Effects of the start time of glycemic control on erectile function in streptozotocin-induced diabetic rats.

Diabetes-induced ED correlates with diabetes duration and glycemic control. This study evaluated the effect of glycemic control start time on erectile function in streptozotocin-induced diabetic rats. Rats were divided into normal controls (C); untreated diabetic rats (DM); and rats treated after 7 weeks (7W), and 10 weeks (10W) from DM. Treated diabetic rats received a timed daily injection of insulin. After 14 weeks of lab-controlled diabetes, experiments were performed. Group DM showed the ratio of intracavernosal pressure, significantly lower than other groups (10W vs DM; P<0.001). Groups 7W and 10W responded similarly, but did not recover to normal level (group C vs 7W; P<0.001). The percentage of α-smooth muscle actin increased more with earlier start times, and group DM's percentages decreased significantly (group 10W vs DM; P<0.001). Apoptosis recovered significantly only in group 7W, comparable to group C. As start times became earlier, for all molecules (eNOS, Akt, MYPT1 and PECAM-1), treatment groups' results neared those of group C. In conclusion, erectile function of diabetic rats recovered closer to normal controls if diabetic treatment started earlier. And the level of glycemic control was expected to be more important than the start time of diabetic treatment.

Pilot study of the clinical efficacy of ejaculatory hood sparing technique for ejaculation preservation in Holmium laser enucleation of the prostate.

We explored the effectiveness of ejaculatory hood sparing technique to Holmium laser enucleation of the prostate (HoLEP) for ejaculation preservation. From June 2010 to July 2011, 52 sexually active patients with sufficient ejaculate underwent HoLEP. Twenty-six patients received the ejaulatory hood sparing technique during HoLEP (EH-HoLEP group). The other 26 patients underwent conventional HoLEP (conventional-HoLEP group). In the EH-HoLEP group, paracollicular and supracollicular tissue >1 cm proximal to the verumontanum was preserved. The mean follow-up period was 9.7 months (range 3-12). There was no significant difference in patient characteristics and perioperative parameters, including age, prostate volume, International Index of Erectile Function score, operation time, weight of the enucleated tissue and the amount of laser energy. Semen was unchanged, decreased or vanished in 4 (15.4%), 8 (30.8%) and 17 (53.8%) EH-HoLEP patients, respectively. In the conventional-HoLEP group, semen was unchanged, decreased or vanished in 0 (0.0%%), 7 (26.9%) and 19 (73.1%) patients, respectively. Overall success rate of ejaculation preservation was 46.2% in the EH-HoLEP group and 26.9% in the conventional-HoLEP group (P = 0.249). Application of an ejaculatory hood sparing technique to HoLEP could not improve the success rate for ejaculation preservation. This was likely due to the surgical characteristics of HoLEP, which enable complete removal of the apical tissue. In this condition, simply preserved ejaculatory hood tissue seems not to be sufficient to obviate retrograde ejaculation. For the maintenance of antegrade ejaculation, it is postulated that a part of apical tissue should be preserved as well.

[Increased expression of hypoxia-inducible factor-1α and connective tissue growth factor accompanied by fibrosis in the rat testis of varicocele]. / Expresión aumentada del factor inducible por hipoxia 1α y del factor de crecimiento del tejido conectivo acompañando a fibrosis en testículos de ratas con varicocele.

