The role of cortisol in erectile function.
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ABSTRACT:
SUBMITTER: Barham DW
PROVIDER: S-EPMC10481202 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
The role of cortisol in erectile function.
Translational andrology and urology 20230718 8
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Project description:BackgroundIt has been speculated for decades whether there is a significance of the adrenal corticosteroid cortisol in the process of male sexual function, including the control of sexual arousal and penile erection. In order to investigate further the role of the adrenocorticotropic axis in the physiological process of penile erection, we aimed to determine the course of cortisol in the cavernous and systemic blood through different stages of sexual arousal in patients suffering from erectile dysfunction (ED) in comparison to a cohort of healthy males.MethodsFifty-four healthy adult males and 45 patients with ED were presented sexually explicit visual material in order to elicit tumescence and (in the healthy males) rigid erection. Blood was collected from the cavernous space (corpus cavernosum penis, CC) and a cubital vein (CV) at different stages of the sexual arousal cycle as indicated by the penile stages flaccidity, tumescence, rigidity (attained only by the healthy males) and detumescence. Cortisol (µg/dL serum) was measured using a radioimmunometric assay (RIA).ResultsIn healthy males, cortisol decreased in both the cavernous and systemic blood with the beginning of sexual stimulation (CV: 15 to 13, CC: 16 to 13). At detumescence, in the systemic circulation, no alterations in cortisol levels were registered, whereas it decreased further in the CC (to 12). In the ED patients, no significant changes in cortisol were noticed in the systemic and cavernous blood.ConclusionsThe findings indicate that cortisol might act as an antagonist of the normal sexual response cycle of the adult male. A dysregulation of the secretion and/or degradation of the hormone might well play a role in the manifestation of ED.
| S-EPMC10251093 | biostudies-literature
Project description:Immunophilin ligands provide potentially new alternatives for the treatment of erectile dysfunction (ED), which occurs after injury of the cavernous nerves (CNs).To review and update current knowledge of the neurotrophic effects and likely mechanism of action of immunophilin proteins with emphasis on the FK506-binding protein (FKBP) subfamily and the role of immunophilin ligands for the treatment of CN injury-induced ED.Review of available reports of studies investigating the effects and neurotrophic mechanisms of immunophilin ligands involved in erectile function recovery in rodent models of CN injury.Erection parameters and molecular correlations associated with CN injury and functional recovery.Treatment with prototype immunosuppressive immunophilin ligands FK506 (FK) and rapamycin (Rapa) improve erectile function in animal models of CN injury. Similarly, non-immunosuppressive analogs such as GPI-1046 and FK1706 are effective in recovery of erections after CN injury. Neuronal nitric oxide may influence the erection recovery effects of immunophilin ligands after CN injury. FKBPs 38 and 65 expression changes in the penis and its innervation coincide with the neurotrophic effects of immunophilin ligands. Antioxidative actions of immunophilin ligands contribute to their neurotrophic effects. Immunophilins are localized to nerves coursing in human prostate and penile tissue.The findings support the hypothesis that immunophilin ligands, working through specific receptor mechanisms that are specific to injured CN, are potentially useful to sustain erectile function in men following radical prostatectomy.
