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Nature Communications Jul 2022The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its...
The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.
Topics: Erectile Dysfunction; Humans; Male; Muscle, Smooth; Penile Erection; Penis; Transcriptome
PubMed: 35879305
DOI: 10.1038/s41467-022-31950-9 -
Andrologia Jul 2021The aim of the present study was to evaluate the size of the penis in flaccidity and in erection of Italian men. A total of 4,685 men living in Italy and who have been...
The aim of the present study was to evaluate the size of the penis in flaccidity and in erection of Italian men. A total of 4,685 men living in Italy and who have been visited at the Italian urology operating units were involved in the study between January 2019 and January 2020. Each patient was given details on how to measure their penis (erect length and circumference) in flaccidity and in erection, from the lower base to the distal penile tip. Mean (standard deviation [SD]) flaccid penis length was 9.47 (2.69), mean (SD) flaccid penis circumference was 9.59 (3.08), mean (SD) erect penis length was 16.78 (2.55) and mean (SD) erect penis circumference was 12.03 (3.82). At the linear regression analysis, height was associated with flaccid penis length (β = 0.04; p-value = .01), and erect penis length was (β = 0.05; p-value < .01) and erect penis circumference was (β = 0.06; p-value < .01). Height is proportional to the length of the penis in flaccidity and in erection, and to the circumference in erection. The increase in BMI leads to a reduction in the length of the erect penis, as well as weight gain reduces the length of the flaccid penis.
Topics: Humans; Italy; Male; Penile Erection; Penis; Regression Analysis
PubMed: 33748967
DOI: 10.1111/and.14053 -
Nature Communications Jun 2023Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of...
Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.
Topics: Animals; Humans; Male; Mice; Rats; Adrenomedullin; Erectile Dysfunction; Penile Erection; Penis; Retrospective Studies; YAP-Signaling Proteins; Transcriptional Coactivator with PDZ-Binding Motif Proteins
PubMed: 37353497
DOI: 10.1038/s41467-023-39009-z -
Asian Journal of Andrology 2016Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen,... (Review)
Review
Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido.
Topics: Aromatase; Estradiol; Germ Cells; Humans; Hypothalamo-Hypophyseal System; Leydig Cells; Libido; Male; Penile Erection; Sertoli Cells; Spermatogenesis; Testis; Testosterone
PubMed: 26908066
DOI: 10.4103/1008-682X.173932 -
The Journal of Sexual Medicine Jun 2015Accurate data regarding the size of the erect penis are of great importance to several disciplines working with male patients, but little high-quality research exists on...
INTRODUCTION
Accurate data regarding the size of the erect penis are of great importance to several disciplines working with male patients, but little high-quality research exists on the subject, particularly in different ethnic groups and for erect penis size.
AIM
The aim of this study was to create a nomogram of erect penile dimensions in a large sample of Middle Eastern men.
METHODS
A retrospective cohort study of 778 men (mean age 43.7; range 20-82) attending urological outpatient clinics in Saudi Arabia was conducted. Exclusion criteria were age under 18 years, a presenting complaint of small or short penis, Peyronie's disease or complaint of congenital curvature, clinical hypogonadism, and previous penile surgery or trauma.
MAIN OUTCOME MEASURES
Three erect penile dimensions following induction of erection using intracavernosal injection of Quadrimix.
RESULTS
Mean patient body mass index (BMI) was 29.09 (standard deviation [SD] 5.76). The mean suprapubic skin-to-penile tip erect length was 12.53 cm (SD 1.93); the mean erect length from the symphysis pubis to the penile tip was 14.34 cm (SD 1.86); and the mean erect shaft circumference was 11.50 cm (SD 1.74). A nomogram was constructed and statistical analysis performed, demonstrating a weak negative correlation between BMI and erect penile length measured from the suprapubic skin (r = -0.283, P < 0.000) but not from bone to tip, and a weak negative correlation between age and both erect penile length measurements (skin to tip r = -0.177, P < 0.0005; bone to tip r = -0.099, P = 0.006).
