Effects of phosphodiesterase 5 inhibitors on sperm parameters and fertilizing capacity

The aim of this review study is to elucidate the effects that phosphodiesterase 5 （PDE5） inhibitors exert on spermatozoa motility, capacitation process and on their ability to fertilize the oocyte. Second messenger systems such as the cAMP/adenylate cyclase （AC） system and the cGMP/guanylate cyclase （GC） system appear to regulate sperm functions. Increased levels of intracytosolic cAMP result in an enhancement of sperm motility and viability. The stimulation of GC by low doses of nitric oxide （NO） leads to an improvement or maintenance of sperm motility, whereas higher concentrations have an adverse effect on sperm parameters. Several in vivo and in vitro studies have been carried out in order to examine whether PDE5 inhibitors affect positively or negatively sperm parameters and sperm fertilizing capacity. The results of these studies are controversial. Some of these studies demonstrate no significant effects of PDE5 inhibitors on the motility, viability, and morphology of spermatozoa collected from men that have been treated with PDE5 inhibitors. On the other hand, several studies demonstrate a positive effect of PDE5 inhibitors on sperm motility both in vivo and in vitro. In vitro studies of sildenafil citrate demonstrate a stimulatory effect on sperm motility with an increase in intracellular cAMP suggesting an inhibitory action of sildenafil citrate on a PDE isoform other than the PDE5. On the other hand, tadalafil＇s actions appear to be associated with the inhibitory effect of this compound on PDE11. In vivo studies in men treated with vardenafil in a daily basis demonstrated a significantly larger total number of spermatozoa per ejaculate, quantitative sperm motility, and qualitative sperm motility; it has been suggested that vardenafil administration enhances the secretory function of the prostate and subsequently increases the qualitative and quantitative motility of spermatozoa. The effect that PDE5 inhibitors exert on sperm parameters may lead to the improvement of the outcome of assisted reproductive technology （ART） programs. In the future PDE5 inhibitors might serve as adjunct therapeutical agents for the alleviation of male infertility.

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

AIM To determine how statins, testosterone(T) replacement therapy(TRT) and phosphodiesterase 5-inhibitors(PDE5I) influence age related mortality in diabetic men.METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them(mean follow-up = 3.8 years) into:(1) Normal T levels/untreated(total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated;(2) PDE5I/untreated and PDE5I/treated; and(3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5 I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality(logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age(OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated(OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated(OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated(OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln(mortality) was plotted against age. The probability of mortality and 95%CI(from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5 I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5 I and TRT reduce mortality in diabetes. PDE5 I, alone and with the other treatments significantly alter age related mortality in diabetic men.

Value of phosphodiesterase 5 inhibitors as a combination therapy for treating erectile dysfunction:A literature review

Erectile dysfunction(ED)is increasing in prevalence,with estimates that 50%of men between 40 and 70 years of age suffer from the disease.Due to a wide array of available medical interventions,significant focus has been put on combination therapies that can treat ED refractory to first-line treatments such as phosphodiesterase 5 inhibitors(PDE5is).However,reviews evaluating monotherapy noninferiority and patient satisfaction of monotherapy versus combination therapy are lacking.A thorough PubMed search was performed to evaluate combination therapy in ED treatment.Articles published between January 2008 and June 2023 were reviewed,including randomized control trials,retrospective analyses,and cohort studies.Combination therapies included PDE5i plus another PDE5i,testosterone supplementation,α-blockers,vacuum erectile devices,intracavernosal injections,and low-intensity shockwave therapy.Based on this review,PDE5i monotherapy is not inferior to combination therapy and has increased satisfaction,convenience,and ease of use for patients with ED.Limitations of current literature on combination therapy include small sample size,limited data on patient satisfaction,possible biases,and limited follow-up time.Further studies will need larger randomized control trials with follow-up times greater than 1 year.

