La sfida globale del diabete rappresenta un'emergenza che avanza lentamente e che, se non affront... more La sfida globale del diabete rappresenta un'emergenza che avanza lentamente e che, se non affrontata al più presto, può portare il mondo ad una catastrofe sanitaria che avrà profonde implicazioni sociali, economiche e politiche. L'organizzazione dei contesti ambientali e sociali è in grado di influenzare e modificare i bisogni emergenti delle persone, gli stili di vita e le aspettative, per questo rappresenta un fattore da considerare nella definizione delle politiche pubbliche. La conoscenza del contesto specifico consente di individuare i punti su cui fare leva per ottenere un cambiamento che possa avere impatto nella riduzione del rischio di salute dei cittadini. Tale sfida deve essere affrontata, con rigore scientifico, sul territorio, e in un quadro di grande collaborazione istituzionale. Infatti, la pianificazione degli agglomerati urbani, soprattutto in un contesto complesso quale quello della città metropolitana di Roma, condiziona profondamente la capacità dei suoi abitanti di condurre una vita lunga, in salute e produttiva. La sua ridefinizione alla luce dei bisogni dei cittadini può permettere di ridurre il crescente carico di malattia e allo stesso tempo contenere la dinamica dei costi del sistema sanitario. Con questo obiettivo, Roma è inserita all'interno del progetto internazionale Cities Changing Diabetes (CCD), in un contesto che vede coinvolte a livello Europeo 10 città per studiare l'impatto dell'urbanizzazione sul diabete di tipo 2 e sull'obesità. L'area metropolitana di Roma ha visto la sua popolazione raddoppiare a partire dal secondo dopoguerra, e allo stesso tempo la condizione socio-economica e la struttura demografica sono arrivate ad evidenziare profonde differenze all'interno dell'area metropolitana. Le difformità sul territorio della città indicano l'esistenza di un ampio margine di miglioramento per quanto riguarda la diagnosi precoce e l'assistenza alle persone con diabete. I mutamenti del contesto socio-demografico della città e l'afflusso interurbano di persone non residenti all'interno dell'area e del comune per ragioni di lavoro, studio, turismo etc. rischiano infatti di limitare la fruibilità e la possibilità di accesso alle strutture di erogazione dei servizi socio-sanitari.
Osteocalcin (OSCA) seems to act as a negative regulator of energy metabolism and insulin sensitiv... more Osteocalcin (OSCA) seems to act as a negative regulator of energy metabolism and insulin sensitivity. Evidence from male rodents suggests that OSCA may also regulate testosterone (T) synthesis. Using a cross-sectional design, we evaluated OSCA, 25(OH) vitamin D, T, 17 -estradiol (E2), homeostasis model assessment of insulin resistance (HOMA-IR), and body composition in 86 obese (mean BMI = 34) male subjects (18-69 yr old). Independently from BMI, an inverse relationship between trunk fat percentage and plasma T ( 2 = −0.26, < 0.01) and between HOMA-IR and OSCA levels ( 2 = −0.22, < 0.005) was found. OSCA levels, as well as vitamin D, decreased significantly for higher BMI with significant differences above 35 ( < 0.01). A direct correlation between T and bone mineral density at lumbar (BMDL) and neck (BMDH) ( < 0.001, 2 = −0.20; < 0.001, 2 = −0.24) was found, independently from age. An inverse correlation between E2 levels, BMDL, and BMDH ( < 0.001, 2 = −0.20; < 0.001, 2 = −0.19) was observed. These data provide new evidences that a relationship between trunk fat mass, insulin sensitivity, OSCA and T synthesis occurs. This new relationship with skeletal health has relevant implications for the aging male, suggesting OSCA as a novel marker of metabolic and gonadal health status.
We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral ... more We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm 2 ; femoral BMD= 0.847 ± 0.117 g/cm 2 ). TU induced a significant improvement of bone mass after 36 months (lumbar BMD = 1.053 ± 0.145 g/cm 2 ; p < 0.002; femoral BMD = 0.989 ± 0.109; p < 0.003 g/cm 2 ) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r 2 = 0.66, p < 0.0001) and femoral (r 2 = 0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middleaged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.
