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1.
Cochrane Database Syst Rev ; 3: CD012799, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33745183

RESUMO

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.


Assuntos
Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adolescente , Adulto , Coito/psicologia , Intervalos de Confiança , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Satisfação do Paciente/estatística & dados numéricos , Placebos/uso terapêutico , Ejaculação Precoce/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Adulto Jovem
2.
Life Sci ; 250: 117545, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173313

RESUMO

AIMS: Chronic stress leads to the development of male sexual problems such as ejaculatory dysfunctions. The rhythmic contractions of vas deferens (VD) play an important role on the ejaculatory process. In the current study, we investigated whether infliximab (IFX) treatment has any beneficial effects on possible alterations in contractility of VD obtained from rats exposed to unpredictable chronic mild stress (UCMS). MATERIALS AND METHODS: The rats were randomly divided into four groups: control, control+IFX, UCMS and UCMS+IFX. IFX (5 mg/kg/week, i.p.) was administrated for 5 weeks during UCMS period. Depressive like-behaviors were evaluated using locomotor activity, forced swimming and sucrose consumption and preference tests. The blood was collected for serum biochemical determinations. VD tissues were harvested for functional studies and, measurements of oxidative stress, inflammatory and apoptotic biomarkers. KEY FINDINGS: We observed increased serum concentration of corticosterone and depressive-like behaviors in rats exposed to UCMS. In VD tissues of UCMS-exposed rats, noradrenaline- and adenosine triphosphate (ATP)-induced contractile responses significantly enhanced and electrical field stimulation (EFS)-induced contractile responses markedly decreased. UCMS exposure induced inflammation, oxidative stress and apoptosis in VD. However, IFX treatment significantly improved all the aforementioned parameters. SIGNIFICANCE: The results of the present study revealed that chronic stress-induced depression caused VD dysfunction by promoting inflammation and oxidative stress in VD. IFX protected against VD dysfunction through its anti-inflammatory and antioxidant effects.


Assuntos
Infliximab/farmacologia , Estresse Oxidativo , Estresse Fisiológico , Ducto Deferente/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Corticosterona/sangue , Depressão/tratamento farmacológico , Relação Dose-Resposta a Droga , Ejaculação/efeitos dos fármacos , Campos Eletromagnéticos , Glutationa/metabolismo , Inflamação/sangue , Peroxidação de Lipídeos , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Sacarose/química , Superóxido Dismutase/metabolismo
3.
J Sex Med ; 17(3): 442-446, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31982359

RESUMO

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.


Assuntos
Pregabalina/administração & dosagem , Ejaculação Precoce/tratamento farmacológico , Adulto , Coito , Método Duplo-Cego , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ejaculação Precoce/fisiopatologia , Comportamento Sexual , Resultado do Tratamento
4.
Int J Clin Pract ; 74(5): e13480, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31927774

RESUMO

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.


Assuntos
Dutasterida/efeitos adversos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Saúde Sexual , Tansulosina/efeitos adversos , Idoso , Método Duplo-Cego , Dutasterida/uso terapêutico , Ejaculação/efeitos dos fármacos , Humanos , Libido/efeitos dos fármacos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Saúde do Homem , Pessoa de Meia-Idade , Ereção Peniana , Estudos Prospectivos , Hiperplasia Prostática/complicações , Comportamento Sexual , Inquéritos e Questionários , Tansulosina/uso terapêutico
6.
Andrologia ; 52(1): e13454, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721272

RESUMO

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.


Assuntos
Infertilidade Masculina/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/complicações , Tramadol/efeitos adversos , Vitamina E/administração & dosagem , Administração Oral , Animais , Modelos Animais de Doenças , Ejaculação/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/patologia , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/patologia , Masculino , Nigéria , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/patologia
7.
Andrologia ; 52(1): e13452, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31657066

RESUMO

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.


