2型糖尿病伴勃起功能障碍的相关发病因素探讨

目的:探讨中青年2型糖尿病(T2DM)患者伴发勃起功能障碍(ED)与血管、神经和雄激素等因素的关系,为ED早期防治提供临床依据。方法:53例50岁以下男性T2DM患者按国际勃起功能指数-5(IIEF-5)评分分为ED组(IIEF评分≤21,n=28)和非ED组(NED组)(IIEF评分≥22,n=28),测定两组血脂、血糖、血清总睾酮(TT)、性激素结合蛋白(SHBG)、硫酸脱氢表雄酮(DHEA-S)、计算法游离睾酮(cFT)等指标,检查两组视网膜病变(DR)、大血管病变和周围神经病变(DPN)等并发症,比较两组各指标及并发症的差异。结果:两组年龄、糖尿病病程、体重指数、血压、血脂、血糖水平具有可比性(P>0.05),ED组DR发生率(39.3%)高于NED组(4.0%)(P<0.05),两组TT、DHEA-S、cFT水平及大血管病变和DPN发生率差异均无统计学意义(P>0.05)。结论:T2DM患者伴ED发生与DR关系密切,对合并DR的T2DM患者尤应早期关注其勃起功能。     

Serum testosterone levels in diabetic men with and without erectile dysfunction

Diabetes mellitus is a common chronic disease, affecting 0.5–2% worldwide. The Massachusetts Male Aging Study reported that up to 75% of men with diabetes have a lifetime risk of developing ED. Type 2 diabetes is associated with low total serum testosterone (TT) identified in several cross‐sectional studies and systemic analyses. There is a lack of consensus regarding what constitutes the lowest level of testosterone within the boundaries of normality. In this retrospective study, we sought to evaluate the effect of associated co‐morbidities on serum total testosterone (TT) level in men with type 2 diabetes DM, either with or without erectile dysfunction (ED). Three hundred and ninety‐one patients were evaluated for erectile function using an abridged, five‐item version of the International Index of Erectile Function‐5. Measurements of TT, fasting lipid profile, blood sugar and glycated haemoglobin (HbA1c) were conducted. Penile hemodynamics was assessed using intracavernosal injection and penile duplex study. Hypogonadism was found in 126 cases (33.2%), and normal TT was observed in 254 (66.8%). ED was detected in 119 cases in the hypogonadal group (94.4%) as compared to 155/254 (61.0%) in eugonadal group, P = 0.0001. TT was lower in diabetic men with ED as compared to those with normal erectile function (EF), 392.4 ± 314.9 versus 524.3 ± 140.2 ng dl^?1, respectively, P < 0.0001. After exclusion of patients with hypertension and dyslipidaemia, 185 men were evaluated, and there was no difference in the mean TT level among men with ED 490.6 ± 498.2 ng dl^?1 versus normal EF 540.6 ± 133.4 ng dl^?1 although, HbA1c remained lower in men with normal erectile function. Receiver operating characteristic (ROC) curve of TT in men without associated co‐morbidities showed that EF was compromised at TT = 403.5 ng dl^?1 or less. Sensitivity of 63.3% and a specificity of 94.0% were detected. At this level, ED was found in 33/38 (86.8%) men with TT 403.5 ng dl^?1, whereas ED was observed in 57/147 (38.8%) men with TT ≥ 403.5 ng dl^?1 (P < 0.0001). We propose a cut‐off value of 403.5 ng dl^?1 of TT blood levels as an indicator for initiation of testosterone replacement therapy in diabetic men with ED. Further prospective controlled trials are recommended.     

Determination of serum testosterone in experimental diabetes with erectile dysfunction

To study the mechanisms of erectile dysfunction (ED) in ex-perimental diabetic (DM) rats, streptozotocin (STZ) was injectedintraperitoneally into Sprague-Dewley rats to make experimentalmodels of DM. Rats showing apparent ED after apomorphine injec-tion were selected for the experiment. Penile erections were studiedon the 6th, 8th and 12th week after injection of apomorphine. Theconcentration of LH, FSH and testosterone (T) were examined andmicrostructure of testes were observed. Results indicated that theserum T was decreased significantly with marked changes in testicu-lar histology; the degree of both was closely related to the durationof DM. The concentration of LH did not change on the early days,but decreased significantly later in the course. FSH concentrationswere not changed. As conclusions, penile erection and synthesis oftestosterone are affected seriously by DM, and the decrease of Tconcentration may be one of the most important mechanisms.(Chin J Androl 2000; 4: 227 - 230)     

