Is bulbospongiosus muscle botox injection safe and effective in treating lifelong premature ejaculation? Randomized controlled study.

PURPOSE: To evaluate the safety and efficacy of botulinum-A toxin injections into the bulbospongiosus muscle for cases of lifelong drug-resistant premature ejaculation (PE). METHODS: Ninety-eight outpatients diagnosed with lifelong PE were randomly assigned to two groups: the botulinum-A toxin group comprising forty-nine patients and the placebo (saline) group also consisting of forty-nine patients. A 100 U botulinum-A toxin was diluted into 10 cc of saline, with 5 cc injected into one side of the muscle (botulinum-A toxin group) guided by ultrasound to distribute across most muscle fibers. The same technique was applied using the same volume of saline injected into the bulbospongiosus muscle. Intravaginal ejaculatory latency time (IELT), scores from the premature ejaculation profile (PEP), Premature Ejaculation Diagnostic Tool (PEDT), International Index of Erectile Function (IIEF), and recording of any complications were obtained. Follow-ups occurred at 1-, 3-, and 6-month post-procedure. RESULTS: Cases receiving injections of botulinum-A toxin into the bulbospongiosus muscle showed notably extended intravaginal ejaculatory latency times compared to their initial performance after treatment. In addition, there were enhancements in PEP scores, and notably, no significant complications were reported. Conversely, the bilateral injection of saline into the bulbospongiosus muscle did not demonstrate any impact on ejaculation latencies. CONCLUSION: Our study demonstrated that the injection of botulinum-A toxin into the bulbospongiosus muscle can serve as a safe and effective option for treating PE. Nonetheless, its clinical application warrants further studies involving larger sample sizes and longer follow-up periods.

Abstinence for sperm sample collection and ART outcome: an unsubstantiated myth.

PURPOSE OF REVIEW: Semen analysis is a basic component of male evaluation. Reproductive centers typically instruct men to provide a semen specimen based on recommendations from WHO Standard for semen examination. Evidence that these recommendations optimize sperm reproductive capacity is lacking. Existing data to optimize sperm quality with shorter abstinence were reviewed. RECENT FINDINGS: Several recent studies have reviewed the effects of shorter ejaculatory abstinence of semen quality and assisted reproductive technology (ART) outcomes. Shorter abstinence was defined as 1 h-1 day in one review, and <4 h in the other systematic meta-analysis and review. SUMMARY: Prior instructions for male patients have not been designed to optimize fertility potential for semen analyses. Optimal sperm quality is obtained by instructing men to have a short abstinence (certainly <1 day, and preferably <4 h) for semen specimens used for in vitro fertilization (assisted reproduction).

A single administration of carbetocin before electroejaculation increases the insemination doses produced from each ejaculate in rams.

The aim of the study was to determine the effect of carbetocin administration (a long-acting analog of oxytocin) 20 or 10 min before electroejaculation (EE) on the duration of semen collection procedure, quantitative and qualitative characteristics of the ejaculate, and stress biomarkers in rams. Semen was collected from 12 Corriedale rams (age, 2.5-5.5 years old) with EE, in a Latin-square design, administrating carbetocin (0.2 mg/100 kg of body weight i.v.) 20 or 10 min before EE, or without carbetocin administration (CB-20, CB-10, and CON treatments, respectively). Each treatment was applied to different rams every 3-4 days, allowing all the rams to receive all three treatments. Carbetocin administered 20 or 10 min before EE increased the number of sperm ejaculated (P = 0.01), the semen concentration (P = 0.02), the number of insemination doses collected in a single collection (P = 0.01), and the number of insemination doses collected/electrical pulses administered (P = 0.05) compared to control rams. Carbetocin administered 20 or 10 min before semen collection prolonged the time required for EE and the number of pulses administered during EE compared to CON rams (P < 0.03 for both). The CB-10 rams required the administration of more electrical pulses during ejaculation than CON rams (P = 0.001), and CB-20 treatment tended to require more electrical pulses than CON rams (P = 0.06). The volume of the ejaculate was greater in CB-10 than in CON rams (P = 0.01), and that of CB-20 treatment tended to be greater than CON rams (P = 0.08). The percentage of sperm with intact membrane was greater in CB-20 than in CON rams (P = 0.01). Total protein, albumin, and globulin concentrations were lower immediately after carbetocin administration 20 or 10 min before EE. The treatments did not affect cortisol concentration, glycemia, rectal and surface temperatures, heart rate, and facial expressions. Carbetocin administration before EE of rams improved the quantitative and qualitative characteristics of the ejaculate, duplicating the number of insemination doses collected. It can be a promising treatment to obtain a greater quantity of doses to inseminate with a lower frequency of semen collections, reducing the negative impacts of EE on animal welfare.

