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.

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.

Psycho-biological correlates of rapid ejaculation in patients attending an andrologic unit for sexual dysfunctions.

INTRODUCTION AND OBJECTIVES: Rapid ejaculation (RE) is the most common sexual dysfunction in males. The aim of the present study is to determine the contribution of intrapsychic, organic and relational factors to the pathogenesis of RE and the relationship between RE and erectile dysfunction (ED) in a sample of patients attending for the first time to an Outpatient Clinic for sexual dysfunction. METHODS: We studied a consecutive series of 755 patients using Structured Interview on Erectile Dysfunction (SIEDY), a brief, recently validated, multidimensional instrument specifically designed by our group for the study of pathogenetic factors of ED. RE was defined as ejaculation within 1 minute of vaginal intromission and its severity was categorized on a 4-point scale using a standard question. A complete physical examination and a series of biochemical, hormonal, psychometric, penile vascular and rigidometric evaluations were performed. RESULTS: Twenty-eight percent (n = 214) of patients attending to our sexology clinic reported RE of any degree. Patients reporting RE were younger (48.5 +/- 12.6 vs. 52.9 +/- 12.9 years old for RE and not RE respectively; p < 0.0001) and showed a higher prevalence of anxiety symptoms when compared to the rest of the sample. Among organic factors subjects with RE showed a higher prevalence of hyperthyroidism and significantly lower fasting plasma glucose (94 [87-110] and 98 [89-113] mg/dl for RE and non-RE respectively; p < 0.01). No difference among groups was observed for other hormones or clinical, biochemical and instrumental parameters. Finally RE patients showed a higher prevalence of partial erection sufficient for penetration when compared to the rest of the sample. Similar differences were observed between patients with and without RE when those without ED were excluded from the analysis. CONCLUSION: Our data suggest a minor involvement of organic factors to the pathogenesis of ED in patients with concomitant RE. On the other hand, in our sample, patients complaining about RE are younger, healthier than the rest of the sample and are characterized by high degree of anxiety symptoms and hyperthyroidism.

Organic, relational and psychological factors in erectile dysfunction in men with diabetes mellitus.

INTRODUCTION AND OBJECTIVES: Diabetes mellitus-induced erectile dysfunction (DMED) is thought to be multifactorial in aetiology and to include vascular, neurological, and psychological components. The aim of the present study is to determine the contribution of organic, relational, and intrapsychic components to the pathogenesis of ED in diabetic in comparison with non-diabetic patients. METHODS: We studied a consecutive series of 1027 using SIEDY structured interview. A complete physical examination and a series of metabolic, biochemical, hormonal, psychometric, penile vascular tests and nocturnal penile tumescence and rigidity evaluations were performed. RESULTS: 15% of patient studied were affected by DMED. Diabetic patients with DMED have a greater severity of erectile dysfunction and are more likely to have an organic, rather than an intrapsychic, component. Impaired sexual desire is less frequent in these patients and they had an higher prevalence of hypogonadism than non-diabetic individuals. CONCLUSION: Diabetic patients seeking treatment for erectile dysfunction have a greater severity of disease, less impaired sexual desire, suggesting that the need for medical care in diabetic patients with ED could be even greater than in their non-diabetic counterparts. Considering the higher prevalence of obesity-related decrease of testosterone levels in DMED, an appropriate screening and treatment of hypogonadism might improve the outcome of pharmacotherapy for ED in diabetic patients.

Aging and pathogenesis of erectile dysfunction.

The prevalence and the severity of erectile dysfunction (ED) increase with advancing age; different pathogenetic factors could contribute to age-related ED. We studied organic, relational and intrapsychic components of ED as a function of patients' age in a consecutive series of 977 patients with ED, using the specifically designed structured interview SIEDY. A complete physical examination and a series of biochemical, hormonal, psychometric and penile vascular tests were also performed. Relational factors seems to be more relevant in patients aged over 60 y, while intrapsychic disturbances play a major role in younger subjects. Organic factors are the most important determinant of ED in all age groups, but their contribution is more important in older patients. In fact, basal and dynamic peak cavernosal velocity at Doppler ultrasound penile examination was reduced in older patients. Among hormonal factors, the body mass index-dependent reduction of testosterone in older patients does not seem to play a crucial role in the pathogenesis of ED. No significant correlation was observed between testosterone level and the severity of ED, although patients reporting hypoactive sexual desire showed significantly lower testosterone levels when compared with the rest of the sample. A better understanding of the relative contribution of age-related pathogenetic factors of ED could be of help in the design of appropriate therapeutic approaches.

