Article

Effect of Niacin on Erectile Function in Men Suffering Erectile Dysfunction and Dyslipidemia

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Abstract

Dyslipidemia is closely related to erectile dysfunction (ED). Evidence has shown that the lipid-lowering agent, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statins), can improve erectile function. However, information about the potential role of another class of lipid-lowering agent, niacin, is unknown. To assess the effect of niacin alone on erectile function in patients suffering from both ED and dyslipidemia. A single center prospective randomized placebo-controlled parallel-group trial was conducted. One hundred sixty male patients with ED and dyslipidemia were randomized in a one-to-one ratio to receive up to 1,500 mg oral niacin daily or placebo for 12 weeks. The primary outcome measure was the improvement in erectile function as assessed by question 3 and question 4 of the International Index of Erectile Function (IIEF Q3 and Q4). Secondary outcome measurements included the total IIEF score, IIEF-erectile function domain, and Sexual Health Inventory for Men (SHIM) score. From the overall analysis, the niacin group showed a significant increase in both IIEF-Q3 scores (0.53 ± 1.18, P < 0.001) and IIEF-Q4 scores (0.35 ± 1.17, P = 0.013) compared with baseline values. The placebo group also showed a significant increase in IIEF-Q3 scores (0.30 ± 1.16, P = 0.040) but not IIEF-Q4 scores (0.24 ± 1.13, P = 0.084). However, when patients were stratified according to the baseline severity of ED, the patients with moderate and severe ED who received niacin showed a significant improvement in IIEF-Q3 scores (0.56 ± 0.96 [P = 0.037] and 1.03 ± 1.20 [P < 0.001], respectively) and IIEF-Q4 scores (0.56 ± 1.03 [P = 0.048] and 0.84 ± 1.05 [P < 0.001], respectively] compared with baseline values, but not for the placebo group. The improvement in IIEF-EF domain score for severe and moderate ED patients in the niacin group were 5.28 ± 5.94 (P < 0.001) and 3.31 ± 4.54 (P = 0.014) and in the placebo group were 2.65 ± 5.63 (P < 0.041) and 2.74 ± 5.59 (P = 0.027), respectively. There was no significant improvement in erectile function for patients with mild and mild-to-moderate ED for both groups. For patients not receiving statins treatment, there was a significant improvement in IIEF-Q3 scores (0.47 ± 1.16 [P = 0.004]) for the niacin group, but not for the placebo group. Niacin alone can improve the erectile function in patients suffering from moderate to severe ED and dyslipidemia.

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... The risk of bias for random sequence generation was low in five studies [26,[34][35][36][37], high in one study [41], and unclear in five studies [30,[38][39][40]. The risk of bias for allocation concealment was low in three studies [35][36][37] and unclear in eight studies [26,30,34,[38][39][40][41][42]. ...
... The risk of bias for random sequence generation was low in five studies [26,[34][35][36][37], high in one study [41], and unclear in five studies [30,[38][39][40]. The risk of bias for allocation concealment was low in three studies [35][36][37] and unclear in eight studies [26,30,34,[38][39][40][41][42]. The risk of blinding bias of the participants and personnel was low in six studies [26,30,34,37,40,42], high in two studies [36,38], and unclear in three studies [35,39,41]. ...
... The risk of bias for allocation concealment was low in three studies [35][36][37] and unclear in eight studies [26,30,34,[38][39][40][41][42]. The risk of blinding bias of the participants and personnel was low in six studies [26,30,34,37,40,42], high in two studies [36,38], and unclear in three studies [35,39,41]. The blinding bias of the assessor was low in two studies [35,40] and unclear in nine studies [25, 30, 34, 36-39, 41, 42]. ...
Article
Sexual dysfunction can adversely affect the quality of life, self-confidence, and interpersonal relationships. Some studies reported a relationship between vitamin supplementation and sexual health. This systematic review aimed to evaluate the effect of vitamins on female and male sexual function. All relevant English and Persian articles published in English databases (Medline, Scopus, Cochrane Library, Web of Sciences, Psycho-Info, and Proquest) and Farsi databases (SID and Magiran) until July 2020 were searched. The Cochrane Handbook for Systematic Reviews of Interventions was used for assessing the risks of bias. A total of 11 randomized controlled trials (RCTs) on 337 women, 472 men, and 35 couples were included. One study reported that vitamin D 300000 IU supplement administrated twice through intramuscular injection (at the beginning and after four weeks) had a significant effect on female sexual function (p<0.05), whereas another study showed that vitamin D 2000 IU supplement for six months did not have any significant effect on female sexual function (p>0.05). A study reported the significant effect of niacin (vitamin B3) 1500 mg daily for 12 weeks on erectile function (p=0.004). The results showed that vitamins A, C, and E had no significant effect on male and female sexual function. The conduction of trials with long-term interventions is recommended to reach a more definitive conclusion about the effect of vitamins on sexual function.
... For example, L-arginine is a NO precursor which is therefore necessary for smooth muscle relaxation in the cavernous corpora 71 . Likewise, nicotinic acid is related to energy production in the endothelium and is a vasodilator and thus may improve erectile function 72,73 . Propionyl -L-carnitine (PLC) is an intracellular superoxide scavenger that enhances mitochondrial function, decreases DNA injury, and may improve corporal endothelial functionl 74 . ...
... p= <0.001) and severe ED (3.31±4.5, p = 0.014) compared to placebo (2.65±5.63, p = < 0.04) 73 . However, no studies have been reported in the diabetic population alone or combined with PDE5i. ...
Article
Full-text available
Introduction: Erectile dysfunction (ED) is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for ED are phosphodiesterase type 5 inhibitors (PDE5i), but data suggests that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices, and penile prosthetic surgery, should be considered in management of diabetic men with ED refractory to PDE5i. Furthermore, combination therapy of PDE5i and other oral treatments such as arginine or L-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem cell therapy which may also be effective targeted treatment modalities. Furthermore, studies suggest that ED can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focussing on the management of ED in diabetic men who have not responded to PDE5i. Conclusions: Both clinicians and patients should be aware of the different management options in Diabetic patients who have responded to PDE5i. This article is protected by copyright. All rights reserved.
... The 15 questions covered 5 domains related to sexual function: erectile function (EF), orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. Among these, the EF domain is the main area assessed in studies related to the treatment response of therapy for erectile dysfunction (2)(3)(4). Although the primary feasibility endpoint of this study was set as an increase of 4 points in the IIEF-6/IIEF-EF domain, the presentation of the results appeared less clear. ...
... Therefore, we were uncertain whether the 59.3% improvement of >4 points was IIEF (total) or IIEF-6 (EF domain). Moreover, the usual practice of presenting the results of treatment for erectile dysfunction is to provide the pre-and post-treatment IIEF-EF domain scores for easier reference (3,4). Unfortunately, this essential information was not shown in the article. ...
... Improvement of sperm count and of libido and desire in both genders [24] Complex B vitamins Complex B vitamins deficiency is associated with erectile dysfunction and this correction can improve erectile function. [25][26][27] Date palm (Phoenix dactylifera L.) pollen ...
... Vitamin B3 (niacin) increases serum high-density lipoprotein cholesterol level and subsequently improves the lipid profile. Literature regarding niacin treatment for sexual dysfunction is scarce; however, there are some studies suggesting that niacin alone could improve the erectile function of patients with dyslipidemia suffering from erectile dysfunction [25]. ...