OBJECTIVE: We investigated hypoxia inducible factor-1α (HIF-1α), connective tissue growth factor (CTGF) expression and fibrosis in the testis of rats with surgically induced varicocele. MATERIAL AND METHODS: A total of 47 adult male Sprague-Dawley rats were arranged in 3 groups, namely group 1 (varicocele operation 4 weeks ago, n=10; sham operation 4 weeks ago, n=5), group 2 (8 weeks, n=11; n=5), and group 3 (12 weeks, n=11; n=5). The rats in every group underwent bilateral orchiectomy 4, 8, and 12 weeks after the operations, respectively. HIF-1α and CTGF expression of both testes in group 3 were studied by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fibrotic change was assessed by quantitative image analysis. RESULTS: HIF-1α mRNA expression in testes tissues in varicocele operation and sham controls showed no significant differences in RT-PCR. However, CTGF mRNA expressions in left testes were found to be significantly different between varicocele operation and sham controls. HIF-1α staining was present in both testes of all specimens and CTGF staining was present in 10 left and 8 right testes of 11 specimens. However HIF-1α and CTGF staining were absent in control group. There were significant fibrotic changes of both testes in groups 2 and 3. There were significant differences in fibrotic change along the durations of surgical varicocele. CONCLUSIONS: This study reveals that experimental varicocele in the rat is associated with HIF-1α and CTGF expression and it is accompanied by fibrotic change in the testis.

Satisfaction with sex and erection hardness: results of the Asia-Pacific sexual health and overall wellness survey.

The Asia-Pacific Sexual Health and Overall Wellness (AP SHOW) survey assessed sexual satisfaction and health and the association with erection hardness in 13 Asia-Pacific countries/regions. Adults aged 25-74 years who had sexual intercourse > 1 time in the past 12 months answered Internet surveys or participated in street-intercept interviews. Data were weighted by demographics and country/region size. Of 3957 (men, n=2016 and women, n=1941) respondents, 41% of men and 34% of women were completely or very satisfied with sex. Satisfaction with sex was linked to satisfaction with life priorities and overall health. Few respondents (men, 38% and women, 26%) were very or completely satisfied with erection hardness. Optimal erection hardness was reported by 45% of men (48% of women regarding their partners' erections). Erection hardness was associated with increased frequency of sex and importance of and satisfaction with erection-related elements of men's sexual performance. Approximately half of respondents (men, 57% and women, 47%) were at least moderately interested in improving the sexual experience. Most Asia-Pacific respondents were less than very satisfied with sex. Satisfaction with sex was associated with satisfaction with life priorities. Erection hardness was associated with sexual satisfaction and activity, satisfaction with life priorities and overall health.

Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is mainly metabolized by N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH). We investigated whether altered cavernosal ADMA-DDAH metabolism might cause impairment of erection in rat model of atherosclerosis (AS). Male Sprague-Dawley rats (3 months old) were divided into an AS group and a normal control (Con) group (n=20 in each group). The AS rats received AS-prone treatment (6 weeks of 1% cholesterol diet plus early 2 weeks of N(G)-nitro-L-arginine methyl ester (3 mg ml(-1) per day) treatment). After 6 weeks, rats underwent cavernosometry measuring the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios as a surrogate marker of erectile function. The amount of cavernosal ADMA was assessed by immunoblot analysis and correlated with the ICP/MAP. Isoform-specific DDAH expression was compared by immunohistochemistry. Cavernosal DDAH and NOS activity were measured. Cavernosal malondialdehyde levels were assayed to determine the degree of lipid peroxidation. Compared to the controls, the AS rats had signs of impaired erectile function. Higher cavernosal ADMA was observed in the AS rats. The cavernosal ADMA had a moderately negative correlation with the ICP/MAP. Immunohistochemistry revealed the expression of both isoforms was not affected by the presence of AS. However, significantly diminished DDAH as well as NOS activity was observed in the AS group. In addition, elevated cavernosal malondialdehyde levels were noted in the AS rats. Our study showed that decreased cavernosal DDAH activity is the cause of cavernosal ADMA accumulation leading to reduced cavernosal NOS activity and impairment of erectile function.

Efficacy and safety of solifenacin succinate in Korean patients with overactive bladder: a randomised, prospective, double-blind, multicentre study.

PURPOSE: We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: The study was randomised, double-blind, tolterodine-controlled trial in Korea. Patients had average frequency of >or= 8 voids per 24 h and episodes of urgency or urgency incontinence >or= 3 during 3-day voiding diary period. Patients were randomised to 12-week double-blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King's Health Questionnaire. RESULTS: A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively). CONCLUSIONS: Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.

