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.     

胰岛素对糖尿病大鼠阴茎内nNOS神经纤维的影响

目的探讨糖尿病性阴茎勃起功能障碍（ED）的发病机制及胰岛素的治疗作用。方法注射链脲佐菌素建立糖尿病（DM）大鼠模型，胰岛素治疗组于成模后注射胰岛素。7周和12周后注射阿扑吗啡（APO）进行大鼠阴茎勃起功能实验，取大鼠阴茎和血浆，用ABC免疫组织化学法观察nNOS神经纤维的变化。测定血浆NOS活性。结果（1）与对照组相比，DM组大鼠阴茎勃起次数明显减少;胰岛素治疗后症状缓解;（2）与对照组相比，DM组血浆NOS活性明显增高;DM组血浆NOS活性与病程延长呈负相关;与DM组比较，胰岛素治疗组血浆NOS活性明显降低;（3）与对照组相比，DM组阴茎内nNOS阳性神经纤维明显减少;与DM组比较，胰岛素治疗组nNOS阳性神经纤维表达增加。结论糖尿病性ED阴茎内nNOS阳性纤维的数量及光密度随DM病程的延长而下降;早期给予胰岛素治疗可预防糖尿病大鼠ED的出现及阴茎内nNOS含量的下降。     

Glycosylated haemoglobin levels and the severity of erectile function in diabetic men

OBJECTIVE: To evaluate the association between the levels of glycosylated haemoglobin (HbA1c) and the severity of erectile dysfunction (ED) in men with diabetes mellitus (DM). PATIENTS AND METHODS: This cross-sectional study included sexually active men with a diagnosis of DM attending a urological medical centre from January 2000 to December 2001. The 115 men with ED (95%) completed the International Index of Erectile Function questionnaire, and fasting serum glucose and HbA1c serum levels were measured. The relationship between the severity of ED and serum HbA1c levels was assessed. RESULTS: Of men with HbA1c levels of < 8%, half had mild, and 18% and 32% had moderate and severe ED, respectively (P = 0.038); of men with HbA1c levels of > or = 8%, 25%, 29%, and 46% had mild, moderate and severe ED, respectively (P = 0.008). In addition, men with HbA1c levels of > or = 11% had a statistically higher prevalence of severe ED (P = 0.002). There was no difference in severity of ED in the HbA1c subgroups when the duration of DM was < or = 5 years (P = 0.87), but most men with HbA1c levels of > or = 8% and a history of DM of 6-10 or > 10 years had severe ED (P < 0.03). CONCLUSION: This study suggests that the severity of ED is associated with increasing HbA1c levels in diabetic men.     

糖尿病大鼠阴茎组织细胞凋亡的研究

目的 研究阴茎海绵体组织细胞凋亡与糖尿病的关系。方法 腹腔内注射链脲佐菌素制备糖尿病大鼠模型，分别于第6、8周观察其阴茎勃起功能，并用TUNEL法检测细胞凋亡。结果 糖尿病组大鼠勃起功能明显下降，且细胞凋亡率高于对照组并随病程而增加。结论 糖尿病严重影响大鼠的勃起功能及增加海绵体组织细胞凋亡。细胞凋亡的增加可能是糖尿病性勃起功能障碍的发病机制之一。     

Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats

To evaluate the protective role of bosentan (BOS), an endothelin‐1 (ET‐1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg^?1 streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg^?1 and 100 mg kg^?1, respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET‐1, eNOS, iNOS, tumour necrosis factor (TNF)‐α, ET‐RA and ET‐RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET‐1, TNF‐α and iNOS gene expressions increased, eNOS, ET‐RA and ET‐RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF‐α expressions in a dose‐dependent manner.     

