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Menthol for the Treatment of Erectile Dysfunction: Generation and Technology Export
Abstract
Erectile dysfunction (ED) is considered a public health problem with numerous risk factors, such as hypertension. Besides the existing oral treatment for ED, there are individuals that do not respond to or present numerous side effects to this therapy. Changes in the TRP channels can lead to several clinical complications, such as hypertension. More specifically, the cooling-sensing TRPM8 channel could be a novel target for the development of new drugs. In this line, menthol, a natural product TRPM8 channel agonist may be a molecule for use to treat erectile dysfunction. Then, we conducted a patent review to evaluate the application of menthol focusing on the treatment of erectile dysfunction. The search was conducted on Espacenet® associating A61K31/045 and A61K36/534 codes or using keywords, “erectile dysfunction AND menthol”. We analyzed 1,331 patents, which fourteen patents were found with the use of menthol in the genitourinary system. Although the patents had menthol in their formulations, none went directly to the development of pharmaceutical applications to treat erectile dysfunction. Taking these data into account, the use of menthol in the treatment of erectile dysfunction has been underexplored and is an opportunity for research and technological development based on a high innovation potential.
... A61K31/045: This class covers patents involving organic active ingredients, with menthol prominently featured, particularly in pharmaceutical preparations [21]. Menthol is extensively studied for its anticancer properties, particularly its ability to induce apoptosis, arrest the cell cycle, and disrupt tubulin polymerization in cancer cells. ...
Introduction:
Erectile dysfunction (ED) is frequently encountered in patients with arterial hypertension and there is a recent functional correlation between the expression of thermoreceptor channels TRPM8 (melastatin 8) and alterations in blood pressure in hypertension. The aim of this study was to investigate the function of cold-sensing TRPM8 channel in internal pudendal artery (IPA) in both normotensive and hypertensive rats.
Methods:
We performed experiments integrating physiological, pharmacological, biochemical and cellular techniques.
Results:
TRPM8 channels are expressed in the IPA and in vascular smooth muscle cells from IPA. In addition, TRPM8 activation, by both a cooling compound icilin (82.1 ± 3.0%, n = 6) and cold temperature [thermal stimulus, basal tone (25 °C, 41.2 ± 3.4%, n = 5) or pre-contracted tone induced by phenylephrine (25 °C, 87.0 ± 3.6%, n = 7)], induced relaxation in IPA. Furthermore, the results showed that the concentration-response curve to icilin was significantly shifted to the right in different conditions, such as: the absence of the vascular endothelium, in the presence of L-NAME (10-4 M), or indomethacin (10-5 M) or by a combination of charybdotoxin (10-7 M) and apamin (5 × 10-6 M), and Y27632 (10-6 M). Interestingly, icilin-induced vasodilation was significantly higher in IPA from spontaneously hypertensive (SHR, E10-4M = 75.3 ± 1.7%) compared to wistar rats (E10-4M = 56.4 ± 2.6%), despite no changes in the TRPM8 expression in IPA between the strains, suggesting that the sensitivity of TRPM8 channels is higher in SHR.
Conclusions:
These data demonstrate for the first time, the expression and function of TRPM8 channels in the IPA involving, at least in part, endothelium-derived relaxing factors and ROCK inhibition. Overall, this channel could potentially be a new target for the treatment of hypertension associated-ED.
Erectile dysfunction (ED) is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED
include cardiovascular disease, hypertension, diabetes mellitus (DM), tobacco use, hyperlipidemia, hypogonadism, lower
urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a
patient’s overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and
increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and
hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can
adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the
disease process.
Background:
Published clinical practice guidelines have addressed antihypertensive therapy and sexual dysfunction (SD) in many different ways.
Objective:
In this systematic review, we evaluated guidelines that address antihypertensive drug-associated SD, guideline recommendations, and recent guideline trends.
Methods:
Thirty sets of guidelines for hypertension management in adults that had been published in the English language since 2000 were reviewed. The primary outcome measure was antihypertensive-associated SD potential, which was independently evaluated using specific questions by 2 authors in a nonblinded standardized manner.