Introduction. Epidemiological studies conducted on erectile dysfunction (ED) have demonstrated i... more Introduction. Epidemiological studies conducted on erectile dysfunction (ED) have demonstrated its close correlation with cardiovascular disease. Since hyperhomocysteinemia is considered an important cardiovascular risk factor, it could also be involved in the pathogenesis of ED.Aim. To study the role of the C677T MTHFR mutation with subsequent hyperhomocysteinemia in the determination of ED.Methods. We studied 75 consecutive patients presenting with ED. Patients were interviewed using the International Index of Erectile Function. Blood samples were drawn for determination of MTHFR gene C677T mutation, homocysteine (Hcy) and folate levels. Penile color Doppler was also performed.Main Outcome Methods. Patients were administered sildenafil citrate for 2 months. The nonresponders were treated with combination of sildenafil, vitamin B6, and folic acid for 6 weeks. Patients were split into three groups, A, B, and C on the basis on their MTHFR genotype, and in a further group defined as “sildenafil nonresponders” (NR).Results. We found 20 patients homozygous for mutant MTHFR 677T, 36 heterozygous, and 19 wild type. Difference in baseline values for Hcy and folic acid was found between groups A and B, and A and C. The NR group (18 patients from group A and B), presented high levels of Hcy and low levels of folic acid. After combination treatment 16 of them (88.9%) revealed an improvement in the IIEF questionnaire. Moreover, it was measured a significant difference between the values of Hcy and folic acid at the baseline and at the end of the study for the nonresponders.Conclusions. Hyperhomocysteinemia in patients homozygotes for the C677T mutation may interfere with erection mechanisms and thus be responsible for ED. In case of hyperhomocysteinemia associated with low levels of folates, the administration of PDE5 inhibitors may fail if not preceded by the correction of the alterated levels of Hcy and folates. Lombardo F, Tsamatropoulos P, Piroli E, Culasso F, Jannini EA, Dondero F, Lenzi A, and Gandini L. Treatment of erectile dysfunction due to C677T mutation of the MTHFR gene with vitamin B6 and folic acid in patients non responders to PDE5i. J Sex Med 2010;7:216–223.
Introduction. Worldwide many aging males practice sports. A high prevalence of late-onset male h... more Introduction. Worldwide many aging males practice sports. A high prevalence of late-onset male hypogonadism has been observed in general population. Sport-participation influences the neuroendocrine system and may decrease serum testosterone.Aim. This preliminary study was designed to estimate the prevalence and the symptoms of undiagnosed testosterone deficiency in aging athletes.Methods. This observational survey was performed in 183 caucasian male athletes >50 years, in the setting of pre-participation screening. Pituitary–gonadal hormones and symptoms of hypogonadism were investigated. Serum total testosterone (TT), sex hormone binding globulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), free-T4, and thyroid stimulation hormone (TSH) were assayed, and free T, bioactive T, and the LH/TT ratio were calculated. The International Index of Erectile Dysfunction (IIEF-15) and the Center for Epidemiological Studies Depression Scale (CES-D) were administered. Hypogonadal athletes were compared with eugonadal athletes as controls.Main Outcome Measures. Prevalence and clinical symptoms of severe (TT < 8 nmol/L) or mild (8 nmol/L ≤ TT < 12 nmol/L) testosterone deficiency were investigated.Results. The mean sample age was 61.9 ± 7.5 years (range 50–75). Severe or mild testosterone deficiency was observed in 12% and 18%, respectively, of overall athletes, with the highest prevalence in athletes >70 years (27.5% and 25.0%, respectively). TT did not correlate with age, training duration, or questionnaire scores. No differences were observed for nonspecific symptoms of hypogonadism, IIEF-15 and CES-D scores between eugonadal and severe hypogonadal athletes.Conclusions. Independently of its etiology, a significant percentage of aging athletes had undiagnosed testosterone deficiency. In a relevant number of these cases, testosterone deficiency was not overtly symptomatic. Our results suggest that sport-participation per se can influence the symptoms of hypogonadism. The history of clinical symptoms may be inaccurate to diagnose testosterone deficiency in aging athletes. Future research should address the clinical relevance and the specific risks of testosterone deficiency in aging athletes, and the need of a systematic pre-participation serum testosterone evaluation. Di Luigi L, Sgrò P, Fierro V, Bianchini S, Battistini G, Magini V, Jannini EA, and Lenzi A. Prevalence of undiagnosed testosterone deficiency in aging athletes: Does exercise training influence the symptoms of male hypogonadism? J Sex Med 2010;7:2591–2601.
