Music from Noise-Canceling Headphones Is Beneficial against Anxiety in Male Bladder Cancer Patients Undergoing Follow-Up Cystoscopy: A Prospective Randomized Trial.

INTRODUCTION: Bladder cancer, with a greater incidence in males than in females, requires frequent cystoscopies. We aimed to evaluate the effect of music played through noise-canceling headphones on male bladder cancer patients during follow-up cystoscopy. METHODS: A total of 160 male bladder cancer patients undergoing follow-up flexible cystoscopy were randomly divided into the noise-canceling headphones without music group and the noise-canceling headphones with music group (groups 1 and 2, respectively; n = 80 per group). The patients' clinical characteristics were examined, and objective and subjective measurements were compared before and after cystoscopy. The primary outcomes that were evaluated included the visual analog scale (VAS, 0-10) and the state-trait anxiety inventory (STAI, 20-80). Other outcomes, including vital signs and scores for assessing satisfaction and the willingness to repeat the procedure, were also examined. RESULTS: The characteristics of the patients in groups 1 and 2, and their pre-cystoscopy status, did not differ significantly. Although post-cystoscopy vital signs for the objective parameters and VAS pain scores were similar between the groups, subjective parameters were not. When compared with group 1, post-cystoscopy STAI-state scores were significantly lower in group 2, whereas patients' satisfaction scores and the willingness to repeat the procedure were significantly higher in group 2 (p = 0.002, 0.001, and 0.001, respectively). Additionally, in group 2, STAI-state scores changed significantly after the procedure when compared with before the procedure (p = 0.002). CONCLUSION: Providing music to male bladder cancer patients through noise-canceling headphones was found to reduce anxiety during cystoscopy and to improve patient satisfaction and willingness to undergo repeat cystoscopy.

The relationship between depressive mood and subjective health in centenarians and near-centenarians: a cross-sectional study from Korean centenarian cohort.

BACKGROUND: With the rapid increase in population longevity, more clinical attention is being paid to the overall health of long-lived people, especially centenarians. Subjective health, which is the perception of one's health status, predicts both mortality and declining physical function in older adults. The purpose of this study was to investigate the factors related to subjective health among centenarians and near-centenarians (ages ≥95) living in a rural area of South Korea. METHODS: A total of 101 participants were enrolled from four different regions (Gurye, Gokseong, Sunchang, and Damyang), known as the Longevity Belt in Korea. Variables assessing physical and mental health, including the results of blood tests, were examined. Factors associated with good subjective health were identified with logistic regression analysis. RESULTS: Fifty-six participants (59.6%) were subjectively healthy among the centenarians and near-centenarians. Logistic regression analysis revealed that depressive mood was the only factor associated with subjective health and was negatively correlated. The regression model explained 39% of the variance in subjective health. CONCLUSIONS: These findings emphasize the importance of mental health at very advanced ages. Because depressive mood negatively correlates with subjective health, more attention is needed to prevent and manage mood symptoms of people of advanced ages, including centenarians.

Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe.

INTRODUCTION: Female sexual arousal disorder (FSAD) can be caused by the change in vaginal structure due to the decline of estrogen and one of the main symptoms is vaginal dryness. FSAD is a prevalent problem afflicting women all over the world and thus the interest is growing on the matter, but related studies of monitoring FSAD using a non-invasive optical method barely have been carried out. AIM: This study aims to investigate the longitudinal changes in female sexual arousal response induced by apomorphine (APO) administration in the ovariectomized rat using near-infrared spectroscopy (NIRS) probe. METHODS: To elicit sexual arousal, APO was administered subcutaneously to animals (n = 6) before and after ovariectomy, and the changes in oxyhemoglobin (OHb), deoxyhemoglobin (RHb), total hemoglobin (THb) concentration, and temperature on the vaginal wall after APO administration were monitored bi-weekly for 8 weeks. Furthermore, estradiol hormone, vaginal secretion, and body weight have been measured for comparison with the results from vaginal hemodynamics. RESULTS: APO administration caused the increase of vaginal OHb and RHb concentration but a decrease in temperature. The amplitude of OHb, RHb, and THb increase induced by APO gradually decreased over 8 weeks after ovariectomy while the decrease in vaginal temperature became profound. The level of estradiol and vaginal secretions also decreased over 8 weeks after ovariectomy, but bodyweight showed an increasing trend. CONCLUSIONS: A comparison between the parameters measured from the NIRS probe and the others (estradiol level, amount of vaginal secretion, and body weight) proved that the NIRS has the potential as a monitoring tool to evaluate female sexual arousal response. Jeong H, Lee HS, Seong M, et al. Changes of Apomorphine-Induced Vaginal Hemodynamics in an Ovariectomized Rat Model Using Near-Infrared Spectroscopic Probe. J Sex Med 2021;18:1328-1336.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