CONCLUSION
A nomogram for Middle Eastern men can be used as a standard when advising men with small penis anxiety. The importance of measuring erect size and allowing for infra-pubic fat interference in measurement is emphasized. We envisage that this tool can be used to educate and reassure concerned men about the size of their penises.
Topics: Adult; Body Mass Index; Humans; Male; Middle Aged; Nomograms; Organ Size; Outcome Assessment, Health Care; Penile Erection; Penis; Pubic Bone; Retrospective Studies; Saudi Arabia
PubMed: 25904106
DOI: 10.1111/jsm.12894 -
BMJ (Clinical Research Ed.) Dec 2023To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile...
OBJECTIVE
To investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.
DESIGN
Two sample cis-mendelian randomisation study.
SETTING
Summary data on genetic associations obtained from the International Consortium for Blood Pressure and UK Biobank.
PARTICIPANTS
Individuals of European ancestry from the International Consortium for Blood Pressure (n=757 601) for estimating PDE5 inhibition (using the surrogate biomarker of diastolic blood pressure reduction), and UK Biobank (n=211 840) for estimating the fertility, sexual behaviour, and subjective wellbeing outcomes in male participants.
INTERVENTION
Genetically proxied PDE5 inhibition.
MAIN OUTCOME MEASURES
Number of children fathered, number of sexual partners, probability of never having had sexual intercourse, and subjective wellbeing.
RESULTS
Genetically proxied PDE5 inhibition was associated with male participants having 0.28 (95% confidence interval 0.16 to 0.39) more children (false discovery rate corrected P<0.001). This association was not identified in female participants. No evidence was found of an association between genetically proxied PDE5 inhibition and number of sexual partners, probability of never having had sexual intercourse, or self-reported wellbeing in male participants.
CONCLUSIONS
The findings of this study provide genetic support for PDE5 inhibition potentially increasing the number of children fathered by male individuals. Absence of this association in female participants supports increased propensity for sustained and robust penile erections as a potential underlying mechanism. Further studies are required to confirm this, however, and these findings should not promote indiscriminate use of PDE5 inhibitors, which can also have harmful adverse effects.
Topics: Child; Male; Humans; Female; Erectile Dysfunction; Sexual Behavior; Penile Erection; Fertility; Biomarkers
PubMed: 38086555
DOI: 10.1136/bmj-2023-076197 -
American Journal of Men's Health 2022We conducted a meta-analysis to evaluate the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). From... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-Analysis of 16 Randomized Controlled Trials of Clinical Outcomes of Low-Intensity Extracorporeal Shock Wave Therapy in Treating Erectile Dysfunction.
We conducted a meta-analysis to evaluate the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). From July 2011 to June 2021, we finally selected 16 randomized controlled trials (RCTs) including 1,064 participants to evaluate the efficacy of LI-ESWT in the treatment of ED from PubMed, EMBASE, and Cochrane databases. The data are analyzed by Review Manager Version 5.4. Fifteen articles mentioned International Index of Erectile Function (IIEF), in the follow-up of 1 month (mean difference [MD] = 3.18, 95% confidence interval [CI] = [1.38, 4.98], = .0005), 3 months (MD = 3.01, 95% CI = [2.04, 3.98], < .00001), and 6 months (MD = 3.20, 95% CI = [2.49, 3.92], < .00001). After treatment, the improvement of IIEF in the LI-ESWT group was better than that in the control group. Besides, eight of the 16 trials provided data on the proportion of patients with baseline Erectile Hardness Score (EHS) ≤ 2 improved to EHS ≥ 3. The LI-ESWT group was also significantly better than the placebo group (odds ratio [OR] = 5.07, 95% CI = [1.78, 14.44], = .002). The positive response rate of Questions 2 and 3 of the Sexual Encounter Profile (SEP) was not statistically significant (SEP2: OR = 1.27, 95% CI = [0.70, 2.30], = .43; SEP3: OR = 4.24, 95% CI = [0.67, 26.83], = .13). The results of this meta-analysis suggest that treatment plans with an energy density of 0.09 mJ/mm and pulses number of 1,500 to 2,000 are more beneficial to IIEF in ED patients. In addition, IIEF improvement was more pronounced in patients with moderate ED after extracorporeal shockwave therapy.
