[Evaluation of the efficacy of dapoxetine in primary and secondary forms of premature ejaculation].

OBJECTIVE: to compare the efficacy of dapoxetine in treatment of primary and secondary premature ejaculation. MATERIALS AND METHODS: The study included 60 patients with premature ejaculation (PE). Depending on the form of premature ejaculation they were divided into two groups: 27 patients with primary PE (group 1) and 33 patients with secondary PE (group 2). Patients were recommended to take dapoxetine 30 mg 1 hour before intercourse. A follow-up visit was scheduled on day 30 after receiving the drug. The intravaginal ejaculation latency time (IELT) and the Premature ejaculation diagnostic tool (PEDT) score were evaluated before dapoxetine was given and after 30 days from the start of the study. The significance of differences between baseline and follow-up values were compared using Wilcoxons test. In both groups, the proportion of patients with an incomplete response (IELT less than 2 minutes, PEDT more than 10) to symptomatic therapy with dapoxetine was evaluated. The proportion of patients with incomplete response to therapy was compared using the chi-square test. RESULTS: The median IELT among all patients before starting therapy was 63 seconds (interquartile interval [IQR]: 28.75-94). After one month of therapy median IELT increased to 119 seconds (IQR: 58.75-321.75). Median PEDT score was 16 (IQR: 13-19) at baseline and 7 (IQR: 4-12) at follow-up. In group 1, the median IELT increased from 57 to 83 seconds (p = 0.02088), and in group 2, the median IELT increased from 70 to 173 seconds (p<0.00001). The mean PEDT score decreased to 7 in both groups (p<0.00001). Incomplete response to therapy was observed in 66.7% of patients in group 1 and in 39.4% of patients in group 2. The difference between two groups was statistically significant (p=0.035456). CONCLUSION: Symptomatic therapy with dapoxetine has a positive effect on the intravaginal ejaculation latency time and patient satisfaction in both primary and secondary premature ejaculation. However, the incidence of incomplete response to therapy is higher in patients with primary premature ejaculation, which may be due to characteristic differences in the pathogenesis of primary and secondary premature ejaculation.

Selective serotonin re-uptake inhibitors for premature ejaculation in adult men.

BACKGROUND: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition. OBJECTIVES: To assess the effects of SSRIs in the treatment of PE in adult men. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE  were administered SSRIs or placebo. We also considered 'no treatment' to be an eligible comparator but did not find any relevant studies. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE. MAIN RESULTS: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better') compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs.  SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of 'good' or 'very good'; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs.  Secondary outcomes: SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good') compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs.  SSRI probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs.  SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs.  SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence). AUTHORS' CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.

A Double Blind, Placebo Controlled, Randomized Trial to Evaluate the Efficacy and Tolerability of On-Demand Oral Pregablin (150 mg and 75 mg) in Treatment of Premature Ejaculation.

INTRODUCTION: Although premature ejaculation (PE) is a common sexual dysfunction, the available options for PE treatment remain unsatisfactory. AIM: To evaluate the effect of on-demand oral pregabalin on the intravaginal ejaculation latency time (IELT). METHOD: We conducted a multiarm double-blinded placebo-controlled randomized clinical trial that enrolled 120 patients with PE who were divided equally into 3 groups (A, B, and C). 4 patients were excluded, 39 patients received 150 mg pregabalin (group A), 39 patients received 75 mg pregabalin (group B), and 38 patients received placebo (group C). All patients were encouraged to engage in sexual relations twice per week for 2 weeks and to take the medication 1-2 hours before sexual intercourse. A stopwatch was used to evaluate IELT. MAIN OUTCOME MEASURE: The main outcome measure are the improvement of IELT and the reported adverse events. RESULTS: IELT significantly improved in patients who received 150 mg pregabalin, but there was no change in the other groups. CLINICAL IMPLICATIONS: Most PE patients showed a significant improvement after receiving on-demand pregabalin (150 mg). STRENGTH & LIMITATIONS: The strength of this study is that it is the first randomized controlled trial to evaluate the efficacy of pregabalin in treatment of PE. The main limitations were the small number of patients, IELT was the only primary outcome of the study, and the pregabalin cap can be identified by the patient. CONCLUSION: Oral pregabalin seems to be a promising drug for additional evaluation as a new treatment for PE. More studies are needed to evaluate the suitable dose, duration, timing, and its safety profile. El Najjar MR, El Hariri M, Ramadan A, et al. A Double Blind, Placebo Controlled, Randomized Trial to Evaluate the Efficacy and Tolerability of On-Demand Oral Pregablin (150 mg and 75 mg) in Treatment of Premature Ejaculation. J Sex Med 2020;17:442-446.