BACKGROUND: The Global Consensus Position Statement on the Use of Testosterone Therapy for Women (Global Position Statement) recommended testosterone therapy for postmenopausal women with hypoactive sexual desire disorder (HSDD). AIM: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with HSDD. METHODS: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. OUTCOMES: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. RESULTS: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. CLINICAL IMPLICATIONS: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. STRENGTHS & LIMITATIONS: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. CONCLUSION: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need. Parish SJ, Simon JA, Davis SR, et al. International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women. J Sex Med 2021;18:849-867.

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women.

AIM: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with hypoactive sexual desire disorder (HSDD). METHODS: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method. OUTCOMES: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up. RESULTS: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data. CLINICAL IMPLICATIONS: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring. STRENGTHS AND LIMITATIONS: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging. CONCLUSION: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need.

Co-culture of smooth muscle cells and endothelial cells on three-dimensional bioprinted polycaprolactone scaffolds for cavernosal tissue engineering.

PURPOSE: In vitro evaluation of polycaprolactone (PCL) scaffolds fabricated by a three-dimensional (3D) printing technique for tissue engineering applications in the corpus cavernosum. MATERIALS AND METHODS: PCL scaffolds were fabricated by use of a 3 D bioprinting system. The 3D-printed scaffolds had interconnected structures for cell ingrowth. Human aortic smooth muscle cells (haSMCs) were seeded on the scaffold and cultured for 5 days, and then human umbilical vein endothelial cells (HUVECs) were also added on the scaffolds and co-cultured with haSMCs for up to 7 days. The ability of these scaffolds to support the growth of HUVECs and haSMCs was investigated in vitro. 3 D strand-deposited scaffolds were characterized by scanning electron microscopy (SEM) images and porosity measurement. RESULTS: SEM images showed the surface of the PCL scaffolds to be well covered by HUVECs and haSMCs. Immunofluorescent staining of α-flk1 and α-smooth muscle actin on the HUVECs and haSMCs seeded scaffolds confirmed that the cells remained viable and proliferated throughout the time course of the culture. CONCLUSION: 3 D bioprinting of a PCL scaffold is feasible for co-culturing of HUVECs and haSMCs. This was a preliminary study to investigate the possibility of fabrication of tissue-engineered corpus cavernosum.

Design of an Optical Probe to Monitor Vaginal Hemodynamics during Sexual Arousal.

An optical probe was developed to measure the change of oxy-hemoglobin (OHb), deoxy- hemoglobin (RHb), and total hemoglobin (THb) along with temperature from the vaginal wall of female rats. Apomorphine (APO, 80 µg/kg) was administered to elicit sexual arousal in female Sprague Dawley rats (SD, 180-200 g). The behavior changes caused by APO administration were checked before monitoring vaginal responses. The changes of oxy-, deoxy-, and total hemoglobin concentration and the temperature from the vaginal wall were monitored before, during, and after APO administration. Animals were under anesthesia during the measurement. After APO administration, the concentration of OHb (55 ± 29 µM/DPF), RHb (33 ± 25 µM/DPF), and THb (83 ± 59 µM/DPF) in the vaginal wall increased in a few min, while saline administration did not cause any significant change. In case of the vaginal temperature change, APO decreased the temperature slightly in the vaginal wall while saline administration did not show any temperature change in the vaginal wall. As the outcomes demonstrated, the developed probe can detect hemodynamic and temperature variation in the vaginal wall. The hemodynamic information acquired by the probe can be utilized to establish an objective and accurate standard of female sexual disorders.

