Seminal Emission Research Articles

Adverse effects of common medications on male fertility.

An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

Silodosin Causes Impaired Ejaculation and Enlargement of Seminal Vesicles in Sexually Active Men Treated for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia

To evaluate the sexual side effects including ejaculation after silodosin treatment in potent men with regular sexual activity, as well as possible alterations in seminal vesicle volume. Sexually active patients aged ≥ 40 years with moderate to severe lower urinary tract symptoms were enrolled prospectively. International Prostate Symptom Score (IPSS) and Quality of Life (QoL), International Index of Erectile Function (IIEF) questionnaire, ejaculation frequency, and seminal vesicle volumes measured by transrectal ultrasonography were determined at study entry, and silodosin 8 mg/d was prescribed for 4 weeks. Alterations in IPSS-QoL, all domains of IIEF, ejaculation frequency, seminal vesicle volumes, and patient-reported side effects were evaluated after silodosin treatment. Thirty patients were included, and mean age was 56.7 ± 6.9 years (44-70 years). IPSS-total, IPSS-storage, and IPSS-voiding subscores and QoL were significantly improved after treatment. Despite a slight decrease in erectile function domain of IIEF (26.7 ± 1.9 vs 22.9 ± 7.5; P <.05), no significant change was determined for orgasmic functions, sexual desire, intercourse satisfaction, and overall satisfaction. Ninety percent of patients (27 of 30) had impaired ejaculation, and seminal vesicles were significantly enlarged at the end of treatment (8.1 ± 6.4 vs 16.4 ± 8.2 cc; P <.001). Impaired ejaculation is a common problem for sexually active men treated with silodosin, and this may result in the slight decrease in erectile functions. Enlargement of seminal vesicles may represent for the loss of seminal emission and accumulation of seminal vesicle secretion. Further studies are required for better clarifying the effects of silodosin on sexual functions including ejaculatory functions.

In vitro characterization of ABC transporters involved in the absorption and distribution of liensinine and its analogs

Ethnopharmacological relevanceLotus plumule, the dried young cotyledon and radicle of the Nelumbo nucifera Gaertn. (Fam. Nymphaeaceae) ripe seed, is a famous Traditional Chinese Medicine to remove heat from the heart, anchor the mind, improve seminal emission, and arrest bleeding for centuries in China. Liensinine and its analogs neferine and isoliensinine are the major active components in lotus plumule. Aim of the study is to investigate the association of liensinine, neferine, and isoliensinine with efflux transporters. Materials and methodsCaco-2, MDCK, MDCK-MDR1, and MDCK-MRP2 were used as cell models for the transcellular transport and accumulation studies. ResultsThe results obtained in Caco-2 cells suggested that P-glycoprotein (P-gp) might be involved in transcellular transport. Cellular accumulation and transport experiments were further performed in MDCK-MDR1 cells. GF120918 and cyclosporine A were found to completely inhibit the efflux, and the net efflux ratios of these alkaloids exhibited saturation over the concentration range. No significant differences in liensinine accumulation and transport were observed between MDCK and MDCK-MRP2 cells. ConclusionsThese results demonstrated that liensinine, neferine, and isoliensinine are substrates of P-gp, whereas MRP2 is not involved in the transport process, suggesting that P-gp might be responsible for the absorption and distribution of the 3 alkaloids.

A comparison of the expression and contractile function of α1-adrenoceptors in seminal vesicle and vas deferens from normotensive and hypertensive rats