Assuntos
Ejaculação/efeitos dos fármacos , Terapia de Reposição Hormonal/métodos , Ejaculação Precoce/tratamento farmacológico , Testosterona/administração & dosagem , Adulto , Benzilaminas/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Satisfação do Paciente , Ejaculação Precoce/etiologia , Estudos Retrospectivos , Inibidores de Captação de Serotonina/administração & dosagem , Testosterona/deficiência , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Andrologia ; 52(1): e13414, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31692024

RESUMO

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.


Assuntos
Ejaculação/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Rauwolfia/química , Agentes Urológicos/administração & dosagem , Animais , Etanol/química , Feminino , Masculino , Modelos Animais , Casca de Planta/química , Extratos Vegetais/isolamento & purificação , Ratos , Comportamento Sexual Animal/efeitos dos fármacos , Citrato de Sildenafila/administração & dosagem , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Testículo/efeitos dos fármacos
9.
Int Braz J Urol ; 45(6): 1209-1215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31808410

RESUMO

PURPOSE: To compare the efficacy and safety of available selective serotonin reuptake inhibi-tors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE). MATERIALS AND METHODS: This study was a randomized clinical trial. Four hundred and eighty pati-ents with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to Fe-bruary 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory laten-cy time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch. RESULTS: Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxeti-ne 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug. CONCLUSIONS: All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.


Assuntos
Citalopram/uso terapêutico , Fluoxetina/uso terapêutico , Paroxetina/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Adulto , Idoso , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
J Sex Med ; 16(12): 1895-1899, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31735615

RESUMO

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.


Assuntos
Fluoxetina/uso terapêutico , Cooperação do Paciente/psicologia , Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Adulto , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Ejaculação Precoce/psicologia , Resultado do Tratamento
11.
BMJ Case Rep ; 12(8)2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31383672

RESUMO

Sexual side-effects are common among those using antipsychotic medication and may result in poor compliance and reduced quality of life. Retrograde ejaculation (RE) has been described occurring with a number of antipsychotic medications (thioridazine, risperidone, iloperidone and clozapine) but there are no guidelines regarding management of antipsychotic-associated RE. Imipramine has been suggested as a treatment for antipsychotic-associated RE in one small study of patients prescribed thioridazine and a case series of patients prescribed iloperidone. Quetiapine is a commonly used antipsychotic and is thought to be associated with less sexual side-effects relative to other antipsychotic medications. This case report describes a 25-year-old man with first episode psychosis who developed RE during treatment with quetiapine which improved with low-dose imipramine. This is the first description of RE occurring with quetiapine and successful treatment of quetiapine-associated RE with imipramine.


Assuntos
Antipsicóticos/efeitos adversos , Imipramina/administração & dosagem , Ejaculação Precoce/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Fumarato de Quetiapina/efeitos adversos , Adulto , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Ejaculação Precoce/induzido quimicamente , Resultado do Tratamento
12.
Theriogenology ; 140: 93-98, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31454723

RESUMO

Tricyclic antidepressives, such as imipramine, indirectly induce ejaculation by increasing the noradrenaline concentration, which triggers an α-adrenergic response, whereas α-adrenergic agonists, such as xylazine and detomidine, directly trigger ejaculation by activating the α-1 adrenergic receptors. Furthermore, serum oxytocin concentrations in stallions increase drastically before ejaculation, but decline immediately thereafter, implicating the role of this hormone in emission. The objectives of the present study were to: 1) compare the efficiency of various protocols for inducing ex copula ejaculation in stallions, 2) evaluate the benefits of including oxytocin in the protocols, and 3) compare the semen characteristics of ex copula versus in copula ejaculates. Nine protocols were used to induce ex copula ejaculation using various combinations of xylazine (X; 0.66 mg/kg, iv); oxytocin (O; 20 IU, iv), imipramine (I; 3 mg/kg, orally), and detomidine (D; 0.02 mg/kg, iv). Imipramine was given 2 h prior to the administration of α-adrenergic agonist (detomidine or xylazine) and oxytocin. If ejaculation did not occur within 10 min after treatment with an α-adrenergic agonist, a half-dose of the same product was injected. Twelve sexually mature stallions (6-26 y) were used; 9 of 12 stallions responded to the treatment. Two stallions responded to X or XO, four stallions responded to IX and IXO, one stallion responded to DO, and five responded to IDO. Stallions that responded to detomidine did not respond to xylazine. No stallion ejaculated in response to D, ID, or IO. Erections and masturbation occurred only in imipramine-treated stallions. Sperm quality was similar among all the protocols and was not significantly different from those in in copula ejaculates collected with an artificial vagina. In a separate trial, none of these protocols induced ex copula ejaculation in 2-3 y old stallions. The side effects included sialorrhea after imipramine administration in all the stallions and sedation after administration of xylazine or detomidine. In conclusion, the new protocol, IDO, and the traditional protocol, IX, had similar results, with IDO being a useful alternative protocol in stallions for which IX was not effective. Therefore, attempts using both the protocols are encouraged, as stallions that ejaculated upon administration of detomidine did not ejaculate when xylazine was administered, whereas those that responded to xylazine did not respond to detomidine.