Effects of Sex Hormones and Age on Brain Volume in Post-Menopausal Women.

BACKGROUND: Investigation of the effect of sex hormones on the brain volume in women provides a unique opportunity to examine menopause-related morphometric alterations. AIM: To evaluate brain morphological alterations in post-menopausal women using voxel-based morphometry and its correlations with sex hormone levels. METHODS: 20 Pre-menopausal women and 20 post-menopausal women underwent structural MRI. OUTCOMES: T1-weighted magnetic resonance data were acquired and serum sex hormones including total estrogen, estriol, estradiol (E2), follicle-stimulating hormone, free testosterone, SHBG, and luteinizing hormone were measured. RESULTS: Post-menopausal women showed decreased gray matter (GM) in the supplementary motor area (SMA), inferior frontal gyrus, olfactory cortex, and superior temporal gyrus as contrasted with pre-menopausal women using analysis of covariance (P < .05). The GM volume (GMV) values of the SMA, inferior frontal gyrus, and superior temporal gyrus were positively correlated with the levels of E2 in the pre-menopausal and post-menopausal women, in which the volume of the SMA was negatively correlated with the duration of time after menopause in post-menopausal women. CLINICAL TRANSLATION: This finding is potentially applicable to assess the brain dysfunction with morphological changes in post-menopausal women. CONCLUSIONS: Our study is the first to evaluate a direct relationship between the level of E2 and GMV change. We directly compared pre-menopausal and menopausal women un-matched in age. This study highlights the menopause-related morphological alterations in post-menopausal women, suggesting that the reduced GMV were closely associated with the symptoms of menopause caused by the decreased levels of E2. Kim G-W, Park K, Jeong G-W. Effects of Sex Hormones and Age on Brain Volume in Post-Menopausal Women. J Sex Med 2018;15:662-670.

Association between hand-grip strength and erectile dysfunction in older men.

OBJECTIVES: To evaluate the association between handgrip strength and erectile dysfunction (ED) in community-dwelling older men. METHODS: This cross-sectional study included 1771 participants of the Dong-gu Study. Handgrip strength was measured with a handheld dynamometer. ED was assessed with the Korean version of the International Index of Erectile Function (IIEF). ED was categorized as none to mild (IIEF-EF scores of 13-30) and moderate to severe (IIEF-EF scores of 0-12). Multivariable logistic regression was conducted with adjustment for potential confounders. RESULTS: The proportion of men with moderate to severe ED was 48.8%. The age-adjusted ED score increased with increasing quartile of handgrip strength (11.0, 12.4, 13.4, and 14.0 in the lowest, second, third, and highest quartiles, respectively). After adjustment for potential confounders, greater handgrip strength was associated with a lower risk of ED (odds ratio (OR): 0.82 per 5 kg; 95% confidence interval (CI): 0.74-0.90). In addition, a high level of moderate to vigorous physical activity was associated with a lower risk of ED (OR: 0.75; 95% CI: 0.61-0.93). CONCLUSION: In this study, aging men with greater handgrip strength had a lower risk of ED. This result suggests that reduced physical functioning may contribute to ED.

Laparoscopic adrenalectomy using the lateral retroperitoneal approach: Is it a safe and feasible treatment option for pheochromocytomas larger than 6 cm?