Results:
Sexual dysfunctions associated with thiazide-class diuretics, β-blockers, and centrally acting sympathoplegics were addressed by half of the guidelines reviewed. There is no clarity on β-blockers and thiazide-class diuretics because one-third of the guidelines are vague about individual β-blockers and diuretics, and there is no statement on third-generation β-blockers and thiazide-like diuretics that can improve erectile function. The revised guidelines never use terms such as loss of libido, ejaculatory dysfunction, lack of orgasm, and priapism. Summary versions of guidelines are inadequate to reflect the key interpretation of the primary guidelines on SD associated with antihypertensives, even in the major guidelines that were updated recently. Therapeutic issues such as exploring SD in clinical history, assessing SD prior to and during treatment with antihypertensives, substituting the offending agents with alternatives that possess a better safety profile, intervening with phosphodiesterase-5 inhibitors, and avoiding the concomitant use of nitrovasodilators are superficially addressed by most guidelines, with the exception of 2013 European Society of Hypertension/European Society of Cardiology and Seventh Joint National Committee recommendations.
Conclusion:
Future guideline revisions, including both full and summary reports, should provide a balanced perspective on antihypertensive-related SD issues to improve the impact of hypertension treatment guidelines on patient care and quality of life.
Intracellular Ca(2+) homeostasis is essential for vascular function and blood pressure regulation. Because of their unique roles in regulating intracellular Ca(2+) concentration and vascular function, a novel class of non-selective cation channels, called transient receptor potential (TRP) channels, have emerged at the frontier of hypertension research. Based on their role in vasculature function regulation, TRP channels can be divided into two functional subtypes: one that participates in vasoconstriction and one that participates in vasodilatation. A functional imbalance of these two subtypes of TRP channels may disturb intracellular calcium ([Ca(2+)]i) homeostasis, and the consequent vascular dysfunction may contribute to the development of hypertension. The potential of these TRP channels as novel pharmacological targets for the treatment of human hypertension is of great interest.
Environmental cold is a nonmodifiable hypertension risk factor. Transient receptor potential melastatin subtype 8 (TRPM8) is a cold-sensing cation channel that can be activated by menthol, a compound with a naturally cold sensation in mint. Little is known about the effect of TRPM8 activation on vascular function and blood pressure. Here, we report that TRPM8 is abundantly expressed in the vasculature. TRPM8 activation by menthol attenuated vasoconstriction via RhoA/Rho kinase pathway inhibition in wild-type mice, but the effect was absent in TRPM8(-/-) mice. Chronic dietary menthol blunted mesenteric arterial constriction and lowered blood pressure in genetic hypertensive rats via inhibition of RhoA/Rho kinase expression and activity in the vivo study. TRPM8 effect was associated with inhibition of intracellular calcium release from the sarcoplasmic reticulum, RhoA/Rho kinase activity, and sustained arterial contraction in the vitro study. Importantly, 8-week chronic menthol capsule treatment moderately lowered systolic blood pressure and diastolic blood pressure in prehypertensive individuals compared with the placebo group. Furthermore, chronic menthol capsule administration also improved flow-mediated dilatation in prehypertensive individuals, but not in the placebo group. In conclusion, our study demonstrates that TRPM8 activation by menthol benefits vascular function and blood pressure by inhibiting calcium signaling-mediated RhoA/Rho kinase activation in the vasculature. These findings add to the evidence that long-term dietary menthol treatment had favorable effects on hypertension treatment.
Erectile dysfunction is recognized as a quality-of-life disorder that needs to be treated. Currently, it is estimated to affect as many as 30 million American men. Thirty percent of hypertensive patients complain of erectile dysfunction. The understanding of common mechanisms involved in the cause of erectile dysfunction associated with hypertension, and the investigation of antihypertensive drugs that impact erectile dysfunction, will provide important tools toward identifying new therapeutic targets that will improve the quality of life for patients in these conditions.
Hypertension and erectile dysfunction are closely intertwined diseases, which have endothelial dysfunction as a common base. During hypertension and/or erectile dysfunction, disturbance of endothelium-derived factors can lead to an increase in vascular smooth muscle (VSM) contraction. Hypertension can lead to erectile dysfunction as a consequence of high blood pressure (BP) or due to antihypertensive treatment. However, growing evidence suggests erectile dysfunction is an early sign for hypertension. Also, some phosphodiesterase-5 inhibitors used to treat erectile dysfunction can improve BP, but the link between these conditions has not been totally understood.
This review will discuss the interplay between hypertension and erectile dysfunction, exploring newest insights regarding hypertension-associated erectile dysfunction, as well as the effect of antihypertensive drugs in erectile dysfunction patients.