Penile vibratory stimulation in men with spinal cord injury: an educational video demonstration.

OBJECTIVES: To demonstrate the different techniques used to perform successful penile vibratory stimulation (PVS) to induce ejaculation in men with spinal cord injuries (SCIs). DESIGN: A video demonstration of the PVS procedure performed in men with SCIs using the FertiCare 2.0 medical vibrator. SETTING: Major University Medical Center. PATIENTS: Men with SCIs. INTERVENTION(S): Spinal cord injury is the leading cause of anejaculation in young men. After SCIs, most of these men will need a method of assisted ejaculation to achieve biological fatherhood. In this study, a newly designed and tested vibrator (FertiCare 2.0) was used to induce ejaculation. The initial assessment of each patient included a standard history, physical examination, level of injury determination using the International Standards for Neurological Classification of Spinal Cord Injury as well as assessment of the hip flexor reflex and the bulbocavernosus reflex. Patients with a level of injury at or rostral to T6 were pretreated with 10-40 mg of sublingual nifedipine to manage autonomic dysreflexia. A single vibrator was applied to the dorsum, or frenulum, of the glans penis. Stimulation is delivered in 2-minute increments to a maximum of 10 minutes per visit. Application of two vibrators or abdominal electrical stimulation concurrently with PVS was used in select patients. Ejaculated semen was collected in a sterile cup and examined after liquefaction. Bladder preparation using sperm wash medium was performed in patients suspected of experiencing retrograde ejaculation. MAIN OUTCOME MEASURE(S): Successful ejaculation after performing the PVS procedure in men with SCIs. RESULTS: Penile vibratory stimulation was successful in 86% of men whose level of injury was T10 or rostral. The total motile sperm count in antegrade ejaculates produced using PVS was >5 million (lower limit considered for intrauterine insemination) in 71% of ejaculates. No complications because of PVS were observed in 3,700 trials performed by our group and none in the patients presented in this video. CONCLUSION(S): Penile vibratory stimulation is a safe and effective method for the management of ejaculatory dysfunction in men with SCIs. Penile vibratory stimulation can be performed by the male partner after an initial evaluation by a specialized provider, and the ejaculate can be used to perform home insemination.

Sperm exposure to accessory gland secretions alters the transcriptomic response of the endometrium in cattle.

In cattle, mating to intact, but not vasectomised, bulls has been shown to modify the endometrial transcriptome, suggesting an important role of sperm in the modulation of the uterine environment in this species. However, it is not clear whether these changes are driven by intrinsic sperm factors, or by factors of accessory gland (AG) origin that bind to sperm at ejaculation. Therefore, the aim of the present study was to determine whether ejaculated sperm, which are suspended in the secretions of the AGs, elicit a different endometrial transcriptomic response than epididymal sperm, which have never been exposed to AG factors. To this end, bovine endometrial explants collected from heifers in oestrus were (co-)incubated for 6 h alone (control), or with epididymal sperm or ejaculated sperm, following which transcriptomic changes in the endometrium were evaluated. Epididymal sperm elicited a more dramatic endometrial response than ejaculated sperm, in terms of the number of differentially expressed genes (DEGs). Indeed, RNA-sequencing data analysis revealed 1912 DEGs in endometrial explants exposed to epididymal sperm compared with control explants, whereas 115 DEGs were detected between endometrial explants exposed to ejaculated sperm in comparison to control explants. The top pathways associated with genes upregulated by epididymal sperm included T cell regulation and TNF, NF-KB and IL17 signalling. Interestingly, ejaculated sperm induced downregulation of genes associated with T cell immunity and Th17 differentiation, and upregulation of genes involved in NF-KB signalling, in comparison to epididymal sperm. These data indicate that factors of AG origin modulate the interaction between sperm and the endometrium in cattle.