| S-EPMC3361063 | biostudies-other
Project description:BackgroundClinical study and practice data have shown sildenafil improves sexual function in men with erectile dysfunction (ED). However, some men treated with placebo in double-blind, placebo-controlled sildenafil studies also report improved erectile function as measured by International Index of Erectile Function (IIEF)-Erectile Function Domain (EFD) scores.AimThis analysis estimated the relationship between post-baseline IIEF-EFD scores and demographic variables, including co-morbidities, in men with ED receiving placebo in flexible-dose sildenafil studies.MethodsPlacebo-treated participants in the intent-to-treat population of 42 double-blind, placebo-controlled, flexible-dose, sildenafil studies were included. A participant was classified as a placebo responder if the IIEF-EFD score was ≥26 at the last visit.OutcomesVariables assessed were age (<45, 45-64, ≥65 years), race, body mass index, co-morbidities (cardiovascular disease/hypertension, diabetes mellitus, depression), date the last study dose was taken, study completion date, ED etiology (psychogenic, organic, mixed), history of cigarette smoking, ED duration, baseline IIEF-EFD score (≤10, 11-16, ≥17), and treatment duration. Stepwise multivariate logistic regression models assessed the odds of being a responder vs a non-responder for each variable.ResultsA total of 4,360 men were included; 13.5% were responders. Odds estimates indicated the largest likelihood of placebo response occurred in men who were black (odds = 20.2, P < .0001), were younger than 45 years (odds = 7.3, P < .0001), had mild ED (baseline IIEF-EFD ≥17; odds >100, P < .0001), and did not have diabetes (odds = 4.5, P < .0001). The likelihood of a placebo response decreased as ED duration increased (odds = 0.74, P < .0001). The frequency of common adverse events was similar between placebo responders and non-responders.Clinical translationThese findings contribute to the improved understanding of predictors of placebo response in sildenafil clinical studies. Elucidation of these factors may contribute to the development of further interventions and treatment strategies and best practices for clinical trials.Strengths and conclusionsStrengths of this analysis include the large and diverse population and the duration of follow-up. Limitations include those associated with retrospective analyses and the inability to ascertain to what extent other demographic factors might have contributed to the placebo responses or how these placebo responses might be related to the natural course of ED.ConclusionsCertain demographics, co-morbidities, and condition characteristics predicted the odds of a placebo response in sildenafil clinical studies of ED. Underlying reasons behind a placebo response warrant further evaluation. Mulhall JP, Carlsson M, Stecher V, et al. Predictors of Erectile Function Normalization in Men With Erectile Dysfunction Treated With Placebo. J Sex Med 2018;15:866-872.
| S-EPMC6834358 | biostudies-literature
Project description:Phosphodiesterase type 5 inhibitors (PDE5is) are the primary therapeutic option for erectile dysfunction. However, 30% of patients do not respond to PDE5is treatment, making the quest for a new treatment modality a central endeavor. Here, we found a new pathway in erectile function control, mechano-regulated YAP/TAZ activate Adrenomedullin transcription, which sustains smooth muscle cells (SMCs) relaxation to maintain the erection. We first found that penile erection stretches the SMCs, dominating YAP/TAZ activity. Subsequently, we showed that YAP/TAZ plays a vital role in erectile function and penile rehabilitation using genetic lesions and several animal models. The mechanism relies on the regulation of Adrenomedullin on penile SMCs contraction, which we identify here as a direct YAP/TAZ transcript. Notably, conventional PDE5is targeting NO-cGMP signaling do not cure YAP/TAZ deficient ED. In contrast, by activating YAP/TAZ-Adrenomedullin cascade, mechano-stimulation improved erectile function, including PDE5is non-responders in both experimental models and clinical trials. Our studies lay the groundwork for exploring mechano-YAP/TAZ-Adrenomedullin as prospective targets in the treatment of ED
2023-03-31 | GSE208293 | GEO
Project description:Erectile dysfunction (ED) is an extremely prevalent condition which significantly impacts quality of life. The rapid increase of ED in recent decades suggests the existence of unidentified environmental risk factors contributing to this condition. Endocrine Disrupting Chemicals (EDCs) are one likely candidate, given that development and function of the erectile tissues are hormonally dependent. We use the estrogenic-EDC diethylstilbestrol (DES) to model how widespread estrogenic-EDC exposure may impact erectile function in humans. Here we show that male mice chronically exposed to DES exhibit abnormal contractility of the erectile tissue, indicative of ED. The treatment did not affect systemic testosterone production yet significantly increased estrogen receptor α (Esr1) expression in the primary erectile tissue, suggesting EDCs directly impact erectile function. In response, we isolated the erectile tissue from mice and briefly incubated them with the estrogenic-EDCs DES or genistein (a phytoestrogen). These acute-direct exposures similarly caused a significant reduction in erectile tissue contractility, again indicative of ED. Overall, these findings demonstrate a direct link between estrogenic EDCs and erectile dysfunction and show that both chronic and acute estrogenic exposures are likely risk factors for this condition.