Visceral adiposity index is useful for evaluating obesity effect on erectile dysfunction

Studies show that erectile dysfunction (ED) is associated with obesity, and it has been shown that the possibility of developing sexual dysfunction in obese men is 30% higher compared to those with normal weight. Obesity is measured using various methods, for example waist circumference (WC) measurement or body mass index (BMI), but recently, visceral adiposity index (VAI) has also been utilised to better assess obesity and metabolic syndrome. In our study, the potential link between VAI and ED was investigated. The data of 176 patients who presented to the urology outpatient clinic with erection complaints were retrospectively screened. A control group was also established with 122 men without complaints of erectile dysfunction. The erectile functions of all participants were determined using the International Erectile Function Index‐5 (IIEF‐5) scoring. In addition, their serum fasting blood glucose, total testosterone (TT), triglyceride (TG), low‐density lipoprotein (LDL) cholesterol and high‐density lipoprotein (HDL) cholesterol levels were measured. The physical examination comprised the measurement of WC, height and weight, and BMI. The mean age of the participants was 58.7 ± 8.4 for the ED group and 57.1 ± 7.5 for the control group. The mean VAI was statistically significantly higher in the ED group (5.32 ± 2.77) compared to the control group (4.11 ± 1.93) (p < 0.001). Since VAI contains both physical and metabolic parameters, our findings suggest that it discloses the effects of WC, BMI, HDL and TG more clearly. VAI is considered useful for the assessment of the effect of obesity on ED patients.     

Prevalence of late-onset hypogonadism in men with type 2 diabetes mellitus

Late-onset hypogonadism (LOH) or age-associated testosterone deficiency syndrome is defined as a clinical and biochemical syndrome associated with advancing age and characterised by symptoms and a deficiency in serum testosterone levels. This condition may result in significant detriment in the quality of life and adversely affect the function of multiple organ systems. It has been suggested that sex steroid hormones may play a causal role in the development of insulin resistance and type II diabetes. This comparative study was aimed at determining the prevalence of LOH in diabetic men with erectile dysfunction and investigating the effect of testosterone replacement therapy on erectile function and on glycaemic control.     

Testosterone levels in men with erectile dysfunction

OBJECTIVE: To investigate the frequency of hypogonadism in men with erectile dysfunction (ED) and to assess which factors are related with low testosterone levels. PATIENTS AND METHODS: In all, 165 men with ED were assessed; the evaluation included: hormonal profiles, serum total and free testosterone (using Vermeulen's formula) levels, and self-reported questionnaires on erectile function and desire domains of the International Index of Erectile Function. The frequency of hypogonadism was established using total and free testosterone levels as diagnostic criteria. The factors that might influence testosterone levels were evaluated by univariate and multivariate statistical analysis, and a logistic regression was used to determine which factors can predict free testosterone levels below normal limits (biochemical hypogonadism). RESULTS: Using the total testosterone levels, 4.8% of the men were hypogonadal, whereas when using the free testosterone levels, 17.6% were hypogonadal. In the univariate analyses, not smoking and hypertension were associated with lower total and free testosterone levels. Ageing, absence of nocturnal erections and a lower erectile function score were only associated with lower free testosterone serum levels. There was no association between total and free testosterone levels and desire. In the multivariate analysis, only total testosterone levels were related to hypertension, while free testosterone levels were related to age and nocturnal erections. For biochemical hypogonadism, simple logistic regression analysis selected age, erectile function score and aetiological diagnosis of ED as predictors. In the multivariate analysis only the erectile function score had significant independent prognostic value. CONCLUSIONS: The frequency of hypogonadism is higher when free testosterone levels are used for diagnosis. The total and free testosterone levels were not related to the level of sexual desire in men with ED. The free testosterone levels could be related to the quality and frequency of nocturnal erections, and when ED is more severe, it is more probable that free testosterone levels are below the 'normal' limit.     

