Positive effects of dietary supplementation with nutraceuticals on male subclinical hypogonadism: a pilot study.

BACKGROUND: Lifestyle modifications (i.e., physical activity [PA] and lower dietary intake) often are not sufficient to improve testosterone (TE) levels and promote weight loss in men with metabolic hypogonadism. The aim of the study was to investigate the effects of a nutraceutical formulation containing myoinositol, alpha lipoic acid, folic acid and SelectSIEVE® as add-on treatment to lifestyle modifications in improving obesity-related subclinical hypogonadism. METHODS: Body composition, insulin resistance, testicular and erectile function were investigated in 15 males (age=39.5±14.5 years; Body Mass Index [BMI]=30.2±3.8 kg/m2, with subclinical hypogonadism (TE levels <14 and normal luteinizing hormone [LH]). After a run-in three months unsupervised PA period (T1), the nutraceutical supplement was administered two-times per day for three additional months (T2). RESULTS: BMI, the percentage fat mass, insulinemia and Homeostasis Model Assessment Index (P<0.01) along with glycemia (P<0.05) were significantly reduced at T2 compared to T1, respectively; fat free mass (FFM) was significantly higher at T2 compared to T1 (P<0.01). Also, TE, LH and 5-item international index of erectile function score were significantly increased at T2 compared to T1 (P<0.01), respectively. CONCLUSIONS: The combination of unsupervised PA and nutraceutical supplement improves body composition, insulin sensitivity and TE production in overweight-obese men with metabolic hypogonadism. Further controlled studies in the long-term are warranted to elucidate potential changes in fertility.

Oleuropein Counteracts Both the Proliferation and Migration of Intra- and Extragonadal Seminoma Cells.

Recent and growing literature has reported that oleuropein (OLE), the main polyphenol in olive leaf extract, inhibits tumor cell proliferation and reduces the invasiveness properties of cancer cells; therefore, OLE may play a significant role in the development of new drugs for cancer treatment. These antineoplastic properties have been reported in many experimental cancer models, but the effect of OLE on seminoma cells is yet to be evaluated. In the present study, we demonstrate, for the first time, that OLE reduces cell viability in both intra- and extragonadal TCAM-2 and SEM-1 seminoma cells, respectively, in a dose-dependent manner. As shown by Western-blot analysis, OLE exposure reduced cyclin-D1 expression and upregulated p21Cip/WAF1, concomitantly affecting the upstream pathway of NF-κB, leading to the reduction of its nuclear content, thereby suggesting that OLE could modulate cell-cycle regulators by inhibiting NF-κB. Moreover, Annexin V staining revealed that OLE induced apoptosis in cancer cells and upregulated the pro-apoptotic factor BAX. Through wound-healing scratch and transmigration assays, we also demonstrated that OLE significantly reduced the migration and motility of TCAM-2 and SEM-1 cells, and downregulated the expression of TGFß-1, which is known to be the main pro-fibrotic factor involved in the acquisition of the migratory and invasive properties of cancer cells. Collectively, our results indicate that OLE reduces seminoma cell proliferation, promotes apoptosis, and counteracts cell migration and motility. Further studies are needed to explore the molecular mechanisms underlying these observed effects.

Effects of Selenium Supplementation on Sperm Parameters and DNA-Fragmentation Rate in Patients with Chronic Autoimmune Thyroiditis.