The paper argues that an economy’s industry/technology structure is endogenously determined by the economy’s endowment structure. For the convergence to occur, the government of an LDC should target the upgrading of endowment structure instead of the industry/technology structure in its development strategy. If the government chooses to pursue an industry/technology structure, which is inconsistent with the comparative advantage determined by the economy’s endowment structure, the firms in the government’s priority sectors will be nonviable and the government needs to suppress the function of market and distort all kinds of prices as a way to protect the nonviable firms. Convergence will fail to occur as a result. Regression results from cross-country panel data are consistent with the predictions of the above arguments.
The objective of this study is to describe the eligibility, consumption, efficacy and patient satisfaction when treating men with diabetes with Sildenafil. The study is a prospective, self-reported, flexible-dose study. In total, 45 patients with diabetes (type 1 or 2), complaining of erectile dysfunction, were treated with Sildenafil over a 12-week period. Efficacy was assessed using a patientlog, a general satisfaction questionnaire and the International Index of Erectile Function (IIEF). Of 326 men, 192 reported erectile dysfunction, 79 did not fulfil the criteria for Sildenafil treatment and 49 declined to participate. In the group of 33 (age 45-75 y, mean+/-s.d.: 58.1+/-7.2) completing the study, erectile function was significantly improved (P < 0.0001). A total of 12 patients (36.4%) experienced no treatment effect at all. Eligibility and desire for treatment was low. Sildenafil is far from being a 'cure all' in the treatment of ED in diabetes.
Sensory nerve fibres can detect changes in temperature over a remarkably wide range, a process that has been proposed to involve direct activation of thermosensitive excitatory transient receptor potential (TRP) ion channels. One such channel--TRP melastatin 8 (TRPM8) or cold and menthol receptor 1 (CMR1)--is activated by chemical cooling agents (such as menthol) or when ambient temperatures drop below approximately 26 degrees C, suggesting that it mediates the detection of cold thermal stimuli by primary afferent sensory neurons. However, some studies have questioned the contribution of TRPM8 to cold detection or proposed that other excitatory or inhibitory channels are more critical to this sensory modality in vivo. Here we show that cultured sensory neurons and intact sensory nerve fibres from TRPM8-deficient mice exhibit profoundly diminished responses to cold. These animals also show clear behavioural deficits in their ability to discriminate between cold and warm surfaces, or to respond to evaporative cooling. At the same time, TRPM8 mutant mice are not completely insensitive to cold as they avoid contact with surfaces below 10 degrees C, albeit with reduced efficiency. Thus, our findings demonstrate an essential and predominant role for TRPM8 in thermosensation over a wide range of cold temperatures, validating the hypothesis that TRP channels are the principal sensors of thermal stimuli in the peripheral nervous system.
Pulmonary hypertension (PH) is characterized by enhanced vasoconstriction and vascular remodeling, which are attributable to the alteration of Ca2+homeostasis in pulmonary arterial smooth muscle cells (PASMCs). It is well established that store-operated Ca2+entry (SOCE) is augmented in PASMCs during PH and it plays crucial roles in PH development. Our previous studies showed that the melastatin-related transient receptor potential 8 (TRPM8) is down-regulated in PASMCs of PH animal models; and activation of TRPM8 causes relaxation of pulmonary arteries (PAs). However, the mechanism of TRPM8-induced PA relaxation is unclear. Here we examined the interaction of TRPM8 and SOCE in PAs and PASMCs of normoxic and chronic hypoxic pulmonary hypertensive (CHPH) rats, a model of human Group 3 PH. We found that TRPM8 was down-regulated and TRPM8-mediated cation entry was reduced in CHPH-PASMCs. Activation of TRPM8 with icilin caused concentration-dependent relaxation of cyclopiazonic acid (CPA) and ET-1 contracted endothelium-denuded PAs; and the effect was abolished by the SOCE antagonist Gd3+Application of icilin to PASMCs suppressed CPA-induced Mn2+quenching and Ca2+entry, which was reversed by the TRPM8 antagonist AMTB. Moreover, the inhibitory effects of icilin on SOCE in PA and PASMCs of CHPH rats were significantly augmented due to enhanced SOCE activity in PH. Our results, therefore, demonstrated a novel mechanism of TRPM8-mediated inhibition of SOCE in pulmonary vasculature. Since SOCE is important for vascular remodeling and enhanced vasoconstriction, down-regulation of TRPM8 in PASMCs of CHPH rats may minimize its inhibitory influence to allow unimpeded SOCE activity for PH development.