The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction

In males, testosterone (T) levels decline with ageing. Several symptoms characteristic of the ageing process are similar to those related to hypogonadism. The aim of the present study was to evaluate the specific association among hypogonadism-related symptoms and signs and the ageing process. A consecutive series of 1647 (mean age 52.4 ± 13.1 years) male patients with sexual dysfunction were investigated. Several hormonal and biochemical, instrumental and psychological parameters were studied. The parameters significantly associated with total levels in the entire cohort, after adjustment for confounders, were studied as a function of age and T quartiles. In all age quartiles, low T was associated with higher waist circumference and triglyceride levels and with an increased prevalence of metabolic syndrome. The prevalence of hypoactive sexual desire decreased as a function of T only in the youngest (17- to 42-year old) age quartile as well as the reported reduction in nocturnal erections. In the oldest age quartile, we found an inverse relationship between T levels and the prevalence of severe erectile dysfunction and a positive relationship with intercourse frequency. Accordingly, in the oldest age quartile, subjects with higher T levels showed better penile flow at penile colour doppler ultrasound as well as a better lipid profile. Finally, an inverse association between somatized anxiety and T levels was observed only in the oldest age quartile. In conclusion, our study shows for the first time that in subjects with sexual dysfunction, some hypogonadism-related symptoms can be age-specific. In particular, low T is associated with sexual dysfunction more often in the oldest subjects.     

Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from l-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). The GSH red blood cell concentration was significantly lower in ED than in C (X +/- SD; 1782.12 +/- 518.02 vs. 2269.20 +/- 231.56 mumol/L, p < 0.001). In particular, GSH was significantly reduced in ED/DM vs. ED/wDM (1670.74 +/- 437.68 vs. 1930.63 +/- 581.01 micromol/L, p < 0.01). In DM, GSH was significantly lower than in C and significantly higher than in ED/DM (2084.20 +/- 118.14 vs. 2269.20 +/- 231.56 and vs. 1670.74 +/- 437.68 micromol/L, p < 0.002 and p < 0.001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r = -0.34, p < 0.01) and with the duration of DM (r = -0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.     

Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone

The role of androgenic hormones in human sexuality, in the mechanism of erection and in the pathogenesis of impotence is under debate. While the use of testosterone is common in the clinical therapy of male erectile dysfunction, hypogonadism is a rare cause of impotence. We evaluated serum testosterone levels in men with erectile dysfunction resulting either from organic or non-organic causes before and after non-hormonal impotence therapy. Eighty-three consecutive cases of impotence (70% organic, 30% non-organic, vascular aetiology being the most frequent) were subjected to hormonal screening before and after various psychological, medical (prostaglandin E1, yohimbine) or mechanical therapies (vascular surgery, penile prostheses, vacuum devices). Thirty age-matched healthy men served as a control group. Compared to controls, patients with impotence resulting from both organic and non-organic causes showed reduced serum levels of both total testosterone (11.1 +/- 2.4 vs. 17.7 +/- 5.5 nmol/L) and free testosterone (56.2 +/- 22.9 vs. 79.4 +/- 27.0 pmol/L) (both p < 0.001). Irrespective of the different aetiologies and of the various impotence therapies, a dramatic increase in serum total and free testosterone levels (15.6 +/- 4.2 nmol/L and 73.8 +/- 22.5 pmol/L, respectively) was observed in patients who achieved normal sexual activity 3 months after commencing therapy (p < 0.001). On the contrary, serum testosterone levels did not change in patients in whom therapies were ineffective. Since the pre-therapy low testosterone levels were independent of the aetiology of impotence, we hypothesize that this hormonal pattern is related to the loss of sexual activity, as demonstrated by its normalization with the resumption of coital activity after different therapies. The corollary is that sexual activity may feed itself throughout the increase in testosterone levels.     

Serum nesfatin-1 is associated with testosterone and the severity of erectile dysfunction

This cross-sectional study aimed to evaluate serum nesfatin-1 concentrations in patients with erectile dysfunction (ED). Patients with ED were selected from the Department of Urology of the Second Affiliated Hospital of Anhui Medical University. The International Index of Erectile Function-5 (IIEF-5) was used to evaluate the severity of ED. Serum nesfatin-1 and gonadal hormone levels, including luteinising hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. The IIEF-5 scores (t = −21.034, p < .001) and nesfatin-1 levels (t = −7.043, p < .001) in patients with ED were significantly lower than in healthy controls. Moreover, patients with ED showed decreased testosterone levels (t = −3.478, p = .001), whereas there were no significant differences in serum levels of FSH (t = −0.088, p = .930) and LH (t = 1.114, p = .270) between the two groups. Furthermore, positive relationships were found between serum nesfatin-1 and testosterone concentrations (r = .742, p = .001) and IIEF-5 scores (r = .395, p = .009) in ED patients. Additionally, based on receiver operating characteristic curve analysis, the area under curve for nesfatin-1 was 0.884 with 83.3% sensitivity and 81.4% specificity in discriminating ED patients from healthy controls. The decrease in serum nesfatin-1 level may be related to testosterone and the severity of ED.     

