Predictors of serum testosterone and DHEAS in African-American men

There are few reported data on biochemical and functional correlates of androgen levels in African-American men. This study aimed at reporting physical and biochemical correlates of serum total testosterone (total T), bioavailable testosterone (BT) and dehydroepiandrosterone-sulphate (DHEAS) levels in community-dwelling, African-American men aged 50-65 years. Home-based physical examinations and health status questionnaires were administered to randomly sampled men. Body composition (dual-energy X-ray absorptiometry), lower limb and hand-grip muscle strength, and neuropsychological functions were assessed. Levels of serum total T, BT, DHEAS, oestradiol (E2), adiponectin, leptin, triglycerides and glucose were measured. Multiple linear regression models were constructed to identify factors independently associated with androgen levels. DHEAS levels declined from age 50 to 65 years (p < 0.0001), but total T and BT levels remained constant. Independent of other associated factors, higher total T levels were associated with lower serum triglyceride levels (beta = -0.142, p = 0.049); higher BT was associated with better performance on the trail-making tests (TMT-B:TMT-A ratio: beta = -0.118, p = 0.024) and higher DHEAS levels were associated with lower adiponectin (beta = -0.293, p = 0.047) and higher mini-mental state examination (MMSE) score (beta = 0.098, p = 0.008). Multiple regression models predicted 21, 18 and 29% of variance in total T, BT and DHEAS, respectively. Higher total T levels were associated with serum metabolic markers, particularly lower triglycerides, whereas higher BT was associated with better cognitive and muscle function and DHEAS with lower adiponectin and higher MMSE scores.     

Age-related prevalence of low testosterone in men with spinal cord injury

Objective

To describe the relationship of advancing age in persons with chronic spinal cord injury (SCI) on the prevalence of low testosterone in men with SCI compared to historical normative data from able-bodied men in the general population.

Design

Retrospective, cross-sectional study. Two hundred forty-three healthy, non-ambulatory outpatient men with chronic SCI from age of 21 to 78 years were included in this retrospective analysis.

Results

Forty-six percent of men with SCI were identified as having low serum total testosterone concentrations (total testosterone <11.3 nmol/l). The age-related decline in SCI for total serum testosterone concentration was 0.6%/year compared to 0.4%/year in the Massachusetts Male Aging Study. Between the third and eighth decade of life, men with SCI had a 15, 39, 50, 53, 58, and 57% prevalence rate of low serum total testosterone, which is higher than values reported for each decade of life for able-bodied men in the Baltimore Longitudinal Study on Aging.

Conclusion

Compared with the general population, low serum total testosterone concentration occurs earlier in life in men with SCI, at a higher prevalence by decade of life, and their age-related decline in circulating total testosterone concentration is greater. Studies of T replacement therapy in men with SCI should assist in determining the possible functional and clinical benefits from reversing low serum total testosterone concentration.     

An association between diet,metabolic syndrome and lower urinary tract symptoms

Diet is a key factor in the aetiology of many diseases, including metabolic syndrome and lower urinary tract disorders. Metabolic syndrome is a growing and increasingly expensive health problem in both the developed and the developing world, with an associated rise in morbidity and mortality. On the other hand, lower urinary tract symptoms affect millions of individuals worldwide, lowering their quality of life. Associations have been established between both conditions in existing literature and the various components of the metabolic syndrome have been linked with the onset and aggravation of symptoms in various forms of LUTS. This current review explores the relationships between these in detail, focusing on their inter-relationships particularly vis-a-vis dietary macronutrient and micronutrient intake.     

Influences of neuroregulatory factors on the development of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction in aging men

As men age, there is an increase in the frequency of pathologic diseases affecting the genitourinary tract. Most notable among these changes are the rising prevalence of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). The pathogenesis of these conditions seems to be multifactorial and includes age-related changes in the nervous system and neuroregulatory factors, such as nitric oxide and RhoA/Rho-kinase. Various pharmacologic agents that target these pathways, such as α-blockers and PDE-5is, underscore the contribution of neuroregulatory factors on the development of LUTS/BPH and ED.     

