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Duration of sexual arousal predicts semen parameters for masturbatory ejaculates.

A man's semen parameters may vary considerably from one specimen to the next, partly due to variability in the conditions under which the specimens are produced. In the present study, the relationship between the duration of preejaculatory sexual arousal and the quality of semen produced by masturbation was investigated. Twenty-five regular semen donors aged 22-44 provided a total of 292 semen specimens (median 11 per donor) over a period of 4 months. Each specimen was produced after a minimum of 3 days of ejaculatory abstinence and measures included the time taken to produce the specimen, ejaculate volume, sperm concentration, and percent motility. Linear regression revealed that, controlling for donor identity, there was a significant (t=2.13, P<.05) positive relationship between the time taken to produce a specimen and sperm concentration. We conclude that the duration of preejaculatory sexual arousal is an important predictor of ejaculate quality for specimens produced by masturbation and that variation in the duration of preejaculatory arousal may contribute to within-male fluctuations in semen parameters over time.

Adult↗

Auditory event-related potentials in patients with premature ejaculation.

OBJECTIVES: To investigate in a descriptive manner the P300 component of the event-related potential (ERP), which is related to aspects of cognitive processing, in patients with premature ejaculation (PE) to determine whether there is a cognitive alteration in this condition. Recent studies with short latency evoked potentials such as cortical somatosensory evoked potentials have indicated that afferent sensory inputs from the genital area to the nervous system are increased in PE. However, the cortical neural process of ejaculation has remained poorly understood. METHODS: We performed ERPs in 20 patients with PE and in 20 age-matched healthy subjects. ERPs were evoked by an auditory oddball paradigm consisting of 150 tone bursts (80% 1 kHz; 20% 2 kHz). The latencies of the N200 and the P300 waves and the amplitude of the P300 wave were measured. RESULTS: The mean latencies of the N200 and P300 waves were significantly longer in the patients with PE than in the controls (P <0.04 and <0.03, respectively). No significant difference was found in the P300 amplitude between the controls and patients (P >0.05). CONCLUSIONS: These data indicate that the greater cortical representation of sensory stimuli from the genital areas that has been shown with somatosensory evoked potential studies might be related to a cognitive/neurobehavioral dysfunction. The dysfunction involves an increased time to evaluate and categorize the stimuli in the central nervous system, with no change in the quality of cognition and neural disinhibition by the prefrontal cortex to early sensory processing in subcortical or primary cortical regions, which are cognitive neural processes underlying ERP generation.

Adult↗

Efficacy of sildenafil as adjuvant therapy to selective serotonin reuptake inhibitor in alleviating premature ejaculation.

OBJECTIVES: To evaluate the efficacy of sildenafil and selective serotonin reuptake inhibitor in alleviating premature ejaculation (PE) in patients in whom other treatments had failed. METHODS: Healthy men evaluated for primary PE graded their ejaculation on a scale of 0 to 8 (0 = almost never, 8 = almost always). The intravaginal ejaculatory latency time (IVELT) was graded on a scale of 0 to 3 (0 = longer than 5 minutes, 3 = shorter than 1 minute). The 138 men who scored their PE as 4 or greater and IVELT as 2 or greater comprised the study group. Psychological and behavioral counseling was provided during the study. PE was graded using the same scales 3 months after the initiation of each treatment. Topical 5% lidocaine ointment comprised the initial treatment: dissatisfied patients (PE grade 4 or greater, IVELT 2 or greater), took one tablet of paroxetine 20 mg for 30 days and then one tablet 7 hours before intercourse. Sildenafil was added to the treatment of patients dissatisfied with paroxetine alone. RESULTS: The mean initial PE grade was 5.67 +/- 0.13 and that for IVELT was 2.9 +/- 0.19 for all participants (mean age 28.7 years). Thirty-eight reported improvement (PE grade 2.0 +/- 0.8, P <0.01; IVELT 0.13 +/- 0.34, P <0.001) after local lidocaine application. Of the 100 treated with paroxetine, 42 reported improvement (PE grade 2.5 +/- 0.1, P <0.01; IVELT 0.28 +/- 0.46, P <0.001), and 56 of the remaining 58 who were treated with a combination of paroxetine and sildenafil reported improvement (PE grade 1.78 +/- 0.23, P <0.001; IVELT 0.16 +/- 0.37, P <0.001). Two patients remained dissatisfied with all treatment modalities. CONCLUSIONS: Sildenafil combined with paroxetine and psychological and behavioral counseling alleviated PE in patients in whom other treatments failed.