Psycho-biological correlates of hypoactive sexual desire in patients with erectile dysfunction.

We studied the psychological and biological correlates of hypoactive sexual desire (HSD) in a consecutive series of 428 patients with erectile dysfunction (ED), by using the structured interview SIEDY. A complete physical examination and a series of biochemical, hormonal, psychometric, and penile vascular tests were also performed. Among the patients studied, 22.8% reported a mild, 12.9% a moderate, and 4.6% a complete loss of sexual interest. Patients reporting HSD showed significantly lower testosterone (T) levels than the rest of the sample, although the prevalence of hypogonadism (T<10 nM) was comparable in the two groups. Only a minority (<2%) had severe hyperprolactinemia (>700 mU/l), which, nonetheless, was closely associated with a relevant HSD. Both mental disorders and use of medication interfering with sexual function were significantly associated with HSD, as well as depressive and anxiety symptoms. HSD patients showed significantly higher scores in SIEDY scale 2, which explores the relational component of ED. In particular, perceived partner's libido and climax were crucially associated with an impairment of patients' sexual desire. In conclusion, HSD in ED is associated with several biological, psychological, and relational factors that can be simultaneously identified and quantified using the SIEDY structured interview.

[Subclinical hyperthyroidism and hypothyroidism]. / Gli ipertiroidismi e gli ipotiroidismi subclinici.

Currently, technical methods to obtain precocious and reliable diagnosis of thyroid disorders are available for physicians. Therefore today, patients affected by mild hypo- or hyperthyroidism are more often diagnosed when they are still asymptomatic; these mild forms of thyroid disorder are known as subclinical hypo- and hyperthyroidism. In comparison with '80ties, over the last few years we have observed that patients come to endocrinological examination for subclinical forms of thyroid disorders (particularly for hypothyroidism) more frequently than for severe thyroid diseases. However, before to start a therapy, it is necessary for these patients to determine the causes of subclinical hypo- and hyperthyroidism. The main goals of therapy are to reduce the prevalence of cardiac arrhythmia and osteoporosis of patients with subclinical hyperthyroidism, and to slow down the course of arteriosclerotic disease (linked to hyperlipidemia and/or to hyperhomocysteinemia) of patients with subclinical hypothyroidism.

Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women.

Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a strong genetic component. The discovery that inactivation of estrogen receptor alpha (ERalpha) gene is associated with low BMD indicated ERalpha as a candidate gene for osteoporosis. We have investigated the role of three ERalpha gene polymorphisms [intron 1 PVU:II and XBA:I RFLPs and TA dinucleotide repeat polymorphism 5' upstream of exon 1] in 610 postmenopausal women. There was a strong linkage disequilibrium between intron 1 polymorphic sites and also between these sites and the microsatellite (TA)(n) dinucleotide polymorphism, with a high degree of coincidence of the short TA alleles and the presence of PVU:II and XBA:I restriction sites. No significant relationship between intron 1 RFLPs and BMD was observed. A statistically significant correlation between (TA)(n) repeat allelic variants and lumbar BMD was observed (P = 0.04, ANCOVA), with subjects with a low number of repeats (TA < 15) showing the lowest BMD values. We observed a statistically significant difference in the mean +/- SD number of TA repeats between analyzed women with a vertebral fracture (n = 73) and the non-fracture group, equivalent to 2.9 (95% CI 1.56-5.72) increased fracture risk in women with a low number of repeats (TA < 15). We conclude that in this large population sample the (TA)(n) dinucleotide repeat polymorphism at the 5' end of the ERalpha gene accounts for part of the heritable component of BMD and might prove useful in the prediction of vertebral fracture risk in postmenopausal osteoporosis.

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.

Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women.