Coagulation of a giant hemangioma in glans penis with holmium laser

A 21-year-old man presented with an enlarged giant hemangioma on glans penis which also causes an erectile dysfunction （ED） that partially responded to the intracavernous injection stimulation test. Although the findings in magnetic resonance imaging （MRI） indicated a glandular hemangioma, penile colored Doppler ultrasound revealed an invaded cavernausal hemangioma to the glans. Surgical excision was avoided according to the broad extension of the gland lesion. Holmium laser coagulation was applied to the lesion due to the cosmetically concerns. However, the cosmetic results after holmium laser application was not impressive as expected without an improvement in intracavernous injection stimulation test. In conclusion, holmium laser application should not be used to the hemangiomas of glans penis related to the corpus cavernosum, but further studies are needed to reveal the effects of holmium laser application in small hemangiomas restricted to the glans penis.     

链脲佐菌素诱导1型糖尿病大鼠股骨生物力学变化及唑来膦酸的影响

目的：观察链脲佐菌素（ STZ ）诱导的1型糖尿病模型大鼠股骨生物力学变化特点和规律以及唑来膦酸（ ZA）对其的影响。方法采用一次性腹腔注射STZ制作1型糖尿病模型。取205只雌性Wistar大鼠,随机分为对照组（C组,n＝40）、模型组（D组,n＝55）、ZA预防组（Z-Ⅰ组, n＝55）和ZA治疗组（ Z-Ⅱ组, n ＝55）。 Z-Ⅰ组和 Z-Ⅱ组分别于造模成功即刻和2周后给予ZA 0.1 mg／kg干预。各组于造模成功后第1、2、3、4、5、8、12和16周分别取5只大鼠,取左侧股骨行三点弯曲试验,记录载荷-变形曲线和应力－应变曲线,获得结构力学指标最大载荷、弹性载荷和材料力学指标弹性模量和能量吸收。结果与C组各生物力学指标自第1周到第16周持续升高的趋势不同,D组各指标在第1周至5周持续升高,第8周、12周降低,第16周再次升高,但结构力学指标组内比较差异无统计学意义（P＞0.05）,而材料力学指标组内比较差异则具有统计学意义（P＜0.05）。组间比较结果：第1周到第5周各组间比较差异均无统计学意义（ P＞0.05）;第8周和第12周时D组、Z-Ⅰ组、Z-Ⅱ组均低于C组,差异具有统计学意义（ P＜0.05）;第16周时各组间比较差异具有统计学意义。结论 STZ诱导的1型糖尿病大鼠各生物力学特性自造模成功后第8周开始明显降低,股骨材料力学改变大于结构力学改变。 ZA能改善1型糖尿病大鼠生物力学特性,预防组比治疗组更加明显。     

Myocardin restores erectile function in diabetic rats: phenotypic modulation of corpus cavernosum smooth muscle cells

This study aimed to investigate whether gene transfer of myocardin to the penis of diabetic rats can modulate corpus cavernosum smooth muscle (CCSM) cells phenotype and restore erectile function. Five normal control rats, and 22 diabetic rats were randomly divided into four groups: rats transfected with adCMV‐myocardin (N = 6), treated with empty vector (N = 6), injected with medium (N = 5), and sham‐operated rats (N = 5). The erectile response was measured 7 days after transfection. The percent of smooth muscle and the expressions of SMα‐actin, smooth muscle myosin heavy chain (SMMHC), calponin were evaluated. The increases in intracorporal pressure(ICP)/mean arterial pressure and total ICP in response to nerve stimulation in the adCMV‐myocardin treated rats were significantly greater than those in the empty vector (P < 0.001 and P < 0.001), medium only (P < 0.001 and P < 0.001), and sham‐operated rats (P < 0.001 and P < 0.001). The suppressed expressions of SMα‐actin, SMMHC and calponin were completely restored, and the amount of smooth muscle in diabetic rats were not restored after treatment. It is concluded that myocardin ameliorated erectile responses in diabetic rats mainly via promoting phenotypic modulation of CCSM cells from a proliferative to a contractile state.     