To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men with id... more To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men with idiopathic infertility.Placebo-controlled, double-blind randomized trial.Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Sixty infertile patients (27–39 years of age) with the following baseline sperm selection criteria: concentration >20 × 106/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study.Patients underwent double-blind therapy with coenzyme Q10, 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.Variations in semen parameters used for patient selection and variations of coenzyme Q10 and ubiquinol concentrations in seminal plasma and spermatozoa.Coenzyme Q10 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 Q10 and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q10 had a statistically significant higher probability to be responders to the treatment.The exogenous administration of coenzyme Q10 increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.
Introduction. Longitudinal studies have demonstrated that male hypogonadism could be considered ... more Introduction. Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease.Aim. To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11 nmol/L or free T at or below 250 pmol/L).Methods. This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57 ± 8) were randomized (4:1) to receive TU 1,000 mg (every 12 weeks) or placebo (PLB) gel (3–6 g/daily) for 24 months.Main Outcome Measures. Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP).Results. At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P < 0.001), CIMT (P < 0.0001), and hsCRP (P < 0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P < 0.0001) and 58% (P < 0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P < 0.0001), visceral fat mass (P < 0.0001), and improvement in HOMA-IR without changes in body mass index (BMI).Conclusions. TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events. Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, and Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late onset hypogonadism and metabolic syndrome: Results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med 2010;7:3495–3503.
Objective: To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month... more Objective: To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month after orchiectomy and before radiotherapy or chemotherapy. Design: Clinical study. Setting: Department of andrology and seminology at a university hospital. Patient(s): One hundred ninety patients with testicular cancer. Intervention(s): Determination of semen parameters and autoimmune reaction evaluated on the sperm surface and in blood serum. Main Outcome Measure(s): Autoimmune reaction on the sperm surface by the direct immunobead test (IBT), and in blood serum by the indirect IBT and the gelatin agglutination test (GAT), was evaluated 1 month after orchiectomy and before beginning chemotherapy or radiotherapy. Result(s): Of the 190 patients, 11 (5.8%) were positive for antisperm antibody by GAT. On indirect IBT, 3 of the 11 GAT-positive patients were positive to IgG class only, with values of 22%, 24%, and 40%. Of the 11 GAT-positive patients, 4 showed no antibody bound to the sperm surface, and 3 were positive to IgG class only (28%, 21%, and 38%), with binding exclusively on the tail. Direct IBT could not be performed in the remaining 4 patients. Conclusion(s): Our data support the hypothesis that testicular cancer might not be a possible cause of antisperm autoimmunization and infertility. (Fertil Steril Ò 2009;91:414-9.
