Activity of the external urethral sphincter evoked by genital stimulation in male rats.

AIMS: To determine whether the external urethral sphincter (EUS) fasciculi of male rats respond to the mechanical stimulation of genital structures and to characterize the pattern of the electromyographic (EMG) activity of the three regions of the EUS: the cranial (CrEUS), the medial (MeEUS) and the caudal (CaEUS). METHODS: Electromyographic signals were recorded from the CrEUS, MeEUS and CaEUS regions of the male rat's EUS, before, during and after the mechanical stimulation of the urogenital structures. RESULTS: The CrEUS, MeEUS and CaEUS regions responded when brushing and squeezing the foreskin and glans as well as to penile and prostatic urethral distension. The CaEUS EMG amplitude (P < 0.01) and frequency (P < 0.05) were lower in comparison to the CrEUS and MeEUS responses to the mechanical stimulation. In addition, the CaEUS was characterized by a short or no afterdischarge. In contrast, the CrEUS and MeEUS responded by presenting a long discharge after the penile or prostatic urethral distension. CONCLUSIONS: The activity of the EUS is modulated by both, cutaneous and visceral genitourinary stimuli, with motor units being activated by mechanoreceptors located in the foreskin, glans, bladder, and urethra. The CrEUS, MeEUS and CaEUS have differential EMG patterns, indicating that the EUS consists of three anatomically and functionally different regions. Precise coordination in the muscular activity of these regions may be crucial for the control of male expulsive urethral functions, i.e., during voiding and ejaculation. Neurourol. Urodynam. 35:914-919, 2016. © 2015 Wiley Periodicals, Inc.

Terminal innervation of the male genitalia, cutaneous sensory receptors of the male foreskin.

PURPOSE: Understanding the types of sensory nerve termini within the glabrous skin of the human male foreskin could throw light on surgical outcomes and therapeutic possibilities for the future. Various receptor types sense changes in temperature, position, pressure, pain, light touch, itch, burning and pleasurable sexual sensations. Similarities and differences in innervation characteristics and density might become apparent when the glans penis is compared with homologous structures in the female genitalia. The aim of this study is to document the presence and characteristics of cutaneous sensory receptors in the human penile foreskin using a histopathological study of the nerve termini to achieve a more complete understanding of sensory experiences. METHODS: Foreskin samples were obtained from ten boys (aged 1-9 years) who had undergone circumcision. Informed consent was obtained from the parent/legal guardian. The samples were examined after modified Bielschowsky silver impregnation of neural tissue, and immunocytochemistry against gene protein product (PGP) 9.5 and neuron-specific enolase (NSE). RESULTS: PGP 9.5 appeared to be the most sensitive neural marker. Free nerve endings were identified in the papillary dermis visualized as thin fibers, mostly varicose, with either branched or single processes, either straight or bent. Two types of sensory corpuscle were identified: capsulated and non-capsulated. Meissner-like corpuscles were located in the papillary dermis. Capsulated corpuscles resembled typical Pacinian corpuscles, comprising a single central axon surrounded by non-neural periaxonic cells and lamellae. The capsulated corpuscles were strongly positive for PGP 9.5 and NSE. CONCLUSIONS: Free nerve endings, Meissner's corpuscles and Pacinian corpuscles are present in the human male foreskin and exhibit characteristic staining patterns.

Immunohistochemical evaluation of androgen receptor and nerve structure density in human prepuce from patients with persistent sexual side effects after finasteride use for androgenetic alopecia.

Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (AGA). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against AGA. Cases were 8 males (aged 29-43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23-49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues.

Cutaneous corpuscular receptors of the human glans clitoris: descriptive characteristics and comparison with the glans penis.

