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5-Hydroxytryptamine in premature ejaculation: opportunities for therapeutic intervention.

Ejaculation, although mediated by a spinal ejaculation generator, is subject to descending supraspinal modulation from several brain regions. 5-Hydroxytryptamine (5-HT or serotonin) is involved in ejaculatory control, with its ejaculation-retarding effects likely to be attributable to activation of 5-HT1B and 5-HT2C receptors, both spinally and supraspinally. By contrast, stimulation of 5-HT1A receptors precipitates ejaculation. Selective serotonin reuptake inhibitors (SSRIs), which are used for treatment of psychiatric disorders, can delay ejaculation in humans and are widely used 'off-label' for treatment of premature ejaculation. SSRIs require 1-2 weeks' chronic dosing to be effective, similar to their use for treatment of depression. However, a new short-acting SSRI is effective 'on demand' and might represent the first of a new generation of therapies targeted to premature ejaculation.

Animals↗

Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection.

OBJECTIVE: To describe the preparation of fresh or frozen-thawed epididymal and testicular sperm for intracytoplasmic single sperm injection and to compare the fertilization, embryo quality, and pregnancy rates (PRs) obtained after using these spermatozoa to the results when freshly ejaculated sperm was used for microinjection. DESIGN: Retrospective analysis of 1,034 consecutive microinjection cycles. Ejaculated (965 cycles), fresh epididymal (43 cycles), frozen-thawed epididymal (9 cycles), and testicular sperm (17 cycles) was used for intracytoplasmic sperm injection. SETTING: Procedures were performed in a tertiary IVF center coupled with an institutional research environment. MAIN OUTCOME MEASURES: Semen density and motility were judged by the World Health Organization criteria and sperm morphology was evaluated by the Tygerberg's strict criteria. After microinjection, oocyte intactness, fertilization, embryo cleavage, transfer, and PRs were evaluated and compared. RESULTS: The median values of total sperm count, total motility and normal morphology were 17.85 x 10(6), 37%, 8% for freshly ejaculated sperm; 46.20 x 10(6), 12%, 9% for fresh epididymal sperm; 0.15 x 10(6), 0%, 0% for frozen-thawed epididymal sperm; and 0.54 x 10(6), 0% for testicular sperm (morphology was not determined). The percentage of intact oocytes after microinjection ranged from 84% to 90%. Normal fertilization rates were high when fresh or frozen-thawed epididymal and testicular spermatozoa were used for the injection (56%, 56%, 48%, respectively) but were significantly lower than for ejaculated sperm (70%). There was a higher proportion of transferable embryos obtained after ejaculated sperm injection than after testicular sperm injection. Forty percent, 58%, 33%, and 46% of cycles had positive serum hCG using ejaculated, fresh, or frozen-thawed epididymal and testicular sperm. Initial pregnancy loss occurred in 26.3% of the conception cycles. CONCLUSION: Intracytoplasmic sperm injection can provide high normal fertilization, cleavage, and PRs when fresh or frozen-thawed epididymal and testicular spermatozoa are used, but normal fertilization rates are significantly lower than after microinjection with ejaculated sperm.

Adult↗

Anxiolytic-Like effect of ejaculation under various sexual behavior conditions in the male rat.

The purpose of the present study was to analyze the anxiety-like effect induced by ejaculation in male rats subjected to different sexual behavior conditions. The animal model of anxiety used was the conditioned defensive burying test. Results showed that experimental anxiety was reduced after one or six consecutive ejaculations. Six ejaculations did not induce a larger reduction in burying behavior than that produced by two, suggesting that this effect is not cumulative. This anxiolytic-like effect endured a short period (less than 24 h), and was not accompanied by a reduction in ambulatory behavior. The present results also showed a facilitating action of a previous ejaculation on the reduction in burying behavior induced by a second ejaculatory response. This potentiation occurred with an interval of 24 h between ejaculations. In sexually exhausted rats two populations are distinguished: one sexually unresponsive, and one achieving one ejaculation. Interestingly, in the ejaculatory population no reduction in burying behavior was observed, while in the unresponsive one a diminution in defensive burying was found. Data reveal differences in the anxiolytic-like properties of ejaculation between nonsatiated rats and the two populations of sexually exhausted animals.

Animals↗

The effect of ejaculation on prostate-specific antigen in a prostate cancer-screening population.