Administration, Topical↗

Intracytoplasmic injection (ICSI) of in vivo or in vitro matured oocytes with fresh ejaculated or frozen-thawed epididymal spermatozoa and additional calcium-ionophore activation in the pig.

In Experiment 1, we performed intracytoplasmic sperm injection (ICSI) of frozen-thawed epididymal and fresh ejaculated in vitro-capacitated spermatozoa into in vivo and in vitro-matured porcine oocytes. Within each group, oocytes were sperm-injected, sham-injected or served as handling controls. After subsequent in vitro-culture for 48 h the number of unchanged, fragmented und cleaved oocytes was recorded. The best result (14% cleaved after ICSI vs 2 and 0% with the sham injection and handling controls; P < 0.01) was achieved with fresh in vitro-capacitated spermatozoa injected into in vivo-matured oocytes. In vitro-matured oocytes displayed high fragmentation rates. In Experiment 2, in vitro matured oocytes were injected with freshly ejaculated in vitro-capacitated spermatozoa, followed by a 5 min-exposure to 0 (control), 50 or 100 microM calcium-ionophore. Comparable groups were sham injected or served as handling controls. It became apparent that Ca-ionophore treatment after injection of spermatozoa was ineffective at 100 microM, where at 50 microM a significant reduction in cleavage rate was observed (6 vs 26% with untreated controls, P < 0.01). Fluorescence staining with Hoechst 33342 revealed that in most cases of sperm-injected oocytes that remained unchanged after 48 h of in vitro-culture, sperm heads had not decondensed. Only few oocytes had continued to the pronucleus stage. In this context no favorable effect of Ca-ionophore was to be observed.

Animals↗

Can smooth muscle represent a useful target for the treatment of rapid ejaculation?

Rapid ejaculation is probably the most common form of male sexual dysfunction. Current research into the treatment of the condition has focused on centrally acting or topical desensitizing agents; however, no treatment has yet been approved. An alternative approach could be to develop drugs that act directly upon the target organ itself and our increasing knowledge of the molecular biology of the accessory sex organs makes this a realistic possibility. This review analyzes the information in the literature that would support such a hypothesis. Particular emphasis has been placed on articles that have investigated smooth muscle cell relaxation. A critical review of the literature has revealed that there are potentially a myriad of targets through which rapid ejaculation can be treated.

Adrenergic alpha-Antagonists↗

Sequence of ejaculation affects the spermatozoon as a carrier and its message.

It is a widespread misunderstanding that the human ejaculation produces a homogeneous fluid with constant environment for the spermatozoa. On the contrary, spermatozoa are mainly expelled together with the zinc-rich prostatic fluid in the first ejaculation fractions. In nature, these spermatozoa most likely enter the cervical mucus before any significant contact with the later, sperm hostile fractions takes place. Spermatozoa collected in the laboratory for diagnosis, treatment or research purposes face challenges in the form of light, high oxygen concentration, low carbon dioxide concentration, increased pH, extreme variations in osmolarity, and changed bioavailability of zinc and calcium in the man-made laboratory product called seminal plasma. Possible future implications of these unphysiological conditions are discussed in relation to assisted reproduction and sperm research.

Calcium↗

DNA strand breaks in ejaculated human spermatozoa: comparison of susceptibility to the nick translation and terminal transferase assays.

The nick translation and terminal transferase assays have been compared to test their relative efficiency in detecting DNA breakage in ejaculated human spermatozoa. The results have been correlated with the percentage of chromomycin A3 positive sperm, a fluorochrome that is indicative of the protamination state of sperm. Examination of the ejaculated sperm of 30 subjects revealed that the percentage of positivity to the nick translation and terminal transferase assays did not differ, even when using different fixatives. It is concluded that the inability of the two assays to distinguish the type of DNA damage, as is possible in somatic nuclei, is most probably linked to the unique nature of sperm chromatin. It is proposed that the presence of the damaged DNA may be the remnants of an imperfect spermiogenesis, probably related to an inadequate protamine deposition. This is supported by the strong correlation between the presence of DNA damage and underprotamination as evidenced by chromomycin A3.