Assuntos
Ejaculação/efeitos dos fármacos , Cavalos/fisiologia , Imidazóis/uso terapêutico , Ocitocina/uso terapêutico , Recuperação Espermática/veterinária , Animais , Imidazóis/administração & dosagem , Imipramina/administração & dosagem , Imipramina/uso terapêutico , Masculino , Ocitocina/administração & dosagem , Análise do Sêmen/veterinária , Contagem de Espermatozoides/veterinária , Xilazina/administração & dosagem , Xilazina/uso terapêutico
13.
J Sex Med ; 16(8): 1178-1187, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31351659

RESUMO

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.


Assuntos
Ejaculação/efeitos dos fármacos , Ejaculação Precoce/tratamento farmacológico , Piridinas/administração & dosagem , Receptores de Ocitocina/antagonistas & inibidores , Triazóis/administração & dosagem , Adulto , Coito , Método Duplo-Cego , Antagonistas de Hormônios/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Comportamento Sexual
14.
J Sex Med ; 16(8): 1188-1198, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31351660

RESUMO

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.


Assuntos
Ejaculação/efeitos dos fármacos , Ejaculação Precoce/tratamento farmacológico , Piridinas/administração & dosagem , Receptores de Ocitocina/antagonistas & inibidores , Triazóis/administração & dosagem , Adulto , Coito , Método Duplo-Cego , Antagonistas de Hormônios/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Resultado do Tratamento
15.
Psychopharmacology (Berl) ; 236(12): 3613-3623, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31359118

RESUMO

RATIONALE: Male rats trained to associate a neutral odor or rodent jacket on a female with their post-ejaculatory reward state display a preference to ejaculate with females bearing the odor or jacket. This conditioned ejaculatory preference (CEP) can be shifted by systemic administration of the opioid antagonist naloxone (NAL) during training, such that NAL-trained males distribute their ejaculations to females without the cue, relative to saline (SAL)-trained males. OBJECTIVE: The present study examined two brain sites, the medial preoptic area (mPOA) or ventral tegmental area (VTA), where the opioid reward state might be induced. METHODS: Sexually naïve Long-Evans males were implanted with bilateral guide cannula aimed at either site before they underwent multi-ejaculatory conditioning trials at 4-day intervals with sexually receptive females that bore either an almond odor or rodent tethering jacket. Infusions of NAL (1 µl/side) or SAL (1 µl/side) were made prior to each conditioning trial. All males were infused with SAL prior to a final open-field choice test with two sexually receptive females, one scented and the other unscented, or one jacketed and the other unjacketed. RESULTS: Males previously conditioned with SAL in either region showed significant CEP. In contrast, prior infusions of NAL to the mPOA shifted the preference towards the unfamiliar female, whereas prior infusions to the VTA abolished CEP for the odor. Subsequent detection of Fos protein induced by the cue showed that, relative to SAL-treated males, prior experience with NAL in the mPOA suppressed Fos in both the mPOA and VTA, whereas prior experience with NAL in to the VTA suppressed Fos in the VTA alone. CONCLUSIONS: Opioid antagonism in the mPOA produces a state of non-reward whereas in the VTA, it produces a state in which the odor does not acquire incentive properties.