Sexual behaviour of young rams is improved and less stressful after intranasal administration of oxytocin.

The aim of this study was to determine if intranasal administration of oxytocin modifies sexual behaviour and the stress response in young rams during sexual tests with ewes in oestrus. Ten rams were used in a cross-over design. At Day 0, the control group (CG, n = 5) received isotonic saline spray intranasally, and the treated group (OTG, n = 5) received oxytocin (24 IU) intranasally, 40 min before the sexual test. At Day 15, the groups were reversed. In each sexual test (20 min) with an oestrous-induced ewe, the sexual behaviour of the young rams was recorded. Serum cortisol concentrations were determined before and after the test. Less flehmen was observed in the OTG, but mounts with ejaculation were increased. The OTG presented lower serum cortisol concentration than the CG. In conclusion, intranasal administration of oxytocin modified the sexual behaviour of rams, evidenced by a decrease in flehmen behaviour and an increase in mounts with ejaculation, making sexual activity more efficacious. In addition, the treatment decreased the stress response of the rams in the sexual tests. Therefore, intranasal administration of oxytocin could be used to increase sexual activity in rams, and with less stress, providing better welfare conditions.

The rs6296 polymorphism in the 5-HT1b receptor in Dutch men with lifelong premature ejaculation: a genetic case-control association study.

BACKGROUND: Lifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders. AIM: In this study we sought to evaluate the genetic association between the rs6296 polymorphism of the 5-HT1b receptor and intravaginal ejaculation latency times (IELTs) in men with LPE compared with men in a control group. METHODS: This study was a prospective observational genetic case-control association study. The LPE definition of the International Society for Sexual Medicine (ISSM) 2013 was used. Patients were recruited in 2005-2009 while attending the department of Neurosexology, HagaZiekenhuis, the Netherlands. We obtained IELTs with the stopwatch method. Polymerase chain reaction (PCR) was used for genotyping rs6296. A randomly selected group of European Caucasian men from the 1000GENOMES project was used as a control group. OUTCOMES: Study outcomes included results of comparisons of analysis of variance (ANOVA) tests between genotypes and IELTs in study participants, genotypes of cases and controls determined with the chi-square test, and expressions of allelotype- and genotype-specific risks for LPE determined with odds ratios. RESULTS: In total, 67 men with LPE were included in this study. The geometric mean (SD) IELT was 32.0 (27.4) seconds and was non-normally distributed. Genotype frequencies consisted of 29 (43.3%) GG, 31 (46.3%) GC, and 7(10.4%) CC individuals in the LPE group. Log-transformed IELTs were not statistically significant (per ANOVA tests) in men with GG, GC, or CC genotypes (P = .54). Genotype frequencies consisted of 16 (6.6%) GG; 93 (38.8%) GC, and 131 (54.6%) CC individuals in the control group (n = 240). Significant differences were found when comparing allele (P = 1.02e-17) and genotype (P = 3.22e-16) frequencies in cases and controls using a chi-square test. A statistically significant increased risk for LPE was found for carriers of the G allele (OR 5.62; 95% CI 4.13-9.42). Statistically significant risks were also found for the CG genotype (OR 6.24; 95% CI 2.63-14.77) and the GG genotype (OR 33.92; 95% CI 12.79-89.93). CLINICAL IMPLICATIONS: By investigating polymorphisms in target genes the neuro-pathophysiology of LPE could be further elaborated, potentially leading to more effective treatment. STRENGTHS AND LIMITATIONS: This is to our knowledge the first study investigating rs6296 with regard to LPE. By using a strict definition for LPE (ISSM 2013) and using the stopwatch method for measuring IELTs, bias in selection of true LPE patients will be relatively low. This study is limited by a relatively small study population and the lack of IELT data in the control group. CONCLUSIONS: This study shows a genetic association in rs6296 in men with LPE compared with healthy controls. This result warrants attempted replication in future studies.