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

Our aim was to assess the impact of the association between elevated oestradiol (E₂) and low testosterone (T) levels on erectile dysfunction (ED) severity. A total of 614 male patients with ED and a normal or low T level in association with normal or elevated E₂ levels were enrolled. Patients underwent routine laboratory investigations in addition to measurements of total T, total E₂, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. We compared the responses to the erectile function domain, Q3 (achieving erection) and Q4 (maintaining erection) of the International Index for Erectile Function (IIEF) score in patients with the following: normal T and E₂ levels; low T level; low T level and elevated E₂ level; and elevated E₂ level. Of the patients included, 449 (73.1%) had normal T and E₂ levels, 110 (17.9%) had a low T level, 36 (5.9%) had a low T level and an elevated E₂ level, and 19 (3.1%) had an elevated E₂ level. Increased ED severity was significantly associated with low T levels, elevated E₂ levels, and both a low T level and an elevated E₂ level. Additionally, the mean values of the EF-domain, Q3 and Q4 were significantly lower in patients with both a low T level and an elevated E₂ level compared to patients with any condition alone. In conclusion, a low T level had the primary effect on erectile function; however, a concomitantly elevated E₂ level had an additive impairment effect.     

Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction

OBJECTIVES

To determine, in the obese Zucker fa/fa rat (OZR), whether the loss in smooth muscle cells (SMCs) as well as the increase in fibrosis that occurs within the corpora cavernosa accompanying corporal veno‐occlusive dysfunction (CVOD), also occurs within the media of the arterial tree.

MATERIALS AND METHODS

The penis and aorta from both 7‐month‐old male diabetic OZR (5 months of diabetes) and aged‐matched nondiabetic lean Zucker rats (LZR) rats were harvested (eight per group). The penis and aorta were subjected to histo‐ or immnohistochemistry, followed by quantitative image analysis (QIA) to determine the contents of SMC, collagen and the pro‐fibrotic transforming growth factor (TGF)β1. The turnover of SMCs was assessed by terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) assays. Quantitative Western blots determined calponin (SMC marker) and PCNA, and hydroxyproline was used for collagen. In vitro relaxation of corporal strips was measured.

RESULTS

In vitro relaxation of corporal tissue from OZR was considerably less than in the LZR. In the media of the penile dorsal artery (PDA) of OZR, there was a considerable reduction in the SMC content and the SMC/collagen ratio, as well as an increase in apoptosis, but there were no changes in PCNA or TGFβ1 expression, or in the intima‐media/lumen ratio. In the aorta of the OZR, in contrast to the PDA, there was a reduction in PCNA as well as a more pronounced decrease in the SMC/collagen ratio, mainly from an increase in collagen, but there were no changes in TGFβ1 or the wall/lumen morphometry. In the OZR, Western blots of aortic tissue confirmed the decrease in PCNA and a reduction in the SMC marker calponin.

CONCLUSIONS

These data show that 5 months after the onset of hyperglycaemia in the OZR, the rats develop both abnormal corporal SMC relaxation and a generalized fibrosis of the arterial media of both the large and small diameter vessels. It is possible that this pan‐fibrosis of the media of the arterial system might contribute to the diabetes‐related ED that occurs during this period in this rat model.     