勃起功能障碍患者及不同年龄与正常人阴茎海绵体平滑肌组织学观察

目的：了解正常及勃起功能障碍（ED）患者阴茎海绵体的差异和改变对阴茎勃起的影响。方法：取10例不同年龄正常及ED病人阴茎海绵体组织，镜下观察阴茎海绵体结构变化。结果：3例ED病人阴茎海绵体平滑肌细胞及弹力纤维减少。老年性阴茎海绵体平滑肌及弹力纤维明显减少。青壮年阴茎海绵体平滑肌细胞及弹力纤维极为丰富。结论：阴茎海绵体结构改变对阴茎勃起功能有较大的影响。     

The administration of folic acid improves erectile function and reduces intracavernosal oxidative stress in the diabetic rabbit

OBJECTIVE

To test the possibility that folic acid (FA) may be a means of treating erectile dysfunction (ED) in diabetes mellitus (DM), by studying the effect of FA administration to DM rabbits on cavernosal function and intrapenile oxidative stress.

MATERIALS AND METHODS

To investigate the effect of administering FA to DM rabbits on erectile function and oxidative stress the formation of superoxide (O₂^‐), 8‐isoprostane F_2α (8‐IPF_2α) and prostacyclin (as 6‐keto‐PGF_1α) were assessed, as well as carbachol‐ and electrical field stimulated (EFS) relaxation and p47^phox content (active component of NADPH oxidase complex). Non‐ketotic DM was induced in New Zealand rabbits with alloxan and FA administered orally daily for 1 month. Rabbits were killed, penises excised and segments prepared. These were mounted in an organ bath and relaxation elicited with carbachol or EFS. O₂^‐ release was measured spectrophotometrically, p47^phox expression by Western blotting and 8‐IPF_2α and 6‐keto‐PGF_1α formation by enzyme‐linked immunosorbant assay. Blood was collected for measurement of homocysteine, red blood cell (RBC) folate and glucose.

RESULTS

In cavernosal tissue from DM rabbits, carbachol‐and EFS‐induced relaxation was significantly impaired compared with the untreated controls. O₂^‐ release, p47^phox expression and 8‐IPF_2α formation were all enhanced and 6‐keto‐PGF_1α formation reduced compared with the controls. All these effects were reversed by FA. Plasma total homocysteine was reduced and RBC folate elevated.

CONCLUSIONS

The administration of FA may constitute a strategy for reducing ED in patients with DM.     

The penis in diabetes: structural analysis of connective tissue and smooth muscle alterations in a rabbit model

Study Type – Aetiology (case control) Level of Evidence 3b OBJECTIVE

• ? To assess the volumetric density of collagen, elastic system fibres and smooth muscle cells in the corpus cavernosum (CC), corpus spongiosum (CS) and tunica albuginea (TA) in the penis of diabetic rabbits.

MATERIALS AND METHODS

• ? Twenty‐six New Zealand white rabbits were used. Diabetes was induced at 8 weeks of age in 13 rabbits by i.v. injection of 100 mg/kg of alloxan. The remaining 13 rabbits served as a control group. After 10 weeks, the rabbits were killed using sodium thiopenthal.
• ? Midshaft penile fragments were obtained and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibres and smooth muscle was performed in 5‐µm sections by using a M42 test grid system.
• ? Data were expressed as volumetric density (Vv; %). Collagen organization was evaluated by Picrosirius red staining under polarization.

RESULTS

• ? In the TA of diabetic rabbits, thickness increased by 88% (P < 0.001) with an enhanced collagen turnover. Moreover, the elastic fibre content was 34% higher (P < 0.001). In the CC of diabetics, collagen was diminished by 45% (P < 0.001) with a more organized collagen.
• ? The elastic fibres were decreased by 46% (P < 0.001). Diabetes induced a 11% increase in CS collagen (P < 0.024) with an enhanced collagen turnover.
• ? Smooth muscle in the CC of diabetic rabbits was increased by 40% (P < 0.001), whereas, in the CS, it was decreased by a similar amount (P < 0.001).

CONCLUSIONS

• ? Penile tissues were affected differently by diabetes, possibly as a result of cellular heterogeneity.
• ? These changes could have an impact on blood flow and tissue resistance, and therefore might adversely affect erection.