Impact of cognitive behavioral therapy on premature ejaculation patients: A prospective, randomized controlled trial protocol.

BACKGROUND: Premature ejaculation (PE) is one of the most common male sexual dysfunctions, with a prevalence of about 4%-39% in the Chinese population. Studies have shown that a variety of biological factors can lead to premature ejaculation, such as central nervous system disorders, hypersensitivity of the penis head, and psychological factors. Based on clinical experience, psychological counseling and education of patients and partners should be ranked as the first priority when treating PE. Cognitive behavioral therapy (CBT) addresses emotional, behavioral, and cognitive disorders by altering beliefs and actions. It has also been demonstrated to be clinically useful in treating a number of diseases. The purpose of this trial is to evaluate the efficacy of a mobile-based CBT intervention on patients with PE compared to conventional routine treatment. METHODS: This study is a prospective randomized controlled trial that will be conducted from May 2023 to Dec 2024 at ten hospitals, primarily including the First Affiliated Hospital of Sun Yat-sen University with an 8-week follow-up. The clinical trial central randomization system will be used to create and implement the specific randomization method. Baseline data of both groups will be measured and collected. The premature ejaculation diagnostic tool (PEDT) and the female sexual distress scale-revised for premature ejaculation (FSDS-R-PE) will be collected on the first day, 28±2 days, and 56±2 days during the intervention period, and the intravaginal ejaculatory latency time (IELT) will be measured in both groups. The Shapiro-Wilk test will be used for normality testing. Pearson correlation analysis will be used for correlation analysis. Differences between groups will be compared using analysis of variance or exact probability calculations. DISCUSSION: This study will investigate the effect of a mobile-based CBT intervention on patients with PE. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070581).

Male responses to sperm competition risk associated with increased macronutrient intake and reduced lifespan.

Increased expenditure on the ejaculate is a taxonomically widespread male response to sperm competition. Increased ejaculate expenditure is assumed to come at a cost to future reproduction, otherwise males should always invest maximally. However, the life-history costs of strategic ejaculation are not well documented. Macronutrient intake is known to affect the trade-off between reproduction and lifespan. Intakes of protein and carbohydrate that maximize reproduction often differ from those that maximize lifespan. Here, we asked whether strategic expenditure on the ejaculate by male crickets, Teleogryllus oceanicus, is mediated by macronutrient intake, and whether it comes at a cost of reduced lifespan. Males were exposed to rival song throughout their lifespan or were held in a silent non-competitive environment. Males exposed to song had a higher intake of both protein and carbohydrate, they reached adulthood sooner, produced ejaculates of higher quality, and died sooner than males living in a silent environment. Our findings provide a rare example of both the mechanisms and life-history costs associated with strategic ejaculation.

Altered reward processing in patients with lifelong premature ejaculation.

Given that sexual behavior is usually pleasurable and highly rewarding, it is surprising that there is as yet no known research to empirically assess how premature ejaculation (PE) patients respond to the rewarding aspect of sexual behavior. This study was designed to address this issue by evaluating how these men respond to the anticipation and hedonic experience of sexual rewards in comparison to non-sexual rewards. Thirty lifelong PE patients and thirty healthy controls (HCs) performed the incentive delay task manipulating both erotic and monetary rewards. Compared to HCs, lifelong PE patients exhibited significantly faster RTs to erotic cues than to monetary cues during reward anticipation. Meanwhile, hedonic experience ratings after obtaining the actual reward showed that erotic rewards were rated as more pleasant than monetary rewards only by lifelong PE patients, which was driven by a decreased sensitivity to experienced monetary rewards in lifelong PE patients compared to HCs. These findings indicate the existence of dysfunctional reward processing in lifelong PE patients, which is characterized by increased incentive motivation elicited by sexual cues and reduced hedonic impact of nonsexual rewards. This study may offer an insightful clue regarding how PE is related to the abnormal regulation of the rewarding aspect of sexual behavior.

Serotonin neurons in mating female mice are activated by male ejaculation.