More effects of extracorporeal magnetic innervation and terazosin therapy than terazosin therapy alone for non-inflammatory chronic pelvic pain syndrome: a pilot study.

The objective of this study was to evaluate whether extracorporeal magnetic innervation (ExMI) combined with alpha-blocker therapy is more effective than alpha-blocker monotherapy for patients with non-inflammatory chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS), category IIIB. Patients were randomized to either terazosin monotherapy (group 1, n=21) or terazosin combined with ExMI therapy (group 2, n=19). Patients in group 2 had 12 treatment sessions of ExMI twice a week during 6 weeks. None of the patients experienced any side effects from treatment. The changes in each domain of the National Institutes of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) measured on week 6 were not significantly different between the groups. However, the difference (median, 25-75th percentiles) between the two groups in total NIH-CPSI scores was -4 (-11.5, -2) for group 1 and -12 (-17.3, -2.3) for group 2, respectively (P=0.047). At 6 weeks, 47.6% (10 of 21) of group 1 had a >25% decrease in total NIH-CPSI compared with 78.9% (15 of 19) of group 2 (P=0.041). Also, more patients in group 2 (78.9%) were rated as responders with a 6-point decrease in NIH-CPSI compared with group 1 (47.6%) (P=0.041). The early results suggest that ExMI combined with alpha-blocker therapy has better effect than alpha-blocker monotherapy for the treatment of CP/CPPS.

Initial validation of a novel rat model of vasculogenic erectile dysfunction with generalized atherosclerosis.

Although rats have been widely used in evaluating various causes of vasculogenic erectile dysfunction (VED), the atherosclerotic rat model has seldom been tried probably due to its inherent tolerance to a cholesterol diet. To enhance endothelial sensitivity to cholesterol diet, we tested the effects of transient interruption of nitric oxide synthase on atherogenesis induced by cholesterol diet in a rat model. Rats with atherosclerosis (AS group) received 1% cholesterol diet for 6 weeks. During the initial 2 weeks, they drank water that contained N(G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/ml). After 6 weeks, we carried out histologic and hemodynamic evaluation to confirm pelvic atherosclerosis and erectile dysfunction, respectively, and the results were compared with those of cholesterol only (Chol) group and normal control (C) group. Compared to the C or Chol group, the mean intima/media (I/M) of the internal pudendal artery, which contributes approximately 70% of the total resistance of the penile vasculature, was markedly increased by the treatment (1.82+/-0.25 vs 0.77+/-0.13, P<0.05). Correspondingly, significantly diminished erectile function was observed. Combined treatment for 2 weeks elicited early atherosclerotic changes in proximal arteries and erectile impairment and further 4 weeks of cholesterol diet spread overt atherosclerosis to the periphery. The Chol group showed no arterial pathology, although they showed mild VED. A correlation study showed that atherosclerosis of the distal artery was better correlated with erectile dysfunction than the proximal artery. Based on these results, our study demonstrates that combination treatment of cholesterol diet with L-NAME would be used as a rapid, effective protocol of developing atherosclerotic rat model of VED.

Nocturia in patients with lower urinary tract symptoms: association with diurnal voiding patterns.

OBJECTIVE: To determine whether diurnal voiding patterns predict nocturia in patients with lower urinary tract symptoms (LUTS), as few studies have evaluated the association between diurnal and nocturnal voiding patterns. PATIENTS AND METHODS: We prospectively analysed the frequency-volume charts (FVCs) of consecutive patients with LUTS. At the initial visit patients had a detailed clinical evaluation and subsequently were requested to complete a 72-h FVC. In all, 104 (41 men and 63 women, mean age 63 years, range 50-83) were included in the primary analyses. Associations between daytime variables and nocturia were described using maximum likelihood estimates of the relative risk and by 95% confidence intervals (CIs) based on logistic regression models. RESULTS: When at least one night-time void was used to define nocturia the multivariate logistic model showed a negative association of mean daytime voided volume with nocturia (P = 0.001). The odds ratio for nocturia decreased with this variable to 0.98 (95% CI 0.96-0.99). When 'voiding at least twice per night' was used to define nocturia only the number of daytime voids was positively related to nocturia (odds ratio 1.22; 95% CI 1.01-1.48; P= 0.040). CONCLUSION: Nocturia may be associated with diurnal voiding patterns; these results also suggest that the causes of nocturia of one or of two or more voids may differ. This highlights the role of bladder function in more severe forms of nocturia.