Men's Sexual Health Questionnaire score changes vs spontaneous sexual adverse event reporting in men treated with dutasteride/tamsulosin combination therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A post hoc analysis of a prospective, randomised, placebo-controlled study.

AIM: To assess the impact of baseline characteristics on Men's Sexual Health Questionnaire (MSHQ) total scores and to evaluate the clinical relevance of MSHQ changes and their association with spontaneously reported sexual adverse events (SexAEs) in patients with benign prostatic hyperplasia. METHODS: This was a post hoc analysis of the Phase 4 FDC116115 study, in which patients aged ≥50 years were randomised 1:1 to receive a fixed-dose combination of dutasteride 0.5 mg and tamsulosin 0.4 mg (DUT-TAM FDC), or placebo. End-points included: change in MSHQ total scores by baseline characteristics and SexAEs; cumulative distribution function for change from baseline to month 12 in MSHQ total score and the ejaculation, erection, satisfaction and sexual desire (libido) domain scores; and relationship between changes in MSHQ scores and SexAEs. RESULTS: The intent-to-treat population comprised 489 patients (DUT-TAM FDC, n = 243; placebo, n = 246). The mean reduction in total MSHQ score was greater in patients with SexAEs across both groups, compared with patients without SexAEs. Most patients reporting any SexAE (86% DUT-TAM FDC, 67% placebo) had a worsening of the MSHQ total score at month 12 compared with baseline. Specifically, 90% (DUT-TAM FDC) and 75% (placebo) of patients reporting an ejaculation SexAE and 73% (DUT-TAM FDC) and 87% (placebo) of patients reporting an erection SexAE had a worsening of MSHQ ejaculation and erection domain scores, respectively, at month 12. A threshold effect for incident SexAE was observed; patients showing a decrease of approximately 6-10 points in the total MSHQ score were more likely to report SexAEs. CONCLUSION: Findings support the clinical utility of the MSHQ tool in assessing the impact of DUT-TAM on sexual function by linking numerical changes in MSHQ scores to spontaneously reported SexAEs for the first time. The threshold effect for incidence of SexAEs warrants further investigation to determine its clinical relevance.

Is testosterone replacement an effective treatment of secondary premature ejaculation?

There are very few studies that have evaluated premature ejaculation characteristics in regard to subtypes. Additionally, to our knowledge, there are no studies which have explored testosterone replacement therapy in secondary premature ejaculation patients with testosterone deficiency. Therefore, our aims were as follows: (a) to determine the characteristics of patients with premature ejaculation in regard to the four subtypes of premature ejaculation and (b) to determine the efficacy of testosterone replacement therapy in the treatment of testosterone-deficient patients with secondary premature ejaculation. Patients who applied to our clinic from May 2010 to August 2018 with premature ejaculation were included in this study. The mean age of the study group was 36.42 (min-max: 24-52) years. Those with secondary premature ejaculation were found to have significantly lower testosterone concentration compared to the other groups. Shortest mean intravaginal ejaculation latency time and lowest International Index of Erectile Function-5 score were found among those with secondary PE. In regard to treatment results, recipients of testosterone replacement demonstrated a 4.8-fold increase in mean intravaginal ejaculation latency time, while dapoxetine recipients had a 1.8-fold increase. Our findings demonstrate that testosterone replacement may be a promising treatment for those with secondary PE in the presence of testosterone deficiency.

In vivo effects of Rauvolfia vomitoria (Apocynaceae) ethanolic extract on sexual performance and reproductive activity in male rats.