Article
Background: Sexual dysfunction and infertility are conditions with high prevalence in general population. Nutritional factors have been reported to have impact in sexual and reproductive health. Objective: The aim of this review is to summarize the data on nutritional factors that have influence in male and female sexual and reproductive function, including nutritional status, specific foods (e.g. dairy food), nutrients and other food components and dietary supplements. Method: A literature search was performed using Cochrane Library, Medline and ScienceDirect databases without time limitations. Results: Obesity has a negative influence in male fertility, and weight loss improves male fertility. Food insufficiency is associated with increased sexual risk behaviours, more significant in women. Regarding to macronutrients and group foods, trans-fatty acids, high glycemic index food, high carbohydrate diet and high animal protein intake prejudices fertility; omega-3 and omega-6 fatty acids, low glycemic index food and low carbohydrate diet, vegetable proteins and antioxidants improves fertility. Isoflavones has a negative impact on men fertility and improves sexual health of menopausal women. Whole milk improves women fertility, but men benefit from skim milk. Concerning to dietary supplements there is weak evidence sustaining efficacy, and the most promising supplements are yohimbine, vitamin B, L-arginine and vitamin D. Conclusion: The compiled results indicate that despite the multifactorial etiology of sexual/reproductive dysfunction, nutritional factors may affect the sexual and reproductive health in both men and women. However, it is necessary further studies to clarify this association, and simultaneously improve the approach and treatment of patients with sexual and/or reproductive problems.
... For example, various lipid-lowering agents (statins and niacin) have been used to counteract the atherosclerotic process. 3,4 Li-ESWT was proved to be useful in various other medical conditions; for example, neovascularization in myocardial ischemia. 5 Recently, Vardi et al. have investigated the impact of Li-ESWT in the treatment of ED, and found a positive short-term clinical effect on men who responded to PDE5I. ...
... Sample size calculation was based on the results from our previous study. 4 To achieve 80% power, assuming 5.2-point difference to detect a two-sided 5% significance and a 20% dropout rate, a total of 70 participants were required for the study. ...
Article
Objectives To investigate the role of low-intensity extracorporeal shockwave therapy in the treatment of erectile dysfunction. Methods This was a double-blinded, single-center, prospective, randomized, placebo-controlled trial. After a 2-week phosphodiesterase type5 inhibitor washout period, patients were assessed with Sexual Health Inventory for Men, International Index of Erectile Function-ED domain scores and Erection Hardness Score. Randomization into either the low-intensity extracorporeal shockwave therapy group or the sham group took place. After the 9-week treatment period, patients were followed up 4weeks later. Follow-up assessment was in the form of International Index of Erectile Function-ED domain score and Erection Hardness Score. ResultsA total of 70 patients were recruited into the study, 58 patients completed the study. A total of 28 patients were randomized into the sham therapy arm, and 30 patients were randomized into the low-intensity extracorporeal shockwave therapy arm. There was no significant difference between these two groups in baseline International Index of Erectile Function-ED domain score and Erection Hardness Score. The mean International Index of Erectile Function-ED domain score of the low-intensity extracorporeal shockwave therapy arm and sham arm in week 13 were 17.84.8 and 15.8 +/- 6.1, respectively (P=0.156). The mean Erection Hardness Scores in week13 were 2.7 +/- 0.5 and 2.4 +/- 0.9, respectively (P=0.163). When patients were stratified into different baseline Sexual Health Inventory for Men subgroups, the pre-intervention and post-intervention difference in low-intensity extracorporeal shockwave therapy was found to be significant in the subgroup with severe erectile dysfunction (low-intensity extracorporeal shockwave therapy International Index of Erectile Function-ED domain improvement: 10.1 +/- 4.1 vs sham therapy International Index of Erectile Function-ED domain improvement: 3.2 +/- 3.3; P=0.003). Conclusion The present trial shows the tolerability and clinical efficacy of low-intensity extracorporeal shockwave therapy in a subgroup of patients with erectile dysfunction.
... The replication study included data from Chinese patients with dyslipidemia who participated in either of 2 clinical studies, which examined the effect of ER niacin on liver fat or erectile dysfunction, respectively, in Chinese patients with dyslipidemia who were attending Out-patient Clinics in Prince of Wales Hospital from August 2008 to March 2011. 16,19 Both studies were approved by the local clinical research ethics committee. In the study that examined the effect of ER niacin on liver fat, 39 patients completed the treatment with ER niacin (Niaspan, Abbott Laboratories, Hong Kong) once daily at bedtime in increasing doses of 375, 500, and 750 mg (each for 1 week); 1000 and 1500 mg (each for 4 weeks); and 2000 mg (for 12 weeks). ...
... Written informed consent for genetic analysis of lipid response to niacin was obtained from 29 patients including 9 patients receiving long-term stable doses of statins or fibrates. 19 The data on the lipid response to ER niacin 1500 mg in these 2 studies were merged for genetic analysis. ...
Article
The acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2 catalyze the final step in triglycerides biosynthesis. This study examined the relationships of baseline phenotypes and the common polymorphisms in DGAT1 and DGAT2 with the lipid responses to niacin. Lipid responses in Chinese patients with dyslipidemia treated with the extended release (ER) niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks (n = 121, the primary study) or with ER niacin 1500 mg for at least 4 weeks (n = 68, the replication study) were analyzed according to genotypes of DGAT1 rs7003945 T>C and DGAT2 rs3060 T>C polymorphisms. Treatment with ER niacin improved all lipid parameters in both studies. Absolute and percentage changes in lipids were related to their baseline levels, particularly for low-density lipoprotein cholesterol (LDL-C). The DGAT2 rs3060 T>C polymorphism was associated with lower baseline LDL-C, apoB, high-density lipoprotein cholesterol (HDL-C), and apoAI in patients on statin therapy in the primary study. Subjects with the DGAT2 rs3060 T>C variant had less reduction in LDL-C in the primary study and smaller changes in triglyceride and HDL-C in the replication study but these associations became non-significant after adjusting for baseline lipid values. The DGAT1 rs7003945 T>C polymorphism was not related to lipid baseline values or changes in either study. Concomitant statin therapy and lower body weight were also associated with greater reduction in LDL-C. Baseline lipid levels were the main determinants of lipid responses especially for LDL-C. The DGAT2 rs3060 polymorphism might influence the lipid responses depending on baseline phenotype, but this association did not persist after adjustment for the baseline lipid levels.
... 42 The vitamins B6, B9, and B12 are known to regulate the levels of homocysteine, the high levels of which can result in decreased NO production and ED. 43 There are also some reports of the improvement of erectile function with vitamin B1 14 and B3 44,45 supplementations. Zinc deficiency has been known to be associated with testosterone deficiency, 46 and zinc supplementation has been shown to reverse the reduced testosterone levels, 47 though the results are mixed. ...
Article
Full-text available
l-arginine, being a natural precursor of nitric oxide, is one of the more commonly used adjuvants to regular medicines in the treatment of erectile dysfunction. Objectives: Here, in this review article, we aim to highlight various studies and the research studies done on l-arginine in the treatment of erectile dysfunction. Method: Reviewing the databases such as Medline (PubMed), Cochrane Library, Excerpta Medica dataBASE, Trip, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, and the British Nursing Index. Results:l-arginine has been studied alone as well as in combination with various other molecules for the treatment of erectile dysfunction, but the studies are very limited in number and have very small sample sizes. Conclusion: Positive evidence is available for the efficacy of l-arginine and its various combinations. Further research with larger sample sizes and standardized tools are required to recommend the routine use of these products in erectile dysfunction.
... The results of some earlier studies showed that the herb Maca (Lepidium meyenii) could significantly increase fertility and sexual activity in humans and animals [10]. In one study, niacin (1500 mg/day for 12 weeks) improved erectile problems in men compared to placebo [11]. Foeniculum vulgare or fennel is a plant in the carrot family and is indigenous to the shores of the Mediterranean Sea [12]. ...