Sexual stimulation triggers changes in female physiology and behavior, including sexual satiety and preparing the uterus for pregnancy. Serotonin (5-HT) is an important regulator of reproductive physiology and sexual receptivity, but the relationship between sexual stimulation and 5-HT neural activity in females is poorly understood. Here, we investigated dorsal raphe 5-HT neural activity in female mice during sexual behavior. We found that 5-HT neural activity in mating females peaked specifically upon male ejaculation and remained elevated above baseline until disengagement. Artificial intravaginal mechanical stimulation was sufficient to elicit increased 5-HT neural activity but the delivery of ejaculatory fluids was not. Distal penis expansion ("penile cupping") at ejaculation and forceful expulsion of ejaculatory fluid each provided sufficient mechanical stimulation to elicit 5-HT neuron activation. Our study identifies a female ejaculation-specific signal in a major neuromodulatory system and shows that intravaginal mechanosensory stimulation is necessary and sufficient to drive this signal.

Ejaculation physiology and dysfunction after BPH surgery: the role of the new MISTs.

BACKGROUND: Human ejaculation can be defined as a complex and still largely unknown function. Since decades, Benign Prostatic Hyperplasia (BPH) surgery-associated loss of antegrade ejaculation has been reported as a bother by many patients. New technologies and modified surgical techniques were developed, to reduce the impact of ejaculatory dysfunction on patients' perceived quality of life. Recently, the emerging of the new Minimally Invasive Surgical Techniques (MISTs) empowered the urological surgeons with the technological means to introduce the ejaculation-sparing principles into everyday clinical practice. METHODS: Our paper was conceived as a state-of-the-art analysis about the anatomical and physiological premises of the human ejaculation and their clinical application in the field of ejaculation-sparing surgery for the treatment of Lower Urinary Tract Symptoms (LUTS). Moreover, we proposed an innovative physiological model for antegrade ejaculation. RESULTS: We analysed the elements of the "ejaculatory apparatus" from an anatomical point of view. We investigated the physio-pathological models of the human ejaculation, from the classical "combustion chamber" paradigm to the new evidences by which it could be overcome. Finally, we provided a synthetic literature review about the ejaculation-sparing techniques for BPH surgery. Particularly, we distinguished them between classical techniques, modified for ejaculation-preserving purposes, and the new MISTs, characterized by the introduction of new technologies and different treatment modalities. CONCLUSIONS: Modified surgical techniques and new technologies opened new perspectives about human ejaculation. Previously established functional paradigms were questioned and overcome by recent clinical evidence. The new MISTs gained a prominent role in the process, opening a whole new era for BPH surgery.

The sensitivity difference between the glans penis and penile shaft in primary premature ejaculation.

The penis is a vital organ of perception that transmits perceived signals to ejaculation-related centers. The penis consists of the glans penis and penile shaft, which differ considerably in both histology and innervation. This paper aims to investigate whether the glans penis or the penile shaft is the main source of sensory signals from the penis and whether penile hypersensitivity affects the whole organ or only part of it. The thresholds, latencies, and amplitudes of somatosensory evoked potentials (SSEPs) were recorded in 290 individuals with primary premature ejaculation using the glans penis and penile shaft as the sensory areas. The thresholds, latencies, and amplitudes of SSEPs from the glans penis and penile shaft in patients were significantly different (all P < 0.0001). The latency of the glans penis or penile shaft was shorter than average (indicating hypersensitivity) in 141 (48.6%) cases, of which 50 (35.5%) cases were sensitive in both the glans penis and penile shaft, 14 (9.9%) cases were sensitive in the glans penis only, and 77 (54.6%) cases were sensitive in the penile shaft only (P < 0.0001). There are statistical differences in the signals perceived through the glans penis and the penile shaft. Penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive. We classify penile hypersensitivity into three categories, namely, glans penis, penile shaft, and whole-penis hypersensitivity, and we propose the new concept of penile hypersensitive zone.

A novel on-demand therapy for lifelong premature ejaculation using a miniature transperineal electrical stimulator-the vPatch: an as-treated analysis.