Systematic review and meta-analysis on phosphodiesterase 5 inhibitors and α-adrenoceptor antagonists used alone or combined for treatment of LUTS due to BPH

The aim of this systematic review is to determine the comparative effectiveness and safety of phosphodiesterase 5 inhibitors （PDE5-1s） and （x-blockers used alone or combined for the treatment of lower urinary tract symptoms （LUTS） due to benign prostatic hyperplasia （BPH）. An electronic search of PubMed, Cochrane Library and Embase up to January 2014 was performed to identify randomized controlled trials comparing the efficacy and safety of PDE5-Is and （x-blockers for treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, which assessed IPSS score, maximum flow rate, postvoided residual urine, quality of life and Erectile Function （IIEF） score as outcomes. Data were analyzed by fixed or random effect models using Cochrane Collaboration review manager software. A total of 12 studies were included, Our novel data demonstrated that there was a trend that （x-blockers were more efficacious than PDE5-Is on decreasing IPSS score and increasing maximum flow rate. （x-blockers were significantly more effective than PDE5-Is on reduction of postvoided residual urine with a mean difference of 3.67 （95% CI 1.56 to 5.77, P = 0.0006） and PDE5-Is showed greater effect than （x-blockers on increasing IIEF score with a mean difference of 9.82 （95% CI 3.80 to 15.85, P = 0.001）. In conclusion, our novel data demonstrated that PDE5-Is plus ABs ranked the highest on the improvement of LUTS/BPH. PDE5-Is monotherapy was also effective in this kind of disorder except less reduction of PVR than ABs, In addition, both combined- or mono-therapy were safe.

Effect of Icariin on Cyclic GMP Levels and on the mRNA Expression of cGMP-binding cGMP-specific Phosphodiesterase (PDE5) in Penile Cavernosum

Summary： To further investigate the mechanisms of action of icariin （ICA）, we assessed the effects of ICA on the in vitro formation of cGMP and cAMP in isolated rabbit corpus cavernosum. Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of ICA and the dose-dependent accumulation of cGMP and cAMP was determined in the tissues samples by means of ^125I radioimmunoassay. Responses of the isolated tissues preparations to ICA were compared with those obtained with the reference compounds sildenafil （Sild）. Furthermore, the effects of ICA on the mRNA expression of specific cGMP-binding phosphodiesterase type Ⅴ （PDE5） in rat penis were also observed. After incubation with ICA for 6 h or 14 h respectively, the levels of PDE5 mRNA were examined by reverse transcriptase polymerase chain reaction （RT-PCR）. The results showed that ICA increased cGMP concentrations directly （P〈0.05）, but there was no significant effect on cAMP concentrations （P〉0.05）. In the presence of sodium nitroprusside （SNP）, a stimulatory agent of cGMP, both ICA and Sild increased cGMP concentrations with increasing dose （P〈0.01）. Their EC50 was 4.62 （ICA） and 0.42 （Sild） μmol/L respectively. Under the same condition, ICA and Sild unaltered cAMP level significantly （P〉0.05）. There were PDE5A 1 and PDE5A2 mRNA expressions in rat cor- pus cavernosum with PDE5A2 being the dominant isoform. ICA could obviously inhibit these two isoforms mRNA expression in rat penis, and decrease PDE5A1 more pronouncedly （P〈 0.01）. The present study indicated that the aphrodisiac mechanisms of icariin involved the NO-cGMP signal transduction pathway, with increasing cGMP levels in the corpus cavernosum smooth muscle. The inhibitory effect of icariin on PDE5 mRNA expression, especially on PDE5A1, might account for its molecular mechanisms for its long-term activity.

Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet-induced obese rats

Aim： To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 （PDE5） inhibitor, on penile erection in obese rats. Methods： The rats were fed a high-energy diet for 12 weeks and divided into three groups： an obesity-resistant （OR） control group, an obesity-prone （OP） control group, and an OP-DA-8159 treatment （DA-8159） group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured. Results： In the OP control group, the maximum intracavernous pressure （ICP） and ICP/blood pressure （ICP/BP） ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve （AUC） of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159. Conclusion： These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction （ED） can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.

Evaluation and diagnostic testing of erectile dysfunction in the era of phosphodiesterase type 5 inhibitors

The diagnosis and treatment of erectile dysfunction has changed dramatically since the availability of safe and effective oral therapies. Unfortunately, not all men can be adequately treated in this way, and might require more invasive testing to diagnose and treat the specific cause of their dysfunction. This review looks at the tests and strategies available for men who cannot be treated by oral therapy alone.