Article
Full-text available
Objective: The aim of this study was to assess the effect of fennel on sexual function in postmenopausal women. It was a randomized controlled trial in 60 postmenopausal women with sexual dysfunction who were randomly assigned to two groups receiving either fennel vaginal cream (n=30) or placebo (n=30). Vaginal atrophy in the women was assessed using symptoms such as pallor, dryness, dyspareunia, itching and burning. The pH of the vagina and cytology of the vaginal mucosa were also measured at baseline and 8 weeks after the intervention. All participants were requested to fill out the Female Sexual Function Index (FSFI) at baseline and after 8 weeks. The intervention group was requested to use fennel vaginal cream (5 grams) every night, while the control group used placebo each night for 8 weeks. The data were analyzed using the independent t-test and Chi-square, Mann-Whitney and Wilcoxon tests. All areas of sexual function including arousal, lubrication, orgasm, sexual satisfaction and pain improved in both fennel and placebo groups after 8 weeks; however, the differences in the fennel group were more evident (p<0.05). The total FSFI score was significantly higher in the fennel group compared to the control group (8.2 ±9.4 and 8.03±10.36 before the intervention and changing to 33.79±0.7 and 18.99±1.09 after the intervention in the fennel and placebo groups, respectively; p<0.001). Discussion: According to our results, fennel vaginal cream is an effective means of improving sexual activity in postmenopausal women. The use of this product in women who have sexual dysfunction and contraindications for hormone therapy is recommended.
... ED was reported in 1.3% of patients on fenofibrate based on findings from several studies [176]. In contrast, niacin was found to have beneficial effects on erectile function [177] in 160 patients with ED and dyslipidemia compared with placebo and in combination with propionyl-L-carnitine and L-arginine in 54 patients with untreated ED [178]. ...
Article
Background: Sexual dysfunction affects millions of people with an increasing prevalence, worldwide. The pathophysiology of the disease shares several similarities with cardiovascular disease (CVD), including atherosclerosis, endothelial dysfunction, structural vascular damage and subclinical inflammation. Erectile dysfunction (ED) and female sexual dysfunction are common among patients with CVD and risk factors such as hypertension, diabetes, obesity and metabolic syndrome. Given the common pathogenesis of the diseases, ED is an independent prognostic factor of future ED events. Patients with overt ED or risk factors are usually treated with several drugs for the management of these conditions. Several of these drugs have been evaluated for their effect on sexual activity. Results and conclusion: Among the antihypertensive drugs, diuretics and beta-blockers seem to exert a detrimental impact on sexual function, with nebivolol being the only beta-blocker with favorable properties through an increase in nitric oxide bioavailability. In contrast, renin-angiotensin system inhibitors and calcium-channel blockers have a neutral effect on sexual activity. Hypoglycemic drugs have been less evaluated in the ED setting, with metformin, pioglitazone and liraglutide presenting favorable results. Statins on the other hand have not provided consistent results with observational studies suggesting a detrimental role in sexual activity and a few randomized studies indicating a neutral or even beneficial effect on erectile function.
... L-arginine in combination with pycnogenol, a product obtained from the pine bark (Pinuspinaster), is found safe and effective in mild to moderate erectile dysfunction in Japanese patients [79]. When Patients suffering from moderate to severe ED and dyslipidemia were kept on Niacin rich diet, significant improvement was observed in patients [80]. ...
... YH is primarily used as a treatment for erectile dysfunction [1]. Addition of VE enhances YH sexual effect through improving circulation and repairing tissue damage [5] while VB improves the erectile function [6]. Also CAF was associated with a higher potency rate in men [7]. ...
Article
A pharmaceutically marketed mixture of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine co-formulated as a promising therapy for erectile dysfunction. Simultaneous determination of the aforementioned pharmaceutical formulation without prior separation steps was applied using mean centering of ratio spectra and triple divisor spectrophotometric methods. Mean centering of ratio spectra method depended on using the mean centered ratio spectra in three successive steps which eliminated the derivative steps and so the signal to noise ratio was improved. The absorption spectra of the prepared solutions were measured in the wavelength range of 215–300 nm in the concentration ranges of 1–15, 3–15, 1–20, and 3–15 μg mL− 1 for Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively. The amplitudes of the mean centered third ratio spectra were measured at 250 nm and 268 nm for Yohimbine and Alpha-tocopheryl acetate, respectively and at peak to peak 272–273 and 262–263 nm for Niacin and Caffeine, respectively. In triple divisor method each drug in the quaternary mixture was determined by dividing the spectrum of the quaternary mixture by a standard spectrum of a mixture containing equal concentrations of the other three drugs. First derivative of these ratio spectra was obtained where determination could be achieved without any interference from the other three drugs. Amplitudes of 1–15, 3–15, 1–15, and 3–15 μg mL− 1 were used for selective determination of Yohimbine, Alpha-tocopheryl acetate, Niacin, and Caffeine, respectively.
Article
Introduction: Use of supplements is common among men seeking urologic evaluation for sexual health matters. With a dizzying array of formulations available and little regulation on the dosage, purity, or ingredients found in these products, the health effects of nutraceuticals are often confusing to patients and medical practitioners alike. Aim: In this review, we set out to concisely summarize the data on ingredients found within the top-selling nutraceutical agents marketed for men's sexual health in order to provide a clinical guide for urologists. Methods: We used sales data from the most popular retail provider of men's health supplements to identify the top-selling products marketed toward improvement of men's sexual health. We summarized the available information related to the ingredients, dosage, cost, and mechanism of action for these substances and performed an extensive literature search to identify and review the current evidence available for each of the most common ingredients found in these nutraceuticals. Results: The top-selling nutraceuticals marked for men's sexual health contain a blend of multiple supplements (up to 33 in one formulation identified), the most common being ginseng, tribulus, zinc, horny goat weed, B complex vitamins/trace minerals, fenugreek, L-arginine, maca, DHEA, ginkgo, and yohimbine. The currently available medical literature evaluating the efficacy of these substances is generally of low quality. Conclusions: Despite the dearth of evidence supporting nutraceutical agents in the men's health arena, these substances are still commonly used by patients. As these products can affect the health and well-being of men presenting to a urology clinic, a familiarity with commonly used agents can help the urologist appropriately counsel their patients. Cui T, Kovell RC, Brooks DC, and Terlecki RP. A urologist's guide to ingredients found in top-selling nutraceuticals for men's sexual health. J Sex Med **;**:**-**.
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Niacin is an important vitamin (B3) that can be used in gram doses to positively modify pathogenetically relevant lipid disorders: elevated LDL cholesterol, elevated non-HDL cholesterol, elevated triglycerides, elevated lipoprotein(a), and reduced HDL cholesterol. This review reports the latest published findings with respect to niacin's mechanisms of action on these lipids and its anti-inflammatory and anti-atherosclerotic effects. In the pre-statin era, niacin was shown to have beneficial effects on cardiovascular end-points; but in recent years, two major studies performed in patients whose LDL cholesterol levels had been optimized by a statin therapy did not demonstrate an additional significant effect on these end-points in the groups where niacin was administered. Both studies have several drawbacks that suggest that they are not representative for other patients. Thus, niacin still plays a role either as an additive to a statin or as a substitute for a statin in statin-intolerant patients. Moreover, patients with elevated triglyceride and low HDL cholesterol levels and patients with elevated lipoprotein(a) concentrations will possibly benefit from niacin, although currently the study evidence for these indications is rather poor. Niacin may be useful for compliant patients, however possible side effects (flushing, liver damage) and contraindications should be taken into consideration.
Chapter
Complementary & Alternative Medicine for Prostate and Urologic Health is designed to capture and clinically review the comprehensive database of clinical research articles that support and do not support the utilization of a variety of dietary supplements and other complementary medicines that physicians are exposed to in their daily practice. This is a critical distinction between this book and any other Complementary & Alternative Medicine (CAM) books published to date. Each section of the book provides an easy to reference guide into the topic of interest for the individual that works in urology. The various sub-specialty groups in urology are adequately represented, which allows for a physician to rapidly and thoroughly investigate their topic of interest regardless of whether it is fertility, bladder cancer, or prostate disease. Rather than having to sort through the now thousands of articles published yearly on CAM in medicine, this volume focuses first on the specialty and secondarily how it compares to the overall CAM literature. Each chapter includes a summary page that will allow the physician a rapid review of the subject with a patient, colleague or student. The practical nature of this book in urology also cannot be overstated. Chapters include a general overview of the CAM agent, whether or not it has data in medicine and urology, and a list of potential drug interactions and specific clinical scenarios where it can be utilized or discouraged in the specialty. Complementary & Alternative Medicine for Prostate and Urologic Health represents a gold standard text for use in teaching, not only for the students interested in the urologic field but for all current urologic health providers.
