Giancarlo Balercia

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.

The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction.

In males, testosterone (T) levels decline with ageing. Several symptoms characteristic of the ageing process are similar to those related to hypogonadism. The aim of the present study was to evaluate the specific association among hypogonadism-related symptoms and signs and the ageing process. A consecutive series of 1647 (mean age 52.4 +/- 13.1 years) male patients with sexual dysfunction were investigated. Several hormonal and biochemical, instrumental and psychological parameters were studied. The parameters significantly associated with total levels in the entire cohort, after adjustment for confounders, were studied as a function of age and T quartiles. In all age quartiles, low T was associated with higher waist circumference and triglyceride levels and with an increased prevalence of metabolic syndrome. The prevalence of hypoactive sexual desire decreased as a function of T only in the youngest (17- to 42-year old) age quartile as well as the reported reduction in nocturnal erections. In the oldest age quartile, we found an inverse relationship between T levels and the prevalence of severe erectile dysfunction and a positive relationship with intercourse frequency. Accordingly, in the oldest age quartile, subjects with higher T levels showed better penile flow at penile colour doppler ultrasound as well as a better lipid profile. Finally, an inverse association between somatized anxiety and T levels was observed only in the oldest age quartile. In conclusion, our study shows for the first time that in subjects with sexual dysfunction, some hypogonadism-related symptoms can be age-specific. In particular, low T is associated with sexual dysfunction more often in the oldest subjects.

Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial.

OBJECTIVE To evaluate the effectiveness of coenzyme Q(10) treatment in improving semen quality in men with idiopathic infertility. DESIGN Placebo-controlled, double-blind randomized trial. SETTING Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy. PATIENT(S) Sixty infertile patients (27-39 years of age) with the following baseline sperm selection criteria: concentration >20 x 10(6)/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study. INTERVENTION(S) Patients underwent double-blind therapy with coenzyme Q(10), 200 mg/day, or placebo; the study design was 1 month of run-in, 6 months of therapy or placebo, and 3 months of follow-up. MAIN OUTCOME MEASURE(S) Variations in semen parameters used for patient selection and variations of coenzyme Q(10) and ubiquinol concentrations in seminal plasma and spermatozoa. RESULT(S) Coenzyme Q(10) and ubiquinol increased significantly in both seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, baseline and after treatment, of seminal plasma or intracellular coenzyme Q(10) and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q(10) had a statistically significant higher probability to be responders to the treatment. CONCLUSION(S) The exogenous administration of coenzyme Q(10) increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.

The specificity of the nonspecific thalamus: The midline nuclei

Publisher Summary The concept of a nonspecific thalamus has been substantially revised in the past several years, so that it is composed of a heterogeneous collection of individually signatured cell groups. The term “nonspecific” has been dismissed, but it has left behind a great deal of confusion and the embarrassing impression that the nonspecific thalamus has not found a satisfactory anatomical identity. This chapter reviews the midline thalamic region, which is part of this complex territory. It aims to define the midline thalamus as a collection of cell groups whose structural features and circuits differ greatly from those of adjacent structures and from all other portions of the “nonspecific” thalamus. The chapter discusses midline in relation to the intralaminar thalamus because these two regions have been unified historically in the same entity, and they are still often considered as a single group. This is due to the common belief that midline and intralaminar nuclei share functional features, based on their preferential innervation from the brain stem core and their robust connections with the basal ganglia.

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–ENDOCRINOLOGY: Hypoprolactinemia: A New Clinical Syndrome in Patients with Sexual Dysfunction

INTRODUCTION The physiological role of prolactin (PRL) in male sexual behavior is poorly understood. Conversely, the association between PRL pathological elevation in both reproductive and sexual behavior is well defined. AIM The aim of the present study is to assess the correlates of normal PRL (PRL < 735 mU/L or 35 ng/mL), in male subjects consulting for sexual dysfunction. METHODS A consecutive series of 2,531 (mean age 52.0 +/- 12.9 years) subjects was investigated. Patients were interviewed using the structured interview on erectile dysfunction (SIEDY), a 13-item tool for the assessment of erectile dysfunction (ED)-related morbidities. Middlesex Hospital Questionnaire was used for the evaluation of psychological symptoms. MAIN OUTCOME MEASURES Several hormonal (testosterone, thyroid stimulation hormone, and PRL) and biochemical parameters (glycemia and lipid profile) were studied, along with penile Doppler ultrasound (PDU) and SIEDY items. RESULTS After adjustment for confounders anxiety symptoms decreased across PRL quartiles (I: <113 mU/L or 5 ng/mL; II: 113-156 mU/L or 5.1-7 ng/mL; III: 157-229 mU/L or 7.1-11 ng/mL; IV: 229-734 mU/L or 11.1-34.9 ng/mL). Patients in the lowest PRL quartile showed a higher risk of metabolic syndrome (MetS; odds ratio [OR] = 1.74 [1.01-2.99], P < 0.05), arteriogenic ED (peak systolic velocity at PDU < 35 cm/sec; OR = 1.43 [1.01-2.03], P < 0.05), and premature ejaculation (PE; OR = 1.38 [1.02-1.85]; P < 0.05). Conversely, comparing subjects with PRL-secreting pituitary adenomas (N = 13) with matched controls, no significant difference was observed, except for a higher prevalence of hypoactive sexual desire in hyperprolactinemia. CONCLUSIONS Our findings demonstrate that, in subjects consulting for sexual dysfunction, PRL in the lowest quartile levels are associated with MetS and arteriogenic ED, as well as with PE and anxiety symptoms. Further studies are advisable in order to confirm our preliminary results in different populations.

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.