OBJECTIVES: To measure the impact of ejaculation on the serum levels of prostate-specific antigen (PSA) in a prostate cancer-screening population. METHODS: Questionnaires regarding history of ejaculation were administered to all participants in a prostate cancer-screening trial. Two groups were analyzed. The first cohort consisted of 618 men who answered the questionnaire, and their serum PSA values were compared according to time since last ejaculation. The second cohort consisted of 89 volunteers who agreed to come back for a postejaculation PSA for whom a before and after ejaculation PSA was measured. Regression analysis was conducted between change in PSA and time since ejaculation as well as in the magnitude of change and baseline PSA. RESULTS: The mean (+/-SD) age of the studied population was 60.43 +/- 9.23 years. A non-statistically significant difference in PSA levels was observed for either cohort. For the 89 volunteers the mean PSA change after ejaculation was -0.62 +/- 0.75 (not significant). Initially, the PSA decreased, and then after 9 hours a steady increase was observed. After 12 hours, the serum PSA returns to baseline. The regression analysis between baseline PSA and magnitude of change showed a strong correlation (r = .557). The higher the baseline PSA, the greater the magnitude of change. CONCLUSIONS: FOR the total screened population, ejaculation has no clinically significant effect. Men should not be asked to abstain from sexual activities before a PSA-screening test.

Adult↗

Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries.

OBJECTIVES: [corrected] We investigated which nerve pathways are necessary to achieve ejaculation using penile vibratory stimulation (PVS) in men with spinal cord injury (SCI). METHODS: Eight men with SCI were selected based on the presence of a bulbocavernosus reflex (BCR) and consistent antegrade ejaculation with PVS. Level of injury was cervical (4), upper thoracic (4), and lower thoracic (1). Mean age was 30.4 years (range 22 to 38). Usual responses to PVS included autonomic dysreflexia (4), erection (4), and consistent somatic responses such as abdominal contractions (8). Local anesthesia of the dorsal penile nerves (penile block) was achieved using 1% plain lidocaine injection. Effective penile block was confirmed by loss of the BCR. Two PVS ejaculation trials were performed: one trial during the penile block and one trial when the penile block had worn off. In 4 subjects, the bladder contents were analyzed for retrograde ejaculation. RESULTS: With the penile block, ejaculation was inhibited in 100% of the subjects. None of the bladder washings demonstrated sperm, indicating absence of retrograde ejaculation. None of the subjects exhibited their usual erectile response, somatic responses, or signs of autonomic dysreflexia. After the penile block wore off, PVS induced ejaculation in all subjects. If subjects usually had erection, somatic responses, or signs of autonomic dysreflexia, these also returned. CONCLUSIONS: Our data suggest that ejaculatory response to PVS in SCI men requires the presence of intact dorsal penile nerves.

Ejaculation↗

Alpha 2-adrenoceptor antagonists: effects on ejaculation, penile erection and pelvic thrusting behavior in dogs.

We previously reported that systemic administration of yohimbine, an alpha2-adrenoceptor antagonist, exerts a biphasic effect (stimulating and suppressing) on ejaculation in dogs, when this function is analyzed using the amount of ejaculated semen in response to genital stimulation. To clarify the effect of alpha2-adrenoceptor blockade on male sexual function, we investigated the effects of four selective alpha2-adrenoceptor antagonists, rauwolscine, idazoxan, RX821002 and mydaglizole, on sexual responses (ejaculation, penile erection and pelvic thrusting behavior) elicited by manual penile stimulation in dogs. Rauwolscine (intraperitoneal, 30 min before the testing) caused a biphasic effect on ejaculation; the amount of ejaculated semen produced by the stimulation was significantly increased by the lower doses (0.1 and 0.3 mg/kg), whereas it was decreased by the higher doses (1.0 and 2.0 mg/kg). The higher doses of rauwolscine also markedly inhibited both penile erection and pelvic thrusting behavior. Idazoxan and RX821002, at doses of 0.1 and 0.3 mg/kg, caused a significant increase in the amount of ejaculated semen without affecting other sexual functions. RX821002 (2.0 mg/kg), but not idazoxan (2.0 mg/kg), moderately inhibited both penile erection and pelvic thrusting behavior. Mydaglizole, a peripherally acting alpha2-adrenoceptor antagonist, did not affect the sexual responses at any doses (0.1-4.0 mg/kg). In the ejaculatory declining test, all alpha2-adrenoceptor antagonists (0.1 mg/kg), except for mydaglizole, completely prevented the decrease in ejaculatory capacity produced by antecedent ejaculation. These results indicate that, though the range of the effective dose is narrow, the alpha2-adrenoceptor antagonists that can block the central alpha2-adrenoceptors have the stimulatory effects on ejaculatory function. The difference of the sexual effects may be based on the action except for the alpha2-adrenoceptor blockade.

Adrenergic Antagonists↗

Antioxidant supplementation in vitro improves boar sperm motility and mitochondrial membrane potential after cryopreservation of different fractions of the ejaculate.