Plants and plant-derived products have a long history in the treatment of sexual disorders. Rauvolfia vomitoria is one of such plant used traditionally for the enhancement of male sexual and reproductive activity. This study was carried out to elucidate the potential activity of R. vomitoria ethanolic extract on sexual behaviour and male reproductive function. Twenty-five male rats were assigned to five groups and orally treated with distilled water (control), sildenafil citrate (standard) and R. vomitoria ethanolic extract (50, 100 and 200 mg/kg BW) for 22 days. Sexual behaviour parameters such as mount latency (ML), intromission latency (IL), ejaculation latency (EL), mount frequency (MF), intromission frequency (IF), ejaculation frequency (IF) and post-ejaculatory interval (PEI) were recorded at day 0, 1, 8, 15 and 22. The reproductive function including reproductive organ weights, testicular histology and sperm parameters was also assessed. Results showed enhancement in sexual behaviour through significant reduction (p < .01) in ML, IL and PEI and significant increase (p < .01) in EL, MF IF and EF. The extract also caused an increase in sperm count, motility and transit. Present findings demonstrate the ability of R. vomitoria ethanolic extract to improve male sexual behaviour and reproductive activity in rats.

Vitamin E administration does not ameliorate tramadol-associated impairment of testicular function in Wistar rats.

Tramadol is widely abused in Nigeria and has been reported to cause fertility decline via testicular oxidative stress. This study investigated the effect of vitamin E, an antioxidant on some reproductive parameters in male Wistar rats administered tramadol. Twenty male Wistar rats (180-200 g) were randomly assigned into four groups (n = 5) thus: Control (0.2 ml vehicle: olive oil), tramadol-treated (20 mg/kg of tramadol), vitamin E-treated (100 mg/kg of vitamin E) and tramadol + vitamin E-treated (received tramadol and vitamin E) groups. Drugs were administered orally and daily for 28 days. Sperm count, Johnsen's score, germinal epithelial height and serum testosterone, follicle-stimulating hormone (FSH) and luteinising hormone (LH) concentrations were significantly (p < .05) decreased in tramadol-treated and tramadol + vitamin E compared with control and vitamin E-treated groups. Sperm motility, morphology, viability, seminiferous tubular diameter, Leydig cell count, Sertoli cell count and malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase concentrations were not significantly different among the groups. Histology of testis and epididymis in all groups showed no toxicity but decreased sperm population in tramadol-treated and tramadol + vitamin E-treated groups. Tramadol did not cause testicular oxidative stress but impaired testicular function by suppressing testosterone, FSH and LH secretion. Vitamin E administration could not attenuate this impairment in testicular function.

Characterization of semen collected by pharmacologically induced ejaculation from a stallion with seminal vesiculitis.

The present study compared the quality of sperm collected by artificial vagina or pharmacologically induced ejaculation from a 10-year-old thoroughbred stallion with seminal vesiculitis. The pharmacological protocol involved intravenous administration of detomidine (0.01 mg/kg) and oxytocin (20 IU) and successfully induced ejaculation in all attempts of semen collection. Sperm motility, plasma membrane and acrosome integrity (PMAI), reactive oxygen species (ROS) levels, polymorphonuclear neutrophil (PMN) percentage, and bacterial profiles of fresh and cooled semen (5°C for 24 hr) were evaluated. Semen obtained by the pharmacological method presented reduced seminal volume, decreased PMN percentage and superior sperm motility in cooled samples. Moreover, higher PMAI and lower ROS levels were observed in semen collected by the pharmacological method. Therefore, pharmacologically induced ejaculation is an alternative to obtain semen with minimal contamination and with sperm of superior quality and longevity from stallions with seminal vesiculitis.

Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.

Prostate carcinoma and benign prostate hyperplasia (BPH) with associated lower urinary tract symptoms (LUTS) are among the most prevalent and clinically relevant diseases in men. BPH is characterized by an enlargement of prostate tissue associated with increased tone of smooth muscle cells (SMCs) which surround the single glands composing the prostate. Secretions of the glands leave the prostate through local excretory ducts during the emission phase of ejaculation. Pharmacological treatment of BPH suggests different local drug targets based on reduction of prostate smooth muscle tone as the main effect and disturbed ejaculation as a common side effect. This highlights the need for detailed investigation of single prostate glands and ducts. We combined structural and functional imaging techniques-notably, clear lipid-exchanged, acrylamide-hybridized rigid imaging/immunostaining/ in situ hybridization-compatible tissue-hydrogel (CLARITY) and time-lapse imaging-and defined glands and ducts as distinct SMC compartments in human and rat prostate tissue. The single glands of the prostate (comprising the secretory part) are characterized by spontaneous contractions mediated by the surrounding SMCs, whereas the ducts (excretory part) are quiescent. In both SMC compartments, phosphodiesterase (PDE)-5 is expressed. PDE5 inhibitors have recently emerged as alternative treatment options for BPH. We directly visualized that the PDE5 inhibitors sildenafil and tadalafil act by reducing spontaneous contractility of the glands, thereby reducing the muscle tone of the organ. In contrast, the ductal (excretory) system and thus the prostate's contribution to ejaculation is unaffected by PDE5 inhibitors. Our differentiated imaging approach reveals new details about prostate function and local drug actions and thus may support clinical management of BPH.-Kügler, R., Mietens, A., Seidensticker, M., Tasch, S., Wagenlehner, F. M., Kaschtanow, A., Tjahjono, Y., Tomczyk, C. U., Beyer, D., Risbridger, G. P., Exintaris, B., Ellem, S. J., Middendorff, R. Novel imaging of the prostate reveals spontaneous gland contraction and excretory duct quiescence together with different drug effects.