Because hypertension related alterations occur in the properties of α1-adrenoceptor in several mammalian tissues and hypertension may impact ejaculatory function, we investigated hypertension related alterations in the functional, biochemical and molecular properties of α1-adrenoceptor in the rat seminal vesicle and vas deferens. Spontaneous seminal emission in male spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats was studied during the 3-day observation period. The characteristics of α1-adrenoceptor in the seminal vesicle and epididymal and prostatic portion of vas deferens of the two strains were determined using an isolated muscle bath, radioligand receptor binding and real-time reverse transcription-polymerase chain reaction techniques. SHRs had significantly higher serum testosterone than WKY rats. However, the daily mean number of ejaculatory plugs emitted and their dry weight in SHRs were significantly lower than those in WKY rats. Although there was no significant difference in the properties of α1-adrenoceptor in the prostatic portion of vas deferens between SHRs and WKY rats, the maximum contractile responses to phenylephrine, total α1-adrenoceptor density and expression of α1A-adrenoceptor mRNA were significantly higher in the seminal vesicle and epididymal portion of vas deferens of SHRs vs. WKY rats. Our data demonstrate the presence of hypertension related alterations in serum testosterone and in α1-adrenergic responsiveness of the rat seminal vesicle and vas deferens and suggest that ejaculatory function in SHRs does not mirror these hypertension related alterations.

Oh Blessed Holy Caffeine Tree: Coffee in Popular Music

Oh Blessed Holy Caffeine Tree: Coffee in Popular Music

Hypertension related alterations in α1‐adrenergic responsiveness of the rat seminal vesicle and vas deferens

As hypertension may impact ejaculatory function, we investigated effects of hypertension on α1‐adrenoceptors in the rat seminal vesicle and vas deferens. Spontaneous seminal emission was studied in male spontaneously hypertensive rats (SHRs) and normotensive Wistar‐Kyoto (WKY) rats. The characteristics of α1‐adrenoceptor in the seminal vesicle and vas deferens of the two strains were determined using an isolated muscle bath, radioligand receptor binding and real‐time RT‐PCR techniques. Although SHRs had significantly higher serum testosterone than WKY rats, the daily mean number of ejaculatory plugs emitted and their dry weight in SHRs were significantly lower than those in WKY rats. The maximum contractile responses to phenylephrine, total α1‐adrenoceptor density and expression of α1A‐adrenoceptor mRNA were significantly higher in the seminal vesicle and epididymal portion of vas deferens of SHRs vs WKY rats. Our data demonstrate the presence of hypertension related alterations in serum testosterone and in α1‐adrenergic responsiveness of the rat seminal vesicle and vas deferens and suggest that ejaculatory function in SHRs does not mirror these hypertension related alterations. Supported by KAKENHI 21791511, Grant‐in‐Aid for Young Scientists (B) provided by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Bitenosh’s Orgasm (1QapGen 2:9-15)

Abstract It is certain that ancient Greek concepts of embryogenesis influenced Jewish theories about the coming-into-being of a foetus. In that light the enigmatic remark of Bitenosh in 1QapGen 2 about her “pleasure” in response to Lamech’s worried question about who fathered their child (Noah) becomes clear: she refers to her orgasm considered as a sign of her own seminal emission during their begetting of the child.

Psychosexual Study of Communist Era Hungarian Twins

Our aim in this study is to describe the characteristics of sexual development in twins and estimate the role of heritability and environmental factors as causes of certain sexual disorders. Two hundred and ten adult same-sex twin pairs (92 monozygotic [MZ] female, 41 MZ male, 55 dizygotic [DZ] female and 22 DZ male pairs) were involved in the study. Data were collected in 1982 by self-administered questionnaires that included items on sexual maturation, sexual life, contraception, mutual sexual activity within twin pairs and alcohol use. The ratio of married to unmarried twins was nearly the same in MZs and DZs, with the exception that the divorce rate was higher in MZ female twins (14%), and DZ and male twins were slightly more likely to be single. Menarche was later in twins compared to non-twin Hungarian women. 57% of MZs experienced menarche within 3 months of each other, 77% within 6 months while it occurred for 30% and 43% respectively in DZs. The first seminal emission indicated some delay in male twins compared with the Hungarian general population sample. MZ first kisses occurred later than DZ's first kisses. The same was true for the first petting, masturbation and first sexual intercourse. Anorgasmy is 27% heritable but the estimate is not statistically significant. Concordance rate for premature ejaculation in MZs was greater than in DZs but the structural equation model showed significant misfit. Age at menarche appeared to be strongly heritable.