There is still considerable controversy concerning the issue of testosterone replacement therapy.... more There is still considerable controversy concerning the issue of testosterone replacement therapy. This is because testosterone replacement therapy is not a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;risk-free&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; treatment and a randomized controlled trial to evaluate safety of prolonged testosterone replacement therapy is not available, nor is it likely to be in the near future. However, recent testosterone delivery systems, such as the 1% gel (Testogel, Androgel and Testim), have proven to have a good physiologic profile, allowing constant monitoring of the possible complications and prompt discontinuation in the event of adverse effects. The aim of this paper is to provide a comprehensive review of the available testosterone preparations to treat male hypogonadism, with special interest in the treatment of ageing men and late-onset hypogonadism. In addition, the experimental and clinical data on the effect of testosterone on sexual function domains is reviewed along with the indication for the combination therapy of androgens with pro-erectile drugs, for example, type 5 phosphodiesterase inhibitors.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2014
Introduction Obesity is a chronic disease as well as a risk factor for cardiovascular, metabolic ... more Introduction Obesity is a chronic disease as well as a risk factor for cardiovascular, metabolic and osteoarticular diseases, affecting the psychosocial health and the quality of life. Recent evidence suggests that the adequate treatment of obesity should provide a multidimensional multidisciplinary approach including nutritional therapy, psycho-educational classes and physical reconditioning/motor rehabilitation. The aim of this approach should be to maintain the results over time with a positive impact on the obesity-related cardiovascular and metabolic risk. Aim of the study To evaluate the effectiveness of a multidisciplinary Nutritional and Psycho-Physical Reconditioning Program (NPPRP) in an outpatient setting. Materials and methods The observational prospective cohort study involved subjects, aged from 18 to 65 years, with a BMI [30 kg/m 2 , who were followed up over 48 months. After the first nutritional and psychological examination, patients who refused NPPRP were treated according to standard nutrition procedures (SNT). Patients were followed through monthly medical examinations and then by annual telephonic structured interviews for 4 years. Changes in body weight, eating behavior, physical activity performance, and the occurrence of clinical obesity-related complications were considered as outcome measures. Results Of 464 enrolled patients, 161 (34.7 %) took part in the follow-up. From the enrollment to the end of followup, weight loss was greater in the NPPRP group than in the SNP group (-8.08 ± 10 kg versus -3.0 ± 6 kg). After 4 years eating behavior improved in both groups. The percentage of patients who continued to perform physical activity was higher in the NPPRP group than in the SNT group (61.0 versus 34.1 %). The SNT group reported complications more frequently than the NPPRP group: hypertension (19 versus 5.8 %), dyslipidemia (19.4 versus 12.7 %), and skeletal problems (26.9 versus 17.5 %). The main reasons for drop-out from the rehabilitation program were logistic problems (distance or time) in both groups; disappointment was higher in the SNT group than in the NPPRP group (37.8 versus 15.6 %). Conclusion A multidimensional multidisciplinary approach including nutritional intervention and psychophysical rehabilitation, set against a conventional diet therapy, was more effective in the long-term outcome of obesity with regard to weight loss, physical activity, possible eating disorders, and obesity-related complications.
We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demon... more We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demonstrated for the first time that PDE5 is localized in discrete cytoplasmic foci and vesicular compartments corresponding to centrosomes. We also found that PDE5 intracellular localization is not cell-or species-specific, as it is conserved in different animal and human cells. PDE5 protein levels are strongly regulated by the mitotic activity of the smooth muscle cells (SMCs), as they were increased in quiescent, contractile myometrial cultures, and conditions in which proliferation was inhibited. In contrast, PDE1C levels decreased in all conditions that inhibited proliferation. This mirrored the enzymatic activity of both PDE5 and PDE1C. Increasing cGMP intracellular levels by dbcGMP or sildenafil treatments did not block proliferation, while dbcAMP inhibited myometrial cell proliferation. Together, these results suggest that PDE5 regulation of cGMP intracellular levels is not involved in the control of SMC cycle progression, but may represent one of the markers of the contractile phenotype.