Differential effects of androgens, estrogens and socio-sexual context on sexual behaviors in the castrated male goat.

The behavioral and endocrine activation of sexual behaviors exhibited by male goats, especially self-enurination (SE), is poorly understood. In the first experiment, to assess the influence of socio-sexual context on SE in bucks, the effects of distance from does, the presence of estrous versus non-estrous does and the presence of another buck on SE and courtship frequencies of intact male goats (bucks; n = 12) were tested using a unique behavior test apparatus. For experiments 2 and 3, to test the relative contributions of sex steroid hormones and socio-sexual context on SE, castrated male goats (wethers; n = 20) were randomly divided into five groups and injected for seven weeks with one of the following: 25 mg testosterone propionate (T), 25 mg dihydrotestosterone propionate (DHT), 100 µg estradiol benzoate (E), 100 µg E and 25 mg DHT (E + DHT), or oil (CON). The effects of these treatments on frequency of SE and courtship were assessed using the behavior test apparatus (social scenarios) adapted from the findings in experiment 1. In one scenario, a wether could observe (from 4.6 m) a buck and estrous female (doe) together in a wire mesh holding pen. In a different scenario, the wether could observe (from the same distance) a buck that could only court the estrous doe through a wire mesh barrier. Finally, to observe the effects of steroid treatment on mounting and ejaculation frequencies, in addition to SE and courtship, each wether was placed in a pen with an estrous doe for 10 min. After a five-week, treatment-washout period, wethers were randomly assigned to different treatment groups and retested. In experiment 1, bucks that were distanced from females displayed more SEs than those with fence-line contact, while those with fence-line contact displayed more bouts of courtship (P < 0.05). In experiments 2 and 3, courtship frequencies displayed in all three scenarios were greater than CON only for groups exposed to estrogen directly or via aromatization (T, E + DHT, E; P < 0.05). Frequencies of SE exhibited during behavior tests in which the wether was watching were greater than CON only for androgen-treated groups (T, E + DHT, DHT; P < 0.05). In contrast, when the wether was free to interact with the female, only the DHT group displayed SE at a higher frequency than CON (P < 0.05). Treatment had no effect on mount frequencies in this test scenario, however ejaculation frequencies were highest for T and E + DHT (P < 0.05). These studies suggest that the courtship behaviors of the male goat are estrogen-dependent. However, SE appears to be activated by androgens. It was also demonstrated that social context contributes as much to behavior expression as steroid treatment, as in social scenario 2 some sexual behaviors were displayed in similar frequencies across groups, despite differing sex steroid treatments.

The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX).