Treatment of benign prostatic hyperplasia and aging: Impacts of alpha-1 blockers on sexual function

Background Alpha-1 blockers are the first option for the medical treatment of benign prostatic hyperplasia (BPH), and differ in their likelihood of causing abnormal ejaculation. Alpha 1A-selective blockers may result in reduced or absent seminal emission via inhibition of smooth muscle contraction. A new alpha-1 blocker, silodosin is 162 times more selective for alpha-1A than for alpha-1B, and is approximately 55 times more selective for alpha-1A than for alpha-1D. In contrast, naftopidil is an alpha 1D-selective blocker, which has been recently reported to less likely induce ejaculatory disorders. To investigate clinical efficacies and impacts on sexual function of these alpha-1 blockers in patients with BPH, we performed a multicenter randomized trial. Methods Eighty-nine patients with of lower urinary tract symptoms (LUTS)/BPH who had International Prostate Symptom Scores (IPSS) of 8 or more were randomly assigned to receive silodosin (8mg/day, n = 48) or naftopidil (75mg/day, n = 41). Before and 4, 8, and 12 weeks after treatment, IPSS, and Quality of Life (QOL) were employed to assess LUTS. Also, IIEF-5 and an original questionnaire were used to evaluate erectile function and ejaculation, respectively. Results Efficacies on LUTS of these blockers are almost equivalent, with a small advantage of silodosin on voiding symptoms. A significant impairment of ejaculation (decreases of ejaculatory volume) was observed in the silodosin group (p < 0.01). Orgasm and satisfaction on ejaculation in the silodosin group was significantly inferior to those in the naftopidil group. Conclusions Alpha 1D-selective blockers may possess superior property of preserving sexual function, compared with Alpha 1A-selective blockers.

Symptomatic and urodynamic responses in patients with reduced or no seminal emission during silodosin treatment for LUTS and BPH

Data from phase 3 studies (NCT00224107, NCT00224120) of silodosin for treatment of BPH symptoms were analyzed to examine the relationship between treatment efficacy and occurrence of abnormal ejaculation. Men aged ⩾50 years with International Prostate Symptom Scores (IPSS) ⩾13 and peak urinary flow rates (Qmax) of 4–15 ml s−1 received placebo or silodosin 8 mg once daily for 12 weeks. Silodosin-treated patients were stratified by absence or presence of ‘retrograde ejaculation' (RE). Groups were compared using analysis of covariance (for change from baseline) and responder analyses. Of the 466 patients receiving silodosin, 131 (28%) reported RE and 335 (72%) did not; 4 of the 457 patients receiving placebo (0.9%) reported RE. Most RE events in silodosin-treated patients (110/134; 82%) were reported as ‘orgasm with absence of seminal emission.' Silodosin-treated patients with (+) and without (−) RE showed significant improvement in IPSS, Qmax and quality of life versus placebo (P<0.02). RE+ patients versus RE− patients experienced numerically greater improvement, but differences were not statistically significant (P>0.05). For RE+ patients, the odds of achieving improvement of ⩾3 points in IPSS and ⩾3 ml s−1 in Qmax by study end were 1.75 times those for RE− patients (P=0.0127). Absence of seminal emission may predict superior treatment efficacy of silodosin in individual patients.

Genital and heart rate response to erotic stimulation in men with and without premature ejaculation

This study compared genital and penile response patterns in men with and without premature ejaculation (PE) so as to identify the potential anomalous psychosomatic relationships among men with PE. Genital and heart rate response profiles of 25 men with PE were compared with those of 13 age-matched sexually functional counterparts during visual sexual stimulation presented in combination with vibrotactile penile stimulation. Although no differences were found between men with PE and controls on maximum penile circumference change, overall penile response was significantly lower in the PE group and PE men who ejaculated during the session exhibited shorter latencies to maximum circumference change. Furthermore, significant differences were found between groups in patterns of heart rate. These findings indicate differences in physiological responses between men with PE and sexually functional counterparts during erectile tumescence and progression toward ejaculation. Such differences might be explained by 'premature' sympathetic activation during the sexual response cycle in men with PE, thereby diminishing parasympathetically controlled penile response and triggering sympathetically mediated seminal emission prematurely.