用PDE-5抑制剂治疗勃起功能障碍的男性患者中前列腺癌的发生率：回顾性研究

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction （ED） treated with phosphodiesterase type 5 inhibitors （PDE-5i） over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups： 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 （4.1%） men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 （9.9%） men with ED in the non-treated group （P〈00001）. A higher percentage of African Americans were treated with PDE-5i vs. those who were not （10.5% vs. 7.1%; P〈O.O001）. The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen （10.0% vs. 13.1%; P=-0.0008） and higher percentage of benign prostatic hyperplasia （38.4% vs. 35.1%; P=0.0149）. Men with ED treated with PDE-5i tended to have less chance （adjusted odds ratio： 0.4; 95% confidence intervals： 0.3-0.5; P〈0.0001） of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of beine diaenosed with orostate cancer. Further research is warranted.

The use of antimuscarinics,phosphodiesterase type Ⅴ inhibitors and phytotherapy for lower urinary tract symptoms in men

Besides the mainstay of α-blockers and 5α-reductase inhibitors,other forms of medical therapy complete the armamentarium in the treatment of lower urinary tract symptoms(LUTS)in men.These treatments can target specific symptoms as well as associated symptoms that would affect the quality of life of the patients.Many patients are bothered by storage symptoms,more so than the voiding symptoms.Antimuscarinics are efficacious and safe,provided the patients do not have high post void residual urine.Many patients with LUTS also have erectile dysfunction,and phosphodiesterase type Ⅴ inhibitors are effective in relieving both LUTS as well as erectile dysfunction for such patients.Phytotherapy provides a popular and safe treatment for LUTS,however,the efficacy of the treatment has not been proven in well conducted prospective randomized controlled studies.

意大利临床实践中的PDE5抑制剂治疗模式：“勃起功能障碍观测研究”的纵向数据

The Erectile Dysfunction Observational Study （EDOS） is a 6-months observational prospective multicentric study enrolling men with erectile dysfunction （ED） who asked, to be started on a treatment or to change a previous treatment. Aims of the study were to analyse the pattern of treatment and compare the efficacy of treatments used. Patients were enrolled during a normal hospital visit and were prescribed a treatment for ED. They were asked at baseline and after 3 and 6 months, to answer a set of questions from the International Index of Erectile Function, Erectile Dysfunction Inventory of Treatment Satisfaction （EDITS） and Short Form of the Psychological and Interpersonal Relationships Scale questionnaires （SF-PAIRS）. Clinicians were free to prescribe any therapy for ED available in the market, and to change therapy at any time during the study. Out of 1 338 patients, available for analysis at 6 months, 624 （47%） changed their treatment during the study and 714 （53%） continued with the drug prescribed at baseline. Patients assuming tadalafil had a significantly higher probability of maintaining the same treatment compared to sildenafil or vardenafil. There was no clinically significant difference in terms of efficacy, patient satisfaction, self-confidence and spontaneity between the different inhibitors of PDE5. The ‘time concerns＇ domain score of SF-PAIRS, was statistically better in patients assuming tadalafil. In conclusion sildenafil, vardenafil and tadalafil show similar efficacy in the clinical practice. However, patients receiving tadalafil display a lower risk to discontinue or change the treatment.

Effect of phosphodiesterase inhibitors in the bladder

Many aging men will experience lower urinary tract symptoms(LUTS).Phosphodiesterase type 5(PDE5)inhibitors have shown promise in treating LUTS in these patients.PDE5 inhibitors mediate their effects through several pathways including cAMP,NO/cGMP,Kchannel modulated pathways,and the L-cysteine/H2S pathway.PDE5 inhibitors exert their effect in muscle cells,nerve fibers,and interstitial cells(ICs).The use of PDE5 inhibitors led to improvement in LUTS.This included urodynamic parameters.PDE5 inhibitors may play a significant role in LUTS due to their effect on the bladder rather than the prostate.

