From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

Comparing Western and traditional Chinese medicine for male sexual dysfunction: can Klotho represent a silk road?

Traditional Chinese medicine (TCM) and Western Medicine both have shown efficacy in treating male sexual dysfunction (MSD). The aim of this perspective paper is to discuss a possible link between Western medicine and TCM in the MSD field as represented by the entity of Klotho. Klotho is a recently discovered protein, mainly expressed in the kidney, encoded by the anti-aging gene klotho. Not only is Klotho significantly correlated with the development and progression of kidney diseases and their complications, but increasing evidence indicates that it is also closely related to MSD. A comprehensive search within PubMed database was performed to retrieve available evidence on Klotho's roles, particularly in kidney and in MSD. Indeed, in the TCM theory, the concept of the "kidney" is entirely different from the Western medicine: it is closely related to metabolism and to the reproductive, nervous, endocrine systems, being more than just a urinary organ. According to the "Kidney storing essence (jing) and governing reproduction" (KSEGR) theory, a cornerstone in TCM, the treatment of MSD mainly consists of restoring the kidney's function. Signs of decreasing kidney essence show a consistent similarity to deficiencies of Klotho, also for what regards the male sexual function. Based on the current evidence, Klotho may represent a potential biological indicator for sexual desire and sexual function and a kind of new scientific Silk Road between TCM and Western medicine for MSD; nevertheless, there is a need to conduct further high-quality research to prove this hypothesis.

Acupuncture for premature ejaculation: a systematic review and meta-analysis.

Background: Although acupuncture is widely used to treat premature ejaculation (PE), its effectiveness remains highly controversial. Aim: To evaluate the efficacy and safety of acupuncture on PE. Methods: According to the relevant keywords, 11 major English and Chinese databases were searched for randomized controlled trials (RCTs) of acupuncture alone or in combination with other treatments for PE. The quality of evidence across studies was assessed by the GRADEpro tool. Outcomes: Study outcome measures included the intravaginal ejaculation latency time (IELT), the Premature Ejaculation Diagnostic Tool (PEDT), the Chinese Index of Premature Ejaculation-5 (CIPE-5), treatment success rate, and adverse events. Results: Seven trials were included in this review for a total of 603 participants. A low quality of evidence suggests that it is not possible to determine whether acupuncture, as compared with a selective serotonin reuptake inhibitor, has an advantage in improving the IELT (standardized mean difference [SMD], -1.75; 95% CI, -6.12 to 2.63; P = .43, I2 = 98%), PEDT scores (SMD, 0.32; 95% CI, -0.68 to 1.32; P = .53, I2 = 85%), and treatment success rate (risk ratio, 0.69; 95% CI, 0.41-1.14; P = .15). However, participants receiving acupuncture had a lower CIPE-5 (SMD, -1.06; 95% CI, -1.68 to -0.44; P < .01). As compared with sham acupuncture, acupuncture significantly improved the IELT (SMD, 1.47; 95% CI, 1.01-1.92; P < .01, I2 = 0%) and PEDT scores (SMD, -1.23; 95% CI, -1.78 to -0.67; P < .01, I2 = 37%). When compared with other treatments alone, a combined treatment with acupuncture can significantly improve the IELT (SMD, 7.06; 95% CI, 2.53-11.59; P < .01, I2 = 97%), CIPE-5 (SMD, 0.84; 95% CI, 0.45-1.22; P < .01, I2 = 0%), and treatment success rate (SMD, 1.60; 95% CI, 1.18-2.16; P < .01, I2 = 53). Clinical Implications: The results suggest a significant effect of acupuncture in the treatment of certain important indicators of PE; however, this finding needs to be treated with caution because of the quality of the RCTs included. Strengths and Limitations: Comprehensive inclusion of available RCTs has been performed. However, limitations include a low number of studies and a lack of detailed information to allow subgroup analysis. Conclusion: The present systematic review and meta-analysis show that acupuncture has a significant effect on several subjective PE parameters, such as improving the feeling of control over ejaculation and distress, particularly when used in an integrated way. However, due to the low quality of evidence, acupuncture still needs larger well-designed RCTs to be confirmed.

Thalamocortical Dysconnectivity In Lifelong Premature Ejaculation: A Functional MRI Study.

OBJECTIVES: To detect seed-based functional connectivity (FC) between various cortical sub-regions and the thalamus in lifelong premature ejaculation (LPE) patients and explore whether specific thalamocortical networks are significantly altered in PE patients compared to healthy controls (HCs) METHODS: Fifty non-medicated LPE patients and 40 age-matched HCs underwent a resting-state functional MRI. FC was adopted to identify specific thalamocortical connectivity between the thalamus and 6 cortical regions of interest (i.e., the motor cortex/supplementary motor, the prefrontal cortex, the temporal lobe, the posterior parietal cortex, the somatosensory cortex and the occipital lobe). In LPE patients, regression analysis was subsequently conducted to assess relationships of thalamocortical connectivity with the Premature Ejaculation Diagnostic Tool (PEDT) score and the Intravaginal Ejaculatory Latency Time (IELT). RESULTS: LPE patients had significantly decreased FC between the motor cortex and bilateral ventral thalamus, between the prefrontal cortex and left dorsomedial thalamus, as well as between the temporal cortex and bilateral ventromedial thalamus. In LPE patients, PEDT score was significantly positively associated with the thalamus-posterior parietal cortex FC, and negatively associated with the thalamus-temporal cortex FC, while IELT was positively associated with the thalamus-temporal cortex and thalamus-motor cortex FC. CONCLUSION: These results enrich the imaging evidence for the understanding of the neurobiological mechanisms and/or consequences of LPE.