Impact of Dry Ejaculation Caused by Highly Selective α1A-blocker: Randomized, Double-blind, Placebo-controlled Crossover Pilot Study in Healthy Volunteer Men

Dry ejaculation with loss of seminal emission is reported in patients who have been administered silodosin, an alpha1A-adrenoceptor antagonist. We investigated the impact of dry ejaculation caused by orally administered silodosin on orgasmic function. In a double-blind crossover study, 50 healthy volunteer men were randomly assigned to receive either a single dose of 4-mg silodosin or placebo with 3 days of washout before crossover. Subjects masturbated 4 hours after administering agents. Numerical rating scale (NRS) score from 0 (highest) to 10 (lowest) for subjective quality of orgasm, the subjective number of contractions of the bulbocavernosus/pelvic floor muscles, and the amount of semen were examined. Results. After the administration of silodosin, the NRS score worsened by 1.3 points (P = 0.003), the number of contractions of the bulbocavernosus/pelvic floor muscles decreased by about 1 (P = 0.003), and there was a decrease of 1.8 mL in the amount of semen produced (P < 0.0001). Eleven men overall (22%) on silodosin administration had less than a 50% decrease from baseline in the amount of semen. Silodosin may adversely affect the subjective orgasmic function by causing an abnormal ejaculation with decreased (or no) semen discharge and a decrease in the number of bulbocavernosus/pelvic floor muscle contractions. Semen passing through the urethra and sufficient rhythmic contraction of the muscle of the pelvic floor may contribute to the subjective pleasure of orgasm.

Characterization of the Effects of Various Drugs Likely to Affect Smooth Muscle Tension on Isolated Human Seminal Vesicle Tissue

To investigate the effects of different classes of drugs on the isometric tension of isolated human seminal vesicle (SV) tissue. The contractility of human SV contributes to the process of seminal emission during ejaculation. Different endogenous compounds, such as serotonin (5-HT), adenosine triphosphate (ATP), and nitric oxide, have been suggested to be involved in the control of contraction and relaxation of human SV smooth muscle. However, only limited data are available regarding the effects of compounds known to affect smooth musculature on SV contractile activity. Using the organ bath technique, the effects of increasing concentrations (10 nm-1 microm/10 microm) of norepinephrine (NE), phenylephrine, endothelin 1, ATP, and 5-HT on human SV tissue at basal tension were studied. In another set-up, SV strip preparations were preincubated with prazosin (alpha-adrenergic blocker), nifedipine and verapamil (Ca(2+)-channel blockers), 2-aminoethoxydiphenyl borate [inositol 1,4,5-trisphosphate (IP(3)) antagonist], cromakalim (K(+)-channel opener), or Y-27632 (ROK inhibitor) (1 microm each, for 10 minutes), followed by the application of NE (0.1 microM, 1 microM, and 10 microm). SV smooth muscle was most effectively contracted by NE (mean = 75% of calibrated scale), phenylephrine (mean = 82% of calibrated scale), and endothelin 1 (mean = 70% calibrated scale), whereas only minor responses to ATP (mean = 10.65% calibrated scale) and 5-HT (mean = 6.3% calibrated scale) were observed. The contraction induced by NE was significantly inhibited after pre-exposure of the tissue to prazosin (-92.4%), cromakalim (-83.7%), 2-aminoethoxydiphenyl borate (-43.1%), Y-27632 (-42.8%), and nifedipine (-32.7%). alpha-adrenoceptor antagonism, activation of potassium channels, and inhibition of Rho-kinase decrease the sympathetic contraction of SV smooth muscle. This might be of significance with regard to the identification of new pharmacologic avenues to affect the male ejaculatory system.