INTRODUCTION: The female genital sensory pathways that initiate sexual arousal reflexes begin with cutaneous corpuscular receptors in the glabrous genital skin, including those of the glans clitoris. AIM: The aim of this study is to characterize the corpuscular receptors of the glans clitoris. In addition, we compared basic features with the receptors of the glans penis. MAIN OUTCOME MEASURE: Number of stained receptors. METHODS: Five cadaveric vulvectomy specimens and four cadaveric penile specimens were used. They were serially sectioned and stained with hematoxylin and eosin. Selected blocks were stained with Masson's trichrome, and immunohistochemical staining was done with neuronal markers S-100 and neurofilament. RESULTS: Using the three stains, we identified an abundance of corpuscular receptors within the glans clitoris, as compared with the surrounding prepuce. These receptors were of varied arrangements, situated in the subepithelial tissues of the glans clitoris. They were indistinguishable from the receptors of the glans penis. The number of receptors per 100× high-powered field ranged from 1 to 14, whereas the receptor density in the glans penis ranged from 1 to 3. A second type of receptor, the Pacinian corpuscle, was identified within the suspensory ligament along the trunks of the dorsal nerve but not within the glans itself. CONCLUSIONS: The glans clitoris is densely innervated with cutaneous corpuscular receptors, and these receptors are morphologically similar to the corpuscular receptors of the glans penis. The glans clitoris has greater variability in receptor density compared with the glans penis.

Male circumcision decreases penile sensitivity as measured in a large cohort.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The sensitivity of the foreskin and its importance in erogenous sensitivity is widely debated and controversial. This is part of the actual public debate on circumcision for non-medical reason. Today some studies on the effect of circumcision on sexual function are available. However they vary widely in outcome. The present study shows in a large cohort of men, based on self-assessment, that the foreskin has erogenous sensitivity. It is shown that the foreskin is more sensitive than the uncircumcised glans mucosa, which means that after circumcision genital sensitivity is lost. In the debate on clitoral surgery the proven loss of sensitivity has been the strongest argument to change medical practice. In the present study there is strong evidence on the erogenous sensitivity of the foreskin. This knowledge hopefully can help doctors and patients in their decision on circumcision for non-medical reason. OBJECTIVES: To test the hypothesis that sensitivity of the foreskin is a substantial part of male penile sensitivity. To determine the effects of male circumcision on penile sensitivity in a large sample. SUBJECTS AND METHODS: The study aimed at a sample size of ≈1000 men. Given the intimate nature of the questions and the intended large sample size, the authors decided to create an online survey. Respondents were recruited by means of leaflets and advertising. RESULTS: The analysis sample consisted of 1059 uncircumcised and 310 circumcised men. For the glans penis, circumcised men reported decreased sexual pleasure and lower orgasm intensity. They also stated more effort was required to achieve orgasm, and a higher percentage of them experienced unusual sensations (burning, prickling, itching, or tingling and numbness of the glans penis). For the penile shaft a higher percentage of circumcised men described discomfort and pain, numbness and unusual sensations. In comparison to men circumcised before puberty, men circumcised during adolescence or later indicated less sexual pleasure at the glans penis, and a higher percentage of them reported discomfort or pain and unusual sensations at the penile shaft. CONCLUSIONS: This study confirms the importance of the foreskin for penile sensitivity, overall sexual satisfaction, and penile functioning. Furthermore, this study shows that a higher percentage of circumcised men experience discomfort or pain and unusual sensations as compared with the uncircumcised population. Before circumcision without medical indication, adult men, and parents considering circumcision of their sons, should be informed of the importance of the foreskin in male sexuality.

The effects of age at circumcision on premature ejaculation.

OBJECTIVE: The objective of this study was to analyze the effect of age at circumcision on premature ejaculation (PE). MATERIALS AND METHODS: The study included 40 healthy male controls and 40 male patients diagnosed as PE according to American Psychiatric Association criteria and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS) premature ejaculation subscale. The 2 groups were compared according to age at circumcision and GRISS score. RESULTS: The PE group and control group were sociodemographically similar, but differed in marital status. The groups differed in GRISS communication, degree of satisfaction, avoidance, sensuality, erectile dysfunction, and PE subscale scores. These differences only displayed a dysfunction in the degree of satisfaction and premature ejaculation subscales. The groups also differed in age at circumcision; accordingly, those that were circumcised at ≥7 years of age had higher GRISS scores and a higher risk of having PE than those that were circumcised at >7 years of age. CONCLUSION: Age at circumcision had an effect on PE; circumcision at ≥7 years of age was associated with an increase in the risk of PE, as compared to circumcision at >7 years of age. We think that families should have their boys circumcised before the age of 7 years and highly recommend that the procedure be performed within in the first 3 years of life.

Free nerve ending density on skin extracted by circumcision and its relation to premature ejaculation.

