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.

Infertile men with semen parameters above WHO reference limits at first assessment may deserve a second semen analysis: Challenging the guidelines in the real-life scenario.

OBJECTIVES: To investigate which infertile men with semen parameters above WHO reference limits at first semen analysis deserve a second semen test. MATERIALS AND METHODS: Data from 1358 consecutive infertile men were analysed. Patients underwent two consecutive semen analyses at the same laboratory. Descriptive statistics and logistic regression models tested the association between clinical variables and semen parameters. A new predicting model was identified through logistic regression analysis exploring potential predictors of semen parameters below WHO reference limits after a previously normal one. Diagnostic accuracy of the new model was compared with AUA/ASRM and EAU guidelines. Decision curve analyses (DCA) tested their clinical benefit. RESULTS: Of 1358, 212 (15.6%) infertile men had semen parameters above WHO reference limits at first analysis. Of 212, 87 (41.0%) had a second semen analysis with results above WHO reference limits. Men with sperm parameters below reference limits at second analysis had higher FSH values, but lower testicular volume (TV) (all p<0.01) compared to men with a second semen analysis above WHO limits. At multivariable logistic regression analysis, lower TV (OR 0.9, p = 0.03), higher FSH (OR 1.2, p<0.01), and lower total sperm count (OR 0.9, p<0.01) were associated with second semen analyses below WHO limits. DCA showed the superior net benefit of using the new model, compared to both AUA/ASRM and EAU guidelines to identify those men with a second semen sample below WHO limits after a previously normal one. CONCLUSIONS: Approximately 60% of infertile men with a first semen analysis above WHO limits have a second analysis with results below limits. The newly identified risk model might be useful to select infertile men with initial semen results above WHO limits who deserve a second semen analysis.

Medications mostly associated with priapism events: assessment of the 2015-2020 Food and Drug Administration (FDA) pharmacovigilance database entries.

A range of drugs have a direct role in triggering ischaemic priapism. We aimed at identifying: a) which medications are associated with most priapism-reports; and, b) within these medications, comparing their potential to elicit priapism through a disproportionality analysis. The FDA Adverse Event Reporting System (FAERS) database was queried to identify those drugs associated the most with priapism reports over the last 5 years. Only those drugs being associated with a minimum of 30 priapism reports were considered. The Proportional Reporting Ratios (PRRs), and their 95% confidence intervals were computed. Out of the whole 2015-2020 database, 1233 priapism reports were identified, 933 of which (75.7%) were associated with 11 medications with a minimum of 30 priapism-reports each. Trazodone, olanzapine and tadalafil showed levels of disproportionate reporting, with a PRR of 9.04 (CI95%: 7.73-10.58), 1.55 (CI95%: 1.27-1.89), and 1.42 (CI95%: 1.10-1.43), respectively. Most (57.5%) of the reports associated with the phosphodiesterase type 5 inhibitors (PDE5Is) were related with concomitant priapism-eliciting drugs taken at the same time and/or inappropriate intake/excessive dosage. Patients taking trazodone and/or antipsychotics need to be aware of the priapism-risk; awareness among prescribers would help in reducing priapism-related detrimental sequelae; PDE5I-intake is not responsible for priapism by itself, when appropriate medical supervision is provided.

Extensive Assessment of Underlying Etiological Factors in Primary Infertile Men Reduces the Proportion of Men With Idiopathic Infertility.

Objective: Up to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple's infertility, by using a thorough and extensive baseline diagnostic work-up. Material and Methods: Cross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification. Results: A possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p>0.43). Conclusions: Due to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up.

Male infertility as a proxy of the overall male health status.

INTRODUCTION: Male infertility (MI) has been widely associated with different comorbid conditions. The aim of this review is to summarize the available evidences investigating the link between MI cancer, chronic non-malignant conditions and overall health. EVIDENCE ACQUISITION: A literature search has been conducted using the MEDLINE/PubMed and Scopus databases for English-language original and review articles and selecting publications from January 2007 to June 2017, although highly regarded older publications were also considered. The following key words and MeSH terms were combined: "male infertility," "semen analysis," "health," "comorbidities," "cancer," "metabolic syndrome," "diabetes," "hypertension," "cardiovascular diseases," and "mortality." EVIDENCE SYNTHESIS: Several studies supported a higher risk of testis cancer for patients with MI; conversely, controversial findings have been reported on the association between prostate cancer and MI. Beside urogenital malignancies, melanoma, bladder, thyroid and hematological malignancies have been also more frequently reported among infertile men. Large cohort studies supported a significant association between diabetes mellitus, metabolic disorders and MI. Similarly, the risk of developing cardiovascular diseases appears to be higher among infertile men. Of note, a significant association between semen alterations and the overall burden of comorbidities, as well as the overall mortality, has been reported. A common genetic background appears as the main pathophysiological link between infertility and other comorbidities. CONCLUSIONS: Male infertility is a proxy of the overall male health status. Physicians should comprehensively assess men presenting for couple infertility and properly followed-up these patients given their higher risk of developing cancer.

Metabolic syndrome in White-European men presenting for secondary couple's infertility: an investigation of the clinical and reproductive burden.

We aimed to determine the impact of metabolic syndrome (MetS) on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorised 0 vs 1 vs 2 or higher). NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 (12%) of 167 men. Patients with MetS were older (P < 0.001) and had a greater BMI (P < 0.001) compared with those without MetS. MetS patients had lower levels of total testosterone (P = 0.001), sex hormone-binding globulin, inhibin B, and anti-Mόllerian hormone (all P ≤ 0.03), and they were hypogonadal at a higher prevalence (P = 0.01) than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology (all P ≤ 0.03). At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple's infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men.

