alteration of lipid profile (higher triglyceride and lower HDL cholesterol in CS than in non-smokers or PS), or due to a higher use of medications potentially interfering with sexual function. This is the first comprehensive evaluation of the biological and intrapsychic correlates to the smoking habit. Our report demonstrates that smoking has a strong negative impact on male sexual life, even if it is associated at an apparently more sexual-favourable hormonal milieu.