In vivo rat model to measure hypogastric nerve stimulation-induced seminal vesicle and vasal pressure responses simultaneously.

This study presents a modified in vivo model in which the intraluminal pressures of the seminal vesicle and vas deferens can be measured simultaneously. Male Sprague-Dawley rats were grouped based on agent administered: serotonin, clomipramine, fluoxetine, sertraline, paroxetine, prazosin, terazosin, and tamsulosin. The control responses to hypogastric nerve stimulation (HNS) were recorded in each animal, and HNS was repeated after each drug administration. Serotonergic agents resulted in concentration-dependent inhibition of the HNS-induced seminal vesicle pressure increases (clomipramine>serotonin>fluoxetine>sertraline approximately paroxetine). On the other hand, only serotonin and clomipramine significantly inhibited vasal pressure responses. alpha-Adrenergic blockers inhibited both intraluminal pressure responses in a concentration-dependent manner. This model illustrates the importance of the hypogastric nerve for the stimulation of the seminal tract, with attention focused on the seminal vesicle. This model may be useful for the evaluation of drugs for the treatment of premature ejaculation.

Clinical efficacy and tolerability of extended-release tolterodine and immediate-release oxybutynin in Japanese and Korean patients with an overactive bladder: a randomized, placebo-controlled trial.

OBJECTIVE: To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB). PATIENTS AND METHODS: Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed. RESULTS: In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients. CONCLUSION: Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.

A double-blind, randomised- placebo, controlled, parallel group, multicentre, flexible-dose escalation study to assess the efficacy and safety of sildenafil administered as required to male outpatients with erectile dysfunction in Korea.

The efficacy and safety of sildenafil was evaluated in a randomiSed, double-blind, placebo-controlled, flexible-dose study in Korean men aged 28-78 y with erectile dysfunction (ED) of broad-spectrum aetiology and more than 6 months duration. A total of 133 patients were randomised at six centres in Korea to receive either sildenafil (50 mg initially, increased if necessary to l00 mg or decreased to 25 mg depending on efficacy and tolerance) (n=66) or matching placebo (n=67) taken on an 'as needed' basis l h prior to anticipated sexual activity for a period of 8 weeks. At the end of this time, the primary efficacy variables relating to the achievement and maintenance of erections sufficient for sexual intercourse, and the secondary efficacy variables, which included: (1) the five separate domains of sexual functioning of the International Index of Erectile Function (IIEF) scale, (2) the percentage of successful intercourse attempts, and (3) a global assessment of erections, were all statistically significantly improved by sildenafil in comparison with placebo (P&<0.0001). Treatment-related adverse events occurred in 56.1% of patients receiving sildenafil and 20.9% receiving placebo. The most common adverse events with sildenafil were vasodilatation (flushing), headache and abnormalities in colour vision (31.8, 22.7 and 6.1% of patients, respectively), and most were mild in nature. The efficacy and safety of sildenafil in this population of Korean men appears similar to that reported in other studies in western populations.

Histological and functional aspects of different regions of the rabbit vagina.

