BACKGROUND AND OBJECTIVES: Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose. METHODS: Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration. RESULTS: The mPAP significantly decreased in both the U50 and U100 (−11 mmHg and −8 mmHg from baseline, respectively, p < 0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=−8.5 mmHg and Δ=−14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events. CONCLUSIONS: This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01553721.
Arterial Pressure ; Catheters ; Connective Tissue Diseases ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Diagnosis ; Erectile Dysfunction ; Hemodynamics ; Humans ; Hypertension ; Hypertension, Pulmonary ; Male ; Phosphodiesterase 5 Inhibitors ; Pulmonary Wedge Pressure ; Vascular Resistance

OBJECTIVE: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples.METHODS: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (<5×10⁶/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded.RESULTS: The mean age of patients was 37 years and the mean duration of infertility was 16.3±11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months.CONCLUSION: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.
Azoospermia ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Family Characteristics ; Female ; Fertility ; Follicle Stimulating Hormone ; Humans ; Hypogonadism ; Infertility ; Infertility, Male ; Male ; Oligospermia ; Reference Values ; Reproductive Techniques, Assisted ; Semen ; Spermatozoa ; Testosterone

PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 µg/d). Furthermore, the hypothalamic expression of TLR4, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) was analyzed after 9 days' treatment with udenafil and/or leptin. We also measured body weight and food intake following 9 days of udenafil and/or leptin treatment in control- and HF-fed mice. RESULTS: Udenafil suppressed hypothalamic TLR4 mRNA expression dose-dependently. The changes were associated with decreased PDE5, NF-κB, and Myd88 expression. Udenafil treatment for 9 days reduced body weight and caloric intake in HF-fed mice. This may have been associated with the suppression of NPY expression that was elevated by HF feeding. POMC expression was not affected by udenafil. However, udenafil did not augment the effects of leptin on the reduction of body weight and caloric intake in HF-fed mice. CONCLUSIONS: These results suggested that udenafil reduced body weight by suppressing hypothalamic TLR4 mRNA expression in HF-fed mice and the combination effect of udenafil and leptin was additive rather than synergistic.
Animals ; Body Weight ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Eating ; Energy Intake ; Epithelial Cells ; Hypothalamus ; In Vitro Techniques ; Leptin ; Mice ; Neuropeptide Y ; Obesity ; Pro-Opiomelanocortin ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Toll-Like Receptor 4 ; Toll-Like Receptors

Fixed drug eruption is a commonly reported mucocutaneous drug eruption. A 61-year-old male presented to our clinic with a complaint of an itchy round erythematous patch on the left hand dorsum with myalgia. On taking medical history, the patient correlated the episode with the intake of an oral sexual enhancer that he had obtained over the counter. We found the medicine contained tadalafil and sildenafil in combination with herbal ingredients. A short course of oral corticosteroid therapy resulted in the complete resolution of the lesion leaving residual hyperpigmentation of the skin involved. Various sexual enhancers with fancy names and attractive packaging are available without requiring a doctor's prescription. Most contain phosphodiesterase-5 inhibitors in various concentrations, often with herbal additions. These drugs are used erratically by the lay public, and often produce side effects. Herein, we report a case of fixed drug rash related to a sexual enhancer, which we believe to be the first report in Korea.
Cyclic Nucleotide Phosphodiesterases, Type 5 ; Drug Eruptions* ; Exanthema ; Hand ; Humans ; Hyperpigmentation ; Korea ; Male ; Middle Aged ; Myalgia ; Phosphodiesterase 5 Inhibitors ; Prescriptions ; Product Packaging ; Sildenafil Citrate ; Skin ; Tadalafil