糖尿病性阴茎勃起功能障碍动物模型血清雄激素测定

ＳＤ大鼠注射链脲佐菌素制造溏尿病（ＤＭ）动物模型后,注射阿朴吗啡观察不同时期大鼠阴茎勃起情况,筛选ＤＭ性阴茎勃起功能障碍（ＥＤ）大鼠模型,测定其血清ＬＨ、ＦＳＨ及睾酮的浓度,并观察睾丸组织的显微结构,研究ＤＭ性ＥＤ的发病机理。结果ＤＭ性ＥＤ大鼠血清睾酮浓度显著降低,睾丸组织显微结构发生明显病理性改变,且上述变化与ＤＭ病程密切相关;ＬＨ在ＤＭ早期无改变、晚期明显降低;ＦＳＨ无明显改变。提示ＤＭ严重影阴茎勃起功能及雄激素的合成分泌,雄激素降低可能是其主要发病机理之一。     

正常高值血压男性人群勃起功能调查

目的:了解正常高值血压的男性人群勃起功能障碍(ED)的患病情况。方法:2010年6～9月,本市行政、事业单位在职人员在我院进行年度健康体检中,对未发现明显器质性疾病的已婚男性,根据血压分为正常血压组、正常高值血压组两组。按参加体检的先后顺序,在两组人群中分别抽取120例男性,用勃起功能国际问卷-5调查表进行问卷调查。结果:正常高值血压的男性人群ED的患病率为25.8%。在控制了年龄、民族、职业、文化程度、经济收入、吸烟、饮酒、体育锻炼、肥胖、脂肪肝、血脂、血糖和血尿酸一系列因素后,正常高值血压组ED的患病率比正常血压组高,差异有统计学意义(25.8%vs 14.2%,P<0.05)。结论:正常高值血压的男性人群ED患病率较正常血压人群高。     

Erectile dysfunction in patients with first-episode psychosis

Sexual dysfunction is more prevalent in psychotic patients than in the nonpsychotic population. The objective of this study was to identify correlations between serum prolactin levels, testosterone levels and erectile dysfunction in patients with first-episode psychosis (n = 40) compared to age-matched healthy controls (n = 40). All subjects underwent clinical evaluation, international index of erectile function (IIEF5) score assessment and measurement of serum prolactin and total testosterone levels. In first-episode psychotic patients, the IIEF-5 score and total testosterone levels were significantly lower, while serum prolactin levels were higher. We concluded that men with first-episode psychosis are at an increased risk for development of erectile dysfunction, and increased duration of untreated psychosis leads to a higher incidence of erectile dysfunction and hyperprolactinemia.     

Diabetes mellitus is associated with subnormal serum levels of free testosterone in men

OBJECTIVE: To evaluate the relationship between diabetes mellitus (DM) and serum levels of free (FT) and total (TT) testosterone. PATIENTS AND METHODS: A cross-sectional study was carried out including 746 men, of whom 116 (15.6%) were diabetics. Both groups, diabetic and nondiabetic, were paired according to age. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated, and a stratification analysis correlating DM and elevated BMI (>25 kg/m(2)) and WHR (>1) with the presence of subnormal FT and TT levels was performed. RESULTS: FT and TT serum levels were subnormal in 46% and 34% of diabetics, respectively, and in 24% and 23% of nondiabetics. Subnormal FT levels were strongly correlated with DM (odds ratio (OR) 2.7; 95% confidence interval (CI) 1.8-4.1) but not with elevated BMI (OR 1.4; 95% CI 1.0-2.0). Subnormal TT levels were more strongly associated with elevated BMI and WHR (OR 2.6; 95% CI 1.7-3.9 and 2.0; 1.4-2.9) than with DM (1.7; 1.1-2.6 and 2.0; 1.3-3.2). CONCLUSION: These data strongly suggest that DM is associated with subnormal FT levels, and that TT levels are influenced more by obesity and central adiposity.     

下尿路症状男性人群勃起功能调查

目的:了解下尿路症状(LUTS)男性人群的勃起功能障碍(ED)患病情况,探讨LUTS与ED之间的相关性。方法:2011年11月~2012年8月,抽取1 000例40~80岁、有固定性伴侣的男性人群,采用国际前列腺症状评分(IPSS)及国际勃起功能指数(IIEF-5)评估LUTS和ED的严重程度,单因素Logistic回归分析LUTS与ED的相关性。结果:40~80岁男性人群的LUTS患病率为42.81%(426/995),ED患病率为76.18%(758/995)。其中426例有LUTS症状患者的ED患病率为82.16%(350/426),569例无LUTS症状的ED患病率为71.70%(408/569)。随着LUTS严重程度的增高,ED的患病率明显升高。Logistic回归分析显示,年龄、LUTS严重程度与ED的关联存在统计学显著意义(P0.01)。结论:LUTS患者存在很高的ED发生率。年龄越大,LUTS症状愈严重者患ED的风险更高。