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PubMed2005

Premature ejaculation: prevalence and associated conditions in a sample of 12,558 men attending the andrology prevention week 2001--a study of the Italian Society of Andrology (SIA).

INTRODUCTION: Premature ejaculation (PE) is the most frequent sexual complaint. AIM: To investigate prevalence of PE and its associated conditions. METHODS: We analyzed information gathered from men attending a free andrologic consultation in 186 Italian medical centers, in the setting of a project focused on andrologic prevention. MAIN OUTCOME MEASURES: Risk factors for PE. RESULTS: Five hundred sixty-nine men suffered from lifelong PE; 1,855 had previously normal ejaculation; and 234 had PE not specified. Men with PE were younger than those without, but after adjusting for concomitant erectile dysfunction the risk of PE significantly decreased with aging. Men more educated, or who had experienced a divorce had a slightly increased risk. Also, lifestyle and occupational status affected the risk of PE. Concerning medical history, a decreased risk of PE emerged in men with treated diabetes, and no association was found with hypertension, cardiopathy, hypercholesterolemia, and peripheral or central neuropathy. CONCLUSIONS: The results of the analysis of a large dataset show that subjects with PE who are seeking treatment either have experienced stress-related problems or have a physical condition predisposing to this dysfunction (genital anomalies, prostate inflammation).

Adolescent↗
PubMed2006

A new combination treatment for premature ejaculation: a sex therapist's perspective.

This article describes the diagnosis and treatment of premature ejaculation (PE) from a sex therapist's perspective and proposes that combination therapy integrating sex therapy and sexual pharmaceuticals is frequently the best treatment approach. Failure to appreciate the multimodal etiology and pathophysiology of PE makes the condition more difficult to diagnose and treat. Many physicians have tried pharmacologic approaches, but are limited to providing topical anesthetics or suggesting off-label uses of antidepressant and erectile dysfunction medications, because no medication is currently indicated specifically for PE. Furthermore, patients frequently relapse after discontinuation of the pharmaceutical. Sex therapists appreciate the multidimensional nature of PE for the patient and partner, but few patients seek out this approach, which is labor-intensive and often lacking long-term follow-up success. Most men with PE are not receiving treatment, secondary to their embarrassment about discussing their condition and a lack of clinician inquiry about sexual dysfunction. Even for those who do engage in discussion, diagnoses may be inconsistent, because a universally accepted definition of the condition and diagnostic criteria are nonexistent. Men with PE experience anxiety and lack sexual self-confidence; subsequently, their sexual and overall relationship frequently suffer. Because PE involves psychosocial and physiologic factors, treatment that addresses both should yield the best balance of function. There is interest in new agents designed specifically for PE to provide an improved pharmacotherapeutic opportunity. Yet, a combination treatment integrating pharmaceuticals and sex therapy would provide an optimized approach. Besides increasing coital latency directly, sexual pharmaceuticals could be used to provide greater opportunity for men to recognize their premonitory sensations to ejaculation more readily, facilitating a "choice point", which is key to facilitating behavioral change and learning. Such a combination approach would result in prolonged ejaculatory latency, improved treatment satisfaction, and superior long-term outcome.

Clinical Competence↗
PubMed2006

Current and future pharmacotherapies of premature ejaculation.

INTRODUCTION: There are currently no oral or topical agents approved by government regulation agencies for the management of premature ejaculation (PE). AIM: To review pharmacologic therapies for treatment of PE. METHODS: The Sexual Medicine Society of North America hosted a State of the Art Conference on Premature Ejaculation on June 24-26, 2005 in collaboration with the University of South Florida. The purpose was to have an open exchange of contemporary research and clinical information on PE. MAIN OUTCOME MEASURE: Data were obtained by extensive examination of peer-reviewed published literature. RESULTS: Chronic administration of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased adverse event profile encompassing dry mouth, nausea, drowsiness, and reduced libido. Their use may also facilitate the development of other sexual dysfunctions, such as anejaculation and erectile dysfunction (ED). Phosphodiesterase-5 (PDE-5) inhibitors have also been investigated for the management of PE, as an indirect consequence of their ability to prolong erections. Trials have found PDE-5 inhibitors to be appropriate for men with PE secondary to ED, or when they are used in conjunction with other agents such as SSRIs. Trials of topical formulations that contain either anesthetic agents or other ingredients report significant increases in ejaculatory latency times; however, long-term safety and efficacy studies are lacking. New agents are being developed specifically for the management of PE. Among these are a topical formulation and numerous oral agents. Only one agent--dapoxetine hydrochloride (DPX)--has undergone Phase III trials. DPX is a serotonin transport inhibitor (STI) with a pharmacokinetic profile conducive to on-demand dosing for the management of PE. Unlike the current oral agents, DPX has a rapid onset of action and is effective from the first dose. CONCLUSIONS: Well-designed clinical trials utilizing appropriate outcome measurements are needed to provide safe and effective pharmacologic options for men with PE.

