The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database.

BACKGROUND: A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal anti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibiotics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, 'unmasking', dataset analyses were carried out as well. RESULTS: Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications, which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed significant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7-20.3), 14.3 (9.1-22.4) and 58.7 (36.3-95.9). CONCLUSIONS: A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.

Risk of unfavorable outcomes after penile prosthesis implantation - results from a national registry (INSIST-ED).

Like all surgeries, penile prosthesis implantation (PPI) has the potential for both postoperative complications and suboptimal patient satisfaction. In order to assess risk factors for poor satisfaction, we reviewed patients who had been prospectively recruited in a national multi-institutional registry of penile prostheses procedures (INSIST-ED) from 2014 to 20121. Patient baseline characteristics and postoperative complications were recorded. The primary endpoint of this study was unfavorable outcomes after inflatable PPI, defined as significant postoperative complications (Clavien-Dindo ≥2) and/or Sexuality with Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) scores below the 10th percentile. A total of 256 patients were included in the study. The median age was 60 years (IQR 56-67). The most common cause of erectile dysfunction (ED) was organic (42.2%), followed by pelvic surgery/radiotherapy (39.8%) and Peyronie's disease (18.0%). Postoperative complications were recorded in 9.6%. High-grade complications (Clavien ≥2) occurred in 4.7%. At 1-year follow-up, the median QoLSPP total score was 71 (IQR 65-76). In all, 14.8% of patients were classified as having experienced unfavorable outcomes because of significant postoperative complications and/or QoLSPP scores below the 10th percentile. Logistic regression analysis demonstrated patient age to be non-linearly associated with the risk of experiencing unfavorable outcomes. A U-shaped correlation showed a lower risk for younger and older patients and a higher risk for middle-aged men. ED etiology and surgical volume were not associated with PPI outcomes. Physicians should, therefore, be aware that middle-aged men may be at higher risk of being unsatisfied following PPI compared to both younger and older patients.

Initial safety outcomes for the Rigicon Infla10® inflatable penile prosthesis.

OBJECTIVE: To analyse data from patient information forms (PIFs) submitted to the manufacturer of a new three-piece inflatable penile prosthesis (IPP), the Rigicon Infla10®, to summarize early outcomes. METHODS: A retrospective review of PIFs from 319 patients implanted with the IPP between 6 January 2019 and 31 December 2021 was performed to assess device durability and rates of reoperation for infection, mechanical failure or medical reasons. RESULTS: The mean ± sd (range) follow-up was 21.2 ± 11 (5-36) months and the mean ± sd patient age was 58.5 ± 8.7 years. Of the total, 4.4% of devices required removal or revision. Complications included mechanical failure (2.5%) and component migration (0.7%). No infections were observed in this series. One patient (0.4%) required revision for inadequate straightening of Peyronie's disease. Three patients (0.9%) requested device removal because of dissatisfaction. A total of 95.6% of the Rigicon Infla10 devices were free from explant or revision 21 months after the original implant date. Kaplan-Meier analysis showed the rates of cumulative survival of the device at 12, 24, 36 months were 95.6%, 94.7% and 93.7%, respectively. CONCLUSIONS: The vast majority of the early Rigicon Infla10 IPPs implanted prior to January 2022 were included in this retrospective analysis of volunteered PIFs. These early results demonstrate initial durability from reoperation equivalent to that of other contemporary devices.

Which patient may benefit the most from penile prosthesis implantation?

BACKGROUND: Penile prosthesis implantation has been associated with overall good functional outcomes. Of relevance, some patients reported higher level of satisfaction and quality of life. AIM: We investigated the profile of the patients who may benefit the most from penile prosthesis implantation. MATERIALS AND METHODS: Data from a national multi-institutional registry of penile prostheses including patients treated from 2014 to 2017 in Italy (Italian Nationwide Systematic Inventarization of Surgical Treatment for Erectile Dysfunction) were analyzed. All data have been prospectively recorded by 45 surgeons on a dedicated website (www.registro.andrologiaitaliana.it) and revised by a single data manager. Patients' baseline characteristics were recorded. In order to simultaneously evaluate perceived penile prosthesis function and quality of life, all patients were re-assessed at 1-year follow-up using the validated questionnaire Quality of Life and Sexuality with Penile Prosthesis. High quality of life after surgery was defined as a score higher than the 75th percentile in each of the subdomains of the Quality of Life and Sexuality with Penile Prosthesis questionnaire. Logistic regression analysis tested the association between clinical characteristics and high quality of life after penile prosthesis implantation. RESULTS: Follow-up data were available for 285 patients (median age 60 years; interquartile range: 56-67) who underwent penile prosthesis implantation. Erectile dysfunction etiology was organic in 40% (114), pelvic surgery/radiotherapy in 39% (111), and Peyronie's disease in 21% (60) of the cases. Patients showed good overall Quality of Life and Sexuality with Penile Prosthesis scores at 1-year follow-up for functional (22/25), personal (13/15), relational (17/20), and social (13/15) domains. Overall, 27.0% (77) of patients achieved scores consistent with the high quality of life definition. These patients did not differ in terms of median age (60 vs. 62), type of prosthesis (inflatable penile prostheses: 95% in both of the cases), and post-operative complications (10% vs. 14%) than those with lower quality of life score (all p > 0.1). At logistic regression analysis, erectile dysfunction etiology was the only factor independently associated with high quality of life at 1 year after surgery (p = 0.02). Patients treated for Peyronie's disease (odds ratio: 2.62; p = 0.01; 95% confidence interval: 1.20-5.74) were more likely to report better outcomes after accounting for age, post-operative complications, and surgical volume. CONCLUSION: Penile prosthesis implantation is associated with an overall good quality of life. The subset of patients affected by erectile dysfunction secondary to Peyronie's disease seemed to benefit the most from penile prosthesis implantation in terms of functional outcomes, relationship with their partners and the outside world, and perceived self-image. The systematic use of validated questionnaires specifically addressed at evaluating quality of life and satisfaction after penile prosthesis implantation should be further implemented in future studies to better define the predictors of optimal satisfaction after penile prosthesis implantation.