| S-EPMC10987563 | biostudies-literature
Project description:BackgroundErectile dysfunction (ED) is common in patients with end-stage renal disease (ESRD). Whether kidney transplantation can improve erectile function in patients with ESRD is still controversial. We conducted a meta-analysis on the relationship between kidney transplantation and erectile function.MethodsA literature search was conducted on PubMed, Embase, Cochrane Library, and Web of Science until May 31, 2019. Primary outcomes were ED prevalence and each domain score of the International Index of Erectile Function (IIEF) questionnaire. We used age-matched dialysis patients or patients before kidney transplantation as a control group and compared them to kidney transplant recipients.ResultsA total of 9 articles were finally enrolled in the study. Compared with the control group, the kidney transplantation group had a lower prevalence of ED (OR 0.49, 95% CI: 0.28-0.86) and higher domain scores for erectile function (SMD 0.53, 95% CI: 0.12-0.94) and sexual desire (SMD 1.19, 95% CI: 0.11-2.27). While there were no significant variations in domain scores for orgasmic function (SMD 0.27, 95% CI: -0.10-0.63), intercourse satisfaction (SMD 0.26, 95% CI: -0.10-0.61), and overall satisfaction (SMD 0.17, 95% CI: -0.21-0.56). Patients in the kidney transplantation group had higher serum testosterone (SMD 1.20, 95% CI: 0.86-1.54) and lower prolactin (SMD -1.46, 95% CI: -2.22 to -0.69) and luteinizing hormone (SMD -0.97, 95% CI: -1.39 to -0.55).ConclusionsKidney transplantation may be associated with improved erectile function in patients with ESRD. This may be attributable to the correction of endocrine hormone disorders in patients after kidney transplantation.
| S-EPMC7658109 | biostudies-literature
Project description:IntroductionIndividuals with erectile dysfunction (ED) have been shown to display lower heart rate variability (HRV), suggesting dysregulation of cardiac autonomic function. No studies have explored whether HRV is predictive of erectile response among men with clinically normal erectile function.AimThe study aims to examine associations between resting HRV and objective measures of genital response (i.e., resting penile circumference; erectile tumescence) and self-reported sexual function.MethodsThe sample comprised 59 male community volunteers (mean age = 20.15 years; SD = 2.52) selected from the control conditions of two previously published studies. Participants reported erectile function in the normal range (scoring ≥ 26 on the International Index of Erectile Function [IIEF]) and had no history of cardiovascular disease or myocardial infarct. During a laboratory visit, self-report, anthropometric, cardiovascular, and electrocardiographic data were assessed, as well as resting penile circumference and erectile tumescence in response to viewing an erotic film.Main outcome measuresResting penile responses, erectile tumescence (circumferential change via penile plethysmography), self-reported sexual function per the IIEF, and both time-domain (standard deviation of beat-to-beat [NN] intervals, square root of the mean squared difference of successive NN intervals, and percent of NN intervals for which successive heartbeat intervals differed by at least 50 msec [pNN50]) and frequency-domain (low frequency [LF], high frequency [HF], LF/HF ratio) parameters of HRV were assessed.ResultsHigher-resting HF power and lower-resting LF/HF ratio were associated with greater erectile tumescence. There were marginally significant positive associations between mean NN interval and pNN50 and penile tumescence. HRV was not associated with self-reported sexual function or with resting penile circumference.ConclusionsResults suggested that, among men without ED, relatively elevated parasympathetic tone was predictive of larger erectile tumescence. Limited variance in sexual function scores may have accounted for the lack of association between HRV and IIEF scores.
| S-EPMC3735845 | biostudies-literature
Project description:IntroductionIschemic Priapism is defined as an abnormally prolonged state of erection, exceeding 6 h, often and irreducible, occurring without any sexual stimulation. Ischemic priapism has a fatal consequence on the sexual function of men if it's not promptly managed. This pathology can cause erectile dysfunction and this can alter the quality of life of patients.ObjectiveThe aim of our study was to determine the factors influencing erectile function after treatment of ischemic priapism.Patients and methodsThis is a ten-year retrospective, descriptive and analytic study of 40 patients who consulted the urology department at the university hospital center for treatment of ischemic priapism (2010-2019).ResultsWe included 40 patients in our study. The mean age was 35.2 [18-62]. Duration of priapism varied from 20 to 360 h (mean 76.6). The most common etiology of priapism was sickle cell disease in 65% of cases. The mean preoperative IIEF-5 score was 23 [21-26]. All patients underwent corporal aspiration with an injection of ephedrine, but detumescence was observed in only 10% of cases. Thirty-six patients had a distal shunt with detumescence in approximately 70% of cases. Eleven patients underwent a distal shunt but seven patients had definitive fibrosis. After the episode of priapism, only eight patients retained normal erectile function. The mean postoperative IIEF-5 score was 14 [ 7-26]. We noted an improvement in erectile function in 8 patients treated with tadalafil. In multivariate analysis, we have demonstrated that a treatment delay exceeding 48 h, fibrosis and the necessity of a distal shunt significantly affects postoperative erectile function (p = 0.001; p = 0.002; p = 0.002 respectively).ConclusionAccording to our study, delayed management exceeding 48 h, fibrosis and the necessity of a surgical distal shunt are three independent factors affecting erectile function after treatment of ischemic priapism.