Lower urinary tract symptoms and risk of prostate cancer in Japanese men

Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer. A total of 3511 men aged 50-79 years who underwent mass screening for prostate cancer between 2002 and 2004 for the first time, and completed the International Prostate Symptom Score (IPSS) questionnaire at the time of the prostate specific antigen (PSA) test, were enrolled in the present study. All men with PSA values greater than 4.0 ng/mL were advised and encouraged to undergo transrectal systematic sextant biopsy. The number of cancers subsequently detected was compared between men with IPSS scores of 0-7 and 8-35. Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL, 178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer. Although the PSA positivity rate for men with IPSS scores of 8-35 was significantly higher than that in the 0-7 group, there were no significant intergroup differences in the cancer detection rates for biopsied men and for total screened subjects. Multivariate logistic regression analysis revealed that prostate volume was the dominant predictor for the detection of prostate cancer, followed by PSA level, but the IPSS made no significant contribution. No significant difference was noted in the IPSS scores between men with cancer and the others of the same age group. Symptomatic Japanese men are not at higher risk of prostate cancer despite their higher PSA values compared with asymptomatic men of the same age group.     

The Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in the Treatment of Lower Urinary Tract Symptoms Related to Benign Prostatic Hyperplasia

Context

Clinical trials of phosphodiesterase type 5 inhibitors (PDE5-Is) have consistently demonstrated a significant reduction in lower urinary tract symptoms (LUTS) and small urinary flow rate changes in men with benign prostatic hyperplasia (BPH).

Objective

This review presents the proposed mechanisms of action of PDE5-Is in the treatment of BPH-LUTS focusing on the localization of PDE5 isoenzymes in the pelvic structures; smooth muscle relaxation in the bladder, prostate, and supporting vasculature; increased blood perfusion of the bladder and prostate; and modulation of sensory impulses from these organs.

Evidence acquisition

Literature describing in vitro, preclinical, or clinical studies of pathologic processes contributing to LUTS or effects of PDE5 inhibition on the lower urinary tract (LUT) was selected for review.

Evidence synthesis

We objectively assessed and summarized the published data focusing on articles published within the past 10 yr. Articles before the time cut-off were included if historically relevant.

Conclusions

The PDE5 isoenzymes are highly expressed in the LUT including the bladder, prostate, and their supporting vasculature. In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. In animals characterized by ischemia/hypoxia of the genitourinary tract, treatment with PDE5-Is increases bladder and prostate tissue oxygenation. PDE5-Is have been shown to reduce nonvoiding contractions and bladder afferent nerve firing in decerebrate spinal cord–injured rats, and to reduce mechanosensitive afferent activities of both Aδ- and C-fibers in an irritated or overextended bladder model.     

血清睾酮与老年男性原发性骨质疏松症的关系

目的 探讨血清睾酮与老年男性原发性骨质疏松的关系，为防治老年男性原发性骨质疏松症提供理论依据。方法 双能X线骨密度仪测定腰椎(L1-4)骨密度；全自动生化分析法测定尿钙、肌酐；AKP用比色法，Ca、Mg用MTB法，P用磷酸亚铁胺法；放射免疫法测定血清E2、T、BGP、CT、PTH-m。获得的参数骨质疏松组与正常对照组比较。结果 男性原发性骨质疏松组骨代谢生化指标与同年龄同性别的对照组比较，血清Ca、P、Mg、Cu以及PTH-m、E2、AKP、BGP两组差异无显著性；血清降钙素显著降低；尿钙与肌酐比值非常明显地增多；男性主导性激素睾酮骨质疏松组非常明显地低于对照组。结论 老年男性原发性骨质疏松的发病因素虽然是多方面的，但血清睾酮水平的降低是老年男性骨质疏松症发病的一个非常重要的原因。     

C-reactive protein levels and ageing male symptoms in hypogonadal men treated with testosterone supplementation

