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The Journal of Sexual Medicine Apr 2021Current treatments for erectile dysfunction (ED) are ineffective in prostatectomy and diabetic patients due to cavernous nerve (CN) injury, which causes smooth muscle...
BACKGROUND
Current treatments for erectile dysfunction (ED) are ineffective in prostatectomy and diabetic patients due to cavernous nerve (CN) injury, which causes smooth muscle apoptosis, penile remodeling, and ED. Apoptosis can occur via the intrinsic (caspase 9) or extrinsic (caspase 8) pathway.
AIM
We examined the mechanism of how apoptosis occurs in ED patients and CN injury rat models to determine points of intervention for therapy development.
METHODS AND OUTCOMES
Immunohistochemical and western analyses for caspase 3-cleaved, caspase-8 and caspase-9 (pro and active forms) were performed in corpora cavernosal tissue from Peyronie's, prostatectomy and diabetic ED patients (n = 33), penis from adult Sprague Dawley rats that underwent CN crush (n = 24), BB/WOR diabetic and control rats (n = 8), and aged rats (n = 9).
RESULTS
Caspase 3-cleaved was observed in corpora cavernosa from Peyronie's patients and at higher abundance in prostatectomy and diabetic tissues. Apoptosis takes place primarily through the extrinsic (caspase 8) pathway in penis tissue of ED patients. In the CN crushed rat, caspase 3-cleaved was abundant from 1-9 days after injury, and apoptosis takes place primarily via the intrinsic (caspase 9) pathway. Caspase 9 was first observed and most abundant in a layer under the tunica, and after several days was observed in the lining of and between the sinuses of the corpora cavernosa. Caspase 8 was initially observed at low abundance in the rat corpora cavernosa and was not observed at later time points after CN injury. Aged and diabetic rat penis primarily exhibited intrinsic mechanisms, with diabetic rats also exhibiting mild extrinsic activation.
CLINICAL TRANSLATION
Knowing how and when to intervene to prevent the apoptotic response most effectively is critical for the development of drugs to prevent ED, morphological remodeling of the corpora cavernosa, and thus, disease management.
STRENGTHS AND LIMITATIONS
Animal models may diverge from the signaling mechanisms observed in ED patients. While the rat utilizes primarily caspase 9, there is a significant flux through caspase 8 early on, making it a reasonable model, as long as the timing of apoptosis is considered after CN injury.
CONCLUSIONS
Apoptosis takes place primarily through the extrinsic caspase 8 dependent pathway in ED patients and via the intrinsic caspase 9 dependent pathway in commonly used CN crush ED models. This is an important consideration for study design and interpretation that must be taken into account for therapy development and testing of drugs, and our therapeutic targets should ideally inhibit both apoptotic mechanisms. Martin S, Harrington DA, Ohlander S, et al. Caspase Signaling in ED Patients and Animal Models. J Sex Med 2021;18:711-722.
Topics: Animals; Caspases; Diabetes Mellitus, Experimental; Disease Models, Animal; Erectile Dysfunction; Hedgehog Proteins; Humans; Male; Penile Erection; Penis; Rats; Rats, Sprague-Dawley
PubMed: 33707045
DOI: 10.1016/j.jsxm.2021.01.175 -
Asian Journal of Andrology Nov 2023This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic...
This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A retrospective study was conducted on 657 CP/CPPS patients who visited The Third Xiangya Hospital of Central South University (Changsha, China) from November 2018 to November 2022. Patients were divided into two groups based on the timeline before and after the COVID-19 outbreak in China. The severity of CP/CPPS, penile erection status, anxiety, and depression was evaluated using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF-5), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. Compared with patients before the COVID-19 outbreak, more CP/CPPS patients developed severe erectile dysfunction (ED) due to depression and anxiety caused by the pandemic. After developing moderate-to-severe ED, mild and moderate-to-severe CP/CPPS patients exhibited more apparent symptoms of anxiety and depression ( P < 0.001 and P = 0.001, respectively), forming a vicious cycle. The COVID-19 pandemic has adversely affected the psychological status of CP/CPPS patients, exacerbating their clinical symptoms and complicating ED. The exacerbation of clinical symptoms further worsens the anxiety and depression status of patients, forming a vicious cycle. During the COVID-19 pandemic, paying more attention to the mental health of CP/CPPS patients, strengthening psychological interventions, and achieving better treatment outcomes are necessary.
