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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 -
Acta Biomaterialia Sep 2023Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN)...
Radical prostatectomy is a highly successful treatment for prostate cancer, among the most prevalent manifestations of the illness. Damage of the cavernous nerve (CN) during prostatectomy is the main cause of postoperative erectile dysfunction (ED). In this study, the capability of a personalized bioactive fibrous membrane to regenerate injured CN was investigated. The fibrous membrane bioactivity is conferred by the selectively bound nerve growth factor (NGF) present in the rat urine. In a rat model of bilateral CN crush, the implanted bioactive fibrous membrane induces CN regeneration and restoration of erectile function, showing a significantly increased number of smooth muscle cells and content of endothelial and neuronal nitric oxide synthases (eNOS; nNOS). In addition, the bioactive fibrous membrane promotes nerve regeneration by increasing the number of myelinated axons and nNOS-positive cells, therefore reversing the CN fibrosis found in untreated rats or rats treated with a bare fibrous membrane. Therefore, this personalized regenerative strategy could overcome the recognized drawbacks of currently available treatments for CN injuries. It may constitute an effective treatment for prostate cancer patients suffering from ED after being subject to radical prostatectomy. STATEMENT OF SIGNIFICANCE: The present work introduces a unique strategy to address post-surgical ED resulting from CN injury during pelvic surgery (e.g., radical prostatectomy, radical cystoprostatectomy, abdominoperineal resection). It comprises a bioactive and cell-free fibrous implant, customized to enhance CN recovery. Pre-clinical results in a rat model of bilateral CN crush demonstrated that the bioactive fibrous implant can effectively heal injured CN, and restore penile structure and function. This implant selectively binds NGF from patient fluids (i.e. urine) due to its functionalized surface and high surface area. Moreover, its local implantation reduces adverse side effects. This tailored regenerative approach has the potential to revolutionize the treatment of ED in prostate cancer patients following radical prostatectomy, overcoming current treatment limitations.
Topics: Male; Humans; Rats; Animals; Rats, Sprague-Dawley; Nerve Growth Factor; Penile Erection; Erectile Dysfunction; Penis; Prostatectomy; Prostatic Neoplasms; Disease Models, Animal
PubMed: 37467838
DOI: 10.1016/j.actbio.2023.07.015 -
JAMA Network Open Feb 2023The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior.
OBJECTIVE
To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021.
INTERVENTIONS
Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo.
MAIN OUTCOMES AND MEASURES
Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal.
RESULTS
Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02).
CONCLUSIONS AND RELEVANCE
Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN17271094.
Topics: Male; Humans; Adult; Penile Erection; Kisspeptins; Sexual Behavior; Sexual Dysfunctions, Psychological; Brain
PubMed: 36735255
DOI: 10.1001/jamanetworkopen.2022.54313 -
BMC Cancer Aug 2020Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors.
BACKGROUND
Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors.
METHODS
GCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5-32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%).
RESULTS
In univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively).
CONCLUSIONS
This study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cancer Survivors; Chemoradiotherapy, Adjuvant; Cisplatin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Orgasm; Penile Erection; Prospective Studies; Quality of Life; Self Report; Sexual Behavior; Sexual Dysfunction, Physiological; Slovakia; Testicular Neoplasms; Time Factors; Young Adult
PubMed: 32819309
DOI: 10.1186/s12885-020-07301-6 -
Clinical Science (London, England :... Jul 2017The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase.... (Review)
Review
The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function.
Topics: Androgens; Apoptosis; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; DNA; Genomics; Humans; Kidney; Penile Erection; Reactive Oxygen Species; Receptors, Androgen; Testosterone
PubMed: 28645930
DOI: 10.1042/CS20170090 -
International Journal of Molecular... Jan 2023Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted... (Review)
Review
Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.
Topics: Male; Humans; Penile Induration; Penis; Penile Erection; Injections; Stem Cells
PubMed: 36614220
DOI: 10.3390/ijms24010777 -
Sensors (Basel, Switzerland) Dec 2021Erection measurements are the most important indicator of male urological disease diagnosis, treatment, and results. Rigiscan has been used widely in studies and...
