Riccardo Mansani

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.

FokI Polymorphism at Translation Initiation Site of the Vitamin D Receptor Gene Predicts Bone Mineral Density and Vertebral Fractures in Postmenopausal Italian Women

A novel T/C polymorphism (ATG to ACG) at the translation initiation site of the vitamin D receptor (VDR) gene, defined by FokI restriction endonuclease, has been recently associated with variation in bone mineral density (BMD) and rates of bone loss in a group of postmenopausal Mexican‐American women. The presence of the restriction site, designated as f, allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at a second ATG. In this study, we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic (n = 164), osteopenic (n = 117), and normal (n = 119) groups. There were 159 (41%) FF homozygotes, 55 (14%) ff homozygotes, and 186 (45%) Ff heterozygotes. In the whole population, we observed a weak association between FokI polymorphism and lumbar BMD (p = 0.06, analysis of covariance [ANCOVA]) but not with femoral neck BMD (p = 0.5, ANCOVA). Interestingly, the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause (p = 0.04, ANCOVA), progressively declining afterward. In addition, a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed (p = 0.04, Chi‐square test). Finally, ff genotype resulted significantly over‐represented in the group of women with a vertebral fracture as compared with controls (p = 0.003, Chi‐square test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36–4.91). We conclude that in this population, FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.

Vitamin D receptor genotypes and intestinal calcium absorption in postmenopausal women

Abstract. Several studies have shown that bone mass and bone turnover are genetically determined. This genetic component is thought to be mediated in part by polymorphisms at the vitamin D receptor (VDR) locus, even though the underlying molecular mechanisms are still unknown. To evaluate a possible site of differential action of the VDR gene alleles we examined their correlation with intestinal calcium absorption in 120 Caucasian postmenopausal women (aged 61 ± 0.6 years). VDR gene polymorphisms for Apa I, Bsm I, and Taq I restriction endonucleases were assessed by Southern blotting analysis. The most common genotypes observed in our population were AaBbTt (37%), AABBtt (20%), aabbTT (15%), AabbTT (15%), and AABbTt (9%). Although there was some evidence of 13% higher lumbar BMD values in aabbTT genotype with respect to AABBtt genotype, this difference of approximately 0.1 g/cm2 did not reach statistical significance, possibly because of the limited number of observations. On the contrary, no relationship was found between genotypes and femoral neck BMD values. Intestinal calcium absorption was significantly lower in BB and tt genotypes than, in bb and TT genotypes, respectively, and in AABBtt genotype than in either aabbTT or AaBbTt genotypes (P= 0.0015 ANOVA). No significant differences in intact PTH, alkaline phosphatase, 25OHD3, and 1,25(OH)2D3 were found among subjects with different VDR genotypes. These results are consistent with a possible role of VDR alleles on intestinal calcium absorption.

The ENDOTRIAL Study: A Spontaneous, Open-Label, Randomized, Multicenter, Crossover Study on the Efficacy of Sildenafil, Tadalafil, and Vardenafil in the Treatment of Erectile Dysfunction

INTRODUCTION The three effective, commercially available drugs for the treatment of erectile dysfunction-sildenafil, vardenafil, and tadalafil-inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date. AIM The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen. METHODS This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg. MAIN OUTCOME MEASURES The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment. RESULTS In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI significantly ameliorated in patients receiving 100 mg of sildenafil. Regression analysis confirmed an independent effect of sildenafil on hemodynamic efficacy parameters. CONCLUSIONS An overall equivalence was demonstrated in the subjective perception of treatment benefits for all the PDE5i tested. However, sildenafil, in a dose-dependent manner, was the unique PDE5i able to ameliorate some of the penile flow parameters within the 8-week treatment period. These findings should be interpreted conservatively because of the observational nature of the study.

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.

Difficulties in achieving vs maintaining erection: organic, psychogenic and relational determinants

Achieving and maintaining a penile erection are two essential components of the male sexual response. It has recently been suggested that distinct molecular mechanism could underlie the two disturbances. The aim of the present study is to verify possible clinical differences on pathogenetic factors underlying difficulties of achieving and maintaining an erection. We studied a consecutive series of 560 patients (aged 51.9±12.8 y old) reporting erectile dysfunction (ED), using SIEDY© structured interview. Patients were classified into two distinct categories: those with difficulties in maintaining, rather than achieving, an erection (sample A) and those with main problems in achieving an erection (sample B). A complete physical examination and a series of metabolic, biochemical, hormonal, psychometric, penile vascular tests and nocturnal penile tumescence and rigidity evaluations (NPT) were also performed. Sample B patients showed a higher prevalence of organic conditions related to ED, when compared with sample A as confirmed by higher SIEDY© scale 1 scores (3[1–5] vs 1[0.1–3] for sample B vs sample A, respectively; P<0.0001) which explores organic component of ED and higher prevalence of pathological instrumental parameters. No difference among groups was observed for SIEDY© scale 2 (relational component) and SIEDY© scale 3 (intrapsychic component) of ED. In conclusion, this study shows for the first time that patients with difficulties in maintaining erection are less likely to be affected by organic disturbances interfering with sexual function, when compared with those unable to achieve a valid erection.

Androgeni: azioni biologiche, uso clinico e abuso nell’uomo

RiassuntoGli androgeni svolgono un ruolo importante in tutte le fasi della vita dell’uomo. Nell’adulto ipogonadico si assiste ad una riduzione della densità ossea, un aumento della massa grassa e una diminuzione della massa e della forza muscolare che vengono ripristinate dalla terapia sostitutiva. Una carenza androgenica si riflette negativamente anche sulla funzione sessuale e sulla libido. Non è possibile tuttavia stabilire la soglia critica di testosterone per una normale sessualità. Nonostante il largo utilizzo in ambito sportivo, solo negli ultimi anni sono stati chiariti i reali effetti derivanti dall’abuso di steroidi anabolizzanti in soggetti eugonadici. In particolare l’abuso di anabolizzanti, specie se associato ad un regime alimentare ed un programma di allenamento appropriati, determina un indiscusso vantaggio in alcune performance sportive come il sollevamento pesi o il lancio del disco, che richiedono una dimostrazione di massima forza volontaria. Più discusso è il loro ruolo in altre discipline sportive. Tali effetti sono comunque gravati da complicanze certe o potenziali che possono condizionare la comparsa di effetti secondari irreversibili o persino fatali che giustificano la campagna preventiva contro il loro utilizzo.