一种新型磷酸二酯酶5抑制剂DA-8159对食源性肥胖大鼠的勃起促进作用

Aim:To examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159,a new phosphodiesterase type 5(PDE5)inhibitor,on penile erection in obese rats.Methods:The rats were fed a high-energy diet for 12 weeks and divided into three groups:an obesity-resistant(OR)control group,an obesity- prone(OP)control group,and an OP-DA-8159 treatment(DA-8159)group.The electrostimulation-induced erectile responses were measured in all groups.The body weight,plasma cholesterol,triglyceride and glucose levels were also measured.Results:In the OP control group,the maximum intracavernous pressure(ICP)and ICP/blood pressure(ICP/BP)ratio after electric stimulation were significantly lower than those in OR control group.The corresponding area under the curve(AUC)of the ICP/BP ratio,the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group,but this difference was not significant.The body weight gain,plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159,a significant increase in the maximum ICP and the ICP/BP ratio were observed.The coerrsponding AUCs in the DA-8159 group were also higher than those in the two control groups.Furthermore,the detumescence time was significantly prolonged after treatment with DA-8159.Conclusion:These results demon- strate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction(ED)can be im- proved by the treatment with DA-8159,indicating DA-8159 might be a treatment option for ED associated with obesity.

Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction:a randomized double-blind,parallel,placebo-controlled clinical study

Aim： To assess the efficacy and safety of tadalafil in comparison to a placebo, when taken on demand for 12 weeks by East/Southeast Asian men with erectile dysfunction （ED）, Methods： This multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August 2002 and February 2003. Men more than 18 years of age with mild to severe ED of various etiologies were randomized to receive a placebo or 20 mg of tadalafil taken as needed （maximum once daily）. Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile diary and Global Assessment Questions. Results： Tadalafil significantly improved erectile function as compared to the placebo （P 〈 0.001）. At the endpoint, the patients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts （Sexual Encounter Profile question 3： 70.9% compared to 33.5% in the placebo） and a greater proportion of improved erections （Global Assessment Question： 86.2% compared to 30.1%）. Most （≥3%） treatment emergent adverse events were mild or moderate. The most common treatment emergent adverse events were headache, back pain, dizziness and dyspepsia. Conclusion： Tadalafil was an effective and well-tolerated treatment for ED in East and Southeast Asian men.

Recent insights into androgen action on the anatomical and physiological substrate of penile erection

Erectile response is centrally and peripherally regulated by androgens. The original insights into the mechanisms of action of androgens were that androgens particularly exert effects on libido and that erections in response to erotic stimuli were relatively androgen-independent. It was shown that sexual functions in men required androgen levels at the low end of reference values of testosterone. So it seemed that testosterone was not useful treatment for men with erectile difficulties, particularly following the advent of the phosphodiesterase type 5 （PDE5） inhibitors. However, approximately 50% of those treated with PDE5 inhibitors discontinue their treatment. A number of recent developments shed new light on testosterone treatment of erectile dysfunction （ED） in aging men. （1） A recent insight is that, in contrast to younger men, elderly men might require higher levels of testosterone for normal sexual functioning. （2） Several studies have indicated that PDE5 inhibitors are not always sufficient to restore erectile potency in men, and that testosterone improves the therapeutical response to PDE5 inhibitors considerably. （3） There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, reversible upon androgen replacement. The synthesis of PDE5 is upregulated by androgens, and the arterial inflow into the penis is improved by giving androgen. The above invites a re-examination of the merits of giving testosterone to aging men with ED. The beneficial effects of PDE5 inhibitors may only be optimally expressed in a eugonadal environment. （Asian J Androl 2006 Jan; 8： 3-9）

Influence of erectile dysfunction course on its progress and efficacy of treatment with phosphodiesterase type 5 inhibitors

Background Erectile dysfunction （ED） is a common impairment among older men, and the prevalence rates increase sharply after age of 60 years. Most studies have focused on the prevalence rate or dangerouse factors. The aim of this study was to investigate the basic epidemiologic data about ED patients with different ED courses. The purpose of this researth was to understand the therapeutic effect of phosphodiesterase type 5 inhibitor （PDE5-1） and see how and why the ED course impact the progress of ED and the therapeutic effect of PDE5-1 treatment. Methods From June 2008 to June 2009, 4252 questionnaires （Quality of Erection Questionnaire, QEQ） were gathered from 46 centers by urology or andrology doctors all around China. Patients with ED （age 〉 20 years） filled in first half of the questionnaires when they came for the first time, and then completed the second half 4 weeks after PDE5-1 therapy. Results ED courses of most patients were less than 5 years （〈5 years, 74.0%; 5-10 years 20.8%; 〉10 years, 5.2%）. As ED course increasing, the incidence of the risk factors of ED, such as smoking, drinking, hypertension, diabetes, heart disease and hyperlipidemia also increase （P 〈0.01）. PDES-I was effective in improving the quality of sexual activities （P 〈0.01）. Administration of PDE5-1 improves satisfaction, enjoyment and frequency of sexual activities. The longer the ED course, the worse the therapeutic effect （〈5 years, 96.1%; 5-10 years, 94.9%; 〉10 years, 89.0%） （P 〈0.01）. Conclusions The ED course greatly affected the therapeutic effect of PDE5-1, the patients with ED should consult doctor at early stage of the disease. Admistration of PDE5-1 effectively improves the penile erection and the quality of sexual life of the patients hence should be considered as first-line medicine in the treatment of ED.