Primary versus revision implant for inflatable penile prosthesis: A propensity score-matched comparison.

Inflatable penile prosthesis (IPP) provides excellent outcomes after virgin implants. However, few data on IPP after revision surgery are available. This study aimed at comparing the outcomes of IPP in patients undergoing primary or revision implant surgery. Patients who underwent revision implant surgery (Group 1) between 2013 and 2020 were identified. Overall, 20 patients (Group 1) could be matched with a contemporary matched pair cohort of surgery-naive patients (Group 2) in a 1:1 ratio. Patients in Group 2 had a significantly shorter operative time [median (IQR): 84 (65-97) vs. 65 (51-75) min; p = .01] and lower rate of overall complications (25% vs. 10%; p = .01). Of note, mean (SD) scores for the Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaire demonstrated high satisfaction and IPP efficacy in both Groups 1 and 2: functional domain [3.9 (1.0) vs. 4.0 (1.2); p = .4], personal [3.9 (1.1) vs. 4.0 (1.1); p = .3], relational [3.8 (1.3) vs. 3.9 (1.1); p = .5] and social [3.9 (1.1) vs. 4.0 (1.2); p = .2]. These results suggest that in experienced hands, IPP offers high satisfaction to both patients and partners even in the setting of revision implant. However, it is mandatory to inform those patients about the increased risk of perioperative complications.

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study.

OBJECTIVES: The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis. BACKGROUND: The evolution of diabetic cardiomyopathy to heart failure affects patients'morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression. METHODS: Five-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up. RESULTS: A total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = -35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = -20.01 ± 19.07 s-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation. CONCLUSIONS: Within 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237).

Surgical blood loss during holmium laser enucleation of the prostate (HoLEP) is not affected by short-term pretreatment with dutasteride: a double-blind placebo-controlled trial on prostate vascularity.

Five α-reductase inhibitors (5ARIs) are able to reduce prostate volume and are a useful treatment for reducing perioperative bleeding during prostate surgery. Holmium laser enucleation of the prostate (HoLEP) is an effective surgical technique for the definitive cure of benign prostate enlargement.We investigated whether pretreatment with dutasteride before HoLEP could reduce intraoperative bleeding. A total of 402 patients were included in this double-blind placebo-controlled trial to receive daily 0.5 mg of dutasteride or placebo over 8 weeks before HoLEP. Vascular endothelial growth factor (VEGF) and microvascular density (MVD) were evaluated. Analysis was also stratified according to prostate volume (<70 mL vs ≥70 mL).Hemoglobin and hematocrit values before and after surgery were not statistically different between the two groups. MVD and VEGF index in smaller prostates were 23.35±1.96 and 4.06±0.76 in the treatment group and 19.04±0.96 and 2.55±0.55 in placebo (p<0.05); in patients with larger prostates MVD and VEGF were 26.83±2.812 and 8.54±1.18 in the treatment group and 20.76±0.79 and 3.21±0.54 in placebo (p<0.05).Vascularization of the prostate was affected by 5ARIs therapy. HoLEP is less burdened in perioperative bleeding and for this reason we did not find any difference in hemoglobin/hematocrit values pre- and post- surgery.

Postoperative vacuum therapy following AMS™ LGX 700® inflatable penile prosthesis placement: penile dimension outcomes and overall satisfaction.