C-reactive protein (CRP) is a marker of systemic low-grade inflammation, and may be associated with subjective symptoms of androgen deficiency. We studied the effects of normalisation of plasma testosterone levels in an open, nonrandomised study. Hypogonadal men (T levels: 5.9–12.1 nmol l⁻¹, aged 34–69 years) were treated for 15 months with parenteral testosterone undecanoate (1000 mg per 12 weeks). In 100 men, plasma CRP and Aging Male Symptom (AMS) self-report data were available at baseline, of 91 men at 6 months, of 59 men at 12 months and of 60 men at 15 months. Testosterone administration resulted in a profound decline in CRP levels and AMS scores (both P < 0.001). There was a positive association between CRP levels and AMS scores over time (r = 0.22; P < 0.001), while adjusting for smoking, alcohol use, age, and body mass index. Low-grade inflammation may be involved in the pathogenesis of subjective symptoms of androgen deficiency in ageing men.     

Lower urinary tract symptoms in the danish population: a population-based study of symptom prevalence, health-care seeking behavior and prevalence of treatment in elderly males and females

OBJECTIVE: To estimate the prevalence of LUTS in the elderly Danish population. Furthermore to evaluate the quality of life, the health-care seeking behavior and the prevalence of treatment with relation to LUTS. METHODS: A mailed questionnaire was sent to a random sample of 8700 men and 1000 females above 50-years. The questionnaire included five demographic questions, the I-PSS and questions concerning previous physician contact and treatment with relation to LUTS. RESULTS: The questionnaire was returned by 61.5% of the males and 47.7% of the females. The median I-PSS was 4 in males and 3 in females. Overall 28% of males and 20% of females had significant LUTS (I-PSS>7). A significant increase in the total burden of symptoms with increasing age was found in males whereas a clear age-trend was not found in females. Overall 9.2% of males and 8.2% of females had seen a physician within the last two years for voiding problems. A high proportion of subjects with moderate or even severe symptoms had not seen a physician within two years due to voiding problems. Of males 13.3% had previous been or were currently being treated for voiding problems while the corresponding number in females was 10.9%. These subjects had significantly more symptoms than untreated age-matched subjects. CONCLUSION: Lower urinary tract symptoms are common in elderly Danish males and females. Overall the same pattern for health-care seeking behavior with regard to LUTS is seen in males and females and the overall treatment prevalence is similar. For both genders it is worth noting that a substantial proportion of subjects with a high symptom burden had not visited their physician within two years and further that subjects who have been treated for LUTS have a higher symptom levels than their untreated peers.     

Change of preoperative symptoms of the late-onset hypogonadism syndrome after robot-assisted radical prostatectomy

Background:As prostate cancer (PCa) is a common cancer among older men, patients with PCa often show aging male symptoms (AMSs). This study aimed to investigate the preoperative AMSs of the late-onset hypogonadism (LOH) syndrome and the effects on them after robot-assisted radical prostatectomy (RARP).Materials and methods:One hundred eighty-eight patients who underwent RARP without androgen deprivation therapy were measured for serum free and serum total testosterone, and were preoperatively assessed for symptoms of the LOH syndrome using a questionnaire containing an AMS score. Patients with a preoperative AMS score higher than 37 and a serum free testosterone level lower than 8.5 pg/mL were classified as Group A, with the remaining classified as Group B. AMS scores were measured at 1, 3, 6, 9, and 12 months after surgery.Results:Of the 188 patients, 49 and 139 patients were classified as Groups A and B, respectively. Preoperative AMS scores were 44.5 ± 8.2 in Group A and 28.6 ± 5.3 in Group B (p < 0.0001). AMS scores in Group A significantly improved 1 month after RARP (30.6 ± 8.4, p < 0.0001) compared with their preoperative scores and remained at the same level from 3 to 12 months postoperatively, whereas those in Group B became significantly worse (32.0 ± 7.8, p < 0.0001) than their preoperative ones. There were no differences between AMS scores in Groups A and B at every postoperative period (p = 0.3259, 0.2730, 0.2429, 0.4629, 0.1771 at 1, 3, 6, 9, and 12 months after surgery, respectively).Conclusions:Our results indicate that AMSs in PCa patients with the LOH syndrome can expect the same level of improvement as patients without it.     