Topics: Erectile Dysfunction; Extracorporeal Shockwave Therapy; Humans; Male; Penile Erection; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35319291
DOI: 10.1177/15579883221087532 -
F1000Research 2018Priapism is an uncommon urological emergency that can lead to permanent impotence if prompt presentation and medical intervention is not performed. It is a breakdown of... (Review)
Review
Priapism is an uncommon urological emergency that can lead to permanent impotence if prompt presentation and medical intervention is not performed. It is a breakdown of the usual physiological mechanisms controlling penile tumescence and detumescence, leading to a prolonged penile erection (>4 hours) that is unrelated to sexual stimulation. Currently, there are three accepted subtypes: ischaemic, non-ischaemic, and stuttering priapism, which is also known as recurrent ischemic priapism. The aim of treatment is the immediate resolution of the painful erection and the preservation of cavernosal smooth muscle function in order to prevent cavernosal fibrosis, which can lead to penile shortening and permanent erectile dysfunction.
PubMed: 29375820
DOI: 10.12688/f1000research.12828.1 -
PloS One 2015Women's preferences for penis size may affect men's comfort with their own bodies and may have implications for sexual health. Studies of women's penis size preferences...
Women's preferences for penis size may affect men's comfort with their own bodies and may have implications for sexual health. Studies of women's penis size preferences typically have relied on their abstract ratings or selecting amongst 2D, flaccid images. This study used haptic stimuli to allow assessment of women's size recall accuracy for the first time, as well as examine their preferences for erect penis sizes in different relationship contexts. Women (N = 75) selected amongst 33, 3D models. Women recalled model size accurately using this method, although they made more errors with respect to penis length than circumference. Women preferred a penis of slightly larger circumference and length for one-time (length = 6.4 inches/16.3 cm, circumference = 5.0 inches/12.7 cm) versus long-term (length = 6.3 inches/16.0 cm, circumference = 4.8 inches/12.2 cm) sexual partners. These first estimates of erect penis size preferences using 3D models suggest women accurately recall size and prefer penises only slightly larger than average.
Topics: Adolescent; Adult; Aged; Choice Behavior; Female; Humans; Male; Middle Aged; Models, Anatomic; Organ Size; Penile Erection; Penis; Sexual Partners; Young Adult
PubMed: 26332467
DOI: 10.1371/journal.pone.0133079 -
The World Journal of Men's Health Apr 2016Priapism is defined as a persistent and painful erection lasting longer than four hours without sexual stimulation. Based on episode history and pathophysiology,... (Review)
Review
Priapism is defined as a persistent and painful erection lasting longer than four hours without sexual stimulation. Based on episode history and pathophysiology, priapism is classified into three subtypes: ischemic (low-flow), non-ischemic (high-flow), and stuttering priapism. Ischemic priapism is characterized by a persistent, painful erection with remarkable rigidity of the corpora cavernosa caused by a disorder of venous blood outflow from this tissue mass, and is similar to penile compartment syndrome. Stuttering priapism is characterized by a self-limited, recurrent, and intermittent erection, frequently occurring in patients with sickle cell disease. Non-ischemic priapism is characterized by a painless, persistent nonsexual erection that is not fully rigid and is caused by excess arterial blood flow into the corpora cavernosa. Because ischemic and non-ischemic priapism differ based on emergency status and treatment options, appropriate discrimination of each type of priapism is required to initiate adequate clinical management. The goal of management of priapism is to achieve detumescence of the persistent penile erection and to preserve erectile function after resolution of the priapism. To achieve successful management, urologists should address this emergency clinical condition. In the present article, we review the diagnosis and clinical management of the three types of priapism.
PubMed: 27169123
DOI: 10.5534/wjmh.2016.34.1.1