Recognition of a major genetic component in bone mass determination represented the basis for studies aiming to the identification of underlying major and minor genes. Bone mineral density (BMD) represents the continuous trait to be quantified in order to evaluate segregation of candidate genes with risk of osteoporosis. Polymorphisms at the vitamin D receptor (VDR), estrogen receptor, (ER), collagen type I, and interleukin 6 (IL6) gene loci have been correlated to BMD. However, in a polygenic disorder, such as osteoporosis, the number of genes expected to influence BMD is very large. In the present study we examined the presence of restriction fragment length polymorphisms (RFLPs) for the calcitonin receptor (CTR) gene in postmenopausal women. We identified a polymorphic (Tt) site at the CTR gene locus using the Taq I restriction fragment enzyme. Three genotypes were observed, whose Tt was the most frequent in our population (49.7%). In addition, Ancova analysis and Tukey's test showed that women with tt genotype had significantly lower lumbar BMD in comparison with Tt genotype (Tukey's test: p = 0.005). In conclusion, evidence of RFLPs at the CTR gene locus in Caucasian postmenopausal women of Italian origin made it possible to identify the involvement of another gene, the CTR gene, in the determination of bone mass.

Allelic variants of human calcitonin receptor: distribution and association with bone mass in postmenopausal Italian women.

Bone mass could be under control of several polymorphic genes which can modulate bone turnover via reciprocal interactions. One of the genes that can be involved in this process is the calcitonin receptor (CTR) gene. Evidence from cDNA cloning has shown that CTRs have seven potential transmembrane domains and they are known to be expressed in several tissues. In a Japanese population was discovered a novel Restriction Fragment Length Polymorphism (RFLP) at the CTR gene by Alu I restriction enzyme at the 1377th nucleotide expressing either proline (CC genotype) or leucine (TT genotype) as the 463rd amino acid. The heterozygote genotypes were indicated as TC. In the present study we analyzed the presence of this CTR gene RFLP in 307 postmenopausal Italian women. We observed that TC and TT genotypes represented the most frequent CTR genotypes in Italian women. In addition, Duncan's test used to compare the genotypes showed that TT genotype has significant lower lumbar BMD in comparison with CC genotype.

Vitamin D and estrogen receptor allelic variants in Italian postmenopausal women: evidence of multiple gene contribution to bone mineral density.

Bone mass and bone turnover are under genetic control. Restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus have been recently correlated to bone mineral density (BMD) and rate of bone loss. However, agreement on this relationship is not universal. The existence of ethnical and environmental differences between populations, a health-based selection bias in several previous studies, and the involvement of other genes could explain these discordant findings. In this study, we examined the relationship of VDR and estrogen receptor (ER) gene RFLPs with lumbar spine and upper femur BMD in 426 Italian postmenopausal women, 57.7 +/- 0.4 yr old (144 normal, 106 osteopenic, and 176 osteoporotic). VDR gene RFLPs for ApaI, Bsm I, and TaqI restriction endonucleases and ER RFLPs for PvuII and XbaI restriction endonucleases were assessed by Southern blotting analysis and were indicated, respectively, as A-a, B-b, T-t, P-p, and X-x (uppercase letters signifying the absence and lowercase letters the presence of the restriction site). After correcting for potential confounding factors (age, height, weight, age since menopause, osteophytosis, and facet joint osteoarthritis), a statistically significant VDR genotype effect on lumbar BMD (P = 0.01, analysis of covariance), but not on femoral BMD, was detected, with subjects in AABBtt genotype showing a 13% lower BMD than those with aabbTT genotype (P < 0.05, Tukey's test). Moreover, a statistically significant prevalence of AABBtt genotype in osteoporotics, and of AabbTT and aabbTT genotypes in nonosteoporotics, were detected. Conversely, there was no significant relationship of ER genotype to either lumbar or femoral BMD, even though a trend for higher BMD values in women with the ER PP genotype (with respect to those with ER pp genotype) was detected. When mean lumbar BMD was calculated for women grouped by ER and VDR genotype, we observed a significant difference between those within the 2 opposite associations AABBtt-PPXX and aabbTT-ppxx (0.71 +/- 0.05 vs. 0.97 +/- 0.03 g/cm2, P < 0.05 Tukey's test). These results are consistent with a segregation of the VDR AABBtt genotype with a higher risk of developing osteoporosis, in the Italian female population. The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.

Vitamin D receptor genotypes and intestinal calcium absorption in postmenopausal women.

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.