Safety and efficacy of traditional Chinese medicine, Qiaoshao formula, combined with dapoxetine in the treatment of premature ejaculation: An open-label, real-life, retrospective multicentre study in Chinese men.

To evaluate the safety and efficacy of Chinese medicine, Qiaoshao formula combined with dapoxetine was used for the treatment of premature ejaculation in a real-life setting. Nine hundred and five males diagnosed with premature ejaculation were reviewed in this retrospective cohort study. We divided the patients into two groups: dapoxetine alone and Qiaoshao formula combined with dapoxetine according to actual interventions provided to patients in clinics. The perceived intravaginal ejaculation latency time and the premature ejaculation profile measures markedly improved in both groups. However, in men with severe premature ejaculation (baseline perceived intravaginal ejaculation latency time <1 min) and those with baseline age ≤30 years, the perceived intravaginal ejaculation latency time was slightly but significantly longer with combined therapy than with dapoxetine alone (p < .05). Therefore, combined therapy involving the Qiaoshao formula and dapoxetine proved to safe as well as effective for treating premature ejaculation while prolonging the perceived intravaginal ejaculation latency time, which significantly improved the overall satisfaction of the patient and likely that of the couple.

Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction-A prospective, randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: The primary objectives were to compare the efficacy of extracts of the plant Tribulus terrestris (TT; marketed as Tribestan), in comparison with placebo, for the treatment of men with erectile dysfunction (ED) and with or without hypoactive sexual desire disorder (HSDD), as well as to monitor the safety profile of the drug. The secondary objective was to evaluate the level of lipids in blood during treatment. PARTICIPANTS AND DESIGN: Phase IV, prospective, randomized, double-blind, placebo-controlled clinical trial in parallel groups. This study included 180 males aged between 18 and 65 years with mild or moderate ED and with or without HSDD: 90 were randomized to TT and 90 to placebo. Patients with ED and hypertension, diabetes mellitus, and metabolic syndrome were included in the study. In the trial, an herbal medicine intervention of Bulgarian origin was used (Tribestan®, Sopharma AD). Each Tribestan film-coated tablet contains the active substance Tribulus terrestris, herba extractum siccum (35-45:1) 250mg which is standardized to furostanol saponins (not less than 112.5mg). Each patient received orally 3×2 film-coated tablets daily after meals, during the 12-week treatment period. At the end of each month, participants' sexual function, including ED, was assessed by International Index of Erectile Function (IIEF) Questionnaire and Global Efficacy Question (GEQ). Several biochemical parameters were also determined. The primary outcome measure was the change in IIEF score after 12 weeks of treatment. Complete randomization (random sorting using maximum allowable% deviation) with an equal number of patients in each sequence was used. This randomization algorithm has the restriction that unequal treatment allocation is not allowed; that is, all groups must have the same target sample size. Patients, investigational staff, and data collectors were blinded to treatment. All outcome assessors were also blinded to group allocation. RESULTS: 86 patients in each group completed the study. The IIEF score improved significantly in the TT group compared with the placebo group (Р<0.0001). For intention-to-treat (ITT) there was a statistically significant difference in change from baseline of IIEF scores. The difference between TT and placebo was 2.70 (95% CI 1.40, 4.01) for the ITT population. A statistically significant difference between TT and placebo was found for Intercourse Satisfaction (p=0.0005), Orgasmic Function (p=0.0325), Sexual Desire (p=0.0038), Overall Satisfaction (p=0.0028) as well as in GEQ responses (p<0.0001), in favour of TT. There were no differences in the incidence of adverse events (AEs) between the two groups and the therapy was well tolerated. There were no drug-related serious AEs. Following the 12-week treatment period, significant improvement in sexual function was observed with TT compared with placebo in men with mild to moderate ED. TT was generally well tolerated for the treatment of ED.

Antitumor effects of saffron-derived carotenoids in prostate cancer cell models.

Crocus sativus L. extracts (saffron) are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE) and crocin (CR) exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa) cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT), and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1) which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT) as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.

Which is first? The controversial issue of precedence in the treatment of male sexual dysfunctions.

INTRODUCTION: In male sexual dysfunction (MSD), the presence of sexual comorbidities is relatively frequent. However, what is still a matter of controversy is what the first-line therapy in these patients should be. METHODS: Three scientists and the editor of the Controversies section, all experts in the medical treatment of MSD, present different perspectives on the use of phosphodiesterase type 5 inhibitors (PDE5), testosterone and dapoxetine in erectile dysfunction (ED), hypogonadism, and premature ejaculation (PE). The psychological aspects are discussed by an outstanding expert in psychosexology. MAIN OUTCOME MEASURE: Expert opinion supported by the critical review of the currently available literature. RESULTS: Testosterone should be used before PDE5s in hypogonadal men with comorbid ED; PDE5s should be used before dapoxetine in PE patients with comorbid ED, and counseling should be offered to all subjects with MSD. CONCLUSIONS: Although the answer to the question "which should be first?" is controversial in almost all MSDs, intuition, experience, and evidence should guide the choice of which treatment should be used first. This decision is highly critical in influencing the therapeutic outcome as well the patient's and couple's adherence to treatment.

Treatment options for sexual dysfunction in patients with chronic kidney disease: a systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model. RESULTS: Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI -2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy. CONCLUSIONS: PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.