Lower urinary tract symptoms and erectile dysfunction are highly prevalent in ageing men

OBJECTIVE: To evaluate a possible correlation between the International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) in an unselected population of men presenting to a clinic, as lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are highly prevalent in ageing men, and recent largely community-based epidemiological studies reported a close association between ED and LUTS. PATIENTS AND METHODS: This was a cross-sectional study in an unselected consecutive sample of 118 men aged >40 years attending a urology clinic; the reason for consulting was not ascertained. While in the waiting room the men were asked to participate in the study and on agreement were given the IPSS and the SHIM to complete. RESULTS: The mean (range) age of the participants was 61.7 (45-82) years. Overall, 19 (16%) and 47 (40%) of the men reported having moderate or severe LUTS, respectively. Erectile problems were also common, the prevalence of moderate ED was 11% and complete ED 29%. The Pearson correlation coefficient between the IPSS and the SHIM was - 0.32 (P < 0.001). CONCLUSION: There was a close correlation between the IPSS and SHIM in this unselected population of men, adding evidence favouring a close association between LUTS and ED.     

Lower urinary tract symptoms revisited: a broader clinical perspective

Context

The term “lower urinary tract symptoms” (LUTS) was introduced to dissociate male urinary symptoms from any implied site of symptom origin, such as the prostate.

Objective

To consider a more expansive view of LUTS, moving beyond an organocentric focus.

Evidence acquisition

Review of the available literature by a consensus panel.

Evidence synthesis

A consensus group reviewed the literature and developed a conceptual framework to facilitate research and clinical practice in patients with LUTS, following steps outlined in the Delphi procedure. Committee discussion, with presentations and review of existing literature and knowledge at four separate occasions, and extensive review and discussion of draft documents encapsulating group views followed. Consensus group findings included evidence that LUTS increase with age and are prevalent in both male and female patients, with differences in the prevalence of individual storage, voiding, and postmicturition symptoms representing underlying pathophysiologic factors between the sexes. Additionally, it was recognised that patients often have underlying and overlapping pathophysiologic mechanisms that may be related to the expression of LUTS and that this global approach to LUTS reflects our contemporary recognition of the lower urinary tract as an integrated functional unit. To improve the current management of patients, education and awareness regarding LUTS, its causes, and associated comorbidities are needed. Major limitations of this work are the potential interpretive bias introduced by prior perceptions and the nature of the study populations drawn conventionally from secondary care.

Conclusions

In conclusion, it is misleading to attribute individual symptoms to sex differences or to a specific underlying organ. LUTS are a non–sex-specific, non–organ-specific group of symptoms, which are sometimes age-related and progressive. A need exists to increase education and awareness regarding LUTS, its causes, and associated comorbidities, and to assess and treat men and women for all LUTS, not just selected symptoms.     

中老年男子睾酮补充治疗的获益与风险

男子中年后血清睾酮水平逐渐降低,并可以引起瘦体量减少、体脂量增加、体能下降、血糖代谢失衡、骨密度降低、勃起功能障碍和情绪改变,需要给予睾酮补充治疗。可用的睾酮制剂包括口服十一酸睾酮,肌肉注射十一酸睾酮和庚酸睾酮,皮肤睾酮贴剂和凝胶以及皮下植入丸。睾酮补充治疗可以缓解因睾酮水平降低引起的症状和体征,但可能导致前列腺增生、前列腺癌、心血管疾病、红细胞增多和阻塞性睡眠呼吸暂停综合征的风险仍存在争议。     

Lower urinary tract symptoms,prostate volume,uroflowmetry, residual urine volume and bladder wall thickness in Turkish men: a comparative analysis

Aim To evaluate the association between lower urinary tract symptoms (LUTS) severity and bladder wall thickness (BWT). Materials and methods The study included 155 patients referred to outpatient clinics for LUTS. Patients were divided into three groups due to their IPSS. Group A included the patients with mild symptoms, group B included patients with moderate symptoms and group C included patients with severe symptoms. The patients were again divided into two groups due to their uroflowmetry results. Group 1 included the patients whose Q _max ≤ 10 ml/s and group 2 included the patients whose Q _max > 10 ml/s. Results The mean BWT was 4.14 + 1.03 mm (from 3 to 9 mm). Although there was no difference between the IPSS groups in BWT (P = 0.325), it was statistically significant between uroflowmetry study groups (P < 0.01). Conclusions BWT seems to be significantly increased in men who have Q _max values smaller than 10 ml/s.     