Chromomycin A3↗

An exploration of emotional response to erotic stimulation in men with premature ejaculation: effects of treatment with clomipramine.

Emotions presumably play an important role in sexual response and dysfunction in men. Yet, few studies have investigated differences in affect between sexually dysfunctional and functional men or changes in dysfunctional men resulting from successful treatment. We compared men having premature ejaculation (PE) with sexually functional counterparts on positive and negative affects, and examined changes in their affective response to pharmacotherapeutic treatment with clomipramine, an ejaculation-retarding agent. Results indicated higher levels of specific negative affects in PE men than controls. Positive affect also differed among groups, and showed variation in response to erotic stimulation and drug treatment. When specific positive affects were analyzed, they diverged in their response to stimulus and drug manipulations. For example, all groups exhibited a decrease in arousal/sensual during clomipramine treatment, but only PE men who responded positively to pharmacological treatment exhibited significant elevation in their enjoyment of the sexual experience. The fact that alleviation of the dysfunction improved positive affect in PE men responsive to clomipramine argues for the efficacy of pharmacotherapy in promoting positive emotional experiences associated with sexual response. But the failure of negative affects to approximate the low levels typical of sexually functional men also suggests the need to consider nonpharmacological methods to ensure complete reinstatement of healthy sexual response.

Adult↗

Effects of ejaculation on levels of testosterone, cortisol, and luteinizing hormone in peripheral plasma of rhesus monkeys.

Plasma levels of testosterone (T), luteinizing hormone (LH), and cortisol were measured in 10 adult male rhesus monkeys before and shortly after coitus. Mean levels of T and LH did not increase significantly after coitus or in control (no ejaculation) tests, but cortisol levels did in both cases. In 10 different males, no significant change was found in the plasma levels of T after electroejaculation; but in control tests (electric current withheld), the mean level of T was significantly lower at 80 and 140 min, but not at 50 min, after the test. According to present evidence, the effect of ejaculation on T levels differs in primate and nonprimate species. The effects on T levels produced by living with sexually receptive female rhesus monkeys may differ from those produced by intimate but brief contact with them.

Animals↗

Successful treatment of retrograde ejaculation with the alpha1-adrenergic agonist methoxamine: case study.

We treated two patients affected by retrograde ejaculation (RE) with the pure alpha1-adrenergic agonist methoxamine; the drug was self-administered intramuscularly by the patients 30 min prior to intercourse or masturbation. A previous trial with oral imipramine had been ineffective in both patients. Sperm count increased substantially, particularly in the first patient who had insulin-dependent diabetes and was seeking fertility. In this patient, total ejaculated sperm increased from 22 millions to 488 and 419.5 millions on two different occasions, with good motility; two clinical pregnancies were obtained in the partner of this patient after 3 and 4 months of treatment, respectively. The second patient did not desire fertility. In both patients, no side effects were seen except for slight piloerection; blood pressure values increased slightly, and heart rate was unchanged. We conclude that self-administered methoxamine can be a useful, noninvasive and inexpensive treatment of RE, when oral agents are ineffective.

Adrenergic alpha-Agonists↗

An in vivo evaluation of the therapeutic potential of sympatholytic agents on premature ejaculation.

OBJECTIVE: To evaluate the therapeutic potential of sympatholytic agents on premature ejaculation in an animal model, using monitoring of rat seminal vesicle pressure change in response to electrical stimulation of the lesser splanchnic nerve. MATERIALS AND METHODS: Male Wistar rats (aged 12-14 weeks) were injected intra-arterially with sympatholytic agents (phenoxybenzamine, prazosin, WB-4101, chloroethylclomidine, yohimbine and RX 821002) at various concentrations 10 min before electrical stimulation of the lesser splanchnic nerve. The change in phasic tension (triangle upmmHg) of the seminal vesicle induced by electrical nerve stimulation before and after the addition of sympatholytic agents was used for statistical analysis. The maximum inhibition and the concentration required to induce 50% inhibition of the maximal contractile response (IC50) were obtained from the concentration-response curves, and used to determine the potency of test agents. RESULTS: The seminal vesicle contractile response to electrical nerve stimulation was suppressed in a dose-dependent manner by all test drugs except RX 821002. The mean (sd) maximal inhibition was 78.4 (9. 3)% by 0.03 mg/kg of phenoxybenzamine, 77.1 (10.1)% by 0.03 mg/kg of WB-4101, 73.4 (6.0)% by 0.1 mg/kg of yohimbine, 67.9 (9.7)% by 0.1 mg/kg of prazosin, 75.5 (7.5)% by 3 mg/kg of chloroethylclomidine and 25.3 (4.8)% by 0.01 mg/kg of RX 821002. The potencies of WB-4101 (IC50 3 microgram/kg) and yohimbine (IC50 0.8 microgram/kg) were similar to that of phenoxybenzamine (IC50 0.5 microgram/kg) and much higher than that of prazosin (IC50 0.03 mg/kg) or chloroethylclomidine (IC50 0.3 mg/kg). CONCLUSIONS: Phenoxybenzamine, prazosin, WB-4101, chloroethylclomidine and yohimbine all inhibit the contractile response of the rat seminal vesicle to electrical nerve stimulation. As phenoxybenzamine is effective in treating premature ejaculation, the comparable in vivo potencies of WB-4101 and yohimbine strongly suggest that they have clinical therapeutic potential.