PURPOSE: To assess the prevalence of phosphodiesterase 5 (PDE5) inhibitor use and associated factors among University of Gondar undergraduate students. MATERIALS AND METHODS: An institution-based, cross-sectional study, using a survey questionnaire, was conducted from October to December 2015 to assess PDE5 inhibitor use and associated factors among male students at the University of Gondar. A Self-Esteem and Relationship questionnaire (14 items), an International Index of Erectile Function questionnaire (15 items) and a questionnaire on PDE5 inhibitor use (14 items) were included in the survey. RESULTS: Across all respondents (age, 21.9±1.88 years), more than half (55.7%, n=233) had heard about PDE5 inhibitors, but only 23 men (5.5%) reported trying a PDE5 inhibitor drug at least once. Older students were more likely to use PDE5 inhibitors compared to younger students (adjusted odds ratio [AOR], 1.40; 95% confidence interval [CI], 1.109~1.768). Those students who were smokers were 5.15 times more likely to use PDE5 inhibitors as compared to their non-smoking counterparts (AOR, 5.15; 95% CI, 2.096~12.687). In addition, multivariate logistic regression showed that being in a relationship, alcohol use, greater number of cigarettes smoked per day, and more sexual partners were significantly associated with PDE5 inhibitor use. CONCLUSIONS: The prevalence of PDE5 inhibitor use among undergraduate students was 5.5%. Cigarette smoking and other substance use, older age, and greater number of sexual partners were significantly associated factors for PDE5 inhibitor use. These findings suggest that restricting access to PDE5 inhibitor drugs is essential to curtailing misuse among university students.
Cross-Sectional Studies* ; Cyclic Nucleotide Phosphodiesterases, Type 5* ; Erectile Dysfunction ; Ethiopia ; Humans ; Logistic Models ; Male* ; Odds Ratio ; Phosphodiesterase 5 Inhibitors* ; Prevalence ; Sexual Partners ; Smoke ; Smoking ; Surveys and Questionnaires ; Tobacco Products

Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Responses to treatments for jackhammer esophagus have been inconsistent in previous trials, possibly due to its heterogeneous manifestation. Thus, we reviewed 10 patients diagnosed with jackhammer esophagus and compared their clinical and manometric features at baseline. Additionally, manometric and symptomatic responses after treatment with known smooth muscle relaxants, including anticholinergic drugs (cimetropium bromide and scopolamine butylbromide) and a phosphodiesterase-5 inhibitor (sildenafil) were compared. We observed two distinct subgroups in the findings: one with hypercontractility and normal distal latencies (“classic jackhammer esophagus,” n=7) and the other with hypercontractility and short distal latencies (“spastic jackhammer esophagus,” n=3). The two types also differed in their responses to medications in that symptoms improved upon treatment with an anticholinergic agent in classic jackhammer esophagus patients, while spastic jackhammer esophagus was unresponsive to both the anticholinergic drugs and the phosphodiesterase-5 inhibitor. In conclusion, hypercontractile esophagus may be a heterogeneous disease with different underlying pathophysiologies. We introduced two novel terms, “classic jackhammer esophagus” and “spastic jackhammer esophagus,” to distinguish the two types.
Classification ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Deglutition Disorders ; Esophageal Motility Disorders ; Esophagus* ; Humans ; Muscle Spasticity* ; Muscle, Smooth ; Scopolamine Hydrobromide

PURPOSE: Combination therapy with an alpha-1-adrenergic blocker and phosphodiesterase type 5 inhibitors (PDE5Is) has shown improvements in lower urinary tract symptoms (LUTS) with negligible side effects. Nonetheless, decisive advantages in symptom improvement were insufficient, and there were no clinical differences between long- or short-acting PDE5Is in combination with combination medication. METHODS: To review the studies on alpha-1-adrenergic blocker monotherapy and combination therapy with long vs. short-acting PDE5Is in their use in LUTS and erectile dysfunction (ED). A search of the MEDLINE, Embase, Cochrane Library, and KoreaMed databases was conducted from 2000 to 2014 using combinations of the relevant terms. Among the 323 relevant references discovered, 10 were selected for meta-analysis. The data showed that 616 men received combination therapy (PDE5Is with alpha-1-adrenergic blockers) or alpha-1-adrenergic blocker monotherapy. RESULTS: Meta-analysis of the combination therapy showed it was more effective than alpha-blockers in improving symptoms, with a mean International Prostrate Symptom Score change difference of -1.93 while those of the long- vs. short-acting PDE5I were -2.12 vs. -1.70. Compared to maximum flow rate (Qmax) value with monotherapy, the Qmax increased more with the combination therapy (mean difference of 0.71) while change values were 0.14 and 1.13 for the long- and short-acting PDE5Is, respectively. Residual urine decreased more with the combination therapy than it did with alpha-1-adrenergic blocker monotherapy with a mean difference of -7.09 while the mean residual urine change values for long- vs. short-acting PDE5Is were -18.83 vs. -5.93. The International Index of Erectile Function value increased by 3.99, 2.85, and 4.85 following combination therapy, and therapy with long- and short-acting PDE5Is. CONCLUSIONS: Our meta-analysis suggests that PDE5Is can signicantly improve LUTS in men with benign prostatic hyperplasia/ED. Furthermore, combination PDE5I and alpha-1-adrenergic blocker could be a more effective treatment than alpha-1-adrenergic blocker monotherapy, and the differences between long and short-acting agents were minimal.
Cyclic Nucleotide Phosphodiesterases, Type 5* ; Erectile Dysfunction* ; Humans ; Lower Urinary Tract Symptoms* ; Male ; Phosphodiesterase 5 Inhibitors* ; Prostatic Hyperplasia