La sfida globale del diabete rappresenta un'emergenza che avanza lentamente e che, se non affront... more La sfida globale del diabete rappresenta un'emergenza che avanza lentamente e che, se non affrontata al più presto, può portare il mondo ad una catastrofe sanitaria che avrà profonde implicazioni sociali, economiche e politiche. L'organizzazione dei contesti ambientali e sociali è in grado di influenzare e modificare i bisogni emergenti delle persone, gli stili di vita e le aspettative, per questo rappresenta un fattore da considerare nella definizione delle politiche pubbliche. La conoscenza del contesto specifico consente di individuare i punti su cui fare leva per ottenere un cambiamento che possa avere impatto nella riduzione del rischio di salute dei cittadini. Tale sfida deve essere affrontata, con rigore scientifico, sul territorio, e in un quadro di grande collaborazione istituzionale. Infatti, la pianificazione degli agglomerati urbani, soprattutto in un contesto complesso quale quello della città metropolitana di Roma, condiziona profondamente la capacità dei suoi abitanti di condurre una vita lunga, in salute e produttiva. La sua ridefinizione alla luce dei bisogni dei cittadini può permettere di ridurre il crescente carico di malattia e allo stesso tempo contenere la dinamica dei costi del sistema sanitario. Con questo obiettivo, Roma è inserita all'interno del progetto internazionale Cities Changing Diabetes (CCD), in un contesto che vede coinvolte a livello Europeo 10 città per studiare l'impatto dell'urbanizzazione sul diabete di tipo 2 e sull'obesità. L'area metropolitana di Roma ha visto la sua popolazione raddoppiare a partire dal secondo dopoguerra, e allo stesso tempo la condizione socio-economica e la struttura demografica sono arrivate ad evidenziare profonde differenze all'interno dell'area metropolitana. Le difformità sul territorio della città indicano l'esistenza di un ampio margine di miglioramento per quanto riguarda la diagnosi precoce e l'assistenza alle persone con diabete. I mutamenti del contesto socio-demografico della città e l'afflusso interurbano di persone non residenti all'interno dell'area e del comune per ragioni di lavoro, studio, turismo etc. rischiano infatti di limitare la fruibilità e la possibilità di accesso alle strutture di erogazione dei servizi socio-sanitari.
Osteocalcin (OSCA) seems to act as a negative regulator of energy metabolism and insulin sensitiv... more Osteocalcin (OSCA) seems to act as a negative regulator of energy metabolism and insulin sensitivity. Evidence from male rodents suggests that OSCA may also regulate testosterone (T) synthesis. Using a cross-sectional design, we evaluated OSCA, 25(OH) vitamin D, T, 17 -estradiol (E2), homeostasis model assessment of insulin resistance (HOMA-IR), and body composition in 86 obese (mean BMI = 34) male subjects (18-69 yr old). Independently from BMI, an inverse relationship between trunk fat percentage and plasma T ( 2 = −0.26, < 0.01) and between HOMA-IR and OSCA levels ( 2 = −0.22, < 0.005) was found. OSCA levels, as well as vitamin D, decreased significantly for higher BMI with significant differences above 35 ( < 0.01). A direct correlation between T and bone mineral density at lumbar (BMDL) and neck (BMDH) ( < 0.001, 2 = −0.20; < 0.001, 2 = −0.24) was found, independently from age. An inverse correlation between E2 levels, BMDL, and BMDH ( < 0.001, 2 = −0.20; < 0.001, 2 = −0.19) was observed. These data provide new evidences that a relationship between trunk fat mass, insulin sensitivity, OSCA and T synthesis occurs. This new relationship with skeletal health has relevant implications for the aging male, suggesting OSCA as a novel marker of metabolic and gonadal health status.
We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral ... more We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm 2 ; femoral BMD= 0.847 ± 0.117 g/cm 2 ). TU induced a significant improvement of bone mass after 36 months (lumbar BMD = 1.053 ± 0.145 g/cm 2 ; p < 0.002; femoral BMD = 0.989 ± 0.109; p < 0.003 g/cm 2 ) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r 2 = 0.66, p < 0.0001) and femoral (r 2 = 0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middleaged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.