Clinical and preclinical treatment of urologic diseases with phosphodiesterase isoenzymes 5 inhibitors： an update

Phosphodiesterase isoenzymes 5 inhibitors （PDE5-1s） are the first-line therapy for erectile dysfunction （ED）. The constant discoveries of nitric oxide （NO）/cyclic guanosine monophosphate （cGMP） cell-signaling pathway for smooth muscle （SM） control in other urogenital tracts （UGTs） make PDE5-1s promising pharmacologic agents against other benign urological diseases. This article reviews the literature and contains some previously unpublished data about characterizations and activities of PDE5 and its inhibitors in treating urological disorders. Scientific discoveries have improved our understanding of cell-signaling pathway in NO/cGMP-mediated SM relaxation in UGTs. Moreover, the clinical applications of PDE5-1s have been widely recognized. On-demand PDE5-1s are efficacious for most cases of ED, while daily-dosing and combination with testosterone are recommended for refractory cases. Soluble guanylate cyclase （sGC） stimulators also have promising role in the management of severe ED conditions. PDE5-1s are also the first rehabilitation strategy for postoperation or postradiotherapy ED for prostate cancer patients. PDE5-1s, especially combined with （z-adrenoceptor antagonists, are very effective for benign prostatic hyperplasia （BPH） except on maximum urinary flow rate （Qmax） with tadalafil recently proved for BPH with/without ED. Furthermore, PDE5-1s are currently under various phases of clinical or preclinical researches with promising potential for other urinary and genital illnesses, such as priapism, premature ejaculation, urinary tract calculi, overactive bladder, Peyronie＇s disease, and female sexual dysfunction. Inhibition of PDE5 is expected to be an effective strategy in treating benign urological diseases. However, further clinical studies and basic researches investigating mechanisms of PDE5-1s in disorders of UGTs are required.

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction

The effectiveness of phosphodiesterase type 5 inhibitors （PDE5-1s） for erectile dysfunction （ED） varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-1s with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration＇s tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-1s were grouped together, Caucasian ethnicity was associated with 15.636% （95% confidence interval [CI]： 0.858% to 32.579%） increase in risk ratio （RR） for Global Assessment Questionnaire question-1 （GAQ-1）, and 1.473 （95% CI： 0.406 to 2.338） score increase in mean difference （MD） for posttreatment International Index of Erectile Function-Erectile Function domain score （IIEF-EF）, compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% （95% CI： -9.120% to -2.017%） reduction in RR for GAQ-1, and -0.229 （95% CI： -0.425 to -0.042） score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-1s are more effective in Caucasians than Asians, and in patients with more severe ED.

首次接受5型磷酸二酯酶抑制剂治疗的中国男性勃起功能障碍患者中比较枸橼酸西地那非和他达拉非治疗的开放、多中心、随机交叉研究

The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate （sildenafil） and tadalafil for treating erectile dysfunction （ED） in Chinese men na＇ive to phosphodiesterase 5 （PDE5） inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire （PITPQ）. Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function （IIEF） erectile function （EF） domain, sexual encounter profile （SEP） Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men （91%） completed the randomized treatment phase. Two hundred and forty-two per 350 （69.1%） patients preferred 20-mg tadalafil, and 108/350 （30.9%） preferred lO0-mg sildenafil （P 〈 0.001） as their treatment in the 8 weeks extension. Ninety-two per 242 （38%） patients strongly preferred tadalafil and 37/108 （34.3%） strongly the preferred sildenafil. The SEP2 （penetration）, SEP3 （successful intercourse）, and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by 〉 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED na＇ive to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.

Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin

BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P