Many studies have shown that skin tissue extracted by circumcision can cause differences in sexual function, especially at the time of ejaculation. Sensitivity changes in penile skin and sexual satisfaction deriving from circumcision starting from premature ejaculation (PE) are discussed. Furthermore, most of these studies rely on questionnaires. Extracted free nerve endings (FNE) on the foreskin, which can detect temperature, mechanical stimuli (touch, pressure, stretch) or pain (nociception), have not been researched. Our aim is to determine FNEs in foreskin and the affects on sexual function, especially PE. This prospective study was done on adults who voluntarily applied to be circumcised between September 2010 and October 2011. The ejaculation latency times (ELT) before circumcision have been assessed, and a PE diagnostic tool (PEDT) form was filled out by the urologist according to the answers given by the volunteers. The proximal and distal ends of the foreskin were marked before circumcision, and the extracted foreskin was sent to the pathology department to determine FNEs. Twenty volunteers (average age 21.25 ± 0.44 years) were included in the study. The average ELT was 103.55 ± 68.39 seconds, and the average PE score was 4.35 ± 3.13. Proximal, middle, and distal tip nerve densities were compared. Proximal and distal (P = .003) and proximal and middle (P = .011) segments differed from each other, whereas middle and distal were similar (P = .119). There were not any correlations between PEDT scores and total nerve endings number (r = .018, P = .942). Also there were not any correlations between mean ELT and PEDT scores (r = .054, P = .822). The tissue extracted by circumcision has intensive FNEs, yet FNE intensity has no relation to PE.

Sensation and sexual arousal in circumcised and uncircumcised men.

INTRODUCTION: Research, theory, and popular belief all suggest that penile sensation is greater in the uncircumcised as compared with the circumcised man. However, research involving direct measurement of penile sensation has been undertaken only in sexually functional and dysfunctional groups, and as a correlate of sexual behavior. There are no reports of penile sensation in sexually aroused subjects, and it is not known how arousal affects sensation. In principle, this should be more closely related to actual sexual function. AIM: This study therefore compared genital and nongenital sensation as a function of sexual arousal in circumcised and uncircumcised men. METHODS: Twenty uncircumcised men and an equal number of age-matched circumcised participants underwent genital and nongenital sensory testing at baseline and in response to erotic and control stimulus films. Touch and pain thresholds were assessed on the penile shaft, the glans penis, and the volar surface of the forearm. Sexual arousal was assessed via thermal imaging of the penis. RESULTS: In response to the erotic stimulus, both groups evidenced a significant increase in penile temperature, which correlated highly with subjective reports of sexual arousal. Uncircumcised men had significantly lower penile temperature than circumcised men, and evidenced a larger increase in penile temperature with sexual arousal. No differences in genital sensitivity were found between the uncircumcised and circumcised groups. Uncircumcised men were less sensitive to touch on the forearm than circumcised men. A decrease in overall touch sensitivity was observed in both groups with exposure to the erotic film as compared with either baseline or control stimulus film conditions. No significant effect was found for pain sensitivity. CONCLUSION: These results do not support the hypothesized penile sensory differences associated with circumcision. However, group differences in penile temperature and sexual response were found.

Fine-touch pressure thresholds in the adult penis.

OBJECTIVE: To map the fine-touch pressure thresholds of the adult penis in circumcised and uncircumcised men, and to compare the two populations. SUBJECTS AND METHODS: Adult male volunteers with no history of penile pathology or diabetes were evaluated with a Semmes-Weinstein monofilament touch-test to map the fine-touch pressure thresholds of the penis. Circumcised and uncircumcised men were compared using mixed models for repeated data, controlling for age, type of underwear worn, time since last ejaculation, ethnicity, country of birth, and level of education. RESULTS: The glans of the uncircumcised men had significantly lower mean (sem) pressure thresholds than that of the circumcised men, at 0.161 (0.078) g (P = 0.040) when controlled for age, location of measurement, type of underwear worn, and ethnicity. There were significant differences in pressure thresholds by location on the penis (P < 0.001). The most sensitive location on the circumcised penis was the circumcision scar on the ventral surface. Five locations on the uncircumcised penis that are routinely removed at circumcision had lower pressure thresholds than the ventral scar of the circumcised penis. CONCLUSIONS: The glans of the circumcised penis is less sensitive to fine touch than the glans of the uncircumcised penis. The transitional region from the external to the internal prepuce is the most sensitive region of the uncircumcised penis and more sensitive than the most sensitive region of the circumcised penis. Circumcision ablates the most sensitive parts of the penis.