Antioxidant supplementation during cooling was assayed to improve the motility of frozen-thawed (FT) boar spermatozoa from two different fractions of the ejaculate, the first component of the sperm-rich fraction (Fraction I) and the rest of the bulk ejaculate (Fraction II). Using a split-sample design, addition of two different concentrations (100 and 200 microMl(-1)) of the water-soluble Vitamin E analogue Trolox (6-hydroxy -2,5,7,8-tetramethylchroman -2-carboxylic acid) was evaluated for an effect on sperm motility (measured both subjectively and by means of a computer assisted motility assessment (CASA)), and on mitochondrial membrane potential using flow cytometry after cell-loading with JC-1. The effect of the Vitamin E analogue was clearly dose-dependent and varied with the fraction of the ejaculate considered. Motility was significantly higher in Trolox-treated spermatozoa (200 microm), from either ejaculate fraction, albeit the effect was more evident in spermatozoa from Fraction II (P<0.05) for any Trolox-concentration. Antioxidant supplementation resulted, also dose-dependent, in a higher number of spermatozoa showing high mitochondrial activity as assessed by the JC-1 staining, in both ejaculate fractions. In the present trial, exogenous Trolox positively affected post-thaw sperm viability (as motility and mitochondrial membrane potential) in both fractions of the ejaculate. The magnitude of the effect appeared, however, to be dependent of the fraction of the ejaculate considered.

Animals↗

Ejaculation. Physiology and dysfunction.

In summary, important events of ejaculation include emission of sperm and the accessory gland fluids into the urethra, simultaneous closure of the bladder neck, and forceful ejaculation of the combined semen through the urethra. Emission and bladder neck closure are primarily alpha-adrenergically mediated thoracolumbar sympathetic reflex events with supraspinal modulation. Ejaculation is a sacralspinal reflex mediated by the pudendal nerve. In stallions, the most common ejaculation disorders are emission and ejaculation failure, and urine contamination of semen. Rare disorders are azoospermia and premature ejaculation. In a large percentage of cases, an ejaculation appears to be a result of musculoskeletal disorders or to be psychogenic in nature rather than attributable to specific ejaculatory dysfunction. Traditional therapeutic approaches for accommodating deficits can extend the breeding life of many stallions. Pharmacologic aids may be useful.

Animals↗

Serum leptin levels in patients with premature ejaculation before and after citalopram treatment.

OBJECTIVE: To evaluate serum leptin levels (an adipocyte hormone involved in the suppression of appetite) in patients with premature ejaculation before and after treatment with citalopram, a selective serotonin reuptake inhibitor, with the hypothesis that leptin levels might become normal during this treatment. PATIENTS AND METHODS: The inhibitory effect of serotonin on libido, ejaculation and orgasm is well documented. Although there is no direct evidence of an association involving brain pathways which are related to sexual behaviour, there is an interaction between leptinergic and serotonergic systems. In a previous study serum leptin levels were high in patients with premature ejaculation. The present study comprised 30 patients with premature ejaculation according to the Diagnostic and Statistical Manual of Mental Disorders Third Revised Version. Fifteen patients (group I) were randomly assigned to 8 weeks of citalopram treatment and the remainder (15, group II) received no therapy. The patients were asked to determine the average intravaginal ejaculation latency time, and their fasting serum leptin levels were measured at baseline and after 8 weeks. RESULTS: There was no significant difference in the mean intravaginal ejaculation latency time between the groups at baseline; it increased after 8 weeks of treatment with citalopram in group I, to a mean (sd) of 209 (72.1) s, but not in group II. No difference was detected in leptin levels between the groups at baseline, but at 8 weeks they were lower in group I. CONCLUSION: As hypothesized, leptin levels decreased in patients with premature ejaculation after treatment with citalopram, and this decrease seemed to be linked to the therapeutic effect. Further experimental studies are needed.

Adult↗

Analysis of measured values of ejaculation time in healthy males.

Although it has been deemed irrelevant to address ejaculation time in terms of mean values, our study was designed as a preliminary step in determining the normal range of ejaculation time (from the start of stimulation of the erect penis to ejaculation) as a criterion for assessing the degree of ejaculation disorder. Ejaculation experiments were performed with informed and consenting healthy volunteers about 20 years of age, using identical manual stimulation by the same woman, and ejaculation time was measured. The mean +/- standard deviation for the ejaculation time was 156.5 +/- 80.7 seconds, which was shown to be erection time dependent.

Adolescent↗

Study of the efficacy of fluoxetine and clomipramine in the treatment of premature ejaculation after opioid detoxification.