BACKGROUND: Selenium (Se) is an essential component of selenoenzymes, which have catalytic and antioxidant functions. A low Se status has been reported in patients with chronic autoimmune thyroiditis (AT) who benefit from Se supplementation. The role of Se in male reproduction is still a matter of debate. Although Se and selenoenzymes ensure sperm viability and protect against increased oxidative stress, only a few studies have assessed the effects of the administration of Se alone on sperm parameters, providing contrasting results. AIM: The aim of this study was to assess the effects of oral Se supplementation on conventional sperm parameters and DNA fragmentation (SDF) in patients with AT of reproductive age with normal thyroid function. PATIENTS AND METHODS: Only patients with AT and normal thyroid function were selected for this study. All included patients underwent oral Se supplementation at the dose of 83 µg once daily (Syrel®, IBSA) for six months. Sperm conventional parameters, SDF, and thyroid function were assessed before and at the end of the treatment. RESULTS: Twenty AT patients with normal weight were enrolled. After Se supplementation, they showed a higher sperm concentration, a higher percentage of sperm with progressive motility, and a higher percentage with normal morphology. They also had lower semen leukocyte concentration, and a lower percentage of spermatozoa with DNA fragmentation compared with pre-treatment values. Free-thyroxine serum levels increased significantly, whereas free triiodothyronine showed an upward trend. The thyroid-stimulating hormone did not change significantly. CONCLUSION: Se supplementation may represent a possible non-hormonal therapeutic choice for the treatment of male infertility, although further studies are needed to confirm this evidence. The possible thyroid hormone dependency of these findings needs to be clarified.

Effects of nutraceuticals on sexual satisfaction and lower urinary tract symptoms in a cohort of young-old men.

The aim of this study was to evaluate the effects of nutraceuticals containing multiple supplemental facts (Virherbe®/Rekupros®) on sexual satisfaction and lower urinary tract symptoms (LUTS) in young-old men. In an open-label trial, 40 males (mean age 66 ± 13) with sexual disturbances and mild LUTS but without cognitive/motor impairment and clinical hypogonadism were enrolled. Sexual desire (SD; IIEF-SD domain) and satisfaction (Global Assessment Question; GAQ), the capacity to perform daily activities (evaluated by 6-min walking test [6MWT]), and International Prostate Symptoms Scores (IPSS) were evaluated before and after oral administration of 2 capsules/day of each supplement for 8 weeks. The difference from baseline for SD was +2.6 (p < .05) and -4.2 points for IPSS (p < .05), with significance in subscales of urinary streaming/nocturia (p < .01), respectively; 6MWT increased from 507 ± 44 versus 527 ± 58 meters (p < .001). GAQ scale-responses showed overall improvement in overall 75% population, with a significant improvement in QoL (p < .01). These changes returned to baseline at 1-month withdrawal follow-up. No adverse events were reported. These supplemental facts improved sexual desire, satisfaction with sex life, physical performance, and LUTS in young-old men, suggesting that they may be effective in patients in whom standard treatments are not suitable.

Testosterone supplementation and sexual function: a meta-analysis study.

INTRODUCTION: The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable. AIM: The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i). METHODS: An extensive Medline, Embase, and Cochrane search was performed. MAIN OUTCOME MEASURES: All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi). RESULTS: Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses. CONCLUSIONS: TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.

Obesity treatment: results after 4 years of a Nutritional and Psycho-Physical Rehabilitation Program in an outpatient setting.

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 follow-up, 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 psycho-physical 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.

Which is first? The controversial issue of precedence in the treatment of male sexual dysfunctions.

INTRODUCTION: In male sexual dysfunction (MSD), the presence of sexual comorbidities is relatively frequent. However, what is still a matter of controversy is what the first-line therapy in these patients should be. METHODS: Three scientists and the editor of the Controversies section, all experts in the medical treatment of MSD, present different perspectives on the use of phosphodiesterase type 5 inhibitors (PDE5), testosterone and dapoxetine in erectile dysfunction (ED), hypogonadism, and premature ejaculation (PE). The psychological aspects are discussed by an outstanding expert in psychosexology. MAIN OUTCOME MEASURE: Expert opinion supported by the critical review of the currently available literature. RESULTS: Testosterone should be used before PDE5s in hypogonadal men with comorbid ED; PDE5s should be used before dapoxetine in PE patients with comorbid ED, and counseling should be offered to all subjects with MSD. CONCLUSIONS: Although the answer to the question "which should be first?" is controversial in almost all MSDs, intuition, experience, and evidence should guide the choice of which treatment should be used first. This decision is highly critical in influencing the therapeutic outcome as well the patient's and couple's adherence to treatment.