Electrophysiological actions of the dopamine agonist apomorphine in the paraventricular nucleus during penile erection

The ability to achieve and maintain penile erection is necessary for successful copulation. Studies have demonstrated that dopamine receptor stimulation in the paraventricular nucleus (PVN) of the hypothalamus induces penile erection in rodents, and the dopamine agonist apomorphine has been used to treat erectile dysfunction. The aim of this study was to determine the electrophysiological characteristics of PVN neuronal firing activity in anaesthetised rodents during apomorphine-induced erection. Our findings can be placed in two categories; those effects that occur immediately upon apomorphine administration and continue for up to several minutes prior to penile erection, deemed ‘pre-erectile’, and those effects that were only observed during penile erection and seminal emission. In the pre-erectile period, apomorphine acts on two different populations of PVN neurons to increase or decrease firing rates and increases alpha1 frequency band power in local field potentials. Decreased delta and increased theta frequency power in PVN local field potentials occur only during penile erection and seminal emission. These studies provide further understanding of the coordinated neuronal activity that occurs in the PVN during apomorphine-induced penile erection.

Orgasm is preserved regardless of ejaculatory dysfunction with selective α1A-blocker administration

We evaluated whether ejaculatory dysfunction induced with a selective α1A-blocker influenced orgasm. Fifteen healthy male volunteers took silodosin or a placebo in a randomized, double-blind crossover design. We investigated the ejaculatory volume before and after administration of the agents. After each ejaculation, participants self-reported the answers to an original questionnaire, which was about discomfort on ejaculation, orgasm and satisfaction with the discomforting ejaculation. All participants on silodosin had a complete lack of seminal emission and expulsion. All participants felt orgasm in spite of a complete lack of seminal emission. Of the 15, 12 (80%) who had a somewhat uncomfortable feeling during orgasm were dissatisfied with this feeling, although 9 of the 12 reported that its degree was mild. Orgasm is preserved regardless of the loss of seminal emission with silodosin administration. Although most participants reported mild discomfort during orgasm, they were greatly dissatisfied with the loss of seminal emission.

Short‐ and long‐term effects of silodosin, a selective α1A‐adrenoceptor antagonist, on ejaculatory function in rats

To investigate the short- and long-term effects of silodosin, a selective alpha(1A)-adrenoceptor antagonist, on spontaneous seminal emission by isolated rats and on the properties of alpha(1)-adrenoceptor subtypes in the rat seminal vesicle, as silodosin produces a relatively high incidence rate of abnormal ejaculation and chronic administration of receptor antagonists causes an up-regulation in the targeted receptor. Rats were treated with two doses (0.1 and 3 mg/kg/day) of silodosin orally for 3 or 30 days. Spontaneous seminal emission was studied during the 3-day observation period before completing treatment. The expression levels of alpha(1A), alpha(1B) and alpha(1D)-adrenoceptor mRNAs in the rat seminal vesicle and prostate were quantified by real-time reverse transcription-polymerase chain reaction using SYBR Green I. The administration of two doses of silodosin for 3 or 30 days caused a significant dose-dependent reduction in the number of ejaculatory plugs and in their dry weight. However, in rats receiving the low dose of silodosin the inhibitory effect of the drug on spontaneous seminal emission diminished significantly with chronic usage over time. Although short-term administration of silodosin did not affect expression levels of any alpha(1)-adrenoceptor subtype mRNAs in the rat seminal vesicle and prostate, long-term administration of silodosin caused a significant up-regulation in the mRNA expression of alpha(1A)-adrenoceptor in a tissue-dependent manner. Silodosin-induced up-regulation of alpha(1A)-adrenoceptor mRNA in the rat seminal vesicle might indicate potential differences in the inhibitory effect of this drug on ejaculatory function with chronic usage over time.

Effects of guanethidine-induced sympathectomy on the spermatogenic and steroidogenic testicular functions of prepubertal to mature rats.