When to perform lymph node dissection in patients with renal cell carcinoma: a novel approach to the preoperative assessment of risk of lymph node invasion at surgery and of lymph node progression during follow-up.

OBJECTIVE: To identify preoperatively patients who might benefit from lymph node dissection (LND). PATIENTS AND METHODS: We assessed lymph node invasion (LNI) at final pathology and lymph node (LN) progression during the follow-up for 1983 patients with RCC, treated with either partial or radical nephrectomy. LN progression was defined as the onset of a new clinically detected lymphadenopathy (>10 mm) in the retroperitoneal lymphatic area. Logistic regression analyses were used to assess the effect of each potential clinical predictor (age, body mass index, tumour side, symptoms, performance status, clinical tumour size, clinical tumour-node-metastasis stage, and albumin, calcium, creatinine, haemoglobin and platelet levels) on the outcome of interest. The most parsimonious multivariable predictive model was developed, and discrimination, calibration and net benefit were calculated. RESULTS: The prevalence of LNI was 6.1% (120/1983 patients) and during the follow-up period, 82 patients (4.1%) experienced LN progression. On multivariable analyses, the most informative independent predictors were tumour stage (cT3-4 vs cT1-2, odds ratio [OR] 1.52, P = 0.05), clinical nodal status [cN1 vs cN0, OR 7.09, P < 0.001], metastases at diagnosis (OR 3.04, P < 0.001) and clinical tumour size (OR 1.14, P < 0.001). The accuracy of the multivariable model was found to be 86.9%, with excellent calibration and net benefit at decision-curve analyses. CONCLUSIONS: By relying on a unique approach, combining the risk of harbouring LNI and/or LN progression during the follow-up period, we have provided the first clinical presurgery model predicting the need for LND.

Right coronary artery arising from pulmonary trunk: assessment with conventional coronary angiography and multislice computed tomography coronary angiography.

We present a case of a 59-year-old man who was admitted to the hospital because of atypical chest pain and dyspnea. Conventional coronary angiography showed an anomalous origin of the right coronary artery from the pulmonary trunk. The patient underwent multislice computed tomography in order to clarify the origin and course of the anomalous vessel. The aim of this report is to emphasize the role of multislice computed tomography as an accurate noninvasive imaging tool in the evaluation of coronary artery anomalies.

[Anomalous origin of the circumflex artery from the right aortic sinus: assessment with conventional coronary angiography and multislice computed tomography]. / Origine anomala dell'arteria circonflessa dal seno di Valsalva destro: valutazione mediante tomografia computerizzata multistrato ed angiografia coronarica convenzionale.

Anomalous origin of the circumflex coronary artery from the right sinus of Valsalva is the most common coronary anomaly. This anomaly is thought to be of little clinical significance without the presence of severe narrowing of the vessel. A 43-year-old woman was referred to our institution for evaluation of atypical chest pain and equivocal results of the exercise stress test. We decided to perform multislice computed tomography coronary angiography before any other invasive studies. The scan was performed with a 16-row scanner (Aquilion 16 CFX, Toshiba Medical Systems, Tokyo, Japan) after intravenous administration of non-ionic contrast material. Scans revealed that the circumflex coronary artery originated from the right sinus of Valsalva; the initial course was retro-aortic until it reached its target in the atrioventricular groove; peripheral distribution of the circumflex coronary artery was then normal. The anomalous vessel presented a significant stenosis in its proximal tract. Coronary angiography confirmed that the origin of the circumflex coronary artery was from the right aortic sinus and the significant stenosis of the proximal portion of this vessel. This case confirms the full capability and accuracy of multislice computed tomography with the aid of post-processing techniques in the identification and evaluation of the ectopic origin of the left circumflex coronary artery from the right sinus of Valsalva, displaying accurately the origin, size, course, and relationship of the anomalous vessel with respect to surrounding structures.

Three-dimensional echocardiographic and magnetic resonance assessment of the effect of telmisartan compared with carvedilol on left ventricular mass a multicenter, randomized, longitudinal study.

BACKGROUND: The hypothesis that left ventricular hypertrophy regression in hypertension relates to blood pressure (BP) control and to non-antihypertensive activity of some drugs was tested by comparing the effects of telmisartan and carvedilol on 24-h mean ambulatory BP and left ventricular mass (LVM) regression, measured using three-dimensional echocardiography (3-DECHO) and magnetic resonance imaging (MRI). METHODS: A total of 82 patients with mild-to-moderate hypertension and an optimal echocardiographic acoustic window were randomized to receive once-daily telmisartan 80 mg or carvedilol 25 mg for 44 weeks. RESULTS: Ten patients withdrew from the study because office diastolic BP remained >90 mm Hg. The 24-h mean ambulatory systolic/diastolic BP reductions were similar in both treatment groups (telmisartan, from 159.6 +/- 10.2/97.8 +/- 5.4 to 128.6 +/- 6.5/78.2 +/- 5.8 mm Hg; carvedilol, from 157.8 +/- 11.1/95.7 +/- 11.9 to 128.2 +/- 5.6/78.7 +/- 5.2 mm Hg). However, night-time and last 6-h mean BP reductions were nonsignificantly greater with telmisartan. Using 3-DE, telmisartan (P< .001) and carvedilol (P< .001) progressively reduced LVM index by 21.97 +/- 5.84 (15.7%) and 12.31 +/- 3.14 (9.1%) g/m2, respectively, at week 44. Similar magnitudes of reductions were observed using MRI (15.5% and 9.6%, respectively). Reductions in LVM index achieved with telmisartan were statistically superior to carvedilol (P< or = .001). CONCLUSIONS: The superior LVM regression with telmisartan versus carvedilol suggests telmisartan has a mechanism that may be beyond that of lowering BP in hypertensive patients.