Assuntos
Ejaculação/efeitos dos fármacos , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Área Pré-Óptica/efeitos dos fármacos , Recompensa , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Ejaculação/fisiologia , Feminino , Infusões Intraventriculares , Masculino , Motivação/efeitos dos fármacos , Motivação/fisiologia , Odorantes , Área Pré-Óptica/fisiologia , Ratos , Ratos Long-Evans , Olfato/efeitos dos fármacos , Olfato/fisiologia , Área Tegmentar Ventral/fisiologia
16.
J Food Biochem ; 43(7): e12885, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31353690

RESUMO

Diabetes mellitus is associated with sexual dysfunction, which leads to infertility in animal models. The aim of this study was to evaluate sexual behavior in diabetic rats administered with naringenin. Rats were classified into five groups including healthy controls, those with STZ-induced diabetes, and those with STZ-induced diabetes then treated with 25, 50, or 100 mg kg-1  day-1 of naringenin. Male rats were introduced to sexually receptive females, and data were collected regarding sexual behavior and erectile activity. Blood samples were taken and histopathological analyses were carried out. ANOVA and the Student-Newman-Keuls t test were used for statistical comparisons. Sexual behavioral, mount latency, intromission latency, ejaculation latency, and postejaculatory interval were significantly increased in diabetic rates compared with controls (p < 0.001). The NG-treated rats showed a significant improvement in testosterone and cyclic guanosine monophosphate levels, and testicular oxidative stress and inflammatory biomarkers were corrected in a dose-dependent manner compared with controls. The treatment protocol used in this study led to the elimination of sexual impairment resulting from DM, and naringenin showed significant antiinflammatory and antioxidant effects in testicular cells. PRACTICAL APPLICATIONS: Erectile dysfunction occurs in more than 50% of men who are diagnosed with diabetes mellitus. The prevalence of ED is 25% in patients younger than 50 years and 75% in those older than 50 years. Chronic DM leads to oxidative stress, which has significant effects on sexual behavior, spermatogenesis, and sperm biology. Phenolic compounds have been reported to reduce streptozotocin-induced oxidative stress in experimental animal models. In addition, they have significant effects on the generation of sperm (spermatogenesis), which is involved in the pathogenesis of chronic DM. Our study was designed to examine the effect of naringenin, a flavone flavonoid, on oxidative stress, the inflammatory process, sexual behavior, erectile activity through spermatogenesis, and cavernous cyclic guanosine monophosphate in streptozotocin-induced diabetic rats.


Assuntos
Complicações do Diabetes/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Flavanonas/administração & dosagem , Animais , GMP Cíclico/metabolismo , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/complicações , Ejaculação/efeitos dos fármacos , Disfunção Erétil/metabolismo , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Ratos , Espermatogênese/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Estreptozocina , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Testosterona/metabolismo
17.
Neuropharmacology ; 158: 107709, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310777

RESUMO

To investigate the roles of mu opioid receptors (MORs) in paraventricular nucleus of the hypothalamus (PVN) on ejaculation and its underlying mechanism in the rats, we performed copulation behavioral testing and acute experiments. During the acute experiments, mean arterial pressure (MAP), heart rate (HR), bulbospongiosus muscle-electromyogram (BSM-EMG) and pressure of vas deferens (PVD) were all recorded. The expression levels and distributions of opioid receptors were also assessed in PVN of male rats. Moreover, adeno-associated virus type 1 (AAV1) was microinjected into PVN to demonstrate whether there are direct projections from PVN to lumbar spinothalamic (LSt) cells. We found that microinjection of MOR agonist, D-A1a2-NM9-Phe4-Gly(ol)5enkephalin (DAGO), into the PVN prolonged the intromission latency and inhibited ejaculation (P = 0.0241, P = 0.0473, respectively), while the opposed results appeared in CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, MOR antagonist) group (P = 0.0021, P = 0.0286, respectively). Moreover, DAGO caused a significant decrease in MAP and HR (P = 0.0065, P = 0.0030, respectively), and PVD decreased significantly after DAGO microinjection in PVN (P = 0.0383). CTAP not only blocked the effect of DAGO but also significantly increased MAP, HR and PVD (P = 0.0003, P = 0.0010, P = 0.0074, respectively). Meanwhile, a significant increase was observed in BSM-EMG activity after microinjecting of CTAP (P = 0.0022), accompanied by visible BSM contraction. Additionally, anterograde monosynaptic transneuronal tracer AAV1 labeling revealed that neurons in PVN projected directly to LSt cells in L3-4 spinal cord. These results indicate that MORs in PVN centrally mediate ejaculation by regulating the sympathetic outflow, which may be treated as a therapeutic target for ejaculation disorders in the future.