Topics: Male; Humans; Erectile Dysfunction; Pandemics; Penile Erection; Prostatitis; Retrospective Studies; East Asian People; COVID-19; Chronic Disease; Pelvic Pain
PubMed: 37695217
DOI: 10.4103/aja202338 -
The Journal of Sexual Medicine Jun 2019Although sex aids have been used in clinical practice for ages, the scientific literature assessing their application in men with sexual dysfunction is limited. (Review)
Review
BACKGROUND
Although sex aids have been used in clinical practice for ages, the scientific literature assessing their application in men with sexual dysfunction is limited.
AIM
To summarize medical literature regarding scientific uses of the most common sex aids in men with sexual dysfunction and assess their clinical applicability.
METHODS
An extensive literature review was performed with regard to the use of sex aids in sexual medicine. Our search included journal articles, books, and guidelines in different databases: Embase, PubMed, and Cochrane. The key words were "sex aids," "sex toys," "pornography," "lubricants," "constriction bands," "dildos," "vibrators," "vacuum devices," "external penile devices," and "sex swings" were searched. Date of last search was December 4, 2018.
MAIN OUTCOME MEASURES
We assessed the utility of sex aids in men with sexual dysfunction and formulated recommendations for clinicians.
RESULTS
Various sex aids are available for men with sexual dysfunction. We present a comprehensive review of the most common sex aids currently available: pornography, lubricants, constriction bands, dildos, vibrators, vacuum devices, external erectile support devices, and aids to positioning. We discuss their indications, outcomes, precautions, and complications.
CLINICAL IMPLICATIONS
This review is intended to provide sexual medicine practitioners and academics an overview of sex aids for men with sexual dysfunction for use in both clinical practice and research.
STRENGTHS & LIMITATIONS
This is a compilation of scientific data for a topic that has broad application in sexual medicine and yet has been poorly addressed in the scientific literature. Because of the lack of sufficient data and the heterogeneous nature of different sex aids, a systematic review could not be performed.
CONCLUSION
Having a comprehensive understanding of the sexual dynamics of individuals and couples combined with the appropriate integration of sex aids may have a positive effect in the treatment of male sexual dysfunctions. Miranda EP, Taniguchi H, Cao DL, et al. Application of Sex Aids in Men With Sexual Dysfunction: A Review. J Sex Med 2019;16:767-780.
Topics: Erectile Dysfunction; Erotica; Humans; Lubricants; Male; Penile Erection; Penis; Photic Stimulation; Play and Playthings; Sexual Behavior; Sexual Dysfunctions, Psychological; Vacuum
PubMed: 31029536
DOI: 10.1016/j.jsxm.2019.03.265 -
Scientific Reports Jun 2021Erectile dysfunction (ED) is mostly due to the lack of blood flow into the penis. In the past 20 years, near-infrared spectroscopy (NIRS) was used in measuring the... (Clinical Trial)
Clinical Trial
Erectile dysfunction (ED) is mostly due to the lack of blood flow into the penis. In the past 20 years, near-infrared spectroscopy (NIRS) was used in measuring the concentrations and temporal dynamics of different hemoglobin types. However, the dynamics of the light absorption (photoplethysmography; PPG) have not been applied to survey penile hemodynamics and erection quality. This paper compared the use of photoplethysmography (PPG) to study vascular ED with standard penile Doppler ultrasonography. Men diagnosed with vascular ED for at least 6 months and nominated for penile ultrasonography were included. PPG signals were collected during the ultrasound examination. All beat-to-beat PPG waveforms were aligned with the peak and averaged to one representative template waveform for feature analysis, including amplitude differences (APD) index, reflection time index (RTI), augmentation index (AI), and perfusion index (PI). An inverse correlation was found between end-erection amplitude and both erection hardness score (EHS) and resistive index (RI). APD index and EHS as well as the international index of erectile function-5 (IIEF) and RI were positively correlated. RTI and AI were inversely correlated to IIEF and RI. PI was positively correlated to RI. PPG may therefore be useful as a noninvasive, convenient, technique for sexual function evaluation.