Relatively little data is available on regional differences in both morphological and functional studies of vaginal smooth muscle in the rabbit. Histological and in vitro strip studies were performed upon the vaginal walls of 10-week-old New Zealand White rabbits discriminately according to location (upper, middle or lower) and the type of muscle arrangement (longitudinal or circular). The contraction and relaxation responses of the vaginal smooth muscle were assessed. The upper and middle third of the vagina were histologically characterized by an abundance of smooth muscle, while the lower third was composed of numerous sinusoids scattered among smooth muscle bundles. The peak amplitudes of 60 mM KCl-induced contraction per tissue strip weight were regionally different (upper>middle>lower). Contractile responses induced by adrenergic agonists (epinephrine, norepinephrine, phenylephrine and isopreterenol) showed regional differences, and were mainly of a tonic nature in lower part and strong phasic in middle and upper vagina. Electrical field stimulation induced a prominent relaxation response in the lower third of the vagina precontracted with phenylephrine (5 microM). This relaxation response was partially inhibited by N-omega-nitro-L-arginine methyl ester (NAME, 43.3+/-6.9%, s.e.), a nitric oxide synthase inhibitor, and D-vasoactive intestinal peptide (VIP) (11.3+/-4.4%), a VIP receptor antagonist. The type of muscle arrangement did not affect the results. Our results demonstrated that rabbit vagina has regional difference, not only histologically but also functionally. The contractile response was induced in all regions of the rabbit vagina by sympathetic agonists, while the prominent nerve-mediated relaxation was identified in the lower third portion of the rabbit vagina. The nature of relaxation and contractile function of vagina awaits future investigation.

Microsurgical single tubular epididymovasostomy: assessment in the era of intracytoplasmic sperm injection.

OBJECTIVE: To reevaluate the role of microsurgical single tubular epididymovasostomy for the treatment of obstructive azoospermia in the era of intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective clinical study. SETTING: University infertility clinic. PATIENT(S): Sixty-one patients with obstructive azoospermia who underwent microsurgical single tubular epididymovasostomy. INTERVENTION(S): Microsurgical single tubular epididymovasostomy. MAIN OUTCOME MEASURE(S): The overall patency and live-birth rates and factors that influenced the surgical outcome. RESULT(S): The overall patency rate after surgery was 68.9% (42/61) and the live-birth rate 31.1% (19/61). Of the 19 live-birth cases, 11 were achieved by natural means and 2 were achieved by conventional IVF soon after the operation, then subsequently by natural conception. The remaining 6 were the result of conventional IVF after surgery. An analysis of the potential prognostic factors previously associated with epididymovasostomy indicated that none had a statistically significant correlation with surgical outcome. In cases of patency, the partners were stratified into a younger group (21-30 years; n = 12) and an older group (31-36 years; n = 30). There was no statistically significant difference between the groups in the live-birth rate regardless of the means of conception (natural versus conventional IVF). CONCLUSION(S): This study demonstrates that the results obtained by microsurgical single tubular epididymovasostomy are comparable to those obtained with the use of IVF and ICSI. Even in this era of ICSI, the option of microsurgical single tubular epididymovasostomy should be considered because ICSI involves surgery to retrieve sperm and complex invasive treatment of the wife.

Transurethral resection of the ejaculatory duct.