Adult↗
PubMed2002

Identification of a potential ejaculation generator in the spinal cord.

We tested the significance of a population of lumbar spinothalamic cells for male sexual behavior in rats. These cells are positioned to relay ejaculation-related signals from reproductive organs to the brain, and they express neurokinin-1 receptors. Ablation of these neurons by the selective toxin SSP-saporin resulted in a complete disruption of ejaculatory behavior. In contrast, other components of sexual behavior remained intact. These results suggest that this population of spinothalamic cells plays a pivotal role in generation of ejaculatory behavior and may be part of a spinal ejaculation generator.

Animals↗
PubMed1998

Study on the origin of seminal leucocytes using split ejaculate technique and the effect of leucocytospermia on sperm characteristics.

The origin of seminal leucocytes and their biological significance were investigated in 76 whole ejaculate samples and 27 split ejaculate samples, obtained from patients attending the Zimbabwe Family Planning Council's Spilhaus Infertility Clinic at Harare. The leucocytes were more prevalent in fractions 1 and 2 than in fraction 3, implying that the testis, epididymis and prostate are the major sources of seminal leucocytes. The contribution from the seminal vesicles was minimal. An inverse relation is apparent between leucocyte count and sperm count (p < 0.01). The percentage of abnormal sperms was higher (p < 0.05) and the sperm motility poorer in leucocytospermic samples (p < 0.01). Fructose, the seminal vesicular marker, citric acid, the prostatic marker and alpha-glucosidase, the epididymal marker were not decreased in leucocytospermia. It is concluded that the epididymis and prostate are the major contributors of granulocytes in semen. Leucocytospermia affects sperm morphology and sperm motility but not the accessory sex gland functions. Probably these cytotoxic effects are mediated by hydrogen peroxide due to activation of seminal leucocytes. However, the presence of leucocytospermia in normozoospermic samples is indicative of the possible peaceful coexistence of leucocytes and sperms.

Adult↗
PubMed1975

Role of alpha-adrenergic receptor mechanism in closure of the internal urethral orifice during ejaculation.

The effects of autonomic drugs on closure of the internal urethral orifice during ejaculation were investigated in dogs. The closure of the internal urethral orifice was induced by the electric stimulation of the lateral fibers of the lower mesenteric plexus. The closing state of the orifice was measured with a latex balloon inserted into the orifice. The autonomic drugs were given into the aorta just above its bifurcation. From the results obtained in this study it was concluded that the closure of the internal urethral orifice during ejaculation is predominantly under the influence of the adrenergic nervous system, particularly through an alpha-adrenergic receptor mechanism.

Adrenergic alpha-Agonists↗
PubMed1984

Evaluation of the quality variations of ejaculates from individual donors for establishing a quality control scheme.

Semen for use in artificial insemination must be of good quality. To satisfy this demand we have to be able to predict the quality of semen from individual donors. Statistical analyses of data on 3,418 ejaculates from 87 donors demonstrated that each donor's ejaculates could be characterized by a lognormal distribution of the sperm concentration, the concentration of motile spermatozoa before freezing and the concentration of motile spermatozoa after thawing. Furthermore, the ratio of the concentration of motile spermatozoa before freezing to the total sperm concentration and the fraction of motile spermatozoa surviving the freezing procedure were found to be constant for individual donors. Based on these observations a statistical quality control scheme for the selection of donors and for the continuous control of semen quality is presented.