The human TRP protein family comprises a family of 27 cation channels with diverse permeation and gating properties. The common theme is that they are very important regulators of intracellular Ca²⁺ signaling in diverse cell types, either by providing a Ca²⁺ influx pathway, or by depolarising the membrane potential, which on one hand triggers the activation of voltage-gated Ca²⁺ channels, and on the other limits the driving force for Ca²⁺ entry. Here we focus on the role of these TRP channels in vascular smooth muscle and cardiac striated muscle. We give an overview of highlights from the recent literature, and highlight the important and diverse roles of TRP channels in the pathophysiology of the cardiovascular system.
The discovery of the superfamily of Transient Receptor Potential (TRP) channels has significantly enhanced our knowledge of multiple signal transduction mechanisms in cardiac muscle and vascular smooth muscle cells (VSMC). In recent years, multiple studies have provided evidence for the involvement of these channels, not only in the regulation of contraction, but also in cell proliferation and remodeling in pathological conditions.
The mammalian family of TRP cation channels is composed by 28 genes which can be divided into 6 subfamilies groups based on sequence similarity: TRPC (Canonical), TRPM (Melastatin), TRPML (Mucolipins), TRPV (Vanilloid), TRPP (Policystin) and TRPA (Ankyrin-rich protein). Functional TRP channels are believed to form four-unit complexes in the plasma, each of them expressed with six transmembrane domain and intracellular N and C termini.
Here we review the current knowledge on the expression of TRP channels in both muscle types, and discuss their functional properties and role in physiological and pathophysiological processes.
Caveolin-1 (Cav-1) is a major component protein associated with caveolae in the plasma membrane and has been identified as a regulator of store-operated Ca(2+) entry (SOCE) and receptor-operated Ca(2+) entry (ROCE). However, the contributions of caveolae/Cav-1 of PASMCs to the altered Ca(2+) signaling pathways in pulmonary arteries during PH have not been fully characterized. The present study quantified caveolae number and Cav-1 expression, and determined the effects of caveolae disruption on ET-1, cyclopiazonic acid (CPA) and 1-Oleoyl-2-acetyl-glycerol (OAG)-induced contraction in PAs and Ca(2+) influx in PASMCs of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH rats. We found that the number of caveolae, and the caveoiln-1 mRNA and protein levels were increased significantly in PASMCs in both PH models. Disruption of caveolae by cholesterol depletion with methyl-β-cyclodextrin (MβCD) significantly inhibited the contractile response to ET-1, CPA and OAG in PAs of control rats. ET-1, SOCE and ROCE-mediated contractile responses were enhanced, and their susceptibility to MβCD suppression was potentiated in the two PH models. MβCD-induced inhibition was reversed by cholesterol repletion. Introduction of Cav-1 scaffolding domain peptide to mimic Cav-1 upregulation caused significant increase in CPA- and OAG-induced Ca(2+) entry in PASMCs of control, CH and MCT-treated groups. Our results suggest that the increase in caveolae and Cav-1 expression in PH contribute to the enhanced agonist-induced contraction of PA via modulation of SOCE and ROCE; and targeting caveolae/Cav-1 in PASMCs may provide a novel therapeutic strategy for the treatment of PH.
Hypogonadism is associated with impaired libido and erectile dysfunction in young men, but the causes of sexual dysfunction in older men are less well understood.
To determine the prevalence and predictors of sexual problems in older men.
Sexual problems, as assessed by a self-reported questionnaire.
This was a population-based, cohort study of 3,274 community-dwelling men aged 75-95 years (mean 82 years) from Perth, Western Australia. Questionnaires in 2001-2004 and 2008-2009 assessed social and medical risk factors. Sex hormones were measured in 2001-2004. Predictors of sexual problems, measured in 2008-2009, were assessed cross-sectionally in the entire sample, and longitudinally in a subset of 1,744 men with sex hormone data.
Sexual problems were highly prevalent, with 49.4% (95% confidence interval 47.7% to 51.1%) reporting erectile problems, 47.7% (45.9% to 49.4%) lacking interest in sexual activity, 38.7% (37.0% to 40.3%) unable to climax, and 20.4% (19.1% to 21.8%) anxious about their ability to perform sexually. Painful and unpleasurable sex were less common (<5%). Overall, 72.0% (70.5% to 73.6%) reported at least one problem. In multivariate binary logistic regression analyses, cardiovascular disease, diabetes, depression, prostate disorders, and insomnia were the factors most commonly associated with sexual problems. Low testosterone levels were associated with lack of interest in sex, but not with other complaints.
Sexual problems are common in elderly men. Chronic disease, depression, and insomnia appear to be the main modifiable risk factors. Androgen deficiency is unlikely to be a major cause of sexual problems in this age group.