Chapter
Sexual function is an essential component of physical and psychological well-being and should be addressed as such in the clinical setting. This is an unconventional chapter regarding sexual function, in which issues for both men and women are combined to illustrate similar complexities in both genders and to minimize the traditional emphasis on gender differences. To this end, the chapter is divided into primary sections, addressing dysfunctions in the realms of desire/libido, arousal (erection/lubrication) and climax/ejaculation as well as metabolic syndrome. The final section briefly addresses nonpharmacological interventions as well as prescribed therapies for respective dysfunction. But the most important take home message is “just ask!”
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Sexual function is an essential component of physical and psychological well-being and should be addressed as such in the clinical setting. Because the many facets of sexuality can be influenced by other physical and mental health issues, sexual concerns should be approached as genuine medical problems. Men may present with one symptom of sexual concern, but after thoughtful interview and evaluation, the symptom may be attributed to a different primary sexual dysfunction or separate health problem. This chapter addresses specific sexual complaints: loss of libido, erectile dysfunction, and disorders of ejaculation in the context of psychosocial factors and the clinical setting. The final section briefly addresses nonpharmacological interventions as well as prescribed therapies. The most important message in this chapter is “just ask!”
Article
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Background: This meta-analysis was performed to investigate the effects of nicotinamide adenine dinucleotide (NAD+) precursor supplementation on glucose and lipid metabolism in human body. Methods: PubMed, Embase, CENTRAL, Web of Science, Scopus databases were searched to collect clinical studies related to the supplement of NAD+ precursor from inception to February 2021. Then the retrieved documents were screened, the content of the documents that met the requirements was extracted. Meta-analysis and quality evaluation was performed detection were performed using RevMan5.4 software. Stata16 software was used to detect publication bias, Egger and Begg methods were mainly used. The main research terms of NAD+ precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide (NMN), Nicotinic Acid (NA), Nicotinamide (NAM). The changes in the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and fasting blood glucose were mainly concerned. Results: A total of 40 articles were included in the meta-analysis, with a sample of 14,750 cases, including 7406 cases in the drug group and 7344 cases in the control group. The results of meta-analysis showed that: NAD+ precursor can significantly reduce TG level (SMD = - 0.35, 95% CI (- 0.52, - 0.18), P < 0.0001), and TC (SMD = - 0.33, 95% CI (- 0.51, - 0.14), P = 0.0005), and LDL (SMD = - 0.38, 95% CI (- 0.50, - 0.27), P < 0.00001), increase HDL level (SMD = 0.66, 95% CI (0.56, 0.76), P < 0.00001), and plasma glucose level in the patients (SMD = 0.27, 95% CI (0.12, 0.42), P = 0.0004). Subgroup analysis showed that supplementation of NA had the most significant effect on the levels of TG, TC, LDL, HDL and plasma glucose. Conclusions: In this study, a meta-analysis based on currently published clinical trials with NAD+ precursors showed that supplementation with NAD+ precursors improved TG, TC, LDL, and HDL levels in humans, but resulted in hyperglycemia, compared with placebo or no treatment. Among them, NA has the most significant effect on improving lipid metabolism. In addition, although NR and NAM supplementation had no significant effect on improving human lipid metabolism, the role of NR and NAM could not be directly denied due to the few relevant studies at present. Based on subgroup analysis, we found that the supplement of NAD+ precursors seems to have little effect on healthy people, but it has a significant beneficial effect on patients with cardiovascular disease and dyslipidemia. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
Chapter
Dyslipidemia plays a significant role in the atherosclerotic process and has well-established detrimental effects on the cardiovascular system, while hypolipidemic therapy results in significant benefits and substantially reduces cardiovascular events. This review aims to analyze the relationship between dyslipidemia and erectile dysfunction (ED), the extent of this correlation, and the pathophysiological mechanisms mediating this relationship. Secondly, we focus critically on the studies defining the impact of statins on ED, once the outcomes are to some extent conflicting and tried to clarify potential within-class and dose differences. Finally, we present the effects of other hypolipidemic agents, such as fibrates and niacin, on erectile function and discuss available data. These are the three main axes of this review, incorporating current evidence.
Chapter
Many cultures throughout history have passed down knowledge rumored to enhance sexual performance of both men and women including sexual techniques, foods, and nutritional supplements. Sexual techniques can take the form of stimulating certain aspects of the female anatomy and sexual positions such as stimulation of the Grafenberg “G” spot. Other techniques focus on the psychological aspects of sex including synchronization of orgasms and ejaculation prolongation. Cultures around the world have imbued foods as aphrodisiacs, in addition to herbs, plants, and other dietary supplements, collectively known as nutraceuticals. Among the more common ones are pomegranates, antioxidant rich foods, omega-3, basil, cardamom, garlic, watermelon, oysters, l-arginine, caffeine, and dehydroepiandrosterone (DHEA). Herbs such as Chlorophytum borivilianum of the Indian subcontinent to Lepidium meyenii of the South American Andes have long been reported to have aphrodisiac qualities. Many of these products are rich in components that promote cardiovascular health, produce anti-inflammatory activity, cause vasodilatation and increase androgen levels—all important factors in sexual performance. This chapter reviews the various sexual enhancement techniques, foods, and nutraceuticals and the evidence to support their use.
Article
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Objectives: To systematically review and discuss the current evidence from placebo-controlled clinical trials that investigated the use of alternative medicines and herbal remedies in the management of erectile dysfunction (ED). Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic review using specific keyword combinations was conducted on the PubMed and Scopus databases. Randomised controlled trials investigating herbal medicine in at least one group and using the International Index of Erectile Function (IIEF) as an outcome in patients primarily diagnosed with ED were included for review. Results: Following the literature search, screening and eligibility analysis, a total of 42 articles were included. The 42 articles were categorised as single herb extractions (n = 14), combination herbal formula (n = 5), combination of herbal formula and non-herbal nutraceuticals (n = 7), non-herbal nutraceuticals (n = 5), acupuncture and moxibustion (n = 2), diet and nutrition (n = 3), exercise (n = 5), and topical treatments (n = 1). Based on the results, Korean ginseng, Pygnogenol and Prelox, Tribulus terrestris, Lepidium meyenii, L-arginine, acupuncture and lifestyle interventions were the more predominantly investigated treatments interventions for ED. Conclusions: Panax ginseng, Pygnogenol, Prelox and Tribulus terrestris have promising evidence as herbal products, alongside L-arginine as a nutritional supplement, for ED based on IIEF outcomes, and warrant further clinical investigation. The mechanisms of action remain unclear, but each of these appears to in part increase nitric oxide synthesis. Importantly, improved diet and exercise should be considered, particularly in patients with obesity or diabetes mellitus.
Chapter
Erectile dysfunction (ED) is defined as an inability to achieve or maintain penile erection sufficiently enough for sexual performance. Sexual function involves an interplay between psychological, vascular, neurological, endocrine functions; thus the various etiologies of ED can be divided into psychosocial or organic causes. Current mainstays of treatment for ED are centered around enhancing levels of nitric oxide at the nerve terminal with pharmacologic agents such as phosphodiesterase inhibitors, followed by more invasive therapies such as intracavernosal injections and penile prosthesis. The market for supplements for ED has been growing in popularity and has warranted further investigation into mechanisms of action and efficacy. This chapter discusses several supplements that have been marketed as therapies for ED, their efficacies in clinical trials, as well as their mechanism of action on the biochemical level, safety profiles, and adverse effects.