BACKGROUND: While premature ejaculation (PE) is a common and disturbing sexual dysfunction in men, current available treatment modalities have limited efficacy and low treatment adherence. AIM: To assess the feasibility, safety, and efficacy of the vPatch, a miniaturized on-demand perineal transcutaneous electrical stimulation device for treating PE. METHODS: This prospective bicenter international first-in-human clinical study consisted of 2 arms, was sham controlled, and had a randomized double-blind design. In terms of statistical power calculation, 59 patients aged 21 to 56 years (mean ± SD, 39.8 ± 9.28) with lifelong PE were included. During the initial visit, intravaginal ejaculatory latency time (IELT) was measured over a 2-week run-in period. Eligibility was confirmed in visit 2, based on IELT values, medical and sexual history, and patients' individualized sensory and motor activation thresholds during perineal stimulation with the vPatch. Patients were randomized to the active (vPatch) and sham device groups in a 2:1 ratio, respectively. The vPatch device's safety profile was determined by comparing the incidence of treatment-emergent adverse events. During visit 3, IELTs, Clinical Global Impression of Change scores, and Premature Ejaculation Profile questionnaire outcomes were recorded. Primary end points assessed vPatch device efficacy as mean change in geometric mean IELT; each person was compared with himself, with and without the device, and the sham group was compared with the active group. OUTCOMES: Outcomes included changes in IELT and Premature Ejaculation Profile before and after treatment, last visit Clinical Global Impression of Change scores, and vPatch safety profile. RESULTS: Of 59 patients, 51 completed the study: 34 in the active group and 17 in the sham group. The baseline geometric mean IELT significantly increased from 67 to 123 seconds (P < .01) in the active group, as compared with an insignificant increase from 63 to 81 seconds (P = .17) in the sham group. The increase in mean IELT in the active group was significantly higher than in the sham group (56 vs 18 seconds, P = .01). IELT significantly increased by 3.1 times in the active vs sham group. The mean ratio of fold change (active:sham) was 1.4, significantly different from 1.0 (P = .02). No serious adverse events were reported. CLINICAL IMPLICATIONS: Therapeutic use of the vPatch during coitus may become an on-demand, noninvasive, and drug-free treatment for PE. STRENGTHS AND LIMITATIONS: To our knowledge, this is the first rigorous study investigating whether transcutaneous electrical stimulation during coitus could improve the symptoms of men with lifelong PE. The study is limited by the small number of patients, the exclusion of patients with acquired PE, the short-term follow up, and the use of a device based on a theoretic mechanism of action. CONCLUSION: We demonstrated the possibility to treat lifelong PE by prolonging coitus on demand, using electric stimulation of ejaculation muscles with the vPatch.Clinical trial registration: NCT03942367 (ClinicalTrials.gov).

Hyperexcited limbic neurons represent sexual satiety and reduce mating motivation.

Transient sexual experiences can have long-lasting effects on behavioral decisions, but the neural coding that accounts for this change is unclear. We found that the ejaculation experience selectively activated estrogen receptor 2 (Esr2)-expressing neurons in the bed nucleus of the stria terminalis (BNST)-BNSTEsr2-and led to persistent decreases in firing threshold for days, during which time the mice displayed sexual satiety. Inhibition of hyperexcited BNSTEsr2 elicited fast mating recovery in satiated mice of both sexes. In males, such hyperexcitability reduced mating motivation and was partially mediated by larger HCN (hyperpolarization-activated cyclic nucleotide-gated) currents. Thus, BNSTEsr2 not only encode a specific mating action but also represent a persistent state of sexual satiety, and alterations in a neuronal ion channel contribute to sexual experience-dependent long-term changes to mating drive.

Urethral pressure profile during ejaculation in men with spinal cord injury.