Adrenergic alpha-Antagonists↗

A bihormonal model of normal sexual stimulation; the etiology of premature ejaculation.

The physiological sexual excitation is mediated both by the sympathetic and the parasympathetic nervous system. The antagonism between testosterone (Tt) and estrogens (Es) as well as the fact that the dynamics of the sexual excitation in the male are antagonistic to those in the female are nowadays well-known; hence, the hypothesis was emitted that the sympathoparasympathetic sexual excitation is bihormonal mediated, consisting in a very active sexual hormone associated with a weak antagonistic hormone. Most studies show a serotonergic (ejaculatory) involvement in premature ejaculation (PE). Nevertheless, an effective treatment of PE is rather difficult with selective serotonin reuptake inhibitor drugs and other clinical data even suggest that changes in PE actually involve at first the sexual excitation process and only secondly the ejaculation reflex.Thus, a therapeutic model for PE is set up, starting from the physiological aspects described and from the presumed pathophysiological mechanism in PE.

Ejaculation↗

Changes in epididymal protein anti-agglutinin on ejaculated boar spermatozoa during capacitation in vitro.

This study is a detailed investigation of changes in epididymal protein anti-agglutinin on ejaculated boar spermatozoa during an incubation designed to promote capacitation in vitro. Ejaculated spermatozoa were collected from six mature boars, washed, and incubated to promote capacitation. Sperm samples were subjected to Western blotting-densitometric analyses, flow cytometry after immunostaining and immunocytochemical observation by indirect immunofluorescence. An antiserum to anti-agglutinin was raised in a rabbit by subcutaneous injection of a purified antigen, as described previously (Harayama et al. 1999). Western blotting-densitometric analyses revealed an approximate halving of the amount of sperm-bound anti-agglutinin during the first 45-min incubation, followed by a gradual decrease thereafter. Comparison between immunostained sperm samples by flow cytometry before and after incubation confirmed this decrease in sperm-bound anti-agglutinin during the incubation. Microscopic characterization established that this decrease occurred mainly on the acrosome. Supplementation with seminal plasma (5% or 10%, v/v) attenuated the decrease. These findings are consistent with the conclusion that a large portion of the anti-agglutinin bound to sperm acrosomes is released at an early stage of the capacitation process in vitro.

Acrosome Reaction↗

The ultrastructure and metabolism of ejaculated tammar wallaby sperm are impaired by swim-up procedures when compared with sperm from the cauda epididymidis.

The metabolism, rate of intracellular accumulation of sugars, motility and ultrastructure of ejaculated tammar sperm were impaired by swim-up into artificial media, particularly when the cells were subsequently exposed to N-acetyl-D-glucosamine (NAG). The inclusion of hyaluronate, serum albumin, catalase or Desferal in swim-up media helped prevent deterioration of sperm motility, but failed to prevent detrimental NAG-induced metabolic and ultrastructural changes. However, the sperm were unavoidably diluted during swim-up into artificial media and their behavioural properties were modified by dilution. Thus, sperm collected from the cauda epididymidis were immotile and their rate of oxygen uptake was low in undiluted caudal epididymal semen (CES). Nevertheless, these sperm were viable, and vigorous motility was induced by 5- to 50-fold dilution in Krebs-Ringer phosphate (KRP). Sperm respiration also dramatically increased with moderate dilution (5- or 15-fold) in KRP, but decreased again at higher rates (50-fold). This suggested that motility and the metabolic properties of tammar sperm are modified both by dilution and on leaving the suppressing conditions of the epididymis. Diluted tammar epididymal sperm also displayed a Pasteur effect, but rapidly lost capacity for motility in an oxygen-depleted atmosphere. It was concluded that swim-up procedures compromise ejaculated tammar sperm by promoting dilution-induced changes. This may alter the permeability of the membrane with loss of the enzymes that process the ammonia generated during the metabolism of NAG in seminal plasma. Subsequent exposure to NAG further promotes ultrastructural damage culminating in loss of viability.