Article
Nicotinic acid has complex effects on lipoprotein metabolism; it increases HDL cholesterol, decreases triglycerides and LDL cholesterol. It also reduces lipoprotein(a) levels by about 25% and exerts certain effects that may be antiatherogenic. Studies performed in the pre-statin era demonstrated a good effectiveness of nicotinic acid on the development of atherosclerotic lesions and on the morbidity and mortality due to cardiovascular diseases. Because of its HDL cholesterol raising properties, nicotinic acid appears to be an ideal companion to statins since low HDL cholesterol concentration has been shown to negatively influence statin-treated patients even when ideal LDL cholesterol concentrations have been reached. In the AIM-HIGH study nicotinic acid did not lead to an improvement in the cardiovascular event rate compared to placebo; however this study has been criticized because of several drawbacks. The results of a large study testing the effect of nicotinic acid in high-risk statin-treated patients are expected to be published in 2013. At present, nicotinic acid can be administered in addition to a statin to patients with a combined hyperlipidemia when the target value of LDL cholesterol has not been reached, and alone to patients suffering from a statin intolerance. An elevation of lipoprotein(a) is not officially recognized as an indication to start a therapy with nicotinic acid. The combination of modified-release nicotinic acid with laropiprant is much better tolerated than previous formulations. New drugs which act on the receptor involved in the action of nicotinic acid are in development.
Article
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Phosphodiesterase-5 (PDE-5) inhibitors are an effective therapy for the majority of men with erectile dysfunction (ED). However, many men with ED still report a suboptimal or partial response even after an adequate trial of oral PDE-5 therapy. Since ED is associated with impaired vascular function and both atorvastatin and quinapril have been previously shown to improve vascular function, we examined the effects of adjunctive treatment with these medications in men with vasculogenic ED who were suboptimal responders to 100 mg of sildenafil. Men with ED and suboptimal response to sildenafil were randomly assigned to 3 months of treatment with atorvastatin 40 mg (n = 12), quinapril 10 mg (n = 10), or placebo (n = 13), along with continued adjunctive sildenafil use. Measured variables included: International Index of Erectile Function (IIEF) questionnaire, brachial artery flow-mediated dilation (FMD), endothelium-independent dilation (EID) via nitroglycerin, penile Doppler blood flow, blood pressure (BP), lipids, and C-reactive protein (CRP). Compared to placebo, quinapril (p < 0.01) significantly improved symptoms of ED as measured by the IIEF-5 questionnaire. There was a trend toward a significant improvement in IIEF-5 with atorvastatin. Similarly, quinapril significantly improved the IIEF ED Domain (p < 0.05). Other peripheral and penile vascular parameters were unchanged with drug therapy as compared to placebo. In conclusion, treatment with quinapril, in combination with sildenafil, improved ED in men with suboptimal response to sildenafil alone. Atorvastatin demonstrated a trend toward improved ED in this group.
Article
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Erectile dysfunction (ED), defined as the inability to achieve and/or maintain a penile erection sufficient for sexual intercourse, is a health problem affecting more than one-half of men between the age of 40 and 70 years. The aim of the present study was to determine the potential factors affecting penile vascular flow and predictability of vascular flow in patients with ED. Totally 163 male patients between 29 and 82 years of age who were admitted to our outpatient clinic with complaints of ED were included. After a detailed medical history was obtained, all patients were asked to complete the International Index of Erectile Function (IIEF) questionnaire. Blood samples were obtained for measurements of serum cholesterol, triglycerides, and fasting blood glucose (FBG), and the body mass index (BMI) was calculated. Penile color Doppler ultrasonography (PDU) was performed to evaluate flow patterns, Mann-Whitney U-test and Spearman correlation analyses were used to assess the relationship of PDU findings with hypertension, obesity (BMI ≥ 25 kg/m(2) ), FBG, and cholesterol levels measurements. The mean age, IIEF score, and BMI of the study population was 51.3 ± 12.1 years, 11.9 ± 6.1 and 28.5 ± 4.0 kg/m(2), respectively. When the vascular pathologies detected with PDU and the presence of risk factors were compared, no significant correlation was determined between arterial insufficiency and metabolic syndrome (MS), whereas there was a significant correlation between veno-occlusive dysfunction and MS. The prevalence of ED increases with advanced age and with the presence of a systemic disease. Basic evaluations may not always be sufficient for assessment of ED. In the presence of MS, the use of penile Doppler ultrasonography should be considered for the evaluation of penile vascular structures in ED patients.
Conference Paper
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Despite the initial enthusiasm, the significant number of patients in whom sildenafil is contraindicated or ineffective is a major challenge to all urologists. Our aim was to determine the safety and efficacy of adjunctive atorvastatin in restoring normal erectile function in hypercholesterolemic (low-density lipoprotein (LDL) cholesterol >120 mg per 100 ml) sildenafil nonresponders. The study comprised 131 men with ED not responding to sildenafil citrate. They were randomized either to 40 mg atorvastatin daily (n=66, group 1) or matching placebo (n=65, group 2) for 12 weeks while they were taking on-demand 100 mg sildenafil. Erectile function was subjectively assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire and response to the global efficacy question (GEQ). Serum biochemical and lipid profile (total cholesterol, triglycerides, LDL cholesterol and high-density lipoprotein cholesterol) analyses were performed at baseline and repeated at post-treatment weeks 6 and 12. Compared with the placebo group (59 patients, mean age+/-s.d. 61.9+/-6.1, mean years ED 3.9+/-1.8), the atorvastatin group (59 patients, mean age+/-s.d. 63.9+/-6.9, mean years ED 3.7+/-1.6) had significantly greater improvements in all IIEF-5 questions (P=0.01) and GEQ (P=0.001). Subgroup analyses did reveal trends in the atorvastatin group to indicate that a change in the IIEF-5 score is affected by age, severity of ED and baseline serum levels of LDL. Patients with moderate (r=0.28, P=0.01) and severe (r=0.20, P=0.01) ED had better positive response rates to adjunctive atorvastatin than patients with mild to moderate ED. None of the patients taking atorvastatin achieved a response of 5 to the IIEF-5 questions and none of the patients regained normal erectile function as defined by the IIEF-5 score >21. Subjects experienced a statistically significant but modest improvement in erectile function. Further investigation is needed to test the usefulness of long-term atorvastatin administration to restore erectile function in sildenafil nonresponders.
Article
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An abridged five-item version of the 15-item International Index of Erectile Function (IIEF) was developed (IIEF-5) to diagnose the presence and severity of erectile dysfunction (ED). The five items selected were based on ability to identify the presence or absence of ED and on adherence to the National Institute of Health's definition of ED. These items focused on erectile function and intercourse satisfaction. For 1152 men (1036 with ED, 116 controls) analyzed, a receiver operating characteristic curve indicated that the IIEF-5 is an excellent diagnostic test. Based on equal misclassification rates of ED and no ED, a cutoff score of 21 (range of scores, 5-25) discriminated best (sensitivity=0.98, specificity=0. 88). ED was classified into five severity levels, ranging from none (22-25) through severe (5-7). Substantial agreement existed between the predicted and 'true' ED classes (weighted kappa=0.82). These data suggest that the IIEF-5 possesses favorable properties for detecting the presence and severity of ED.
Article
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Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL. In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group. Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.
Article
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The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. It is has been recommended as a primary endpoint for clinical trials of erectile dysfunction (ED) and for diagnostic evaluation of ED severity. The IIEF was developed in conjunction with the clinical trial program for sildenafil, and has since been adopted as the 'gold standard' measure for efficacy assessment in clinical trials of ED. It has been linguistically validated in 32 languages and used as a primary endpoint in more than 50 clinical trials. This review summarizes early stages in the psychometric validation of the instrument, its subsequent adoption in randomized clinical trials with sildenafil and other ED therapies, and its use in classifying ED severity and prevalence. The IIEF meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity, and correlates well with other measures of treatment outcome. It has demonstrated consistent and robust treatment responsiveness in studies in USA, Europe and Asia, as well as in a wide range of etiological subgroups. Although only one direct comparator trial has been performed to date, the IIEF is also sensitive to therapeutic effects with treatment agents other than sildenafil. A severity classification for ED has recently been developed, in addition to a brief screening version of the instrument. This review includes the strengths as well as limitations of the IIEF, along with some potential areas for future research.