Topics: Aged; Hemodynamics; Humans; Male; Middle Aged; Penile Erection; Penis; Photoplethysmography
PubMed: 34103629
DOI: 10.1038/s41598-021-91582-9 -
Scientific Reports May 2023The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human...
The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human penis differs from the penes of other hominids. The lack of a baculum makes the human penis dependent on erectile tissue, which is under control of neural signals activated by tactile stimulation. Accordingly, the penile sensory innervation is crucial for human sexual behavior. To clarify penile innervation, we analyzed the architecture of the dorsal penile nerve of five male subjects who donated their body. We stained the sensory fibers in the penile dorsal nerve with anti-neurofilament H antibody, and identified myelinated axons with Luxol fast blue staining. Furthermore, we visualized nerve bundles as they travel along the shaft of the penis by performing microfocus computed tomography scans after counterstaining penes with iodine. Our results show that the dorsal penile nerve is organized in 25-45 loosely packed nerve bundles, running mediodorsally in the shaft of the penis. This organization corresponds to that in penes of other mammalian species, but differs from the organization of the other peripheral sensory nerves. Around half of the dorsal penile nerve fibers were myelinated and a human hemipenis contained a total of 8290 ± 2553 (mean ± SD) axons. Thus, the number of sensory axons in the human dorsal penile nerve is higher than in other species described so far. The large fraction of unmyelinated nerve fibers suggests that the conduction speed is not a crucial aspect of penile sensory transmission.
Topics: Animals; Humans; Male; Pudendal Nerve; Penis; Penile Erection; Axons; Peripheral Nerves; Mammals
PubMed: 37258532
DOI: 10.1038/s41598-023-35030-w -
Journal of Oncology Practice Apr 2016Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with... (Review)
Review
Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with subsequent effects on libido. Erectile dysfunction (ED), the inability to obtain or maintain an erection firm enough for sexual intercourse, can also result from adverse effects of cancer treatment, such as fatigue, pain, or anxiety about therapy. In addition, depressed feelings about having cancer can affect sexuality, causing a range of signs and symptoms that can lead to ED. Chemotherapy, hormone therapy, surgery, and radiation can all cause sexual adverse effects. Additional factors that play a role include patient age and degree of ED before starting cancer treatment. In this article, we discuss how chemotherapy, hormone therapy, surgery, and radiation affect erectile function as well as possible treatment options for ED.
Topics: Combined Modality Therapy; Disease Management; Erectile Dysfunction; Humans; Male; Neoplasms; Penile Erection; Treatment Outcome
PubMed: 27072383
DOI: 10.1200/JOP.2016.010678 -
The Epidemic of COVID-19-Related Erectile Dysfunction: A Scoping Review and Health Care Perspective.Sexual Medicine Reviews Apr 2022COVID-19 infection is expected to be associated with an increased likelihood of erectile dysfunction (ED). Considering the high transmissibility of COVID-19, ED may be a... (Review)
Review
INTRODUCTION
COVID-19 infection is expected to be associated with an increased likelihood of erectile dysfunction (ED). Considering the high transmissibility of COVID-19, ED may be a concerning consequence for a large segment of the population.
AIMS
To (1) summarize existing published evidence for the impact of COVID-19 on the prevalence, severity, treatment, and management of ED; and (2) identify health-related trends in the emerging literature and identify gaps in the existing research literature and make recommendations for future research needs in the area.
METHODS
A scoping literature search was conducted on April 27, 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-ScR) checklist was followed. The literature search was performed in PubMed using the terms: COVID-19, erectile, sexual, and dysfunction. A total of 693 publications were screened for relevance. Studies were appraised for their level of evidence based on study design and the rigor of methodology.
RESULTS
The evidence that COVID-19 infection causes or impacts ED is compelling. Four topics emerged regarding the nature of the association between COVID-19 and ED: (1) the biological impact of COVID-19 infection on ED; (2) the mental health impact of COVID-19 on ED; (3) the impact of COVID-19 on the management of ED and access to ED treatment; and (4) health disparities and the impact of COVID-19 on ED. Long-term and well-designed studies are needed to clarify the extent of the impact of COVID-19 on ED. The pandemic exposed several vulnerabilities within worldwide healthcare and social systems.