Ejaculation↗
PubMed1979

The use of Midodrin in the treatment of ejaculation disorders following retroperitoneal lymphadenectomy.

The long-term treatment of retrograde ejaculation disorders following retroperitoneal lymphadenectomy with the alpha-sympathomimetic, Midodrin, administered orally, led to improvements in the intensity of orgasm and the degree of erection. Normal ejaculation was induced in 7 out of 12 patients and emission of spermatozoa into the posterior urethra was restored in 3 out of 12 patients by a single intravenous injection of 25--30 mg Midodrin.

Adult↗
PubMed1995

Alpha-1 blockade pharmacotherapy in primitive psychogenic premature ejaculation resistant to psychotherapy.

alpha 1-Blocking agents (alphuzosine and terazosine) have been tested to determine their effectiveness over a placebo in the treatment of premature ejaculation. A total of 91 patients, all of whom were resistant to psychological therapy, were submitted to a double-blind controlled cross-over trial. Side effects were recorded as well. Alphuzosine and terazosine proved effective in approximately 50% of the cases and were, thus, significantly more active than the placebo; moreover no significant difference was found between them in terms of side effects. It is concluded that alpha 1 blockers are reasonably safe active drugs, effective in the treatment of premature ejaculation which does not respond to the psychological approach.

Adrenergic alpha-Antagonists↗
PubMed2003

Immunolocalization of sperm protein 17 in human testis and ejaculated spermatozoa.

Sperm protein 17 (Sp17) is a highly conserved mammalian protein whose primary function is still poorly understood. Immunohistochemistry (IHC) in the human testis reveals the presence of Sp17 in some spermatocytes and abundantly in spermatids. All spermatogonia, Sertoli cells, and Leydig cells appear to be immunonegative for Sp17, whereas some interstitial cells are immunopositive. IHC recognized two distinct populations (immunopositive or not for Sp17) in the ejaculated spermatozoa. Although it will be necessary to clarify why some ejaculated spermatozoa do not contain Sp17, its distribution suggests that this protein may be associated with some phases of germinal cell differentiation.

Antigens, Surface↗
PubMed2006

Detection of estrogen receptors ER-alpha and ER-beta in human ejaculated immature spermatozoa with excess residual cytoplasm.

BACKGROUND: A key role of estrogens in human sperm biology has been recently suggested by aromatase and estrogen receptor detection in human testicular germ cells and ejaculated spermatozoa. However, the involvement of these hormones in the sperm maturation process is still not defined. The aim of this work was to investigate the expression of estrogen receptors, ER-alpha and ER-beta, in human ejaculated immature spermatozoa with excess residual cytoplasm. METHODS: Immunofluorescence labelling has been used to localize ER-alpha and ER-beta proteins in immature spermatozoa isolated by Percoll gradient, while Western blot analysis was carried out on sperm protein extracts. RESULTS: Both estrogen receptors were localized in excess residual cytoplasm of immature sperm, while sperm tails showed only ER-beta. Furthermore, in the same cells, immunoblots detected the presence of the full-length (approximately 67 kDa) ER-alpha and (approximately 59 kDa) ER-beta proteins, together with a approximately 50 kDa ER-beta species, lacking in mature sperm. CONCLUSION: The present investigation demonstrated ER-alpha and ER-beta presence in excess residual cytoplasm of human abnormal sperm cells, suggesting the hypothesis that both the 'classical' ERs could be able to mediate estrogen action in spermatogenetic cells. Furthermore, the presence of the short ER-beta form in abnormal germ cells and its disappearance in mature sperm, support estrogen modulation via different ER forms during sperm maturation.

Blotting, Western↗
PubMed2004

Estrogen receptor (ER)alpha and ER beta are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway.