INTRODUCTION: Cligosiban is an orally administered oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AIM: To determine the safety and efficacy of cligosiban capsules (dose range 400-800 mg) to improve intravaginal ejaculation latency time (IELT) and patient-reported outcomes in men with severe lifelong PE. METHODS: Patients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if they rated their control of ejaculation as poor/very poor and their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts. Eligible patients were randomized to an 8-week treatment period with double-blind cligosiban or placebo (to be taken 1 to 6 hours prior to sexual activity). The starting dose was 400 mg (not more than 1 dose per day) which could be increased to 800 mg after 2 and/or 4 weeks of treatment. Assessments were conducted at 2, 4, and 8 weeks. MAIN OUTCOME MEASURE: Efficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, and the Clinical Global Impression of Change. RESULTS: The mean ratio of fold change from baseline in IELT to the last 4 weeks of treatment (cligosiban/placebo) was 1.9 compared to a baseline of 1.0 (P = .0079). The mean increase in IELT from baseline to the last 4 weeks of treatment was 61.0 seconds for cligosiban, which was significantly different from (and 3.6-fold greater than) the mean increase of 16.4 seconds for placebo (P = .0086). Statistically significant improvements in ejaculation control and ejaculation-related personal distress scores were also observed for cligosiban compared to little or no change with placebo. Cligosiban was generally well tolerated, with no serious or severe adverse events or other safety parameters. CLINICAL IMPLICATIONS: This proof-of-concept study demonstrated the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE. STRENGTHS AND LIMITATIONS: This was a Phase II, randomized, double-blind, placebo-controlled study that was adequately powered to detect a clinically meaningful difference in change in IELT between cligosiban and placebo. Larger studies will be needed to confirm these findings, determine the optimal dose of cligosiban and assess efficacy in men with acquired PE. CONCLUSIONS: Cligosiban was well tolerated, and resulted in significant benefits in both objective and subjective measures of ejaculatory control in men with lifelong PE and therefore offers significant potential as an on-demand, orally administered agent for the treatment of PE. McMahon C, Althof S, Rosen R, et al. The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX). J Sex Med 2019; 16:1178-1187.

The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX).

INTRODUCTION: Cligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AIM: To determine the efficacy of 3 dose levels of cligosiban caplets to prolong intravaginal ejaculation latency time (IELT) and improve patient-reported outcomes in men with lifelong PE. METHODS: Patients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts and if they met other diagnostic criteria for lifelong PE. Eligible patients (target 220 evaluable) were randomized to double-blind cligosiban 400, 800, or 1200 mg or matching placebo caplets (to be taken 1 to 6 hours prior to sexual activity). Assessments were conducted at 2, 4, and 8 weeks. MAIN OUTCOME MEASURE: Efficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, Patient's Global Impression of Severity, and the Clinical Global Impression of Change. RESULTS: There were no clinically or statistically significant differences between cligosiban (at any dose level) and placebo for the primary endpoint (change in geometric IELT) or any of the secondary endpoints. Cligosiban was well tolerated with a side-effect profile similar to placebo. CLINICAL IMPLICATIONS: This Phase IIb study failed to demonstrate the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE at doses up to 1200 mg. STRENGTHS AND LIMITATIONS: This was a Phase IIb, randomized, double-blind, placebo-controlled study that was adequately powered but failed to detect a clinically meaningful or statistical difference in change in IELT between cligosiban at 3 dose levels and placebo. This is in contrast to a similarly designed proof-of-concept study where cligosiban was flexibly dosed at doses up to 800 mg and did demonstrate clinically meaningful and statistically significant changes in efficacy parameters. The reasons for this disparity are not known. CONCLUSIONS: Cligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg. Althof S, Osterloh IH, Muirhead GJ, et al. The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX). J Sex Med 2019; 16:1188-1198.

Compliance With Fluoxetine Use in Men With Primary Premature Ejaculation.