Article
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Nicotinic acid (niacin) has long been used for the treatment of lipid disorders and cardiovascular disease. Niacin favorably affects apolipoprotein (apo) B-containing lipoproteins (eg, very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], lipoprotein[a]) and increases apo A-I-containing lipoproteins (high-density lipoprotein [HDL]). Recently, new discoveries have enlarged our understanding of the mechanism of action of niacin and challenged older concepts. There are new data on (1) how niacin affects triglycerides (TGs) and apo B-containing lipoprotein metabolism in the liver, (2) how it affects apo A-I and HDL metabolism, (3) how it affects vascular anti-inflammatory events, (4) a specific niacin receptor in adipocytes and immune cells, (5) how niacin causes flushing, and (6) the characterization of a niacin transport system in liver and intestinal cells. New findings indicate that niacin directly and noncompetitively inhibits hepatocyte diacylglycerol acyltransferase-2, a key enzyme for TG synthesis. The inhibition of TG synthesis by niacin results in accelerated intracellular hepatic apo B degradation and the decreased secretion of VLDL and LDL particles. Previous kinetic studies in humans and recent in vitro cell culture findings indicate that niacin retards mainly the hepatic catabolism of apo A-I (vs apo A-II) but not scavenger receptor BI-mediated cholesterol esters. Decreased HDL-apo A-I catabolism by niacin explains the increases in HDL half-life and concentrations of lipoprotein A-I HDL subfractions, which augment reverse cholesterol transport. Initial data suggest that niacin, by inhibiting the hepatocyte surface expression of beta-chain adenosine triphosphate synthase (a recently reported HDL-apo A-I holoparticle receptor), inhibits the removal of HDL-apo A-I. Recent studies indicate that niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress and vascular inflammatory genes, key cytokines involved in atherosclerosis. The niacin flush results from the stimulation of prostaglandins D(2) and E(2) by subcutaneous Langerhans cells via the G protein-coupled receptor 109A niacin receptor. Although decreased free fatty acid mobilization from adipose tissue via the G protein-coupled receptor 109A niacin receptor has been a widely suggested mechanism of niacin to decrease TGs, physiologically and clinically, this pathway may be only a minor factor in explaining the lipid effects of niacin.
Article
Background Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin–niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of high-density lipoprotein (HDL) cholesterol. Methods In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels, and normal low-density lipoprotein (LDL) cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, antioxidants, simvastatin–niacin plus antioxidants, or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). Results The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by –42 percent and +2...
Article
Background: Erectile dysfunction (ED) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction. Statin drugs may improve endothelial function, even before altering the lipid profile. Objective: We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil. Methods: Men with moderate-to-severe ED despite an adequate sildenafil trial were enrolled in this randomized, double-blind, placebo-controlled pilot study. ED was defined using a validated self-administered questionnaire as a score of <or=16 on the International Index of Erectile Function (erectile function domain score range of 6-30). Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin (80 mg daily) or matching placebo. Results: Twelve men (mean age 58 +/- 13 years) with a mean domain score of 8.2 +/- 6.9 and a mean duration of ED of 3.7 years were enrolled in the study. Treatment with atorvastatin decreased mean low-density lipoprotein cholesterol by 43% and resulted in an improvement with sildenafil in domain score of 7.8 (P = 0.036); an effect was apparent by 6 weeks. The increase in domain score in placebo patients was not statistically significant. Conclusions: Treatment with atorvastatin improved sexual function and the response to oral sildenafil in men who did not initially respond to treatment with sildenafil. The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial.
Article
Introduction: For many years, erectile dysfunction (ED) has been considered as a complication of cardiovascular disease (CVD) or regarded as a late consequence of generalized arterial disease. However, a growing body of evidence suggests that ED is an early manifestation of atherosclerosis and a precursor to systemic vascular disease. Aim: We conducted a meta-analysis to evaluate the association between ED and the risk of CVD events. Methods: Relevant studies published between January 1966 and September 2009 were identified by searching Medline, Embase, and The Cochrane Library. Studies were selected using a prior defined criteria. The strength of the relationship between ED and CVD events was assessed by adjusted relative risks (RRs). Main outcome measures: The adjusted RRs of CVD events. Results: A total of 45,558 participants from seven cohort studies (eight full-text articles) were identified in this meta-analysis. The studies provided adjusted RRs estimates for ED subjects comparing with health subjects, leading to a pooled adjusted RR of 1.47 (95% confidence interval [CI], 1.29-1.66, P < 0.001; P for heterogeneity = 0.152; I(2) = 36.2%) for CVD events. The risks of CVD, all-cause mortality and myocardial infarction were 1.41 (95% CI, 1.22-1.64 P < 0.001), 1.23 (95% CI, 1.02-1.48; P = 0.034), and 1.43 (95% CI, 1.10-1.85 P = 0.007), respectively. The overall adjusted RR decreased significant from 1.63 (<7 years) to 1.37 (≥ 7 years) along with the elongation of follow-up. Conclusions: There is evidence of an increased risk of CVD events for patients with ED. Patients who are discovered to have ED are supposed to be thoroughly assessed for cardiovascular risk and occult systemic vascular disease.
Article
Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins; however, the incremental impact of adding niacin to background statin therapy is unknown. This was a double-blind randomized placebo-controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of high-density lipoprotein cholesterol (HDL-C; <45 mg/dL). The primary end point was the change in common carotid intima-media thickness (CIMT) after 1 year. Baseline CIMT (0.884+/-0.234 mm), low-density lipoprotein cholesterol (89+/-20 mg/dL), and HDL-C (40+/-7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90%, and 149 patients (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (0.044+/-0.100 mm; P<0.001) and was unchanged in the niacin group (0.014+/-0.104 mm; P=0.23). Although the overall difference in IMT progression between the niacin and placebo groups was not statistically significant (P=0.08), niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P=0.026). Clinical cardiovascular events occurred in 3 patients treated with niacin (3.8%) and 7 patients treated with placebo (9.6%; P=0.20). The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.
Article
Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Outcomes in subjects with LDL-C < 100, > or = 100 to < 130, or > or = 130 mg/dL [< 2.59, > or = 2.59 to < 3.36, or > or = 3.36 mmol/L]; TC/HDL-C ratio < 3.5 vs. > or = 3.5, and presence or absence of metabolic syndrome. Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (> or = 3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed.
Article
One of the proposed mechanisms responsible for diabetes-related erectile dysfunction (ED) is overactivity of RhoA/ROCK signaling, as seen in experimental models of chemical diabetes. Because statins may interfere with RhoA/Rho-kinase (ROCK) signaling through the reduction of geranyl-geranyl pyrophosphate (GGPP), required for RhoA activation, we investigated whether atorvastatin ameliorated diabetes-related ED. Streptozotocin-induced (8 weeks) diabetic rats and alloxan-induced (8 weeks) diabetic rabbits received atorvastatin (5 mg/kg daily) for the last 2 weeks. In vitro contractility studies were conducted in the rabbit model. In the rat model, sildenafil effect on electrical stimulation (ES)-induced erection was investigated. Atorvastatin action was also analyzed using human fetal penile smooth muscle cells (hfPSMCs) exposed to low (5 mM), high (22 mM), and very high (40 mM) glucose. Atorvastatin effect on hyperglycemia-induced RhoA/ROCK signaling was evaluated using the ROCK inhibitor Y-27632 in both animal models and by analyzing functional effects downstream to RhoA activation in hfPSMCs. In both diabetic models, atorvastatin did not affect glycemia, lipid plasma levels, and the hypogonadal state. In diabetic rats, atorvastatin ameliorated the erectile response to the ES of the cavernous nerve and normalized sildenafil effect on erectile function, strongly decreased by diabetes. In penile tissue from diabetic animals, atorvastatin completely restored the diabetes-induced hypersensitivity to Y-27632 and prevented RhoA membrane translocation/activation. In hfPSMCs, high glucose significantly increased not only membrane RhoA expression, but also ROCK activity (increased phosphorylation of the ROCK substrate myosin phosphatase target subunit 1) and several RhoA-dependent functions such as proliferation, migration, and smooth muscle-related gene expression. Atorvastatin restored all the high-glucose-induced effects, an action specifically reverted by GGPP. Atorvastatin improves diabetes-related ED and restores sildenafil responsiveness, most probably by inhibiting RhoA/ROCK signaling, which underlies several high-glucose-induced derangements in penile smooth muscle cell commitment.