Human and animal models have evidenced how estrogen insufficiency is associated with abnormal spermatogenesis and male infertility. We previously demonstrated that estradiol is able to influence both capacitation and acrosome reaction in human ejaculated spermatozoa. It remains to be elucidated whether the biochemical changes induced by estradiol, in a rapid nongenomic way, are mediated by a single estrogen receptor (ER) or by the two ER subtypes, ER alpha and ER beta. In the present study, we have first demonstrated the concomitant expression of ER beta and ER alpha in human ejaculated spermatozoa. By RT-PCR and Southern blot, transcripts of both ERs were detected. Western blot analysis showed ER alpha and ER beta proteins at the same size as the "classical" ERs. The localization of ER alpha and ER beta with the immunocytochemistry shows a differential distribution of the two ER subtypes, the former being prevalently located in the midpiece, but the latter being in the tail. Estradiol has been associated with sperm longevity; however, the mechanism through which estradiol acts in sperm survival was never investigated. Upon estradiol exposure, we observed an enhanced phosphorylation of the proteins involved in the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway like PDK1, Akt, GSK-3, Bcl-2, together with ERK1/2, which was also involved in cell survival signals. Moreover, such phosphorylations were reduced in the presence of ICI 182, 780, addressing the role of estradiol and ERs in sperm survival. For instance we have provided, for the first time, a different interaction of the two ERs with the PI3K/Akt pathway, because ER alpha interacts with the p55 regulatory subunit of PI3K, whereas ER beta interacts with Akt1. However, it still remains to be elucidated whether the functional role of each of the ER subtypes in sperm survival signaling is redundant or distinct.

Blotting, Southern↗
PubMed2005

Pharmacological treatment for premature ejaculation.

Premature ejaculation is a common male sexual dysfunction. Treatment modalities as recommended by the British Association of Sexual Health and HIV include behavioural therapy, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and local anaesthetic creams. We audited the clinical cohort from our dedicated sexual dysfunction clinic to determine the success of prescribed treatment and co-existing prostatitis/male pelvic pain, erectile dysfunction, phosphodiesterase-5 (PDE5) inhibitor use and anxiety. The use of SSRIs was successful in the treatment of premature ejaculation with or without the use of local anaesthetic cream. Co-existing prostatitis/male pelvic pain, erectile dysfunction, PDE5 inhibitor use and anxiety were high.

Antidepressive Agents, Tricyclic↗
PubMed1991

Hyperactivation and acrosome reaction in vitro in spermatozoa ejaculated by cryptorchid dogs after orchiopexy.

Orchiopexy of the cryptorchid (CR) testis and castration of the scrotal testis were performed in three unilaterally CR beagles at six months of age. Induction rates for ejaculated sperm hyperactivation (HA) and the acrosome reaction (AR) in vitro in these orchiopexied dogs were compared with five those in normal beagles one year later. Canine spermatozoa were incubated for 9 hr at 38 degrees C under 5% CO2 in air in canine capacitation medium at a concentration of 30 x 10(6) sperm/ml. HA was observed using high-speed videomicrography. The AR spermatozoa were evaluated by the triple stain technique. As a result, there was no significant difference between 'the CR dogs after orchiopexy' (CDO) and the normal dogs (ND) with respect to sperm motility just after ejaculation. However, sperm motility of CDO decreased markedly during incubation. There was a significant difference in sperm motility between CDO (Mean +/- SD; 47 +/- 12%) and ND (80 +/- 9%) after three hours of incubation (p less than 0.01). No significant difference was observed between CDO and ND with respect to the HA rate of motile spermatozoa throughout the incubation period. The peak of HA rate was found in both CDO (58 +/- 5%) and ND (61 +/- 16%) after seven hours of incubation. The AR rate of spermatozoa in CDO was lower than that in ND after six hours of incubation. The AR rate of CDO (26 +/- 4%) was significantly lower than ND (46 +/- 5%) after eight hours of incubation (p less than 0.01). It is assumed that there might be relation between a rapid decrease of motility and low AR rate in spermatozoa of CDO during incubation.

Acrosome↗
PubMed1994

Immunolocalization and quantitation of acidic seminal fluid protein (aSFP) in ejaculated, swim-up, and capacitated bull spermatozoa.