BACKGROUND: Premature ejaculation (PE) is a common sexual dysfunction for which selective serotonin reuptake inhibitors (SSRIs) have been used effectively for treatment. However, compliance with therapy and predictors of long-term SSRI use in the treatment of PE are not well known. AIM: To analyze our experience with drop-out rates with fluoxetine in the primary PE population and to identify predictors of continued use of this agent. METHODS: Men with primary PE constituted who used fluoxetine and had at least 12 months follow-up constituted the study population. Subjects underwent a comprehensive interview to ascertain self-reported (non-stopwatch) intravaginal ejaculatory latency time (IELT), self-rated control over ejaculation, and personal and patient-reported partner distress due to PE. Patients were treated with fluoxetine 20 mg daily, with the possibility of dose titration up or down based on efficacy and side effects. OUTCOMES: The PE parameters of interest included self-reported IELT, self-rated control over ejaculation, personal and partner distress due to PE, and medication adherence. RESULTS: 130 men were included in the study. Dropout rates at 6 and 12 months were 56% and 72%. Self-rated "poor" ejaculatory control decreased from 98%-41% (P < .01), high personal distress from 47%-11% (P < .01), and high partner distress rates from 72%-27% (P < .01). Predictors of continued use at 12 months included high partner distress, being unpartnered, and having a post-treatment IELT ≥5 minutes (P < .01). Overall side effects included headache (5%), dizziness (4%), nausea (5%), nervousness (5%), and sleepiness (8%); however, moderate to severe side effects reported included nausea (2%), sleepiness (2%), headache (2%), and dizziness (2%). CLINICAL IMPLICATIONS: Compliance with SSRIs is a well-described problem in the depression literature, but data are sparse regarding continued use of SSRIs in the treatment of PE. STRENGTHS AND LIMITATIONS: We report on 12-month compliance with SSRIs for the treatment of PE. Our early compliance rates were more encouraging than what has been reported in the past. However, IELT was self-reported and not measured objectively, and we did not use validated patient-reported outcomes but rather self-reported ejaculatory control and distress levels, which have limitations. CONCLUSIONS: Fluoxetine is an effective agent for the treatment of PE with significant improvement realized in IELT, ejaculatory control, and distress levels for both men and their partners. Despite its efficacy, continued use of fluoxetine beyond 6 months is poor. Jenkins LC, Gonzalez J, Tal R, et al. Compliance with Fluoxetine Use in Men with Primary Premature Ejaculation. J Sex Med 2020;16:1895-1899.

Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats.

INTRODUCTION: Although premature ejaculation (PE) is the most common sexual dysfunction in young men, its true pathophysiology has not yet been clearly elucidated. AIM: To investigate the quantitative changes that occurred in an ejaculation model induced by para-chloroamphetamine (PCA) after botulinum-A toxin injection into the bulbospongiosus (BS) muscle in rats. METHODS: A total of 21 male rats weighing 300 to 350 grams were used in the study. The animals were divided into 3 groups: control, 1 unit of botulinum-A toxin injected, and 5 units of botulinum-A toxin injected. The botulinum-A toxin was percutaneously injected into the BS muscle, and the experiment was carried out 96 hours (5 days) after the injection. MAIN OUTCOME MEASURE: The seminal vesicle (SV) was cannulated, and the BS muscle was dissected and connected to an amplifier (Biopac; Goleta, CA) to record the pressure and electromyography measurement. The ejaculation parameters were obtained after the PCA injection. RESULTS: The ejaculation latency time of the group receiving 5 units of botulinum-A toxin was statistically significantly longer (1092 ± 657 seconds) compared to the control group (298 ± 81 seconds) and the group receiving 1 unit of botulinum-A toxin (439 ± 100 seconds) (P = .003). Furthermore, the BS EMG area under the curve values for the group receiving 5 units of botulinum-A toxin were significantly lower (7.4 ± 1.2 V/s × 10-4) than those of the control group (13.6 ± 4.0 V/s × 10-4) and the group receiving 1 unit of botulinum-A toxin (13.6 ± 5.0 V/s × 10-4) (P = .009). No statistically significant difference was found between the groups in terms of the basal SV pressure, number of SV phasic contractions, maximum amplitude of the SV phasic contraction, and intervals between the SV phasic contractions and the BS muscle contractions. CLINICAL IMPLICATIONS: Botulinum-A toxin injection is a potential treatment option for PE and should be further investigated by future clinical studies. STRENGTHS AND LIMITATIONS: Ease of administration and prolonged duration of botulinum-A toxin are advantages of the existing treatment options. The risk of anejaculation due to the dosage should be kept in mind. CONCLUSIONS: Injection of botulinum-A toxin into the BS muscle in rats significantly delayed the ejaculation latency time and affected the expulsion phase. Ongün S, Acar S, Koca P, et al. Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats. J Sex Med 2019;16:1338-1343.

Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats.