OBJECTIVES: To evaluate the surgical feasibility of laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of large pheochromocytomas, and to identify the preoperative risk factors for intraoperative hypertension. METHODS: We retrospectively reviewed 51 patients who underwent laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of pheochromocytomas. Patient characteristics and perioperative outcomes were analyzed and compared between the two study groups based on tumor size: group A (n = 27, ≤6 cm) and group B (n = 24, ˃6 cm). RESULTS: There was no significant difference in preoperative characteristics between the two groups except for tumor size (P = 0.001) and urinary metanephrine (P = 0.011). Group B patients required longer operating time (P = 0.008), had a greater estimated blood loss (P = 0.001) and hemoglobin change (P = 0.002). However, no significant differences were observed in perioperative complications and mortality. Multivariate analysis showed that symptomatic pheochromocytomas (P = 0.004) and tumor size (P = 0.007) were significant risk factors for intraoperative hypertension. CONCLUSIONS: Laparoscopic adrenalectomy using the lateral retroperitoneal approach for pheochromocytomas can be regarded as a treatment option, even for tumors measuring >6 cm. Symptomatic pheochromocytomas and large tumor size seem to represent risk factors for intraoperative hypertension.

Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial.

BACKGROUND: Phosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). AIMS: To assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED. METHODS: A randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg. OUTCOMES: The primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24. RESULTS: The mean changes in total IPSS and IIEF-EF scores were -9.46 and 9.17 for FDC 0.4/5 mg and -8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period. CLINICAL IMPLICATIONS: The FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED. STRENGTHS AND LIMITATIONS: The study clearly demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower incidence of side effects, and the simplification and convenience of therapy, which led to better overall patient compliance. However, the lack of a tamsulosin monotherapy control group was a limitation of this study. CONCLUSION: The FDC 0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that combination therapy could provide clinical benefits for patients with BPH-associated LUTS complaints and ameliorate the comorbidity of ED. Kim SW, Park NC, Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. J Sex Med 2017;14:1018-1027.

A Randomized, Placebo-Controlled, Double-Blind, Multi-Center Therapeutic Confirmatory Study to Evaluate the Safety and Efficacy of Avanafil in Korean Patients with Erectile Dysfunction.

A multi-center, randomized, double-blind, placebo-controlled study was conducted with 158 subjects who were randomized to placebo or avanafil 50, 100, and 200 mg on demand for 8 weeks to evaluate the safety, tolerability, and efficacy of avanafil in the treatment of erectile dysfunction (ED) in Korean men. The primary outcome was the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) questionnaire. Secondary outcomes included changes in the scores of IIEF questions 3 and 4 (IIEF Q3, Q4) from baseline, changes in all domain scores in the IIEF from baseline, Sexual Encounter Profile questions 2-5 (SEP2-5), the Global Efficacy Assessment Question (GEAQ), and the number of subjects whose EF domain score at the 8th week visit was ≥ 26. After 8 weeks of treatment, the dose groups except avanafil 50 mg scored significantly higher on the IIEF-EF domain from baseline than the placebo group. The changes from baseline in the avanafil group in IIEF Q3 (all doses) and Q4 (200 mg alone) were higher than the placebo group. The differences between avanafil and placebo groups were significant in SEP2 (100 and 200 mg) and SEP3-5 (200 mg). The differences in the GEAQ "Yes" response were also significant in the avanafil 100 and 200 mg groups. Regarding the ratio of normal EF at the end of the study, avanafil 200 mg differed significantly from the placebo. Most treatment-associated adverse events were mild and resolved spontaneously. This is a clinical trial study and was registered at www.ClinicalTrials.gov (Identifier: NCT02477436).

Testosterone modulates endothelial progenitor cells in rat corpus cavernosum.