Article
We provide current, normative data on the prevalence of impotence, and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study. The Massachusetts Male Aging Study was a community based, random sample observational survey of noninstitutionalized men 40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston, Massachusetts. Blood samples, physiological measures, socio-demographic variables, psychological indexes, and information on health status, medications, smoking and lifestyle were collected by trained interviewers in the subject's home. A self-administered sexual activity questionnaire was used to characterize erectile potency. The combined prevalence of minimal, moderate and complete impotence was 52%. The prevalence of complete impotence tripled from 5 to 15% between subject ages 40 and 70 years. Subject age was the variable most strongly associated with impotence. After adjustment for age, a higher probability of impotence was directly correlated with heart disease, hypertension, diabetes, associated medications, and indexes of anger and depression, and inversely correlated with serum dehydroepiandrosterone, high density lipoprotein cholesterol and an index of dominant personality. Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension. We conclude that impotence is a major health concern in light of the high prevalence, is strongly associated with age, has multiple determinants, including some risk factors for vascular disease, and may be due partly to modifiable para-aging phenomena.
Article
To develop a brief, reliable, self-administered measure of erectile function that is cross-culturally valid and psychometrically sound, with the sensitivity and specificity for detecting treatment-related changes in patients with erectile dysfunction. Relevant domains of sexual function across various cultures were identified via a literature search of existing questionnaires and interviews of male patients with erectile dysfunction and of their partners. An initial questionnaire was administered to patients with erectile dysfunction, with results reviewed by an international panel of experts. Following linguistic validation in 10 languages, the final 15-item questionnaire, the international index of Erectile Function (IIEF), was examined for sensitivity, specificity, reliability (internal consistency and test-retest repeatability), and construct (concurrent, convergent, and discriminant) validity. A principal components analysis identified five factors (that is, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) with eigenvalues greater than 1.0. A high degree of internal consistency was observed for each of the five domains and for the total scale (Cronbach's alpha values of 0.73 and higher and 0.91 and higher, respectively) in the populations studied. Test-retest repeatability correlation coefficients for the five domain scores were highly significant. The IIEF demonstrated adequate construct validity, and all five domains showed a high degree of sensitivity and specificity to the effects of treatment. Significant (P values = 0.0001) changes between baseline and post-treatment scores were observed across all five domains in the treatment responder cohort, but not in the treatment nonresponder cohort. The IIEF addresses the relevant domains of male sexual function (that is, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), is psychometrically sound, and has been linguistically validated in 10 languages. This questionnaire is readily self-administered in research or clinical settings. The IIEF demonstrates the sensitivity and specificity for detecting treatment-related changes in patients with erectile dysfunction.
Article
We have characterized the prostanoid receptors involved in the regulation of human penile arterial and trabecular smooth muscle tone. Arachidonic acid induced relaxation of human corpus cavernosum strips (HCCS) that was blocked by the cyclo-oxygenase inhibitor, indomethacin, and augmented by the thromboxane receptor (TP) antagonist, SQ29548, suggesting that endogenous production of prostanoids regulates penile smooth muscle tone. TP-receptors mediate contraction of HCCS and penile resistance arteries (HPRA), since the agonist of these receptors, U46619, potently contracted HCCS (EC50 8.3±2.8 nM) and HPRA (EC50 6.2±2.2 nM), and the contractions produced by prostaglandin F2α at high concentrations (EC50 6460±3220 nM in HCCS and 8900±6700 nM in HPRA) were inhibited by the selective TP-receptor antagonist, SQ29548 (0.02 μM). EP-receptors are responsible for prostanoid-induced relaxant effects in HCCS because only prostaglandin E1 (PGE1), prostaglandin E2 and the EP2/EP4-receptor agonist, butaprost, produced consistent relaxation of this tissue (EC50 93.8±31.5, 16.3±3.8 and 1820±1284 nM, respectively). In HPRA, both prostacyclin and PGE1 (EC50 60.1±18.4 and 109.0±30.9 nM, respectively) as well as the selective IP receptor agonist, cicaprost, and butaprost (EC50 25.2±15.2 and 7050±6020 nM, respectively) caused relaxation, suggesting co-existence of IP- and EP-receptors (EP2 and/or EP4). In summary, endogenous production of prostanoids may regulate penile smooth muscle contractility by way of specific receptors. TP-receptors mediate contraction in HCCS and HPRA, while the relaxant effects of prostanoids are mediated by EP2- and/or EP4-receptors in HCCS and by EP- and IP-receptors in HPRA. British Journal of Pharmacology (2002) 136, 23–30; doi:10.1038/sj.bjp.0704675
Article
Prostaglandin D(2) (PGD(2)) binds to specific G-protein coupled receptors (DP) and induces smooth muscle relaxation by stimulating the synthesis of intracellular cAMP. In this study, we examined the role of PGD(2) and DP receptors in regulating human penile smooth muscle contractility. We determined that human corpus cavernosum tissue and smooth muscle cells in culture expressed functional DP receptor and lipocalin-like prostaglandin D synthase by reverse-transcribed polymerase chain reaction (RT-PCR). Functional PGD synthase activity was confirmed by the synthesis of PGD(2) in human corpus cavernosum smooth muscle cells upon addition of exogenous arachidonic acid. Organ bath preparations of human corpus cavernosum tissue strips, contracted with phenylephrine, relaxed in a dose-dependent fashion to either PGD(2) or the DP selective agonist BW245C. Cultures of human corpus cavernosum smooth muscle cells treated with BW245C showed a two-fold increase in cAMP synthesis. These data are consistent with the expression of functional DP receptors in human corpus cavernosum. This suggests the presence of an intact prostanoid autocrine system that may play a role in regulating penile erectile function.
Article
Niacin (nicotinic acid) is the broad-spectrum lipid drug, which lowers the concentration of all atherogenic plasma lipids/lipoproteins and at the same time raises the levels of the protective HDL (high-density lipoprotein). Niaspan is a prolonged release (PR) formulation of niacin, which has considerable advantages over both immediate release (IR) and slow release (SR) formulations of this drug. The major early side effect of IR niacin, the flush, is reduced with Niaspan. The hepatotoxic effects with SR niacin are not present with Niaspan. It is suitable for once daily prescription at bedtime. Niaspan is effective as monotherapy and in combination with other lipid-lowering drugs such as statins and fibrates. It is particularly useful for treatment of the dyslipidaemia of type 2 diabetes, where IR but not PR niacin may deteriorate the diabetic condition. Overall, niacin, now available as the well-tolerable drug formulation Niaspan, is the unique broad-spectrum lipid drug for the prevention and treatment of clinical atherosclerosis.