Assuntos
Ejaculação/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Pressão , Receptores Opioides mu/metabolismo , Medula Espinal/fisiologia , Sistema Nervoso Simpático/metabolismo , Ducto Deferente/fisiologia , Analgésicos Opioides/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Ejaculação/efeitos dos fármacos , Eletromiografia , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Vértebras Lombares , Masculino , Antagonistas de Entorpecentes/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Períneo , Ratos , Receptores Opioides mu/agonistas , Receptores Opioides mu/antagonistas & inibidores , Somatostatina/farmacologia , Tratos Espinotalâmicos , Sistema Nervoso Simpático/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos
18.
Artigo em Inglês | MEDLINE | ID: mdl-31314740

RESUMO

Background We investigated the effects of a polyherbal formulation prepared from the extracts of Mondia whitei (Periplocaceae), Dracaena arborea (Dracaenaceae), and Bridelia ferruginea (Euphorbiaceae) (MDB) on the sexual behavior of normal rats (NR) and prediabetic rats (PR). Methods Male Wistar rats were administered with drinking fructose solution (21%) or tap water for 16 weeks. After induction of prediabetic status, NR (n = 30) and PR (n = 30) were randomly distributed into 10 groups of six animals each and orally treated with distilled water (10 mL/kg), sildenafil citrate (5 mg/kg), or MDB (50, 100, or 500 mg/kg) for 21 days. Sexual behavior parameters per series (S) of ejaculation were evaluated on days 1, 7, 14, and 21. Results Drinking fructose solution (21%) induced prediabetic status in rats, characterized by a significant (p < 0.01) increase in glycemia by 43.41% compared with the control group. MDB improved sexual performances of NR and PR by increasing the mount frequency (MF) and the intromission frequency (IF) as well as the number of rats capable of ejaculating. For instance, the MF and the IF were significantly increased in animals administered with MDB for 7 (50 mg/kg, S1 and S2), 14 (100 mg/kg, S3), or 21 days (100 or 500 mg/kg, S2). This increase was more pronounced on days 7 and 14 in NR and PR treated with sildenafil citrate or MDB extracts, respectively. Conclusions The mixture of MDB improved sexual activity in NR and PR. This result may further justify the traditional use of these plants as sexual performance enhancers.


Assuntos
Apocynaceae/química , Dracaena/química , Euphorbiaceae/química , Extratos Vegetais/farmacologia , Estado Pré-Diabético/tratamento farmacológico , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual/efeitos dos fármacos , Animais , Ejaculação/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
19.
J Sex Med ; 16(9): 1338-1343, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31277970

RESUMO

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.


Assuntos
Clostridium botulinum , Ejaculação/efeitos dos fármacos , Fármacos Neuromusculares/farmacologia , Ejaculação Precoce/tratamento farmacológico , Glândulas Seminais/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ejaculação/fisiologia , Eletromiografia , Masculino , Contração Muscular , Fármacos Neuromusculares/administração & dosagem , Ejaculação Precoce/fisiopatologia , Ratos , Glândulas Seminais/fisiopatologia
20.
Med Sci Monit ; 25: 4225-4232, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31171764

RESUMO

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.


Assuntos
Benzilaminas/administração & dosagem , Naftalenos/administração & dosagem , Ejaculação Precoce/tratamento farmacológico , Adulto , Benzilaminas/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Naftalenos/farmacologia , Inibidores de Captação de Serotonina/uso terapêutico , Resultado do Tratamento
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