Erection measurements are the most important indicator of male urological disease diagnosis, treatment, and results. Rigiscan has been used widely in studies and diagnoses for nocturnal penile tumescence for evaluating erectile dysfunction by measuring the number and timing of erectile dysfunctions during sleep. However, this device has limitations such as the weight and bulk of the device and has been questioned for its role as a standard for ED Erectile Dysfunction (ED) diagnosis. In this study, we propose a real-time wearable monitoring system that can quantitatively measure the length and circumference of the penis using electronic textiles (E-textile) and carbon nanotube (CNT) sensors. The E-textile sensor is used to measure the length, circumference, and gradient with portability, convenience, and comfort. Sensors were created by coating CNTs on latex for flexibility. The CNT-based latex condom-type sensor in our proposed system shows the length, circumference, and curvature measurements with changes in resistance, and the E-textile performance shows a 1.44% error rate and a cavity radius of 110 to 300. The results of this conceptual study are for supplementary sensor development with a combination of new technologies with alternatives or existing methods for measuring erection function.
Topics: Erectile Dysfunction; Humans; Male; Nanotubes, Carbon; Penile Erection; Textiles; Wearable Electronic Devices
PubMed: 35009773
DOI: 10.3390/s22010231 -
International Journal of Molecular... Sep 2021A continuously increasing amount of research shows that oxytocin is involved in numerous central functions. Among the functions in which oxytocin is thought to be... (Review)
Review
A continuously increasing amount of research shows that oxytocin is involved in numerous central functions. Among the functions in which oxytocin is thought to be involved are those that play a role in social and sexual behaviors, and the involvement of central oxytocin in erectile function and sexual behavior was indeed one of the first to be discovered in laboratory animals in the 1980s. The first part of this review summarizes the results of studies done in laboratory animals that support a facilitatory role of oxytocin in male and female sexual behavior and reveal mechanisms through which this ancient neuropeptide participates in concert with other neurotransmitters and neuropeptides in this complex function, which is fundamental for the species reproduction. The second part summarizes the results of studies done mainly with intranasal oxytocin in men and women with the aim to translate the results found in laboratory animals to humans. Unexpectedly, the results of these studies do not appear to confirm the facilitatory role of oxytocin found in male and female sexual behavior in animals, both in men and women. Possible explanations for the failure of oxytocin to improve sexual behavior in men and women and strategies to attempt to overcome this impasse are considered.
Topics: Animals; Erectile Dysfunction; Female; Humans; Male; Oxytocin; Penile Erection; Sexual Behavior
PubMed: 34638719
DOI: 10.3390/ijms221910376 -
PloS One 2023Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment... (Observational Study)
Observational Study
BACKGROUND
Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool.
METHODS
Observational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80-20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models.
RESULTS
For model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps.io/EPIC-26-Prediction/.
CONCLUSION
The final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients.
Topics: Male; Humans; Erectile Dysfunction; Penile Erection; Urinary Incontinence; Prostatic Neoplasms; Prostatectomy
PubMed: 38039308
DOI: 10.1371/journal.pone.0295179 -
Sexual Development : Genetics,... 2021Erectile dysfunction (ED) is one of the most prevalent chronic conditions affecting men. ED can arise from disruptions during development, affecting the patterning of... (Review)
Review
Erectile dysfunction (ED) is one of the most prevalent chronic conditions affecting men. ED can arise from disruptions during development, affecting the patterning of erectile tissues in the penis and/or disruptions in adulthood that impact sexual stimuli, neural pathways, molecular changes, and endocrine signalling that are required to drive erection. Sexual stimulation activates the parasympathetic system which causes nerve terminals in the penis to release nitric oxide (NO). As a result, the penile blood vessels dilate, allowing the penis to engorge with blood. This expansion subsequently compresses the veins surrounding the erectile tissue, restricting venous outflow. As a result, the blood pressure localised in the penis increases dramatically to produce a rigid erection, a process known as tumescence. The sympathetic pathway releases noradrenaline (NA) which causes detumescence: the reversion of the penis to the flaccid state. Androgen signalling is critical for erectile function through its role in penis development and in regulating the physiological processes driving erection in the adult. Interestingly, estrogen signalling is also implicated in penis development and potentially in processes which regulate erectile function during adulthood. Given that endocrine signalling has a prominent role in erectile function, it is likely that exposure to endocrine disrupting chemicals (EDCs) is a risk factor for ED, although this is an under-researched field. Thus, our review provides a detailed description of the underlying biology of erectile function with a focus on the role of endocrine signalling, exploring the potential link between EDCs and ED based on animal and human studies.
Topics: Adult; Androgens; Animals; Endocrine Disruptors; Erectile Dysfunction; Humans; Male; Penile Erection; Penis
PubMed: 34134123
DOI: 10.1159/000516600