Introduction. Epidemiological studies conducted on erectile dysfunction (ED) have demonstrated i... more Introduction. Epidemiological studies conducted on erectile dysfunction (ED) have demonstrated its close correlation with cardiovascular disease. Since hyperhomocysteinemia is considered an important cardiovascular risk factor, it could also be involved in the pathogenesis of ED.Aim. To study the role of the C677T MTHFR mutation with subsequent hyperhomocysteinemia in the determination of ED.Methods. We studied 75 consecutive patients presenting with ED. Patients were interviewed using the International Index of Erectile Function. Blood samples were drawn for determination of MTHFR gene C677T mutation, homocysteine (Hcy) and folate levels. Penile color Doppler was also performed.Main Outcome Methods. Patients were administered sildenafil citrate for 2 months. The nonresponders were treated with combination of sildenafil, vitamin B6, and folic acid for 6 weeks. Patients were split into three groups, A, B, and C on the basis on their MTHFR genotype, and in a further group defined as “sildenafil nonresponders” (NR).Results. We found 20 patients homozygous for mutant MTHFR 677T, 36 heterozygous, and 19 wild type. Difference in baseline values for Hcy and folic acid was found between groups A and B, and A and C. The NR group (18 patients from group A and B), presented high levels of Hcy and low levels of folic acid. After combination treatment 16 of them (88.9%) revealed an improvement in the IIEF questionnaire. Moreover, it was measured a significant difference between the values of Hcy and folic acid at the baseline and at the end of the study for the nonresponders.Conclusions. Hyperhomocysteinemia in patients homozygotes for the C677T mutation may interfere with erection mechanisms and thus be responsible for ED. In case of hyperhomocysteinemia associated with low levels of folates, the administration of PDE5 inhibitors may fail if not preceded by the correction of the alterated levels of Hcy and folates. Lombardo F, Tsamatropoulos P, Piroli E, Culasso F, Jannini EA, Dondero F, Lenzi A, and Gandini L. Treatment of erectile dysfunction due to C677T mutation of the MTHFR gene with vitamin B6 and folic acid in patients non responders to PDE5i. J Sex Med 2010;7:216–223.
Introduction. Worldwide many aging males practice sports. A high prevalence of late-onset male h... more Introduction. Worldwide many aging males practice sports. A high prevalence of late-onset male hypogonadism has been observed in general population. Sport-participation influences the neuroendocrine system and may decrease serum testosterone.Aim. This preliminary study was designed to estimate the prevalence and the symptoms of undiagnosed testosterone deficiency in aging athletes.Methods. This observational survey was performed in 183 caucasian male athletes >50 years, in the setting of pre-participation screening. Pituitary–gonadal hormones and symptoms of hypogonadism were investigated. Serum total testosterone (TT), sex hormone binding globulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), free-T4, and thyroid stimulation hormone (TSH) were assayed, and free T, bioactive T, and the LH/TT ratio were calculated. The International Index of Erectile Dysfunction (IIEF-15) and the Center for Epidemiological Studies Depression Scale (CES-D) were administered. Hypogonadal athletes were compared with eugonadal athletes as controls.Main Outcome Measures. Prevalence and clinical symptoms of severe (TT < 8 nmol/L) or mild (8 nmol/L ≤ TT < 12 nmol/L) testosterone deficiency were investigated.Results. The mean sample age was 61.9 ± 7.5 years (range 50–75). Severe or mild testosterone deficiency was observed in 12% and 18%, respectively, of overall athletes, with the highest prevalence in athletes >70 years (27.5% and 25.0%, respectively). TT did not correlate with age, training duration, or questionnaire scores. No differences were observed for nonspecific symptoms of hypogonadism, IIEF-15 and CES-D scores between eugonadal and severe hypogonadal athletes.Conclusions. Independently of its etiology, a significant percentage of aging athletes had undiagnosed testosterone deficiency. In a relevant number of these cases, testosterone deficiency was not overtly symptomatic. Our results suggest that sport-participation per se can influence the symptoms of hypogonadism. The history of clinical symptoms may be inaccurate to diagnose testosterone deficiency in aging athletes. Future research should address the clinical relevance and the specific risks of testosterone deficiency in aging athletes, and the need of a systematic pre-participation serum testosterone evaluation. Di Luigi L, Sgrò P, Fierro V, Bianchini S, Battistini G, Magini V, Jannini EA, and Lenzi A. Prevalence of undiagnosed testosterone deficiency in aging athletes: Does exercise training influence the symptoms of male hypogonadism? J Sex Med 2010;7:2591–2601.