No abstract available.
Cyclic Nucleotide Phosphodiesterases, Type 5*

PURPOSE: To compare the safety and efficacy of tamsulosin and tamsulosin with the phosphodiesterase-5 inhibitor tadalafil in combination with prednisolone as medical expulsive therapies for lower ureteric stones. MATERIALS AND METHODS: Between July 2011 and December 2012, 62 adult patients presenting with distal ureteric stones sized 5 to 10 mm were randomized equally to treatment with tamsulosin (group A) or tamsulosin with tadalafil (group B). Therapy was given for a maximum of 6 weeks. In addition, patients in groups A and B were given 5-mg prednisolone once daily (maximum 1 week). The stone expulsion rate, time to stone expulsion, analgesic use, number of hospital visits for pain, follow-up and endoscopic treatment, and adverse effects of the drugs were noted. Statistical analyses were done by using Student t-test and chi-square test. RESULTS: There was a higher expulsion rate (83.9% in group B and 74.2% in group A) and a lower time to expulsion in both treatment groups than in historical controls used in earlier studies. However, these results were not statistically significant (p=0.349, p=0.074, respectively). Statistically significant differences were noted in hospitalization for colic and analgesic requirement, which were less in group B than in group A. There were no serious adverse events. Another important finding was improvement in erectile function in group B. CONCLUSIONS: Medical expulsive therapy for distal ureteric stones using tamsulosin and tadalafil with prednisolone is safe and efficacious. Also, the prescription of tadalafil in cases of erectile dysfunction with the development of lower ureteric stones may provide additional advantages.
Adult ; Colic ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Follow-Up Studies ; Hospitalization ; Humans ; Male ; Prednisolone* ; Prescriptions ; Ureter* ; Urinary Calculi

PURPOSE: A nationwide survey was conducted of Korean urologists to illustrate physicians' perceptions and real practical patterns regarding Peyronie disease (PD). MATERIALS AND METHODS: A specially designed questionnaire exploring practice characteristics and attitudes regarding PD, as well as patient satisfaction with each treatment modality, was e-mailed to 2,421 randomly selected urologists. RESULTS: Responses were received from 385 practicing urologists (15.9%) with a median time after certification as an urologist of 12 years. Regarding the natural course, 87% of respondents believed that PD is a progressive disease, and 82% replied that spontaneous healing in PD occurred in fewer than 20% of patients. Regarding diagnosis of PD, the methods used were, in order, history taking with physical examination (98%), International Index of Erectile Function questionnaires (40%), intracavernous injection and stimulation (35%), and duplex sonography (28%). Vitamin E was most preferred as an initial medical management (80.2%), followed by phosphodiesterase-5 inhibitors (27.4%) and Potaba (aminobenzoate potassium, 20.1%). For urologists who administered intralesional injection, the injected agent was, in order, corticosteroid (72.2%), verapamil (45.1%), and interferon (3.2%). The most frequently performed surgical procedure was plication (84.1%), followed by excision and graft (42.9%) and penile prosthesis implantation (14.2%). Among the most popular treatments in each modality, the urologists' perceptions regarding the suitability of treatment and patient satisfaction were significantly different, favoring plication surgery. CONCLUSIONS: The practice pattern of urologists depicted in this survey is in line with currently available Western guidelines, which indicates the need for development of further local guidelines based on solid clinical data.
4-Aminobenzoic Acid ; Certification ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Data Collection ; Diagnosis ; Electronic Mail ; Humans ; Injections, Intralesional ; Interferons ; Male ; Patient Satisfaction* ; Penile Implantation ; Penile Induration* ; Physical Examination ; Potassium ; Questionnaires ; Transplants ; Verapamil ; Vitamin E ; Vitamins