中国男性十一酸睾酮酯注射避孕有效性多中心研究

目的评估十一酸睾酮酯（TU）注射避孕的安全性、有效性、可复性和可接受性。方法1,045名健康的有生育力的中国男性,每月一次TU500mg肌注共30个月,统计分析其配偶的妊娠率、精液参数、睾丸体积、生殖激素水平及安全性评估。结果在6个月的抑制期内有43名对象（4．8％）未达到无精子或严重少精子症;855名对象进入起效期,其中733名完成每月一次TU注射和恢复阶段。在避孕有效期的24个月,暴露1,554／人年中有9次妊娠,累计避孕失败率为1．1／100人;综合失败率6．1％,其中包括1．3％抑制不充分和4．8％短暂抑制后的精子反跳。本研究无严重不良事件报告。除了2名对象以外全部恢复生精功能,达到正常有生育力参考值范围。结论每月一次TU500mg肌注可以为健康有生育力的中国男性提供安全、有效、可逆的避孕。     

Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences

INTRODUCTION: Erectile dysfunction (ED) and decline of testosterone levels are frequently observed with age and also in illnesses with a common basis of endothelial damage. OBJECTIVES: To review molecular mechanisms underlying androgen action upon its receptor and phosphodiesterase type 5 (PDE5) expression and regulation by testosterone in cavernous tissue and their clinical implication in the treatment of ED refractory to PDE5 inhibitors (PDE5-Is). METHODS: From January 2003 to May 2006 [corrected] we performed an extensive, unsystematic MEDLINE literature search reviewing relevant data on basic and clinical studies regarding the efficacy of combination therapies. RESULTS: Most trials using testosterone alone for treatment of ED in hypogonadal men suffer from methodologic problems and report inconsistent results, but overall the trials suggest that testosterone is superior to placebo. Orally effective PDE5-Is, such as sildenafil, tadalafil, or vardenafil, may be ineffective depending on the demonstration of testosterone regulation of PDE5 expression in human corpus cavernous, and their efficacy may be enhanced by testosterone adjunction whenever necessary. CONCLUSIONS: Screening for hypogonadism in all men with ED is necessary to identify men with severe hypogonadism and some cases of mild to moderate hypogonadism, who may benefit from testosterone treatment. Identification of threshold values for testosterone supplementation to appropriately benefit from PDE5-Is failure may improve clinical management of unresponsive patients with minimization of unwanted effects.     

A new oral testosterone undecanoate formulation

Testosterone undecanoate has been available on the market for more than 20 years. This testosterone ester is used worldwide for oral treatment of male hypogonadism. So far, testosterone undecanoate has been dissolved in oleic acid, leading to inconvenient storage conditions. It will now be available in a new formulation with castor oil and propylene glycol laurate instead of oleic acid, thus improving storage conditions markedly (stable at room temperature for approximately 3 years). Pharmacokinetic and pharmacodynamic studies have demonstrated bioequivalence of the old and the new formulation of testosterone undecanoate. Therefore, the results of studies that were performed with the old formulation can be transferred to the clinical use of the new formulation. Controlled studies have shown its efficacy in the treatment of symptoms associated with reduced serum testosterone levels. In these cases testosterone undecanoate improves bone mineral density, quality of life, muscle mass, libido and mood. Further studies will help evaluate the efficacy and safety of the new formulation in the treatment of elderly men with late-onset hypogonadism.     

