The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue.

BACKGROUND: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment. OBJECTIVES: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (Tonset ) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate. MATERIAL AND METHODS: An online PubMed literature search was conducted to identify English language publications from inception to January 2019. RESULTS: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long Tonset , further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a 'difficult' molecule, but Tonset can be improved following absorption by buccal mucosa using appropriate excipients. CONCLUSIONS: We conclude that several ODT and ODF formulations can improve the 'discretion' issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter Tonset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed.

The clinical usefulness of a novel grading system for varicocoeles using duplex Doppler ultrasound examination based on postsurgical modifications of seminal parameters.

BACKGROUND: The existing classifications of varicocoeles have poor predictive value regarding the effects of surgery on sperm count. OBJECTIVE: To develop a new grading system for varicocoeles, useful as an indication for surgery. MATERIALS AND METHODS: This is a three-center prospective study which examined 173 men having clinically detectable left varicocoeles and oligo ± astheno ± terato-spermia. The patients underwent medical history collection, objective examination, duplex Doppler ultrasound scrotal examination, hormonal profiles, two semen analyses before surgery, and two semen analyses after surgery. Sperm concentration, motility, and morphology (standard semen parameters) were evaluated 6 months after surgery in function of the following preoperative variables: patient age, follicle-stimulating hormone, clinical grade of varicocoele, right and left testicular volume, extension of venous reflux, and semen parameters. The venous reflux was graded in two centers using duplex Doppler ultrasound: reflux visible only with Valsalva and continuous reflux. Spearman's rank semiquantitative analysis was used. All patients had their varicocoeles corrected according to the Colpi technique. RESULTS: The variables capable of determining an improvement in semen parameters after varicocoele correction were in order of decreasing importance: venous reflux extent assessed by scrotal duplex Doppler ultrasound examination, varicocoele clinical grade, basal semen parameters, and follicle-stimulating hormone. Male age did not influence postoperative semen quality. Only patients with continuous reflux had their standard semen parameters improved after surgery. DISCUSSION: Venous reflux extent is the most critical variable capable of predicting semen improvement after varicocoelectomy. CONCLUSIONS: A correct duplex Doppler assessment of venous reflux is mandatory for predicting postoperative improvement of the sperm count.

Peak systolic velocity thresholds of cavernosal penile arteries in patients with and without risk factors for arterial erectile deficiency.

To simultaneously assess the peak systolic velocity (PSV) and the end-diastolic velocity (EDV) at dynamic duplex examination of the cavernosal penile arteries, and penile rigidity in subjects with satisfactory erectile function with and without risk factors for arterial erectile deficiency (ED). This multicenter prospective study examined two populations having satisfactory sexual function with dynamic duplex examination of the cavernosal arteries; one population had risk factors for arterial ED (65 patients, Group 1) and the other (60 patients, Group 2) had no risk factors. Penile rigidity was assessed using the Schramek grading system score (SGSS). The PSV, the EDV, and the SGSS values of Group 1 and of Group 2 were measured and compared using analysis of variance. The EDV and PSV data presented in this abstract are the arithmetical means of the data of the left and right cavernosal arteries. The Group 1 patients showed a mean ± standard deviation PSV of 26.4 ± 13.2 cm/sec and the Group 2 patients showed a PSV of 44.7 ± 9.6 cm/sec (p = 0.002). The EDV of Group 1 was -15.6 ± 16.1 cm/sec and the EDV of Group 2 was -14.9 ± 13.7 cm/sec (p = 0.329). The SGSS in Group 1 was 3.2 ± 0.3 and the SGSS in Group 2 was 4.8 ± 0.2 (p = 0.008). Intra- and inter-operator variability were not statistically significant. The PSVs and the SGSSs of patients with risk factors for ED and satisfactory erectile function were subnormal and significantly lower than the PSVs and the SGSSs of patients without risk factors. It has been hypothesized that compensatory mechanisms, probably of psychological origin, might allow satisfactory erectile response, even in the presence of a subnormal PSV.

Seminal tract washout: a new diagnostic tool in complicated cases of male infertility.

The diagnosis of azoospermia or severe oligospermia that is made using conventional techniques (testicular biopsy, epididymal exploration, and vasovesiculography) may in some cases remain a dilemma. In such circumstances, post-testicular causes of obstruction must be evaluated. Following the clinical experience acquired in a selected population of 150 severely infertile subjects, the total sperm count in the fluid obtained from the bladder after a seminal tract washout during vasovesiculography has proved to be a valid tool to diagnose the location of the (sub-)obstruction in the seminal tract in complicated cases. Some representative cases are presented. In particular, seminal tract washout (STW) helps to identify functional distal seminal tract emptying disturbances and epididymal incomplete obstruction.

Epididymal ultrasonographic findings in case of obstructive pathology.

Epididymal ultrasonography has proved effective in finding anatomic obstructive alterations affecting the epididymis. The authors investigated two groups: 1. Bilateral vas agenesia (20 epididymis)--(sensitivity of EUS--100%) 2. Normozoospermic noninfertile patients (before different surgical exploration)--(45 epididymis) EUS resulted "ideal" epididymis in 36 out of 45. EUS was "altered" in 9 cases. They call the attention for the impotence of EUS investigation in andrology.