Acidic seminal fluid protein (aSFP, 12.9 kDa), a major protein of bull seminal plasma, belongs to the spermadhesin protein family. Boar spermadhesins become bound to the sperm head's surface at ejaculation and are thought to play a role as capacitation factors and/or in gamete recognition and binding. Here, we have investigated the topographical distribution and fate of bovine spermadhesin aSFP during sperm capacitation in order to assess whether aSFP could be involved in similar aspects of the fertilization process as its boar homologous proteins. 5.7 +/- 2.1 x 10(6) molecules/spermatozoa were quantitated on the surface of fresh ejaculated and washed sperm. The binding site of aSFP was restricted to a thin coat at the apical part of the acrosomal cap. The amount of aSFP in swim-up sperm was 1.8 +/- 1.0 x 10(6) molecules/spermatozoa, but decreased dramatically to 22 +/- 10 x 10(3) and to undetectable levels after incubation of sperm for 1.5 h and 18 h, respectively, in capacitation medium. This indicates that the bull spermatozoa surface may be completely depleted of spermadhesin aSFP before spermatozoa reach the surroundings of the investing egg. Therefore, our results suggest that aSFP may act as a decapacitation factor on bull spermatozoa rather than as a zona pellucida binding molecule.

Animals↗
PubMed1975

The split ejaculate of the boar: contributions of the epididymides and seminal vesicles.

The epididymal and seminal vesicular contributions to split-ejaculate fractions from boars were analysed for sperm concentration, glycerylphosphorylcholine (GPC), total-N, ethanol-soluble and insoluble N, citrate, zinc and haemagglutinin. The same components were also determined in epididymal plasma (EP), vesicular secretion (VS) and whole seminal plasma (SP). Isoelectric focusing of protein patterns was studied in the fractions. With the exception of haemagglutinin, the components were present to a major extent in either VS or EP and in lower concentrations in the other secretion. The parameters in VS or EP were positively correlated among themselves and negatively correlated with most of the parameters of the other fluid. The correlation coefficients were not significant in all cases for individual animals, but the degree of significance was greater for the over-all correlations. The EP components were mainly secreted in the first three or four fractions, but occasionally from fraction four onwards. Those of VS were emitted during the entire ejaculation, the maximum occurring in the sperm-rich fraction or the immediately succeeding fraction. The first fractions were devoid of VS components in only one case. The majority of the EP proteins could be identified electrophoretically in the sperm-rich fractions, but the protein patterns in the other fractions were similar to those of VS. The results are discussed and compared with previous findings.

Animals↗
PubMed1977

Short-latency effect of testosterone on copulatory behaviour and ejaculation in sexually experienced intact male rats.

The effect of a single injection of testosterone on the number of stimuli required to trigger ejaculation and on copulatory behaviour was investigated in sexually experienced intact male rats. An intraperitoneal injection of 100 microgram free testosterone 1 h before testing facilitated the copulatory behaviour and decreased the number of mounts and intromissions needed for ejaculation; the latter effect was obtained in a test in which a constant interval was kept between each intromission.

Animals↗
PubMed1982

Influence of incubation in utero on motility and head-to-head agglutination of ejaculated rabbit spermatozoa.

Ejaculated spermatozoa were rendered immotile by incubation for 8 h at 37 degrees C in 2.9% sodium citrate. Immotile spermatozoa (5 x 10(6)) were surgically inseminated into the uterine lumen of does and samples were recovered from the uterus 5, 15, 30 and 60 min after insemination. Incubation in utero led to a resumption of progressive motility and induced head-to-head agglutination. Motility and head-to-head agglutination were highest (64 and 70% respectively) at 5 min, and declined (48 and 49%) by 60 min. The percentage of spermatozoa with an intact acrosome did not change during the in-utero incubation. When spermatozoa from a single ejaculate were evaluated in different females there was significant variation (P less than 0.01) in the reinitiation of motility and agglutination. Most agglutinated spermatozoa (greater than 96%) had an intact acrosomal membrane while acrosomal integrity of single spermatozoa differed greatly among females. We conclude that the agglutinated (motile with intact acrosomes) and non-agglutinated (usually immotile and with disrupted acrosomes) represent different populations within the uterine lumen.

Acrosome↗