BACKGROUND: Although numerous reports have shown that α1-adrenoceptor (α1-AR) antagonists, which are used to treat benign prostatic hyperplasia (BPH), can cause ejaculatory disorders, few studies have investigated whether the phosphodiesterase 5 (PDE5) inhibitor tadalafil has such adverse effects. In this study, we compared the effects of tadalafil and α1-AR antagonists on seminal emission and their mechanisms of action. AIM: To evaluate in normal rats the possible effects of tadalafil on spontaneous seminal emission (SSE) and seminal contraction evoked by hypogastric nerve stimulation. METHODS: Male Sprague-Dawley rats were used. To assess SSE, plastic corsets were fitted around the thorax and upper abdomen of male Sprague-Dawley rats to prevent genital autogrooming. Rats were treated orally with tadalafil or an α1-AR antagonist (silodosin, naftopidil, or tamsulosin) for 3 days and housed in wire-bottomed cages. Ejaculatory plugs dropped on the bottoms of the cages were counted and weighed. To assess the intraluminal pressure of seminal vesicles, the hypogastric nerve of urethane-anesthetized rats was isolated and electrically stimulated. After stabilization of seminal vesicle contraction, the rats were intravenously administered test drugs. The expression of PDE5, endothelial nitric oxide synthetase (eNOS), and neuronal NOS (nNOS) in the seminal vesicle and vas deferens were measured by reverse-transcription polymerase chain reaction. MAIN OUTCOME MEASURE: The number and weight of the ejaculatory plugs produced by corset-fitted rats and the intraluminal pressure of the seminal vesicle were evaluated. RESULTS: Tadalafil did not affect the number or weight of the ejaculatory plugs of corset-fitted rats, whereas all α1-AR antagonists decreased both in a dose-dependent manner. The α1-AR antagonists, but not tadalafil, inhibited the seminal vesicle contraction evoked by electrical stimulation of the hypogastric nerve. The seminal vesicle and vas deferens expressed higher levels of PDE5 and eNOS mRNA and lower levels of nNOS mRNA relative to the urethra. CLINICAL IMPLICATIONS: Tadalafil can be a treatment option in cases where there is concern about negative effects on seminal emission. STRENGTHS AND LIMITATIONS: We demonstrated different effects of tadalafil and 3 α1-AR antagonists on rat SSE and their mechanisms of action by measuring seminal vesicle contractility in vivo. A limitation is that we used normal rats, not BPH model rats, and so our results might not apply to human BPH patients. CONCLUSION: Tadalafil did not inhibit spontaneous seminal emission or electrical field stimulation-induced seminal vesicle contraction in normal rats. The NO-cyclic guanosine monophosphate pathway is unlikely to be involved in the inhibition of seminal vesicle contraction in normal rats. Yoshinaga R, Fukui T, Yoshifuji M, et al. Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats. J Sex Med 2019;16:680-690.

Adverse Sexual Effects of Treatment with Finasteride or Dutasteride for Male Androgenetic Alopecia: A Systematic Review and Meta-analysis.

Treatment of male androgenetic alopecia with 5α-reductase inhibitors is efficacious. However, the risk of adverse sexual effects remains controversial. This systematic review and meta-analysis investigated the risk of adverse sexual effects due to treatment of androgenetic alopecia in male patients with finasteride, 1 mg/day, or dutasteride, 0.5 mg/day. Fifteen randomized double-blinded placebo-controlled trials (4,495 subjects) were meta-analysed. Use of 5α-reductase inhibitors carried a 1.57-fold risk of sexual dysfunction (95% confidence interval (95% CI) 1.19-2.08). The relative risk was 1.66 (95% CI 1.20-2.30) for finasteride and 1.37 (95% CI 0.81-2.32) for dutasteride. Both drugs were associated with an increased risk, although the increase was not statistically significant for dutasteride. As studies into dutasteride were limited, further trials are required. It is important that physicians are aware of, and assess, the possibility of sexual dysfunction in patients treated with 5α-reductase inhibitors.

Efficacy and Safety of "On-Demand" Dapoxetine in Treatment of Patients with Premature Ejaculation: A Meta-Analysis.

BACKGROUND The aim of this study was to assess the efficacy and safety of "on-demand" dapoxetine in the treatment of premature ejaculation (PE). MATERIAL AND METHODS We performed a meta-analysis of intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGIC), perceived control over ejaculation (PCOE), and drug-related adverse effects (AEs). We searched Medline, PubMed, Embase, CNKI, Wanfang, and VIP databases up to May 30, 2018 with the following search terms: "dapoxetine" or "SSRIs" and "premature ejaculation" or "sexual dysfunction". RESULTS Our analysis included 11 RCTs (8521 cases and 4338 controls). We found that IELT, PGIC, and PCOE in PE patients with "on-demand" dapoxetine were significantly higher than in the control group, and we observed higher proportions in 60 mg vs. 30 mg dapoxetine. The AEs were mild and tolerable. CONCLUSIONS "On-demand" dapoxetine is effective and safe for patients with PE, and a dose of 60 mg may be more effective than 30 mg.