OBJECTIVE: To investigate the effects of testosterone on cavernosal endothelial progenitor cells (EPCs) in a castrated rat model. MATERIALS AND METHODS: In all, 45 male Sprague-Dawley rats (12-weeks old) were divided into control, surgical castration, and castration with testosterone replacement groups. The rats were castrated under ketamine anaesthesia, and testosterone was administered by daily subcutaneous injection of 3 mg/kg testosterone propionate. The corpus cavernosum was obtained after perfusion with 10 mL saline via the abdominal aorta 4 weeks later. The expression of EPC-specific markers [cluster of differentiation 34 (CD34), fetal liver kinase 1 (Flk1), and vascular endothelial (VE)-cadherin] was evaluated by flow cytometry analysis and immunofluorescence staining. RESULTS: CD34+/Flk1+ and CD34+/VE-cadherin+ cells were detected in the cavernosal sinusoidal endothelial space. Flow cytometry analysis showed that CD34 and Flk1 double positive cells (EPCs) comprised ≈3.79% of the corpus cavernosum in normal rats. The percentage of EPC marker-positive cells decreased significantly in the castration group (2.8%; P < 0.05) and was restored to 3.56% after testosterone supplementation. Confocal microscopy revealed that the numbers of CD34+/Flk1+ and CD34+/VE-cadherin+ cells decreased in castrated rats compared with controls, but were similar to control levels in rats receiving testosterone replacement. CONCLUSIONS: The EPC markers were expressed in the cavernosal sinusoidal endothelial space, and the numbers of resident EPCs were regulated by testosterone. These results suggest that testosterone replacement therapy may improve erectile function by modulating EPCs in patients with hypogonadism.

The Physiology of Female Sexual Function and the Pathophysiology of Female Sexual Dysfunction (Committee 13A).

INTRODUCTION: The article consists of six sections written by separate authors that review female genital anatomy, the physiology of female sexual function, and the pathophysiology of female sexual dysfunction but excluding hormonal aspects. AIM: To review the physiology of female sexual function and the pathophysiology of female sexual dysfunction especially since 2010 and to make specific recommendations according to the Oxford Centre for evidence based medicine (2009) "levels of evidence" wherever relevant. CONCLUSION: Recommendations were made for particular studies to be undertaken especially in controversial aspects in all six sections of the reviewed topics. Despite numerous laboratory assessments of female sexual function, genital assessments alone appear insufficient to characterise fully the complete sexual response.

A Phase 3 Study to Evaluate the 1-Year Efficacy and Safety of Udenafil 75 mg Once Daily in Patients With Erectile Dysfunction.

INTRODUCTION: Once-daily administration of phosphodiesterase type 5 inhibitors has been shown to correct erectile dysfunction (ED). AIM: To evaluate the long-term efficacy and safety after once-daily oral administration of udenafil 75 mg in men with ED. METHODS: This clinical trial was an open-label, fixed-dose, 24-week extension study (DA8159_EDDL_III) of a 24-week double-blinded efficacy and safety study of once-daily udenafil (parent study: DA8159_EDD_III). Subjects received udenafil 75 mg once daily for 24 weeks during this extension study, and the follow-up visit occurred during the 4-week ED treatment-free period. MAIN OUTCOME MEASURES: Subjects were asked to complete the International Index of Erectile Function questionnaire and the Global Assessment Questionnaire at the 24-week extension and after the 4-week ED treatment-free period, and the development of adverse drug reactions was investigated. RESULTS: In total, 302 subjects were enrolled in this extension study. Improvement was shown with an increased erectile function (EF) domain score compared with baseline (14.60 ± 4.57) at extension week 48 (23.98 ± 5.44) and a slight increase in EF domain score compared with the last time point (week 24) of the parent study (P < .001). The Global Assessment Questionnaire showed a high improvement rate of 95.4% at the extension 48-week time point. For shift to normal, almost half the subjects (45.1%) recovered "normal" EF, and 14.2% of subjects reported normal erections after the 4-week ED treatment-free period. The occurrence rate of adverse drug reactions was 8%, which consisted mainly of flushing and headache. CONCLUSION: Once-daily dosing of udenafil 75 mg showed excellent efficacy and safety with long-term administration and allowed a more spontaneous sexual life.

Efficacy of once-daily administration of udenafil for 24 weeks on erectile dysfunction: results from a randomized multicenter placebo-controlled clinical trial.