     

应用Rho激酶抑制剂对大鼠阴茎勃起的作用

目的 :探讨将RhoA/Rho激酶抑制剂Y 2 76 32涂抹于阴茎白膜表面以及阴茎龟头皮肤表面有无促进阴茎勃起的作用及其对体循环的影响。　方法 :2 0只成年雄性SD大鼠 ,体重为 2 5 0～ 30 0g ,随机分为实验组和对照组。全身麻醉后颈动脉和海绵体插管连续监测平均动脉压 (MAP)和阴茎海绵体内压 (CCP)的变化。寻找盆腔星状神经节(MPG)并以系列电刺激诱发勃起。向海绵体白膜表面及阴茎龟头皮肤表面涂抹Y 2 76 32 ,观察用药前后阴茎勃起的改变及MAP的改变。　结果 :将Rho激酶抑制剂Y 2 76 32涂抹于大鼠阴茎白膜表面和阴茎龟头皮肤表面均可促进在无阴茎支配神经电刺激下发生勃起 (ICP/MAP明显升高 ) ,在系列电刺激MPG时用药后发生的勃起反应较用药前亦明显增强。表面用药后还发现大鼠体循环血压有不同程度的降低。　结论 :阴茎皮肤表面应用Rho激酶抑制剂是一种安全有效的ED治疗方法 ,其临床应用价值仍有待于进一步探索     

阴茎、手掌和足底交感皮肤反应的比较研究

目的 比较研究健康人及阴茎勃起障碍(ED)病人阴茎、手掌和足底交感皮肤反应(SSR)潜伏期和波幅。方法 对25例健康人和59例ED病人采用电流刺激正中神经,金属盘状表面电极同时在阴茎体部、手掌和足底皮肤表面记录阴茎(PSSR)、手掌(HSSR)和足底交感皮肤反应(FSSR)。结果 正常组阴茎、手掌和足底SSR的潜伏期(PLP0、HLP0和FLP0)分别为(134286)ms、(129191)ms和(2055268)ms。病人组PLP0、HLP0和FLP0分别为(1790370)ms(P<0.01)、(1329106)ms(P>0.05)和(2095281)ms(P>0.05)。正常组阴茎、手掌和足底SSR的AN1波幅(PAN1、HAN1和FAN1)分别为(994441)μv、(1129589)μv和(1083412)μv。病人组PAN1、HAN1和FAN1分别为(442372)μv(P<0.01)、(1238438)μv(P>0.05)和(1015499)μv(P>0.05)。结论 阴茎交感皮肤反应潜伏期和波幅及其与手掌或足底交感皮肤反应的相应比值可以用来评价阴茎自主神经结构与功能状况。     

Nitric oxide synthase gene transfer for erectile dysfunction in a rat model

OBJECTIVE: To determine whether over-expression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis improves erectile function, as NO is an important transmitter for genitourinary tract function, mediating smooth muscle relaxation and being essential for penile erection. MATERIALS AND METHODS: The inducible form of the enzyme NOS (iNOS) was introduced into the corpus cavernosum of adult Sprague-Dawley rats (250-300 g) by injecting a solution of plasmid, adenovirus or adenovirus-transduced myoblast cells (adeno-myoblasts). Plasmid, adenovirus and adeno-myoblasts encoding the expression of the beta-galactosidase reporter gene were also injected into rats. RESULTS: Throughout the corpora cavernosum there was expression of beta-galactosidase after injecting each of the three solutions. Maximum staining was greatest for adeno-myoblast, then adenovirus and then plasmid. The mean (sd) basal intracavernosal pressure (ICP) of iNOS-treated animals (adenovirus and adeno-myoblast) increased to 55 (23) cmH2O, compared with naive animals with a basal ICP of 5 (6) cmH2O (P = 0.001). Stimulating the cavernosal nerve (15 Hz, 1.5 ms, 10-40 V, 1 min) resulted in a doubling of the ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO showed the release of 1-1.3 micro mol/L in the adeno-myoblast penis. CONCLUSION: Myoblast-mediated gene therapy was more successful for delivering iNOS into the corpus cavernosum than direct adenovirus injection or plasmid transfection. Surprisingly, implanting muscle cells into the penis is not only feasible but also beneficial. Gene therapy for NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.     