Complete bilateral ejaculatory duct obstruction has long been recognized as an uncommon, treatable form of male infertility. Partial ejaculatory duct obstruction reflects a disturbance of ejaculation where sperm quality is impaired during transit through the distal vas deferens and ejaculatory ducts. With the advent and increased use of high-resolution transrectal ultrasonography, abnormalities of the distal ejaculatory ducts related to infertility have been well documented. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, several clinical findings are highly suggestive. In an infertile man with oligospermia or azoospermia with low ejaculate volume, normal secondary sexual characteristics, testes and hormonal profile and dilated seminal vesicles, midline cyst, or calcification on transrectal ultrasonography, ejaculatory duct obstruction is suggested. Of course, other causes of infertility may be concomitantly present and need to be searched for and treated as well. In selected cases, transurethral resection has resulted in marked improvement in semen parameters and pregnancies have been achieved. As is the case with all surgical procedures, proper patient selection and surgical experience are necessary to obtain optimal results. However, it appears that the treatments currently available for relief of ejaculatory obstruction are not optimally effective. Only approximately one half of treated patients will have an improvement in semen parameters and only about one quarter of treated patients will contribute to a pregnancy. What remains to be determined is how to manage the additional nearly 50% of patients who do not benefit from transurethral resection of ejaculatory obstruction. Based on my experience, I suggest that transrectal ultrasonography should be the first diagnostic procedure used when infertile men are suspected of having ejaculatory duct obstruction; however, vasography should still be considered for a more comprehensive diagnosis of ejaculatory duct obstruction. In patients showing atrophic seminal vesicles on transrectal ultrasonography and having a history of pulmonary tuberculosis, further study is not necessary and microscopic epididymal sperm aspiration is recommended for in vitro fertilization. Qualitative measurement of semen fructose may be helpful in the diagnosis of partial ejaculatory duct obstruction. Patients having midline cyst and being treated by transurethral resection are expected to have the best outcome.

Short-term analysis of the effects of as needed use of sertraline at 5 PM for the treatment of premature ejaculation.

OBJECTIVES: Pharmacotherapy using selective serotonin reuptake inhibitors (SSRIs) for men with primary premature ejaculation is promising. In particular, the strategy of taking a pill "as needed" may offer an attractive option. To investigate the possibility of self-therapy for the treatment of premature ejaculation, we compared the efficacy of sertraline taken as needed with that of continuous medication. METHODS: Since 1996, we have treated 24 men with sertraline on an as needed basis for primary premature ejaculation. Sertraline was chosen from among the SSRIs because a large dose need not be divided and because peak plasma levels occur 4 to 8 hours after oral administration, making 5 PM a suitable time for administration (by which time a man may know whether sexual intercourse is likely to occur later that evening). Each patient was started on 50 mg daily for 2 weeks, and the dose was then adjusted to 50 or 100 mg on the day of intercourse only (PRN). RESULTS: After 6 weeks, 18 men were still taking medication, and 6 had dropped out. Among the 18, the mean ejaculation latency was 23 +/- 19 seconds before treatment, 5.9 +/- 4.2 minutes after 2 weeks of 50 mg daily, 5.1 +/- 3.8 minutes after 2 weeks of 50 or 100 mg PRN, and 4.5 +/- 2.7 minutes after 4 weeks of 50 or 100 mg PRN. Mean sexual satisfaction scores (5, extremely satisfied; 0, extremely unsatisfied) for men were 0.8 +/- 0.8 before treatment, 3.8 +/- 1.2 after 2 weeks of 50 mg daily, 3.4 +/- 1.0 after 2 weeks of 50 or 100 mg PRN, and 3.2 +/- 0.7 after 4 weeks of 50 or 100 mg PRN. For their partners, mean sexual satisfaction scores were 1.1 +/- 0.7 before treatment, 3.2 +/- 1.6 after 2 weeks of 50 mg daily, 3.1 +/- 1.4 after 2 weeks of 50 or 100 mg PRN, and 3.3 +/- 1.2 after 4 weeks of 50 or 100 mg PRN. Side effects were intermittent excessive delay of ejaculation in 1 patient, fatigue in 2, and numbness in 1. CONCLUSIONS: If our results are supported by additional long-term clinical studies, self-therapy with sertraline taken PRN at 5 PM for the treatment of premature ejaculation could be as attractive as self-injection therapy for the treatment of erectile dysfunction.

Microdeletions within the azoospermia factor subregions of the Y chromosome in patients with idiopathic azoospermia.