INTRODUCTION: The method of administration of oral phosphodiesterase-5 inhibitors has been expanded to once-daily repeated administration with lower initial dosage than on-demand administration. AIM: The aim of this study was to evaluate the efficacy and safety of once-daily udenafil as a treatment for erectile dysfunction (ED) for intermediate-term period. METHODS: This multicenter, randomized, double-blind clinical trial included 346 ED patients (placebo, udenafil 50 mg, udenafil 75 mg). Subjects were treated with each medication once daily for 24 weeks. MAIN OUTCOME MEASURES: Subjects were asked to complete the International Index of Erectile Function (IIEF)-erectile function (EF) domain at baseline, 12 weeks, and 24 weeks and the development of adverse drug reactions (ADRs) was inspected. RESULTS: Both dosages of udenafil induced a significant increase in IIEF-EF compared with placebo at both 12 and 24 weeks. When patients were divided according to the severity of baseline EF score, significant improvement was observed only with udenafil 75 mg regardless of the degree of ED. At 24 weeks, the proportions of patients who reported a return to normal EF (IIEF-EF over 26) were 39.1% for udenafil 50 mg and 47.0% for udenafil 75 mg. In terms of safety, ADRs were observed in 6.1%, 12.9%, and 17.9% for placebo, udenafil 50 mg, and 75 mg, respectively. Although a statistically higher rate of ADRs was observed in the udenafil 75 mg group (P = 0.024), the majority were mild and recovered without treatment. CONCLUSIONS: Once-daily administration of udenafil 50 mg and 75 mg for 24 weeks resulted in improvement of EF. In particular, udenafil 75 mg improves EF regardless of the baseline degree of ED.

Prostate-Specific Antigen fluctuation: what does it mean in diagnosis of prostate cancer?

OBJECTIVE: To investigate whether prostate-specific antigen (PSA) fluctuation correlates with a prostate cancer and to assess whether PSA fluctuation could be used for diagnosis of prostate cancer. MATERIALS AND METHODS: Our study included 229 patients who were performed a prostate biopsy (non-cancer group, 177; prostate cancer group, 52). Enrolled patients were provided twice PSA tests within 6 months. PSA fluctuation (%/month) was defined as a change rate of PSA per a month. Independent t test was used to compare between two groups. Receiver operator characteristic curve was used to assess the availability as a differential diagnostic tool and the correlation. Simple linear regression was performed to analyze a correlation between PSA fluctuation and other factors such as age, PSA, PSA density, and prostate volume. RESULTS: There were significant differences in PSA, PSA density, percentage of free PSA, and PSA fluctuation between two groups. PSA fluctuation was significantly greater in non-cancer group than prostate cancer group (19.95 ± 23.34%/month vs 9.63 ± 8.57%/ month, P=0.004). The most optimal cut-off value of PSA fluctuation was defined as 8.48%/month (sensitivity, 61.6%; specificity, 59.6%; AUC, 0.633; P=0.004). In a simple linear regression model, only PSA level was significantly correlated with PSA fluctuation. CONCLUSION: Patients with wide PSA fluctuations, although baseline PSA levels are high, might have a low risk of diagnosis with prostate cancer. Thus, serial PSA measurements could be an option in patients with an elevated PSA level.

Is larger tumor size a contraindication to retroperitoneal laparoscopic adrenalectomy?