Article
Nicotinic acid has, like the Roman God Janus, two faces. One is the vitamin. The other is the broad-spectrum lipid drug. The Canadian pathologist Rudolf Altschul discovered 50 years ago that nicotinic acid in gram doses lowered plasma levels of cholesterol. From the point of view of treatment of the dyslipidaemias that are risk factors for clinical atherosclerosis nicotinic acid is a miracle drug. It lowers the levels of all atherogenic lipoproteins--VLDL and LDL with subclasses as well as Lp(a)--and in addition it raises more than any other drug the levels of the protective HDL lipoproteins. Trials have shown that treatment with nicotinic acid reduces progression of atherosclerosis, and clinical events and mortality from coronary heart disease. The new combination treatment with statin-lowering LDL and nicotinic acid-raising HDL is reviewed. A basic effect of nicotinic acid is the inhibition of fat-mobilizing lipolysis in adipose tissue leading to a lowering of plasma free fatty acids, which has many metabolic implications which are reviewed. The very recent discovery of a nicotinic acid receptor and the finding that the drug stimulates the expression of the ABCA 1 membrane cholesterol transporter have paved the way for exciting and promising new 50 years in the history of nicotinic acid.
Article
Nicotinic acid, used for atherosclerosis treatment, has an adverse effect of skin flushing. The flushing mechanism, thought to be caused by the release of prostaglandin D(2) (PGD(2)), is not well understood. We aimed to identify which cells mediate the flushing effect. Nicotinic acid receptor (GPR109A) gene expression was assessed in various tissues and cell lines. Cells expressing GPR109A mRNA were further assayed for PGD(2) release in response to nicotinic acid. Of all samples, only skin was able to release PGD(2) upon stimulation with nicotinic acid. The responsive cells were localized to the epidermis, and immunocytochemical studies revealed the presence of GPR109A on epidermal Langerhans cells. CD34+ cells isolated from human blood and differentiated into Langerhans cells (hLC-L) also showed GPR109A expression. IFNgamma treatment increased both mRNA and plasma membrane expression of GPR109A. IFNgamma-stimulated hLC-Ls released PGD(2) in response to nicotinic acid in a dose-dependant manner (effector concentration for half-maximum response=1.2 mM+/-0.7). Acifran, a structurally distinct GPR109A ligand, also increased PGD(2) release, whereas isonicotinic acid, a nicotinic acid analog with low affinity for GPR109A, had no effect. These results suggest that nicotinic acid mediates its flushing side effect by interacting with GPR109A on skin Langerhans cells, resulting in release of PGD(2).
Article
The ARBITER 2 trial showed that extended-release niacin (ERN) when added to statin monotherapy slowed the progression of carotid atherosclerosis over 12 months. Whether longer treatment with ERN would have a greater effect on carotid intima-media thickness (CIMT) is unknown. We examined the long-term effects of ERN on high density lipoprotein (HDL-C) cholesterol and CIMT during 12-24 months treatment with ERN in ARBITER 2 participants who were either continued or were crossed over (from placebo) to ERN 1000 mg daily. Among 149 subjects completing ARBITER 2, 130 (88%) enrolled in ARBITER 3. The prespecified primary endpoints were the within-group change in CIMT and HDL-C in patients receiving placebo for 12 months (n = 71), ERN for 12 months (comprised of subjects from ERN treatment during ARBITER 2 (n = 78) and those crossed over to ERN from placebo after ARBITER 2 (n = 47)), and ERN for 24 months spanning ARBITER 2 and 3 (n = 57). Five subjects discontinued the study due to flushing side effects. The study was completed by 104 subjects (47 crossed over from placebo; 57 with ERN continued from ARBITER 2). HDL-C increased in the ERN group from 39.5 +/- 6.7 to 48.6 +/- 13.3 mg/dl (p < 0.001) along with modest reductions in LDL-C and TG. Among 125 participants treated with ERN for 12 months, there was a net regression of CIMT of -0.027 +/- 0.011 mm (p < 0.001 vs. placebo). Among 57 participants treated with ERN for 24 months, there was additional significant regression of CIMT of -0.041 +/- 0.021 mm (p = 0.001 vs. placebo). Controlling for changes in LDL and triglycerides, only changes in HDL-C were independently associated with regression of CIMT (beta = -0.25; p = 0.001). When added to statin therapy, ERN significantly increases HDL-C and induces atherosclerosis regression measured by CIMT over 24 months. Limitations to this study include its open-label design and the inability to relate CIMT effects to clinical outcomes.
Article
With three effective and safe phosphodiesterase type 5 (PDE5) inhibitors, the clinician now has multiple choices in the treatment of patients who have erectile dysfunction of all severities and etiologies. Based on pharmacokinetics, pharmacodynamics, efficacy, and safety, each of these agents can be used. Because no well-controlled head-to-head selection or patient preference studies are available, each clinician must choose an agent based on the profile of the patient, his tolerance, risk factors, and side effects. This discussion summarizes some of the current data on PDE5 inhibitors and their efficacy, safety, and use in other conditions.
Article
There is a close link between hyperlipidemia/dyslipidemia and erectile dysfunction (ED), with endothelial dysfunction as a common mechanism. Both ED and hyperlipidemia/dyslipidemia are rising in prevalence with mounting evidence that these conditions are harbingers of cardiovascular disease. This review was conducted to provide an update on the epidemiology and oral therapy of both dyslipidemia and ED, the connection between these two conditions, and clinical outcomes relating to the use of statins and phosphodiesterase type-5 (PDE5) inhibitors in men with ED who have associated dyslipidemia. A systematic search was performed of MEDLINE and EMBASE research databases to obtain articles pertaining to the epidemiology, mechanism, and clinical outcomes of statins and PDE5 inhibitors in men with ED and associated dyslipidemia. The clinical and preclinical studies related to ED and dyslipidemia are analyzed and their findings are assessed and summarized. Results. Hyperlipidemia/Dyslipidemia constitute a vascular risk factor having a considerable impact on erectile function. Furthermore, the role of endothelial dysfunction in the pathophysiology of both ED and dyslipidemia is paramount suggesting the importance of comanaging these conditions. Therefore, hyperlipidemia/dyslipidemia when present in patients with ED should prompt management with diet/exercise as well as appropriate pharmacotherapy. With ED being often associated with comorbidities, the use of concomitant pharmacotherapies enhances opportunities for managing the overall global cardiometabolic risk. Newer studies assessing the effect of PDE5 inhibitors in men with dyslipidemia will shed more light on the clinical profile of these agents when used in this patient population. While dyslipidemia and ED are important concerns for clinicians, there exists a gap that needs to be closed between the number of individuals who have either or both conditions and those who are receiving appropriate therapy based on evidence and patient-driven goals regarding clinical outcomes.
Article
This study evaluated the effect of correction of serum cholesterol levels on erectile function and sildenafil treatment in patients with erectile dysfunction who have only hypercholesterolaemia as a risk factor for erectile dysfunction. Twenty-five patients with a single risk factor (hypercholesterolaemia, serum cholesterol > 200 mg/dl) for erectile dysfunction were included in the study. The patients were recommended to take sildenafil (minimum two 100 mg tablets/week) 1 h before sexual intercourse for 4 weeks. After 1 month washout period, the patients received a single dose of atorvastatin 10 mg/day for 1 month. Similarly, after a 1 month washout period, atorvastatin 10 mg/day and sildenafil (minimum two 100 mg tablets/week) were administered for 1 month as combination therapy. Erectile function was evaluated before and after all treatment regimens using the International Index of Erectile Function (IIEF). Following each treatment modality mean IIEF scores were significantly higher than baseline IIEF scores (p < 0.01). The IIEF score after sildenafil treatment was significantly higher than in the atorvastatin treatment group (p < 0.01); and the IIEF score after combined treatment was significantly higher than in the sildenafil and atorvastatin treatment groups. Correction of serum cholesterol levels with atorvastatin could improve erectile function in patients who have only hypercholesterolaemia as a risk factor for erectile dysfunction. Furthermore, atorvastatin could improve sildenafil's effects on erectile function in hypercholesterolaemic patients with erectile dysfunction.