A novel metered-dose 2% testosterone gel treatment for male hypogonadism

Background

Male hypogonadism arises from a deficiency in testosterone secretion that may occur naturally with increasing age, or as a result of malfunction of the hypothalamus, pituitary gland or testes. Tostran^® (also known as Fortigel^®, Itnogen^® and Tostrex^®) is a metered-dose gel formulation of 2% testosterone that was recently developed to treat male hypogonadism and to overcome the disadvantages exhibited by some testosterone formulations.

Methods

A prospective Phase II trial of Tostran in men with primary or secondary hypogonadism evaluating the effect of showering was conducted.

Results

This trial demonstrated that showering 2 h after application of Tostran has no significant effect on serum testosterone levels.

Conclusion

Market research in the UK and Germany has indicated that endocrinologists would consider switching patients to Tostran from other formulations, especially other gels. Their preference is due to the dosage and administration advantages of Tostran, the flexibility of the metered-dose formulation, and the ability to shower 2 h after application.     

Decline of plasma 5alpha-dihydrotestosterone (DHT) levels upon testosterone administration to elderly men with subnormal plasma testosterone and high DHT levels

The study was performed to measure the impact of testosterone (T) administration on circulating levels of 5alpha-dihydrotestosterone (DHT). Group 1 (32 men; mean age 61 years; mean T 6.9 +/- 1.9 nmol l(-1)) were treated for 15 months with long-acting T undecanoate. Group 2 (23 men, mean age 60 years, mean T 7.6 +/- 2.0 nmol l(-1)) were treated for 9 months with T gel. Plasma T and DHT were measured before and after 9 months T administration. In the men treated with T undecanoate plasma T and DHT were also measured after 12 and 15 months. Before T administration, plasma DHT ranged from 0.39 to 1.76 nmol l(-1) (0.30-1.90 nmol l(-1)). Mean DHT declined upon T administration from 0.95 +/- 0.50 to 0.55 +/- 0.30 nmol l(-1) (P < 0.05). With an arbitrary cut-off at 0.60 nmol l(-1), all 21 values of DHT > 0.60 nmol l(-1) had fallen from 1.29 +/- 0.50 to 0.70 +/- 0.60 nmol l(-1) (P < 0.01). Below this cut-off point 13 values rose and 21 fell upon T administration. Below this cut-off point values on average declined from 0.39 +/- 0.12 to 0.30 +/- 0.14 nmol l(-1) (P < 0.05). The study revealed that in a cohort of elderly men with subnormal plasma T levels plasma DHT levels declined upon T administration when they were in the higher range of normal (>0.6 nmol l(-1)), with a profound shift of DHT/T ratios presumed to be an indicator of a reduced 5alpha-reductase activity. Below plasma DHT levels of 0.6 nmol l(-1), responses of plasma DHT to T administration varied.     

庚酸睾酮诱导的无及少精子症者生殖激素和精子功能指标变化的观察

本文报道两组接受庚酸睾酮(TE200mg/周16个月)正常育龄男子的精液分析、血清生殖激素、精子特殊功能的动态变化。结果:第一组(8名)血清 FSH、LH 和 T 给药前平均自身对照值分别为2.7、6.2IU/L和16.5nmol/L,注射后3、6、9、12个月 FSH 下降了63％;LH 下降了69.4～72.6％;T 升高176％～198％。平均经117.5±2.87天治疗后全部受试者均达到无精症,连续给药1年的女方无妊娠。3种激素在停药3个月后恢复到给药前水平,精子计数10～12个月恢复到正常范围。第二组(16名)在给药第一个月后精子计数开始下降的同时3种精子特殊功能均有显著下降,而同期精子活动率(a+b)却无显著改变。我们的结果表明:(1)同一剂量和疗程的 TE 导致中国人的无精于发生率远高于白种人,(2)这一激素方法是有效、可靠和可逆的男性避孕措施,(3)TE 的避孕机理除抑制精子发生外,似还有精子功能的早期损伤的抗生育效应。这一机理不同于 GnRH 拮抗剂(Nal-glu),后者仅降低精子计数和活动率,而无精子多元运动速度指标的任何改变。