Penile shortening after inflatable penile prosthesis for erectile dysfunction is a common postoperative patient complaint and can reduce overall satisfaction with the procedure. In this prospective study we report our results regarding penile dimensions and patient satisfaction outcomes after 1 year of follow-up from AMS™LGX700® penile prosthesis implant with 6 months of vacuum erectile device therapy. Seventy-four selected patients with medically refractory erectile dysfunction underwent AMS™ LGX 700® IPP placement. Postoperatively, patients were assigned vacuum device therapy for 5 min twice daily. Follow-up continued for 1 year after surgery. Dimensional and functional results were assessed. Baseline median preoperative stretched penile length and girth were 14 cm (range 10-17) and 9 cm (range 7-12), respectively. At the end of the study penile median dimensional outcomes were 17 cm (range 13-23) for length and 11 cm (range 10-13) for girth while a median number of 24 pumps (range 18-29) to fully inflate the device was seen. Baseline median International Index of Erectile Function (IIEF-5) score was 9 (range 5-11), at 6 months 20 (range 18-26) and at 1 year was 25 (range 20-27) (p < 0.0001). Median Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score at the end of the follow-up was 74 (range 66-78). Our postoperative rehabilitation program is feasible and should be recommended after prothesis surgery in order to increase overall satisfaction with the procedure. Penile postoperative dimensional outcomes were statistically significant improved and complications were negligible.

Inflatable Penile Prosthesis Placement, Scratch Technique and Postoperative Vacuum Therapy as a Combined Approach to Definitive Treatment of Peyronie's Disease.

PURPOSE: Peyronie's disease is a devastating condition resulting in penile malformation, erectile dysfunction, pain and emotional distress. In this prospective, 2 institution study we evaluated a multimodal surgical and mechanical combined approach to the definitive treatment of Peyronie's disease and concomitant erectile dysfunction. MATERIALS AND METHODS: A total of 145 select patients underwent endocavernous disruption of Peyronie's disease plaques via the scratch technique, followed by inflatable penile prosthesis insertion. Postoperatively patients were assigned to vacuum device therapy for 3 minutes twice daily to continue penile curvature correction. Followup continued for 1 year after surgery. Anatomical and functional results were assessed. RESULTS: Patients with plaques in the proximal third, middle third and subcoronal areas of the penis had a mean ± SD postoperative residual curvature of 21.5 ± 4.5, 17.3 ± 4.8 and 14.1 ± 3.1 degrees, respectively. After 24 weeks of vacuum therapy the mean penile curvature deviation decreased to 8.7 ± 2.5, 9.1 ± 2.9 and 7.7 ± 0.9 degrees, respectively. The mean IIEF-5 (International Index of Erectile Function) score was 9.8 ± 2.3 preoperatively, 18.9 ± 3.1 at 6 months (p <0.001) and 24.1 ± 3.6 at 1 year (p <0.001). The mean EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) score at the end of followup was 64.6 ± 11.8. Operative and postoperative complications were minimal. CONCLUSIONS: Our novel combination of intraoperative and postoperative therapies in the treatment of patients with Peyronie's disease and an inflatable penile prosthesis was safe and efficacious with excellent functional outcomes. Penile curvature corrections were statistically significant and complications were negligible.

Penoscrotal versus minimally invasive infrapubic approach for inflatable penile prosthesis placement: a single-center matched-pair analysis.

PURPOSE: To compare perioperative results, safety and efficacy profile in patients receiving inflatable penile prosthesis (IPP) via penoscrotal (PS) or minimally invasive infrapubic (MII) approach for erectile dysfunction. METHODS: A matched-pair analysis was performed including 42 patients undergoing IPP implantation via PS (n = 21) or MII (n = 21) between 2011 and 2016. Clinical and surgical data were prospectively collected. Patients' and partners' outcomes were assessed by the International Index of Erectile Function (IIEF), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) questionnaires. RESULTS: Mean (SD) operative time was 128 (40.6) min in group PS and 91 (43.0) min in group MII (p = 0.041). Complications occurred in 3/21 (14%) and 2/21 (10%) patients in groups PS and MII (p = 0.832). Overall, no differences were observed concerning the device utilisation (p = 0.275). However, in group MII 4/21 (19%) patients were able to resume sexual activity prior to 4 postoperative weeks, while in group PS no patient was (p = 0.012). Mean (SD) scores for questionnaires were similar between groups PS and MII: IIEF [20.9 (7.3) vs. 20.7 (4.8); p = 0.132], patient EDITS [76.0 (25.6) vs. 74.7 (20.8); p = 0.256] and partner EDITS [72.5 (29.1) vs. 73.1 (21.4); p = 0.114]. Similarly, QoLSPP showed comparable results among the groups PS and MII: functional domain [3.9 (1.4) vs. 4.0 (1.2); p = 0.390], personal [4.0 (1.2) vs. 4.1 (1.0); p = 0.512], relational [3.7 (1.5) vs. 3.9 (1.2); p = 0.462] and social [4.0 (1.2) vs. 3.9 (1.2); p = 0.766]. CONCLUSIONS: PS and MII demonstrated to be safe and efficient techniques, leading to high level of both patients and partners satisfaction. Additionally, the minimally invasive infrapubic approach showed a shorter operative time and a tendency for a faster return to sexual activity.