Outcome of Modification of Dose and Time of Administration of Tamsulosin in Men with Abnormal Ejaculation.

INTRODUCTION: Alpha-adrenergic blockers are now the cornerstone medication in management of lower urinary tract symptom (LUTS); however, the associated treatment-related abnormal ejaculation could be a bothersome event. This is a comparative study among different methods of tamsulosin administration in terms of efficacy, recoverability of ejaculatory function, and quality of life (QoL) in men with tamsulosin-related abnormal ejaculation. PATIENTS AND METHODS: Sexually active men receiving tamsulosin for LUTS who were bothered by treatment-related abnormal ejaculation following initiation of tamsulosin were randomized into 3 groups; group A received intermittent-full-standard-dose, group B received low-dose-tamsulosin, and group C received full-standard-dose tamsulosin The status of ejaculatory function, IPSS, QoL score, and Q-Max were measured at baseline and 3 months later. RESULTS: A total of 93 men with mean age of 53.1 years were included in the study, 3-months after randomization, statistically significant improvements in IPSS, QoL index, and Q-Max in comparison to pre-treatment levels were noted. Restoration of normal ejaculation was reported by 74.1 and 90.3% of patients in group A and B, respectively, versus none in group C. The QoL score was significant when comparing group A to the other groups; finally, the Q-Max was significant when comparing group C to the other groups. CONCLUSION: For patients bothered by tamsulosin-related abnormal ejaculation, a significant improvement in the QoL, without deviation from the therapeutic purpose of treatment, can be achieved by administration of 0.4 mg tamsulosin every other day.

Aphrodisiac properties of hydro-alcoholic extract of Cassia auriculata flower in male rats.

Cassia auriculata is a commonly found plant in Asia, widely used in Ayurveda and Siddha medicines as a tonic, astringent and in general for diabetes. Herbal tea made from this plant has been marketed as a product for restoring sexual vitality, to increase sperm count and counteract ejaculatory disorders. However, the scientific evidences are scarce to prove this concept. Here, we examined the effect of hydro-alcoholic extract obtained from C. auriculata flower upon the expression of male Wistar albino rat's sexual behaviour. Sildenafil was used as a positive control. Penile erection index (PEI), mount latency (ML), intromission latency (IL), ejaculation latency (EL), mounting frequency (MF), intromission frequency (IF), ejaculation frequency (EF) and post-ejaculatory interval (PEjI) were recorded for days 0, 7, 14 and 28 and also after the withdrawal of the treatment on days 7 and 15. Significant reduction in ML, IL and PEjI, and increment in EL, PEI, MF, IF and EF were observed (p < 0.05, <0.01). However, neither extract nor sildenafil sustains the effect after withdrawal of the treatment. The present finding demonstrates the aphrodisiac potential of hydro-alcoholic extract of C. auriculata flower in vivo and lends support to the traditional utilisation as a sexual stimulating agent.

Effect of premature ejaculation desensitisation therapy combined with dapoxetine hydrochloride on the treatment of primary premature ejaculation.

To evaluate the overall treatment benefits of premature ejaculation desensitisation therapy combined with 30 mg dapoxetine hydrochloride treatment on patients with primary premature ejaculation (PPE). Ninety-nine PPE patients were randomly divided into two groups at the ratio of 2:1. Sixty-six PPE patients received premature ejaculation desensitisation therapy accomplished by Weili Automatic Semen Collection-Penis Erection Detection and Analysis workstation (WLJY-2008) combined with 30 mg dapoxetine hydrochloride treatment (DTCD group), and another 33 patients received 30 mg dapoxetine hydrochloride-only treatment (DO group). Intravaginal ejaculation latency time (IELT) and premature ejaculation profile (PEP) were recorded before and during the treatment, and clinical global impression of change (CGIC) in PPE was recorded at the fourth week and the end of the treatment and the items. In both groups were significantly improved (p < 0.0001) in IELT, PEP and CGIC for premature ejaculation compared with baseline, and DTCD treatment showed a more significant improvement on PPE patients in the items compared with DO treatment (p < 0.05). Thus, premature ejaculation desensitisation combined with dapoxetine therapy may be a better choice for improving premature ejaculation with PPE.