Review

Authors: Robert C Dean, Tom F Lue

This article reviews the physiology of penile erection, the components of erectile function, and the pathophysiology of erectile dysfunction. The molecular and clinical under-standing of erectile function continues to gain ground at a particularly fast rate. Advances in gene discovery have aided greatly in working knowledge of smooth muscle relaxation/contraction pathways. The understanding of the nitric oxide pathway has aided not only in the molecular understanding of the tumescence but also greatly in the therapy of erectile dysfunction.

Topics: Erectile Dysfunction; Hemodynamics; Humans; Male; Muscle Contraction; Muscle, Smooth; Penile Erection; Penis

PubMed: 16291031
DOI: 10.1016/j.ucl.2005.08.007

Authors: LiangYu Zhao, Sha Han, HengChuan Su...

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

Authors: Marina Di Mauro, Camilla Tonioni, Andrea Cocci...

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

Review

Authors: B A Akorede, S A Hassan, R E Akhigbe...

Penile erection (PE) is a hemodynamic event that results from a neuroendocrine process, and it is influenced by the cardiovascular status of the patient. However, it may also modulate an individual's cardiovascular events. The present study provides the mechanisms involved in the association of PE and cardiovascular function. Erection upsurges the cardiac rate, blood pressure, and oxygen uptake. Sex-enhancing strategies, such as phosphodiesterase inhibitors, alprostadil, and testosterone also promote vasodilatation and cardiac performance, thus preventing myocardial infarction. More so, drugs that are used in the treatment of hypertensive heart diseases (such as angiotensin system inhibitors and β-blockers) facilitate vasodilatation and PE. These associations have been linked with nitric oxide- and testosterone-dependent enhancing effects on the vascular endothelium. In addition, impaired cardiovascular function may negatively impact PE; therefore, impaired PE may be a pointer to cardiovascular pathology. Hence, evaluation of the cardiovascular status of an individual with erectile dysfunction (ED) is essential. Also, employing strategies that are used in maintaining optimal cardiac function may be useful in the management of ED.

Topics: Male; Humans; Penile Erection; Erectile Dysfunction; Hypertension; Nitric Oxide; Testosterone

PubMed: 38567396
DOI: 10.1080/13685538.2024.2336627

Review

Authors: Michael Schulster, Aaron M Bernie, Ranjith Ramasamy...

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

Review

Authors: Neelesh Malviya, Sanjay Jain, Vipin Bihari Gupta...

An aphrodisiac is a type of food or drink that has the effect of making those who eat or drink it more aroused in a sexual way. Aphrodisiacs can be categorized according to their mode of action into three groups: substances that increase libido (i.e., sexual desire, arousal), substances that increase sexual potency (i.e., effectiveness of erection) and substances that increase sexual pleasure. Some well-known aphrodisiacs are Tribulus terrestrins, Withania somnifera, Eurycoma longifolia, Avena sativa, Ginko biloba, and Psoralea coryifolia. Ethnobotanical surveys have indicated a large number of plants as aphrodisiacs. The paper reviews the recent scientific validation on traditionally used herbal plants as aphrodisiac herbs for the management of sexual disorder erectile dysfunction.

Topics: Aphrodisiacs; Arousal; Erectile Dysfunction; Humans; Male; Penile Erection; Phytotherapy; Plant Preparations; Sexual Behavior; Sexual Dysfunction, Physiological

PubMed: 21485695
DOI: No ID Found

Authors: Mohamad Habous, Alaa Tealab, Ben Williamson...

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

Authors: Arthur L Burnett

This literature review presents two unusual and mystifying disorders of penile erection: painful nocturnal erections, alternatively termed sleep-related painful erections, and idiopathic stuttering priapism, a variant of recurrent ischemic priapism in which no cause is discernible. The disorders are closely related although they are distinct clinically and pathologically. The main subject areas of discussion are recognition, clinical evaluation and management although current concepts surrounding their causes and mechanisms are also addressed. It is acknowledged that despite the perceived rarities of these disorders they are impactful in terms of their disease profiles and consequences. Future advances in their management will require continued development of evidence-based treatments.

Topics: Humans; Male; Penile Erection; Priapism; REM Sleep Parasomnias; Rare Diseases

PubMed: 32033724
DOI: 10.1016/j.fertnstert.2019.11.013

Authors: Mintao Ji, Dongsheng Chen, Yinyin Shu...

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

Authors: Yang Xiong, Feng Qin, Shanzun Wei...

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock-out mice (ADA, A1, A2a, A2b, and A3), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine-induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age-related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus-induced ED. In single-cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock-out abolishes adenosine-induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF-1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60-6583 improves erectile function and down-regulates HIF-1α and TGF-β. Administering Dipyridamole (40 mg Kg) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine-induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

Topics: Animals; Humans; Male; Mice; Rats; Adenosine; Disease Models, Animal; Erectile Dysfunction; Mice, Knockout; Penile Erection; Penis; Rats, Sprague-Dawley; Receptor, Adenosine A2B

PubMed: 38874549
DOI: 10.1002/advs.202306514