PURPOSE: To evaluate the surgical feasibility of retroperitoneal laparoscopic adrenalectomy for tumors exceeding 5 cm. METHODS: A retrospective review was carried out on all adrenalectomies performed between 2002 and 2011. All surgical procedures were performed or supervised by one of two experienced laparoscopic surgeons. A total of 133 patients who underwent retroperitoneal laparoscopic adrenalectomy were divided according to tumor size: group I (n = 57) had tumors <5 cm and group II (n = 76) had tumors ≥5 cm. The operative outcomes included surgical time, change in hemoglobin level, estimated blood loss, necessity for blood transfusion, time to ambulation, hospitalization duration, postoperative complications according to the Clavien-Dindo classification, and the rate of conversion to open surgery. RESULTS: The estimated blood loss (271.75 ± 232.98 mL vs. 367.24 ± 275.11 mL; p = 0.037), time to ambulation (1.60 ± 0.49 days vs. 1.89 ± 0.31 days; p = 0.001), and postoperative hospitalization (7.88 ± 3.08 days vs. 9.264 ± 3.10 days; p = 0.012) were significantly higher in group II. The operation time and hemoglobin level change were not statistically different between groups. Blood transfusions were performed in 3 patients from group I and 6 patients from group II (5.3 vs. 7.9 %; p = 0.449). No patients experienced conversion to open surgery. CONCLUSIONS: Retroperitoneal laparoscopic adrenalectomy can be used in patients with tumors larger than 5 cm.

Altered brain morphology and functional connectivity in postmenopausal women: automatic segmentation of whole-brain and thalamic subnuclei and resting-state fMRI.

The transition to menopause is associated with various physiological changes, including alterations in brain structure and function. However, menopause-related structural and functional changes are poorly understood. The purpose of this study was not only to compare the brain volume changes between premenopausal and postmenopausal women, but also to evaluate the functional connectivity between the targeted brain regions associated with structural atrophy in postmenopausal women. Each 21 premenopausal and postmenopausal women underwent magnetic resonance imaging (MRI). T1-weighted MRI and resting-state functional MRI data were used to compare the brain volume and seed-based functional connectivity, respectively. In statistical analysis, multivariate analysis of variance, with age and whole brain volume as covariates, was used to evaluate surface areas and subcortical volumes between the two groups. Postmenopausal women showed significantly smaller cortical surface, especially in the left medial orbitofrontal cortex (mOFC), right superior temporal cortex, and right lateral orbitofrontal cortex, compared to premenopausal women (p < 0.05, Bonferroni-corrected) as well as significantly decreased functional connectivity between the left mOFC and the right thalamus was observed (p < 0.005, Monte-Carlo corrected). Although postmenopausal women did not show volume atrophy in the right thalamus, the volume of the right pulvinar anterior, which is one of the distinguished thalamic subnuclei, was significantly decreased (p < 0.05, Bonferroni-corrected). Taken together, our findings suggest that diminished brain volume and functional connectivity may be linked to menopause-related symptoms caused by the lower sex hormone levels.

Altered expression of caveolin 2 and 3 in smooth muscle of rat urinary bladder by 17ß-estradiol.

BACKGROUND: The purpose of this study was to investigate the effect of estrogen alteration on the expression of caveolin 2 and 3 in rat smooth muscle of urinary bladder. METHODS: Female Sprague-Dawley rats were divided into three groups: control, bilateral ovariectomy (Ovx), and bilateral ovariectomy followed by subcutaneous injections of 17ß-estradiol (Ovx+Est). After 4 weeks, urodynamic measurements were taken to ascertain the contraction interval and contraction pressure. The expression and cellular localization of caveolin 2 and 3 were determined by Western blot and immunohistochemistry in rat urinary bladder smooth muscle. RESULTS: In cystometrograms, the contraction interval (min) was significantly lower in the Ovx group (3.1±1.5) than in the control group (5.6±1.2), but was increased after estrogen treatment (9.3±1.0). Conversely, the average contraction pressure (mmHg) was higher in the Ovx group (26.2±2.3) than in the control group (21.9±3.1), and was decreased after estrogen treatment (23.8±3.5). Caveolin 2 and 3 expression was localized in the cell membrane of the smooth muscle. The protein expression of both caveolin 2 and 3 was significantly lower after ovariectomy and was restored to the control levels after 17ß-estradiol treatment. CONCLUSIONS: Hormonal alteration causes a significant change in the expression of caveolin 2 and 3 in smooth muscle of rat urinary bladder. These findings suggest that these molecules might have functional roles in the detrusor overactivity that occurs in association with hormonal alteration.