Acetylglucosamine↗

An unusual cause of retrograde ejaculation and hypertension.

A 39-year-old man presented with a 1-year history of retrograde ejaculation and a 10-year history of drug-resistant hypertension. Diagnostic abdominal ultrasound revealed an open bladder neck during the filling phase and a retroperitoneal tumor. After surgical excision histology revealed an extra-adrenal pheochromocytoma, which should be included in the differential diagnosis of patients presenting with retrograde ejaculation and hypertension.

Adult↗

Comorbidity between social phobia and premature ejaculation: study on 242 males affected by sexual disorders.

Several studies have reported high comorbidity between psychiatric and sexual disorders, particularly between anxiety and mood disorders and sexual dysfunction. The goal of the present study is to examine the comorbidity between premature ejaculation and Axis I psychiatric disorders. Of 242 males referred to an outpatient clinic of sexology between November 2000 and July 2003, 52 were diagnosed with premature ejaculation (PE). These patients were also administered the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID; First, Spitzer, Gibbon, & Williams, 1995) for the evaluation of Axis I psychiatric disorders and a modified SCID based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 2000) criteria for the evaluation of sexual disorders. We also determined the age of onset of the disorders. We found that 21.5% of the overall clinical population was affected by PE, and 64.4% of PE patients were affected by at least one Axis I psychiatric disorder. PE was highly associated (p=0.015) with social phobia (SP), with an odds ratio of 2.55. The debut of SP preceded the onset of PE. Social phobia may represent risk factor for the development of PE, and adrenergic hyperactivity may represent a pathophysiology common to both disorders.

Adult↗

Effects of penile implant surgery on ejaculation and orgasm.

Thirty-five patients who had received a penile implant were interviewed to assess their pre- and postsurgical ejaculatory and orgasmic experience. Prior to surgery, most men were able to experience ejaculation (71%) and orgasm (80%) even though erectile capability was impaired or lost completely. The implantation of a prosthetic device did not interfere with ejaculation or orgasmic functioning. Two patients who lost their ejaculatory functioning following surgery did so because of advances in their illnesses. Five men who had been non-orgasmic earlier reported having orgasm after surgery. In these cases of psychogenic orgasmic dysfunction, the penile prosthesis helped overcome the psychological barriers to this function.

Ejaculation↗

Clomipramine in the treatment of rapid (premature) ejaculation.

Twenty-three premature ejaculators (PEs) and 11 control subjects were administered 25 mg of clomipramine in a double-blind, placebo-controlled, crossover design study. During 2-week trials, subjects took either the drug or the placebo 4 to 6 hours prior to sexual activity. Daily diary data revealed that, for both groups, orgasmic latency was significantly increased when taking the clomipramine. For the PEs, the average increase in orgasmic latency during intercourse was from less than 1 minute to more than 3.5 minutes. Subjects also participated in two laboratory sessions while on the drug and placebo. During these lab sessions they were exposed to erotic videos with and without the addition of vibrotactile stimulation to the penis. Results from the laboratory data support those from the diaries. Specifically, PEs were significantly less likely to reach orgasm during the lab sessions while on the clomipramine than while on the placebo. Further, they reported a significantly greater sense of control over their orgasm while on the drug. The results of this study, along with previous research, strongly support the value of low doses of clomipramine in the treatment of premature ejaculation, specifically when taken on an as-needed basis as little as 4 hours prior to sexual activity. It is important to note, however, that the beneficial effects of the drug were not uniform across clinical subjects. In this study, those PEs with the shortest orgasmic latencies while on the placebo were the least likely to substantially improve while on the drug. Additional research is necessary to determine whether changes in the timing and dosage of the clomipramine administration can extend the benefits of the drug to those with the shortest latencies.

Adult↗