CONCLUSION
COVID-19 has a uniquely harmful impact on men's health and erectile function through biological, mental health, and healthcare access mechanisms. As the pandemic wanes, strategies to identify long-term effects and additional health care support may be needed to adequately mitigate the impact of COVID-19 on men's health. Hsieh T-C, Edwards NC, Bhattacharyya SK, et al.The Epidemic of COVID-19-Related Erectile Dysfunction: A Scoping Review and Health Care Perspective. Sex Med Rev 2022;10:286-310.
Topics: COVID-19; Delivery of Health Care; Erectile Dysfunction; Humans; Male; Penile Erection; Prevalence
PubMed: 34732316
DOI: 10.1016/j.sxmr.2021.09.002 -
Andrologia Dec 2015Cigarette smoking is a leading cause of preventable morbidity and mortality in the United States. Although public policies have resulted in a decreased number of new... (Review)
Review
Cigarette smoking is a leading cause of preventable morbidity and mortality in the United States. Although public policies have resulted in a decreased number of new smokers, smoking rates remain stubbornly high in certain demographics with 20% of all American middle-aged men smoking. In addition to the well-established harmful effects of smoking (i.e. coronary artery disease and lung cancer), the past three decades have led to a compendium of evidence being compiled into the development of a relationship between cigarette smoking and erectile dysfunction. The main physiologic mechanism that appears to be affected includes the nitric oxide signal transduction pathway. This review details the recent literature linking cigarette smoking to erectile dysfunction, epidemiological associations, dose dependency and the effects of smoking cessation on improving erectile quality.
Topics: Erectile Dysfunction; Humans; Male; Penile Erection; Smoking; Smoking Cessation
PubMed: 25557907
DOI: 10.1111/and.12393 -
Urologia Internationalis 2021Infection by COVID-19, being a respiratory disease caused by SARS-CoV-2, can predispose to arterial and venous thrombotic disease, in response to excessive inflammation,...
Infection by COVID-19, being a respiratory disease caused by SARS-CoV-2, can predispose to arterial and venous thrombotic disease, in response to excessive inflammation, platelet activation, endothelial dysfunction, and venous stasis. During the COVID-19 pandemic period, the technological and resource availability for the care of these patients with thrombotic disease is critical, marking a factor of morbidity and poor prognosis in these cases. We describe a case of priapism in a patient with COVID-19, during the course of systemic inflammatory response syndrome and respiratory distress syndrome with a procoagulant state, seeking to relate the pathophysiological factors of ischemic priapism in patients with infection with SARS-Cov-2.
Topics: Adult; COVID-19; Fatal Outcome; Humans; Ischemia; Male; Penile Erection; Penis; Priapism; Regional Blood Flow
PubMed: 34107472
DOI: 10.1159/000514421 -
Asian Journal of Andrology 2021Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but...
Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but less attention has been paid to preserving penis length. N-acetylcysteine (NAC) has the effect of antioxidation and antifibrotic, which may be beneficial to improve those postoperative complications. This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush (BCNC) and its underlying mechanism. Twenty-four male rats were randomly divided into three groups: control group, BCNC group, and BCNC + NAC group. NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks. The initial and end penile lengths were measured. Intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio was calculated to assess erectile function. Hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, and Western blot were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, the penile length, ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC + NAC group were improved significantly (all P < 0.05), and the expressions of endothelial nitric oxide synthase, α-smooth muscle actin, glutathione, and glutathione peroxidase 1 were significantly increased after NAC treated (all P < 0.05), along with the decreased expressions of hypoxia-inducible factor-1α, transforming growth factor-β1, collagen I, collagen III, collagen IV, malonaldehyde, and lysine oxidase (all P < 0.05). This study demonstrated that NAC could maintain penile length and partly improve erectile function. Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.
Topics: Acetylcysteine; Actins; Animals; Collagen; Crush Injuries; Disease Models, Animal; Erectile Dysfunction; Fibrosis; Free Radical Scavengers; Glutathione; Glutathione Peroxidase; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Malondialdehyde; Nitric Oxide Synthase Type III; Organ Size; Penile Erection; Penis; Peripheral Nerve Injuries; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Protein-Lysine 6-Oxidase; Rats; Transforming Growth Factor beta1; Glutathione Peroxidase GPX1
PubMed: 32394901
DOI: 10.4103/aja.aja_17_20