Transient receptor potential (TRP) channels are polymodal cellular sensors involved in a wide variety of cellular processes, mainly by changing membrane voltage and increasing cellular Ca(2+). This review outlines in detail the history of the founding member of the TRP family, the Drosophila TRP channel. The field began with a spontaneous mutation in the trp gene that led to a blind mutant during prolonged intense light. It was this mutant that allowed for the discovery of the first TRP channels. A combination of electrophysiological, biochemical, Ca(2+) measurements, and genetic studies in flies and in other invertebrates pointed to TRP as a novel phosphoinositide-regulated and Ca(2+)-permeable channel. The cloning and sequencing of the trp gene provided its molecular identity. These seminal findings led to the isolation of the first mammalian homologues of the Drosophila TRP channels. We now know that TRP channel proteins are conserved through evolution and are found in most organisms, tissues, and cell-types. The TRP channel superfamily is classified into seven related subfamilies: TRPC, TRPM, TRPV, TRPA, TRPP, TRPML, and TRPN. A great deal is known today about participation of TRP channels in many biological processes, including initiation of pain, thermoregulation, salivary fluid secretion, inflammation, cardiovascular regulation, smooth muscle tone, pressure regulation, Ca(2+) and Mg(2+) homeostasis, and lysosomal function. The native Drosophila photoreceptor cells, where the founding member of the TRP channels superfamily was found, is still a useful preparation to study basic features of this remarkable channel.
Folk medicine comprises "unofficial health beliefs and practices" which rely heavily (but not exclusively) on oral transmission. It is one form of alternative medicine, and a major source for many other forms such as phytotherapy and mind/body medicine. While many folk medicine ideas and practices are associated with particular ethnic groups, many others are widely distributed throughout American society. Folk medicine is not dying out in the modern world. Because it has both medical benefits and risks, effective medical care with folk medicine requires awareness and discussion of its influence.
The amount of blood flow into the penis that will produce an erection is dependent on the sum of inflow resistance from the feeder arteries, arterioles and the intra-penile vasculature. In the present study, our objective was to determine quantitatively the contribution to inflow resistance of these different components of the rat penile vasculature. Using methods developed previously, we determined the resistance properties of the isolated perfused whole penis in situ, both in an intact system and after serial transactions of the vessels. These cuts eliminated progressively larger distal segments of the vascular bed. Perfusion pressures were recorded at different flow rates (0.5-3 ml/min/kg body weight) under conditions of maximal dilatation and maximal vasoconstriction induced by methoxamine (MXA, 40 microg/ml). Regardless of the level of vascular tone, the pudendal artery contributes approximately 70% of the total resistance of the penile vasculature. In contrast, the vasculature within the penis (tip, shaft, crus) contributes only about one quarter of the resistance. Penile arterial inflow resistance properties both at maximal vasodilation and maximal alpha1-adrenergic constriction are dominated by the extra-penile vasculature in the rat. The implications of these findings are that alterations in the pudendal-artery (eg vasodilation, vasoconstriction, stenosis) would have primary control of arterial inflow and suggest an important role for pharmacological agents which can promote a more generalized vasodilation (eg phosphodiesterase inhibitors) in contrast to selective corpus cavernosal agents.
To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS).
A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire.
Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P <0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P <0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events.
Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.
Long-term efficacy and safety of sildenafil was assessed in 1008 patients with erectile dysfunction (ED) enrolled in four flexible-dose (25 - 100 mg), open-label, 36- or 52-week extension studies. After 36 and 52 weeks, 92% and 89% of patients felt that treatment with sildenafil had improved their erections. Responses to a Sexual Function Questionnaire indicated that 52 weeks of sildenafil treatment resulted in clinically significant improvements in the duration and firmness of erections, overall satisfaction with sex life, and the frequency of stimulated erections. Commonly reported adverse events (AEs) were headache, flushing, dyspepsia, and rhinitis, which were generally mild to moderate. Reports of abnormal vision were consistent with previous clinical trials. The occurrence of treatment-related cardiovascular AEs, such as hypertension, tachycardia, and palpitation, was <1%. Discontinuations due to treatment-related AEs were low (2%). Long-term therapy does not diminish the efficacy of sildenafil in patients with ED and remains well tolerated.
The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease.
300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments.
Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001).
Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.