| S-EPMC9142696 | biostudies-literature
Project description:AbstractIn order to explore the impact of circadian disturbance on erectile function, we randomly divided 24 adult male rats into groups of control (light on at 8:00 a.m. and off at 8:00 p.m.), dark/dark (DD; constant dark), light/light (LL; constant light), and shift dark/light (DL; light off at 8:00 a.m. and on at 8:00 p.m.). Four weeks later, erectile function was measured and corpora cavernosa were harvested for analysis. The maximum intracavernous pressure (mICP) and mICP/mean arterial pressure (MAP) ratio in the DD, LL, and DL groups were significantly lower than that in the control group. The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase (eNOS), while DD, LL, and DL showed reduced neuronal nitric oxide synthase (nNOS) at both mRNA and protein levels. The production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was inhibited by altered light/dark cycles to varying degrees. Circadian disturbance impaired endothelial function and contributed to erectile dysfunction. For the core circadian elements, mRNA expression of circadian locomotor output cycles kaput (Clock) and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) was elevated in the DL group, but their protein expression was not significantly changed. DD, LL, and DL increased period 1 (Per1) and Per3 levels, while LL and DL increased PER1 levels. No significant difference was found for Per2 levels, and PER2 and PER3 concentrations were not significantly changed. Moreover, LL and DL significantly increased cryptochrome-1 (CRY1) and CRY2 at both mRNA and protein levels. The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function. Meanwhile, the core circadian elements were detected in the corpora cavernosa, but these were disrupted. However, which circadian element regulates erectile function and how it works need further analysis.
| S-EPMC10919418 | biostudies-literature
Project description:BackgroundThe simplified International Index of Erectile Function (IIEF-5) is a convenient, reliable and validated diagnostic tool for erectile dysfunction (ED). However, few studies focused on IIEF-5 in ED patients with different pathophysiological causes. ,We aim to compare the IIEF-5 score among ED patients with specific pathophysiologies in this study.MethodsThe IIEF-5 score of 3,327 ED patients (median age 39 years) was analyzed. The primary causes of ED were determined by comprehensive diagnostic procedures in the urology/andrology clinics in five training hospitals. Patients with uncertain pathophysiologic cause were excluded.Results176 patients were excluded, 3151 patients with ED history between 0.5 year and 20 years, were enrolled. The causes of ED was classified as psychogenic (59.2%), vasoculogenic (21.3%), neurogenic (4.1%), anatomical/structural (2.8%), hormonal (7.1%) or drug-induced (5.5%). A significant difference was detected in the median IIEF-5 score between psychogenic ED and organic ED (15 (IQR 13, 17) versus 12 (IQR 9.5, 14.5), P < 0.001). There was no significant difference of IIEF-5 scores among the organic groups (P = 0.073), or between arteriogenic and venogenic groups (13 (IQR 10.5, 15.5) versus 13 (IQR 11-15), P = 0.912 (adjusted α = 0.017)). However, the median IIEF-5 score of those with a mixed vascular cause was the lowest among vasculogenic patients (11 (IQR 8.5-13.5), scores for the three groups: P = 0.003.).ConclusionsThe IIEF-5 scores of men with psychological ED are higher than those with organic causes, but there is no difference among patients with different organic pathophysiologies. Our data indicate that IIEF-5 is not a definitive diagnostic tool to discriminate the pathophysiological causes of ED.
| S-EPMC4094415 | biostudies-literature