To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men with id... more To evaluate the effectiveness of coenzyme Q10 treatment in improving semen quality in men with idiopathic infertility.Placebo-controlled, double-blind randomized trial.Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy.Sixty infertile patients (27–39 years of age) with the following baseline sperm selection criteria: concentration >20 × 106/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study.Patients underwent double-blind therapy with coenzyme Q10, 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.Variations in semen parameters used for patient selection and variations of coenzyme Q10 and ubiquinol concentrations in seminal plasma and spermatozoa.Coenzyme Q10 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 Q10 and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q10 had a statistically significant higher probability to be responders to the treatment.The exogenous administration of coenzyme Q10 increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.
Introduction. Longitudinal studies have demonstrated that male hypogonadism could be considered ... more Introduction. Longitudinal studies have demonstrated that male hypogonadism could be considered a surrogate marker of incident cardiovascular disease.Aim. To evaluate the effects of parenteral testosterone undecanoate (TU) in outclinic patients with metabolic syndrome (MS) and late-onset hypogonadism (total testosterone (T) at or below 11 nmol/L or free T at or below 250 pmol/L).Methods. This is a randomized, double-blind, double-dummy, placebo-controlled, parallel group, single-center study. Fifty patients (mean age 57 ± 8) were randomized (4:1) to receive TU 1,000 mg (every 12 weeks) or placebo (PLB) gel (3–6 g/daily) for 24 months.Main Outcome Measures. Homeostasis model assessment index of insulin resistance (HOMA-IR), carotid intima media thickness (CIMT), and high-sensitivity C-reactive protein (hsCRP).Results. At baseline, all patients fulfilled the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) and International Diabetes Federation (IDF) criteria for the definition of MS. An interim analysis conducted at 12 months showed that TU markedly improved HOMA-IR (P < 0.001), CIMT (P < 0.0001), and hsCRP (P < 0.001) compared with PLB; thus, all patients were shifted to TU treatment. After 24 months, 35% (P < 0.0001) and 58% (P < 0.001) of patients still presented MS as defined by NCEP-ATPIII and IDF criteria, respectively. Main determinants of changes were reduction in waist circumference (P < 0.0001), visceral fat mass (P < 0.0001), and improvement in HOMA-IR without changes in body mass index (BMI).Conclusions. TU reduced fasting glucose, waist circumference, and improved surrogate markers of atherosclerosis in hypogonadal men with MS. Resumption and maintenance of T levels in the normal range of young adults determines a remarkable reduction in cardiovascular risk factors clustered in MS without significant hematological and prostate adverse events. Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, and Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late onset hypogonadism and metabolic syndrome: Results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med 2010;7:3495–3503.
Objective: To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month... more Objective: To evaluate the presence of antisperm antibodies in testicular cancer patients 1 month after orchiectomy and before radiotherapy or chemotherapy. Design: Clinical study. Setting: Department of andrology and seminology at a university hospital. Patient(s): One hundred ninety patients with testicular cancer. Intervention(s): Determination of semen parameters and autoimmune reaction evaluated on the sperm surface and in blood serum. Main Outcome Measure(s): Autoimmune reaction on the sperm surface by the direct immunobead test (IBT), and in blood serum by the indirect IBT and the gelatin agglutination test (GAT), was evaluated 1 month after orchiectomy and before beginning chemotherapy or radiotherapy. Result(s): Of the 190 patients, 11 (5.8%) were positive for antisperm antibody by GAT. On indirect IBT, 3 of the 11 GAT-positive patients were positive to IgG class only, with values of 22%, 24%, and 40%. Of the 11 GAT-positive patients, 4 showed no antibody bound to the sperm surface, and 3 were positive to IgG class only (28%, 21%, and 38%), with binding exclusively on the tail. Direct IBT could not be performed in the remaining 4 patients. Conclusion(s): Our data support the hypothesis that testicular cancer might not be a possible cause of antisperm autoimmunization and infertility. (Fertil Steril Ò 2009;91:414-9.