OBJECTIVE: To examine the patterns of submicroscopic DNA deletions in the AZF (AZoospermia Factor) subregions of the Y chromosome in patients with idiopathic azoospermia. DESIGN: Controlled clinical study. SETTING: University-based infertility clinic. PATIENT(S): Infertile men (n = 40) with nonobstructive, idiopathic azoospermia. The control group consisted of proven fathers (n = 14) and healthy women (n = 4). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis; polymerase chain reaction amplification of the 37 loci spanning the AZFa, AZFb, and AZFc subregions of the Y chromosome; serum FSH, LH, and testosterone levels; and testicular histologic analysis. RESULT(S): Testicular histologic analysis of the subjects revealed Sertoli cell-only syndrome (n = 36) and spermatogenic arrest (n = 4). Microdeletions of the Y chromosome were found in eight (20%) of the patients with azoospermia. All eight affected patients had interstitial microdeletions within the AZFc subregion. Patients with Sertoli cell-only syndrome had additional microdeletions in regions distal to DAZ (Deleted in Azoospermia), although DAZ deletion was observed in seven of the eight affected patients. In five patients, microdeletions were found in the AZFb region containing RBM (RNA Binding Motif). CONCLUSION(S): Our results add to the evidence supporting the current suggestion that there is a cause-and-effect relation between Yq11 microdeletions in the AZF region and azoospermia.

Effects of androgens on the expression of nitric oxide synthase mRNAs in rat corpus cavernosum.

OBJECTIVE: To examine the effects of androgens on erectile response and the expression of nitric oxide synthase (NOS) isoform mRNAs in the penile corpus cavernosum of castrated rats. MATERIALS AND METHODS: The study comprised 50 adult male Sprague-Dawley rats in five groups: sham controls; castrated; castrated and receiving testosterone; castrated and receiving dihydrotestosterone (DHT); castrated and receiving testosterone and 5alpha-reductase inhibitor (finasteride). Androgen replacements were administered via implants of silicone tubing. After 7 days, some animals underwent electrical stimulation of the cavernosal nerves and the remainder were used for further analysis. NOS activity was measured in the soluble fraction of the corpus cavernosum, using the Griess reaction. Total RNA was isolated and nNOS and eNOS mRNA expression examined using semiquantitative reverse-transcriptase polymerase chain reaction. RESULTS: Castration caused a marked decrease in erectile response and the ratio of maximal intracavernosal pressure (ICPmax) to systemic blood pressure (SBP), although both testosterone and DHT effectively restored the response to normal. NOS activity and the amount of nNOS mRNA were reduced in castrated rats but restored by androgen replacement. Although there was no significant difference in NOS activity between the androgens, nNOS mRNA expression was higher in rats treated with DHT. There were no effects of androgen in rats treated with finasteride, as the ICPmax/SBP ratio, NOS activity and amount of nNOS mRNA decreased. eNOS mRNA expression was independent of androgen. CONCLUSIONS: Androgens enhance nNOS gene expression in the penile corpus cavernosum of rats, suggesting that they play an important role in maintaining NOS activity. Of the two androgens, DHT was more potent.

The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat.

AIM: To investigate the effects of androgen on penile erection through the reflex arc and penile corpus cavernosum, and study the respective roles of testosterone (T) and dihydrotestosterone (DHT) in penile erection in rats. METHODS: Male Sprague-Dawley rats were castrated and implanted with silastic brand silicone tube containing T or DHT, with or without daily injections of a 5alpha-reductase inhibitor, MK-434. The penile reflex, erectile response to electrical stimulation (ES) of the cavernous nerves and penile nitric-oxide synthase (NOS) activity were observed under varying androgenic status. RESULTS: Penile reflex erection in the rat was, on the whole, related to serum T levels though the number of glans engorgements was not. The number of cups and flips was significantly decreased by castration, and restored to the control level by T supplementation. Erectile response to ES and NOS activity in penile tissue was also related to serum T level. T administered together with a 5alpha-reductase inhibitor no longer restored the number of reflex erection, erectile responses to ES and NOS activity in the corpus caveenosum. CONCLUSION: Androgen influenced the penile reflex arc, corpus cavernosum, and the perineal striated muscles. In reflex erection, erectile response to ES and penile NOS activity in the rat, T seems to be first converted to DHT, the more active androgen modality.