Regenerative treatment with platelet-rich plasma in patients with refractory erectile dysfunction: short-term outcomes and predictive value of mean platelet volume.

BACKGROUND: The vast majority of erectile dysfunction (ED) treatments are currently symptomatic and do not influence disease progression. Regenerative medicine may potentially reverse or stop the progression of complicated ED by restoring erectile capacity. We aimed to evaluate potential safety and effectiveness and the clinical correlates of platelet function before platelet-rich plasma (PRP) injection in men with vascular ED unresponsive to phosphodiesterase-5 inhibitors (PDE-5is). METHODS: A number of 150 patients with vascular ED were enrolled in an open-label, single arm, multicenter, prospective, interventional, non-randomized study. After 1-month pharmacological washout from PDE-5is, the 5-item International Index of Erectile Function (IIEF-5) questionnaire was administered and dynamic penile duplex ultrasound (d-PDU) was performed. Patients then underwent intracavernous PRP injection. One month after treatment, IIEF-5 and d-PDU were evaluated. Primary aim of the study was to assess efficacy and safety of PRP treatment by evaluating the proportion of patients achieving minimal clinically important differences (MCID) in the IIEF-5 questionnaire. Secondary endpoint was to determine whether MPV could correlate with improvement in d-PDU parameters. RESULTS: Most patients (80%) had a significant improvement in ED symptoms (IIEF-5 Score: 12±2.6 vs. 19±3.0; P<0.0001) and in PSV (32±3.5 cm/s vs. 42±7.6 cm/s; P<0.0001) after d-PDU evaluation. The ROC curve analysis showed a significant accuracy (72.1%, CI: 64.0-80.2, P≤0.0001) for MPV in identifying men clinically responding to PRP with favorable MCID≥5 at 1 month follow-up. The MPV<8.95 fL was identified as the best predictor of success rate with a sensitivity of 90% and a specificity of 54.1%. CONCLUSIONS: This study provides the first evidence that PRP could represent an effective and safe option for patients poorly responding to PDE-5is. MPV higher than 8.95 fL may identify patients with poor response to treatment that might benefit of successive re-challenge with PRP.

Global olfactory function correlates with global sexual functioning in men and women.

BACKGROUND: Olfaction is intimately involved in reproductive behaviors. However, there is limited evidence about the relationship between olfactory and sexual functioning, and whether this relationship is modulated by gender. This study aimed to investigate the correlates between olfactory and sexual functioning in a cohort of young healthy individuals; secondary outcomes were the possible correlates between disgust and perceived vulnerability to illness, with particular relation to sexual attitudes. METHODS: Between January 2019 and December 2022, we enrolled 125 participants (51 males and 74 females) without known sexual disorders. The mean age was 28.47±8.6, and the mean Body Mass Index (BMI) was 23.86±3.3 without major disease or concomitant drug assumption, except for nutraceutical use. Olfactory sensitivity was tested with the Sniffin' Sticks Test (SST). Body Odor Disgust Scale (BODS) and Perceived Vulnerability to Disease (PVD) questionnaires were administered for the evaluation of perceived susceptibility to illness along with the Sexual Attitude Scale (SAS) for the evaluation of sexual attitudes. Sexual function was evaluated by the Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF) questionnaires, respectively. RESULTS: Overall, a close relationship between sexual function and olfaction in both sexes (P<0.05) was found. In the male sample, better olfactive scores were positively correlated to all IIEF sub-domains but negatively with BMI and age, respectively (P<0.05). Moreover, olfaction was negatively correlated with a restrictive attitude towards sexuality (SAS) (P<0.05). The latter was also positively correlated with PVD (P<0.01). In the female sample, all FSFI subscales but sexual desire was positively correlated with olfaction (P<0.05). CONCLUSIONS: We herein confirm that olfactory capacities positively correlate with sexual behavior in both sexes. In males, these findings were mostly dependent upon increasing age and BMI. In females all domains of sexual function but sexual desire correlated with olfactory capacity, thus suggesting independent neural pathway activation for sexual desire. Finally, better olfactory capacities seem to determine sexual attitudes and disease avoidance behaviors irrespective of gender.

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.

Predicting the response to SGLT-2 inhibitors as add-on therapy to multiple day injection insulin with glycated albumin: a pilot study.

BACKGROUND: Achieving optimal glycemic targets is the main therapeutic goal in patients with type 2 diabetes (T2D) mellitus. HbA1c is the reference biomarker for monitoring glycemic control; however, in specific conditions affecting erythrocyte turnover or in patients on multiple daily injection (MDI) insulin regimens, the determination of glycated albumin (GA) may be preferable. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent a novel class of antidiabetic drugs that lower plasma glucose concentrations quickly, with insulin-independent mechanisms. Herein, we explored the role of GA in predicting the short-term response to SGLT-2 inhibitors as add-on to MDI insulin. METHODS: Sixteen patients with long-standing, poorly controlled T2D on MDI insulin starting an SGLT-2 inhibitor were subjected to plasma GA and HbA1c measurements at 30 days intervals for up to 3 months in order to examine the temporal changes of these glycemic biomarkers. RESULTS: At the end of the study, grossly coincident with the life span of erythrocytes, a significant decrease in median HbA1c was observed, (from 8.7 [range: 8.2-9.3%] at baseline to 7.2 [range: 7.0-7.9%]), with the advantage of less insulin dose requirements. However, significant, and incremental reductions in median GA determinations could be already evident after 30 days (-3.5 [range: -7.5, -2.5%]) and 60 days (-6.4 [range: -10.5, -4.7%]) from the start of SGLT-2 inhibitor treatment and persisted for up to 3 months (-8.6 [range: -12.1, 6.1%]). The decrements of HbA1c observed at the 3-month visit were highly correlated with the concurrent absolute reductions of plasma GA (ρ=0.550, P=0.027), whereas a borderline significance could be demonstrated with reference to reductions in plasma GA at 30 and 60 days. CONCLUSIONS: Although limited by the small number of participants, these preliminary findings suggest that GA, rather than HbA1c, could represent a useful and reliable biomarker in T2D to monitor the early glucose-lowering effects of antidiabetic drugs with rapid onset of action, such as SGLT-2 inhibitors and MDI insulin.

The Variant p.Ala84Pro Is Causative of X-Linked Hypophosphatemic Rickets: Possible Relationship with Burosumab Swinging Response in Adults.

Loss of function mutations in the PHEX gene could determine X-linked dominant hypophosphatemia. This is the most common form of genetic rickets. It is characterized by renal phosphate wasting determining an increase in fibroblast growth factor 23 (FGF-23), growth retard, bone deformities and musculoskeletal manifestations. In recent decades, analysis of the PHEX gene has revealed numerous different mutations. However, no clear genotype-phenotype correlations have been reported in patients with hypophosphatemic rickets (XLH). We report two cases of a 28-year-old-male (patient 1) and a 19-year-old male (patient 2) affected by XLH initially treated with phosphate and 1,25-dihydroxyvitamin-D admitted to the Endocrinology unit because of the persistence of muscle weakness, bone pain and fatigue. After phosphate withdrawal, both patients started therapy with burosumab and symptoms ameliorated in three months. However, patient 1's biochemical parameters did not improve as expected so we decided to investigate his genetic asset. We herein describe a possible clinical implication for the missense "de novo" mutation, c.250G>C (p.Ala84Pro) in the PHEX gene, reported in the PHEX database and classified as a variant of uncertain significance (VUS). The clinical implication of this mutation on disease burden and quality of life in adults is still under investigation.