Premature ejaculation is a common symptom that can provoke relapse in formerly opioid-dependent men after detoxification. The purpose of this study was to compare the efficacy of clomipramine and fluoxetine for the treatment of premature ejaculation in formerly opioid-dependent men after detoxification. Sixty opium-detoxified men with A & B DSM-IV diagnostic criteria for premature ejaculation participated in a prospective two-week descriptive inferential clinical trial after a two-week washout period. The subjects did not consume any other medications but naltrexone for maintenance of an opium-free state. The subjects were randomly divided into two groups of thirty subjects, one group received fluoxetine (10 mg/d for the first and 20 mg/d for the second week), and the other received clomipramine (25 mg/d for the first and 50 mg/d for the second week). Twenty five subjects did not continue the treatment and were lost to follow-up. The severity of the premature ejaculation was graded regarding the subjects' report in weeks 0, 1, and 2. Mann Whitney-U and Wilcoxon non-parametric tests were used for statistical analysis. Fluoxetine (10 mg/d then 20 mg/d) and clomipramine (25 mg/d then 50 mg/d) were both effective in the treatment of premature ejaculation and did not show any difference in efficacy. The severity of premature ejaculation did not show any relation to the subjects' age, education level, opioid type, or route of abuse. Fluoxetine and clomipramine both can be equally used in the treatment of premature ejaculation following opioid detoxification, depending on their side effects and other symptoms in the subjects.

Adult↗

Bladder neck resection with preservation of antegrade ejaculation: Basir technique.

PURPOSE: To evaluate a new method of bladder neck resection and to determine if antegrade ejaculation is preserved thereafter. PATIENTS AND METHODS: Two groups of patients were treated for their bladder neck obstruction. Group A, composed of 20 patients, was treated by bladder neck resection with preservation of more than 1 cm proximal to the verumontanum. Group B, also consisting of 20 patients, was treated by the old technique. Patients were evaluated before and after resection by semen volume, sperm count, symptoms, and urodynamic testing. RESULTS: In group A, antegrade ejaculation was maintained in 17 of the 20 patients (85%), while in 2 patients, only a small amount of semen was ejaculated and in 1 patient, complete retrograde ejaculation was reported. In group B, only 4 patients (20%) preserved antegrade ejaculation, and retrograde ejaculation occurred in 16 patients (80%). CONCLUSION: With preservation of >1 cm of the supramontanal part of the urethra during bladder neck resection, we could avoid the complication of retrograde ejaculation in those young patients who wish to preserve fertility.

Adult↗

Fertility of ejaculated and testicular megalohead spermatozoa with intracytoplasmic sperm injection.

In this study the fertility and outcome of intracytoplasmic sperm injection (ICSI) using megalohead spermatozoa from the ejaculates and testicles was evaluated. Seventeen males with megalohead and pinhead sperm forms in their ejaculate were studied in 22 cycles. A high number of sperm heads without tails and abundant round spermatid forms were commonly observed. Round-headed spermatozoa were seldom accompanied by these severely abnormal spermatozoa. The majority of megalohead spermatozoa were observed to have multiple tails, were predominant in the sample, and were used for ICSI. Ejaculated megalohead spermatozoa were used for ICSI in 15 cycles, while testicular spermatozoa were used in seven cycles where there were no vital spermatozoa or spermatozoa of low vitality in the ejaculate. The same abnormal morphology was observed in the testicles as in the ejaculated spermatozoa in the same males. Mean (+/- SD) low motility 4.7 +/- 5.6% and sperm count (3.8 +/- 4.19 x 10(6)) were common findings in these severely teratozoospermic patients. A low fertilization rate (43.2%) was achieved by using megalohead sperm forms (group I, n = 17) in comparison with the control group (60.2%) which had zero normal sperm morphology according to strict criteria (group II, n = 30) (P <0.01). Furthermore, a low pregnancy rate (9.1%) was obtained in the megalohead sperm group in comparison with the control group (40%) (P <0.05). Low fertilization and pregnancy rates may be due to a high incidence of chromosomal abnormalities from severely defective spermatozoa in the ejaculate. Couples should be counselled and warned about possible low fertilization and pregnancy rates with ICSI when only pinhead and megalohead forms with a high number of sperm heads without tails are present in the ejaculate.

Adult↗

Sertraline treatment for premature ejaculation.