Selective chemical sympathectomy of the internal genital organs of prepubertal to mature male Wistar rats was performed by chronic treatment with low doses of guanethidine. Sympathetic denervation caused an increase in intratesticular progesterone levels in prepubertal and early pubertal rats in addition to a decrease in androstenedione and testosterone levels in prepubertal animals, thus indicating a decrease in the conversion of progesterone into androgen, probably by blocking the steroidogenic enzymatic pathway at the 17 alpha-hydroxylase/17, 20 desmolase level. A lower degree of testicular maturation, probably related to reduced androgen activity, was observed in prepubertal and early pubertal sympathectomized rats. Concentration of spermatozoa, on the other hand, was increased in the enlarged cauda epididymidis of late pubertal and mature denervated animals. This result is discussed in terms of the impairment of epididymal mechanisms of seminal emission, fluid resorption and spermatozoal disposal.

Changes of ejaculation due to suppression of noradrenaline biosynthesis by diethyldithiocarbamate in dogs: a supplemental report with reference to changes of posterior urethral pressure.

In the preceding paper (Kimura et al.-1979) it was reported that diethyldithiocarbamate suppresses ejaculation, although penile erection is maintained, and that the suppression is not mediated by the central nervous system but by the decrease of catecholamine contents in the organs relating to sperm transport. In this paper, changes of ejaculation following administration of diethyldithiocarbamate was studied with the posterior urethrogram; measurement of the posterior urethral pressure during hypogastric nerve stimulation. From the results obtained in this study the above results were confirmed. It was also confirmed that both seminal emission and ejaculation are under the influence of an alpha-adrenergic receptor mechanism. Also, a dopamine receptor mechanism was suspected to be present in the male accessory sexual glands.

Effects of insulin replacement on ejaculatory dysfunction in streptozotocin‐induced diabetic rats

To investigate the effects of insulin replacement on ejaculatory dysfunction in streptozotocin (STZ)-induced diabetic rats. Rats were divided into three groups: (i) STZ-treated group; (ii) STZ-treated + insulin replacement (5 and 2 international units [IU]) group; and (iii) control group. The ejaculatory function in rats was evaluated using the spontaneous seminal emission (SSE) test. The amount of seminal vesicle fluid (SVF) stored in seminal vesicle was measured after the SSE test. Blood glucose was measured using a simplified blood glucose meter. In the SSE test, the ejaculatory capacity in STZ-induced diabetic rats deteriorated with time after the onset of diabetes, and the incidence of SSE and the amount of ejaculated seminal material (SM) were significantly decreased from 5 weeks after STZ administration. Likewise, the amount of SVF was also significantly decreased in a time-dependent manner. One week after STZ administration when ejaculatory capacity had not yet diminished, insulin replacement (for 4 weeks) completely prevented the decrease in frequency of SSE, the amount of SM and SVF. However, insulin replacement after the dysfunction had occurred (5 or 15 weeks after STZ administration) did not allow all parameters for ejaculatory function to be restored to the levels of the control group. This study demonstrates that at an early stage following the onset of diabetes, insulin replacement can prevent ejaculatory dysfunction in STZ-induced diabetic rats, but once the dysfunction occurs, treatment with insulin alone does not restore the ejaculatory capacity to normal levels. In addition, this study suggests that the loss of seminal emission that results from a decrease in SVF may be involved in the mechanism of ejaculatory dysfunction in diabetic rats.

Inhibition of Seminal Emission Is the Main Cause of Anejaculation Induced by a New Highly Selective α1A-Blocker in Normal Volunteers

Recent studies have highlighted the influence of alpha1-adrenoceptor antagonists on ejaculatory function. We evaluated the effect of a new, highly selective alpha1A-blocker, silodosin, on ejaculatory function of normal volunteers. The study included 15 healthy male urologists who voluntarily participated in the study. They took 4 mg of silodosin or a placebo twice daily for 3 days in a randomized, double-blind crossover design. We investigated the ejaculatory volume, sperm count in urine after ejaculation, and fructose concentration in seminal plasma before and after administration of the agents. All volunteers on silodosin had a complete lack of ejaculation. Three days after completion of silodosin, the mean ejaculatory volume recovered to the baseline level. There was no sperm in urine after ejaculation under silodosin administration in any volunteer. All volunteers on silodosin had anejaculation and did not show post-ejaculate sperm in their urine. The mechanism of ejaculatory dysfunction caused by silodosin is a loss of seminal emission.