Because of its frequency, erectile dysfunction must be systematically screened for in diabetic patients because, according to a survey by the ADIRS-AFD, it has affected 66% of patients for a mean of 6 years, and 77% wish it could be treated. From a physiopathological point of view, erectile disorders in diabetic patients are related to the vascular and neurological complications of diabetes and the various associated risk factors. The treatment to propose is at first iPDE5, although there is a risk of lesser efficacy in a diabetic patient and potential contraindications with the administration of derived nitrates. Intracavernous injections of PGE1 are efficient and safe second line and specialised advice is only required in the case of failure.
Erectile dysfunction (ED) is a highly prevalent condition in aging men with significant interpersonal and psychosocial consequences. Large-scale epidemiologic studies have demonstrated a consistent age-related loss of erectile function in men from different geographic and ethnic backgrounds, with approximately half of men over 70 years of age reporting moderate to severe symptoms. ED is associated strongly with specific comor-bidities, such as cardiovascular disease and hypertension, diabetes mellitus, lower urinary tract symptoms, prostate cancer, and depression. Lifestyle factors, including obesity and exercise frequency, also have been implicated in recent studies.
The transient receptor potential (TRP) superfamily consists of a large number of cation channels that are mostly permeable to both monovalent and divalent cations. The 28 mammalian TRP channels can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are expressed in almost every tissue and cell type and play an important role in the regulation of various cell functions. Currently, significant scientific effort is being devoted to understanding the physiology of TRP channels and their relationship to human diseases. At this point, only a few channelopathies in which defects in TRP genes are the direct cause of cellular dysfunction have been identified. In addition, mapping of TRP genes to susceptible chromosome regions (e.g., translocations, breakpoint intervals, increased frequency of polymorphisms) has been considered suggestive of the involvement of these channels in hereditary diseases. Moreover, strong indications of the involvement of TRP channels in several diseases come from correlations between levels of channel expression and disease symptoms. Finally, TRP channels are involved in some systemic diseases due to their role as targets for irritants, inflammation products, and xenobiotic toxins. The analysis of transgenic models allows further extrapolations of TRP channel deficiency to human physiology and disease. In this review, we provide an overview of the impact of TRP channels on the pathogenesis of several diseases and identify several TRPs for which a causal pathogenic role might be anticipated.
To assess the prevalence of erectile dysfunction and to quantify associations between putative risk factors and erectile dysfunction in the US adult male population.
Cross-sectional analysis of data from 2126 adult male participants in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Erectile dysfunction assessed by a single question during a self-paced, computer-assisted self-interview. These data are nationally representative of the noninstitutionalized adult male population in the US.
The overall prevalence of erectile dysfunction in men aged >/=20 years was 18.4% (95% confidence interval [CI], 16.2-20.7), suggesting that erectile dysfunction affects 18 million men (95% CI, 16-20) in the US. The prevalence of erectile dysfunction was highly positively related to age but was also particularly high among men with one or more cardiovascular risk factors, men with hypertension, and men with a history of cardiovascular disease, even after age adjustment. Among men with diabetes, the crude prevalence of erectile dysfunction was 51.3% (95% CI, 41.9-60.7). In multivariable analyses, erectile dysfunction was significantly and independently associated with diabetes, lower attained education, and lack of physical activity.
The high prevalence of erectile dysfunction among men with diabetes and hypertension suggests that screening for erectile dysfunction in these patients may be warranted. Physical activity and other measures for the prevention of cardiovascular disease and diabetes may prevent decrease in erectile function.
Erectile dysfunction (ED) is a highly prevalent disease associated with aging as well as with several risk factors including hypertension, heart disease, obesity, dyslipidemia, diabetes, hypogonadism, drugs-related, and pelvic surgery. Many of these factors are components of the metabolic syndrome, a multiplex risk factor for cardiovascular disease (CVD). ED shares common risk factors with CVD. Endothelial dysfunction seems to be the early underlying pathophysiology across both conditions. The efficacy, tolerability and cardiovascular safety of sildenafil has been evaluated in numerous large, randomized, doubleblind, placebo-controlled clinical studies in the broad population of men with ED including men with several co-morbid conditions. Sildenafil is effective in several specific patient populations including the difficult-to-treat subpopulations such as diabetes mellitus and after radical prostatectomy. It is associated with rapid onset of action--within 14 minutes for some men--and an extended duration of action for up to 12 hours. Sildenafil improves quality of life and satisfaction for treated men and is well tolerated with a favorable safety profile. New data suggest that sildenafil has beneficial effects in several chronic conditions. It has been approved for the treatment of idiopathic pulmonary hypertension. Numerous articles have suggested that it improves endothelial function and a possible role on premature ejaculation or treatment of lower urinary tract symptoms has been suggested.
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