Ejaculation is often impaired in men with spinal cord injury (SCI). The aim of this prospective study was to assess sequence of sphincteric events and ejaculation dyssynergia during penile vibratory stimulation (PVS) in SCI men. Simultaneous recordings of bladder, bladder neck, prostate and external urethral sphincter pressures were performed using a microtip catheter with 5 pressure transducers. Between 2017 and 2019, ten men participated in the study for a total of 17 procedures. Antegrade ejaculation was found in three men with upper motor neuron (UMN) lesion. Ejaculation was preceded by a progressive increase in all urethral pressures, reaching sustained (plateau) or intermittent peaks above 220 cm H20. Antegrade ejaculation occurred after intermittent decreases in pressure at the external urethral sphincter level down to 100 cm H20, while the pressure at the bladder neck remained high (up to or above 220 cm H20). PVS was ineffective in eliciting ejaculation in seven men. In the five patients with UMN lesions, PVS elicited an increase in the external urethral sphincter pressure (mean 51 cm H20), while there was no pressure change in the two patients with lower motor neuron lesions. Due to lack of enough retrograde retrieval attempts, the hypothesis of ejaculatory dyssynergia could not be verified.

Understanding and treating ejaculatory dysfunction in men with diabetes mellitus.

Diabetes mellitus is a rapidly rising metabolic disorder with important systemic complications. Global figures have demonstrated the prevalence of diabetes mellitus has almost quadrupled from 108 million in 1980 to 422 million in 2014, with a current prevalence of over 525 million. Of the male sexual dysfunction resulting from diabetes mellitus, significant focus is afforded to erectile dysfunction. Nevertheless, ejaculatory dysfunction constitutes important sexual sequelae in diabetic men, with up to 35%-50% of men with diabetes mellitus suffering from ejaculatory dysfunction. Despite this, aspects of its pathophysiology and treatment are less well understood than erectile dysfunction. The main disorders of ejaculation include premature ejaculation, delayed ejaculation, anejaculation and retrograde ejaculation. Although ejaculatory dysfunction in diabetes mellitus can have complex multifactorial aetiology, understanding its pathophysiological mechanisms has facilitated the development of therapies in the management of ejaculatory dysfunction. Most of our understanding of its pathophysiology is derived from diabetic animal models; however, observational studies in humans have also provided useful information in elucidating important associative factors potentially contributing to ejaculatory dysfunction in diabetic men. These have provided the potential for more tailored treatment regimens in patients depending on the ejaculatory disorder, other co-existing sequelae of diabetes mellitus, specific metabolic factors as well as the need for fertility treatment. However, evidence for treatment of ejaculatory dysfunction, especially delayed ejaculation and retrograde ejaculation, is based on low-level evidence comprising small sample-size series and retrospective or cross-sectional studies. Whilst promising findings from large randomised controlled trials have provided strong evidence for the licensed treatment of premature ejaculation, similar robust studies are needed to accurately elucidate factors predicting ejaculatory dysfunction in diabetes mellitus, as well as for the development of pharmacotherapies for delayed ejaculation and retrograde ejaculation. Similarly, more contemporary robust data are required for fertility outcomes in these patients, including methods of sperm retrieval and assisted reproductive techniques in retrograde ejaculation.

The complexity of female orgasm and ejaculation.

The anatomy and physiology of the female orgasm are often neglected. The female orgasm is a normal psychophysiological function to all women, and some even can achieve ejaculation as part of the normal physiological response at the height of sexual arousal. The complexity of female sexuality requires a deep understanding of genital anatomy. The clitoris is the principal organ for female pleasure. The vaginal stimulation of the anterior vaginal wall led women to orgasm due to the stimulation of the clitourethrovaginal complex and not due to stimulation of a particular organ called the G spot in the anterior distal vaginal wall. Female ejaculation follows orgasm. It consists of the orgasmic expulsion of a smaller quantity of whitish fluid produced by the female prostate. Squirting can be differentiated from female ejaculation because it is the orgasmic transurethral expulsion of a substantial amount of diluted urine during sexual activity, and it is not considered pathological. The female orgasm is influenced by many aspects such as communication, emotional intimacy, long-standing relationship, adequate body image and self-esteem, proper touching and knowledge of the female body, regular masturbation, male sexual performance, male and female fertility, chronic pain, and capacity to engage in new sexual acts. Stronger orgasms could be achieved when clitoral stimulation, anterior vaginal wall stimulation, and oral sex is involved in the same sexual act.