Expression of oxytocin receptor in diabetic rat penis

Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.     

糖尿病性勃起功能障碍相关因素分析

目的 研究糖尿病性勃起功能障碍(ED)的发病情况及其影响ED程度的相关因素。 方法 调查90例男性2型糖尿病病人的性功能状态、年龄、糖尿病病程、测量血压,同时测定其糖化血红蛋白(HbA1C)血脂等指标。结果 糖尿病病人中ED患病率为75.6%(68/90),患病率随年龄的增加而增加,在非ED组与不同程度ED组之间,年龄存在非常显著差异(P<0.01),DM病程、HbA1C存在显著差异(P<0.05)结论 糖尿病病人ED患病率高,糖尿病性ED的程度随年龄、DM病程、HbA1C的增加而加重,长期良好的血糖控制有助于延缓糖尿病性ED的加重。     

Improvement of erectile function by Korean red ginseng (Panax ginseng) in a male rat model of metabolic syndrome

The seriousness of metabolic syndrome is not due to the disease itself but its promotion of other diseases, such as erectile dysfunction and cardiovascular and cerebrovascular diseases. We investigated the effects of Korean red ginseng (KRG, Panax ginseng) extract on erectile function in a rat model of metabolic syndrome. We divided the rats into three groups: control, metabolic syndrome+normal saline (N/S) and metabolic syndrome+KRG. To determine the occurrence of metabolic syndrome in all groups, body weight and various biochemical parameters (e.g., blood glucose, insulin, cholesterol) were measured, and the intra-abdominal glucose tolerance test was performed. To investigate penile erection, the peak intracavernosal pressure (ICP), mean arterial pressure (MAP) and Masson''s trichrome stain were evaluated. Erectile function was also investigated by measuring the cyclic guanosine monophosphate (cGMP) levels of the corpus cavernosum. We found that the various biochemical parameters and body weight were similar in the metabolic syndrome+KRG group and the control group, although the values were slightly higher. The peak ICP/MAP ratio of the metabolic syndrome+N/S group was markedly decreased compared to the other groups. The cGMP level of the corpus cavernosum in the metabolic syndrome+N/S group was significantly lower than that of the other groups. As demonstrated in this model of metabolic syndrome with erectile dysfunction, KRG may improve erectile function.     

增龄大鼠阴茎组织中一氧化碳含量与细胞凋亡的相关性研究

目的:通过研究不同月龄大鼠阴茎组织内细胞凋亡及CO含量变化,进一步探讨勃起功能障碍发生机制。方法:雄性Wistar大鼠24只分为3组(每组8只),成年组(8月龄)、老年组(16月龄)和衰老组(24月龄)。取阴茎组织用苏木精-伊红(HE)染色,原位末端转移酶标记法(TUNEL)检测细胞凋亡,改良双波长法检测CO含量。结果:增龄大鼠阴茎组织中细胞凋亡显著增多(成年组:4.38±1.06,老年组:9.38±1.69,衰老组:18.50±1.60),CO含量减少[成年组:(12.19±0.87)nmol/μg,老年组:(7.93±0.63)nmol/μg,衰老组:(5.68±0.62)nmol/μg],组间差异均有显著性(P<0.05)。CO含量与细胞凋亡的变化呈现良好的负相关性(r=-0.889,P<0.01)。结论:增龄大鼠阴茎组织中细胞凋亡与CO含量呈负相关,CO可能通过调控细胞凋亡机制从而参与了雄性性功能障碍的发生。     

糖尿病患者瞳孔功能异常的研究现状

糖尿病患者瞳孔功能异常是糖尿病患者自主神经系统损害的临床表现,其异常严重影响了糖尿病患者眼底疾病的检查及治疗,目前临床针对该病变的应对措施非常有限。本文对糖尿病患者瞳孔功能异常的发病机制、临床表现及应对措施进行综述。