There is still considerable controversy concerning the issue of testosterone replacement therapy.... more There is still considerable controversy concerning the issue of testosterone replacement therapy. This is because testosterone replacement therapy is not a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;risk-free&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; treatment and a randomized controlled trial to evaluate safety of prolonged testosterone replacement therapy is not available, nor is it likely to be in the near future. However, recent testosterone delivery systems, such as the 1% gel (Testogel, Androgel and Testim), have proven to have a good physiologic profile, allowing constant monitoring of the possible complications and prompt discontinuation in the event of adverse effects. The aim of this paper is to provide a comprehensive review of the available testosterone preparations to treat male hypogonadism, with special interest in the treatment of ageing men and late-onset hypogonadism. In addition, the experimental and clinical data on the effect of testosterone on sexual function domains is reviewed along with the indication for the combination therapy of androgens with pro-erectile drugs, for example, type 5 phosphodiesterase inhibitors.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2014
Introduction Obesity is a chronic disease as well as a risk factor for cardiovascular, metabolic ... more Introduction Obesity is a chronic disease as well as a risk factor for cardiovascular, metabolic and osteoarticular diseases, affecting the psychosocial health and the quality of life. Recent evidence suggests that the adequate treatment of obesity should provide a multidimensional multidisciplinary approach including nutritional therapy, psycho-educational classes and physical reconditioning/motor rehabilitation. The aim of this approach should be to maintain the results over time with a positive impact on the obesity-related cardiovascular and metabolic risk. Aim of the study To evaluate the effectiveness of a multidisciplinary Nutritional and Psycho-Physical Reconditioning Program (NPPRP) in an outpatient setting. Materials and methods The observational prospective cohort study involved subjects, aged from 18 to 65 years, with a BMI [30 kg/m 2 , who were followed up over 48 months. After the first nutritional and psychological examination, patients who refused NPPRP were treated according to standard nutrition procedures (SNT). Patients were followed through monthly medical examinations and then by annual telephonic structured interviews for 4 years. Changes in body weight, eating behavior, physical activity performance, and the occurrence of clinical obesity-related complications were considered as outcome measures. Results Of 464 enrolled patients, 161 (34.7 %) took part in the follow-up. From the enrollment to the end of followup, weight loss was greater in the NPPRP group than in the SNP group (-8.08 ± 10 kg versus -3.0 ± 6 kg). After 4 years eating behavior improved in both groups. The percentage of patients who continued to perform physical activity was higher in the NPPRP group than in the SNT group (61.0 versus 34.1 %). The SNT group reported complications more frequently than the NPPRP group: hypertension (19 versus 5.8 %), dyslipidemia (19.4 versus 12.7 %), and skeletal problems (26.9 versus 17.5 %). The main reasons for drop-out from the rehabilitation program were logistic problems (distance or time) in both groups; disappointment was higher in the SNT group than in the NPPRP group (37.8 versus 15.6 %). Conclusion A multidimensional multidisciplinary approach including nutritional intervention and psychophysical rehabilitation, set against a conventional diet therapy, was more effective in the long-term outcome of obesity with regard to weight loss, physical activity, possible eating disorders, and obesity-related complications.
We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demon... more We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demonstrated for the first time that PDE5 is localized in discrete cytoplasmic foci and vesicular compartments corresponding to centrosomes. We also found that PDE5 intracellular localization is not cell-or species-specific, as it is conserved in different animal and human cells. PDE5 protein levels are strongly regulated by the mitotic activity of the smooth muscle cells (SMCs), as they were increased in quiescent, contractile myometrial cultures, and conditions in which proliferation was inhibited. In contrast, PDE1C levels decreased in all conditions that inhibited proliferation. This mirrored the enzymatic activity of both PDE5 and PDE1C. Increasing cGMP intracellular levels by dbcGMP or sildenafil treatments did not block proliferation, while dbcAMP inhibited myometrial cell proliferation. Together, these results suggest that PDE5 regulation of cGMP intracellular levels is not involved in the control of SMC cycle progression, but may represent one of the markers of the contractile phenotype.
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Papers by Andrea Lenzi