This study was designed to examine the efficacy and safety of sertraline as a treatment for premature ejaculation. Fifty-two heterosexual male patients with self-reported premature ejaculation were randomly assigned to receive either sertraline or placebo. After a 1-week placebo washout period, the dose was titrated during treatment weeks 1 to 3 from 50 to 200 mg of sertraline per day until clinical response was optimal or dose-limiting adverse experiences emerged. Medication was maintained at this level through week 8. The primary outcome measures used to assess efficacy included patient assessment of time to ejaculation (from penetration), number of successful attempts at intercourse, and incidence of ejaculation during foreplay. Sertraline treatment produced significant improvements relative to placebo in time to ejaculation and number of successful attempts at intercourse, as well as overall clinical judgements of improvement. Medication was well tolerated by most patients. Because sertraline therapy caused significant prolongation of time to ejaculation, this agent may be useful as a treatment for selected patients with premature ejaculation.

1-Naphthylamine↗

An open clinical trial of fluoxetine in the treatment of premature ejaculation.

There have been an increased number of recent reports on orgasm-related sexual dysfunction coincident with selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, it has also been reported that SSRIs improve sexual dysfunction. Low doses of clomipramine and paroxetine, potent 5-hydroxytryptamine reuptake blockers, have been found to retard ejaculation time. We hypothesized that the SSRI fluoxetine might be effective in treating premature ejaculation. In an 8-week open-label clinical study, 11 male patients with premature ejaculation were treated with fluoxetine. After a washout period of 2 weeks, each patient was assigned to receive fluoxetine, 20 mg/day for 2 weeks, and then titrated to 60 mg/day, depending on the patient's tolerability and clinical response. A within-subjects comparison of pre- and posttreatment intravaginal ejaculation latency time revealed a significant improvement. Fluoxetine treatment produced significant improvements in self-visual analogue scale scores for sexual desire, anxiety for rapid ejaculation, and partner's satisfaction with ejaculation and overall sexual function. These data suggest that serotonergic antidepressants may be effective in treating rapid ejaculation in men and underline the need to carry out a double-blind, placebo-controlled trial to confirm these results.

Adult↗

SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.

Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

Adolescent↗

The split ejaculate: assessment of fertility potential using two in vitro test systems.

Semen samples (split & whole ejaculates) were obtained from 12 normal men (group A) and 8 oligospermic infertile men with sperm concentrations of less than 20 x 10(6) sperm/ml (group B). All samples were evaluated by standard semen analysis, bovine cervical mucus penetration assay (CMPT), and, in all cases with sufficient sperm, in the human spermatozoa zona-free hamster in vitro penetration assay (SPA). In group A the motile sperm concentration was significantly higher in the ejaculated material of the first two contractions (fraction I or FI) than in the remainder of the ejaculate (fraction II or FII) (p less than 0.02). No significant differences were observed in sperm penetration into zona-free hamster ova or bovine cervical mucus by sperm from FI, FII or the whole ejaculate. Motile sperm concentration was significantly correlated with sperm penetration into bovine cervical mucus (r = 0.65, p less than 0.01), but not into zona-free hamster ova (r = 0.01 NS). In the samples collected by group B, the mean sperm concentration and motile sperm concentration were higher in the first (FI) than in the second (FII) fractions of the split ejaculate or the whole ejaculate (p less than 0.05). No significant differences were found among the FI, FII and the whole ejaculate semen samples for penetration of sperm into bovine cervical mucus. Sperm concentration and motile sperm concentration were significantly correlated with sperm penetration into bovine cervical mucus (r = 0.58, p less than 0.01 and r = 0.57, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Cervix Mucus↗

Chronic prostatitis in premature ejaculation: a cohort study in 153 men.

INTRODUCTION: Premature ejaculation is a common male sexual dysfunction, affecting 30-40% of sexually active men in an age-dependent manner. Chronic prostatitis has been suggested as an important organic cause of premature ejaculation. AIM: The aim of this study was to confirm previous data reported on the incidence of chronic prostatitis in a large cohort of patients with primary and secondary premature ejaculation. METHODS: A total of 153 consecutive heterosexual men aged 29-51 years with premature ejaculation and another 100 male healthy subjects were included in this study. Sequential microbiologic specimens were obtained according to the standardized Meares and Stamey protocol. Nonbacterial prostatitis was defined by the evidence of prostatic inflammation but negative cultures of urine and prostatic fluids in men with various genitourinary symptoms. RESULTS: There was no significant difference between patients and control subjects regarding age, education, or intercourse frequency. Prostatic inflammation was found in 64% and chronic bacterial prostatitis in 52% of the patients with premature ejaculation, respectively, showing statistical significance compared with control subjects (P < 0.05). CONCLUSIONS: Results in our study showed a high prevalence of chronic prostatitis in patients with premature ejaculation. Examination of the prostate, physically and microbiologically, should be considered during assessment of patients with premature ejaculation.

Adult↗