Challenges in the Diagnosis of the Right Patient for Testosterone Replacement Therapy

Diagnosis of testosterone deficiency is important to identify patients who might benefit from testosterone replacement therapy. Unfortunately, the diagnosis of hypogonadism may be a challenge for many practicing physicians, including endocrinologists and urologists. Signs and symptoms, such as sexual dysfunction, change in body composition, lethargy, and mood changes, are nonspecific and the available questionnaires are generally not useful in clinical practice. The diagnosis of testosterone deficiency is ultimately based on measurement of serum testosterone levels. However, marked variations in the reference ranges of serum testosterone levels among laboratories pose a challenge for physicians when interpreting the results. In addition, initial laboratory assessments usually determine total testosterone levels. About 1–2% of total testosterone is free and a further 30–50% is bound with low affinity to albumin; only these two components are bioavailable to the target tissues. In general, assuming the normal reference range for serum total testosterone in adult men is 300–1000 ng/dl (10–35 nmol/l), levels of < 250 ng/dl (8.7 nmol/l) suggest the patient is likely to be hypogonadal, whereas levels of > 350 ng/dl (12.7 nmol/l) suggest the symptoms may not be due to androgen deficiency. Values between 250 to 350 ng/dl warrant a repeat morning serum testosterone determination with assessment of free or bioavailable testosterone. In men with symptoms suggestive of androgen deficiency and borderline serum testosterone levels, where there are no contraindications to androgen therapy, a short therapeutic trial of testosterone may be justified.     

Transdermal testosterone delivery: testosterone patch and gel

Testosterone replacement treatment is usually life-long. Fortunately, testosterone administration is relatively safe and until the age of 50 years few side effects are noted with normal doses of testosterone. After the age of 50 years when prostate disease becomes more prevalent, shorter-acting testosterone preparations, allowing a fast reduction of circulating testosterone levels, may be an advantage. Testosterone has an impact on sexual and non-sexual behaviour and short-acting testosterone preparations may be better suited for the initiation of long-term administration allowing the monitoring of behavioural effects. Testosterone can be delivered to the circulation through the intact skin, both genital and non-genital. Transdermal administration delivers testosterone at a controlled rate into the systemic circulation, avoiding hepatic first pass and reproducing the diurnal rhythm of testosterone secretion and without the peak and trough levels observed with the use of the traditional long-acting testosterone injections. In conclusion, both the testosterone patch and testosterone gel are valuable contributions to androgen replacement treatment meeting the requirements specified for testosterone replacement treatment.     

Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction

The most common cause of erectile dysfunction (ED) is penile vascular insufficiency. This is usually part of a generalized endothelial dysfunction and is related to several conditions, including type 2 diabetes mellitus, hypertension, hyperlipidemia, and obesity. These conditions underlie the pathophysiology of metabolic syndrome (MetS). Hypogonadism, or testosterone deficiency (TD), is an integral component of the pathology underlying endothelial dysfunction and MetS, with insulin resistance (IR) at its core. Testosterone replacement therapy for TD has been shown to ameliorate some of the components of the MetS, improve IR, and may serve as treatment for decreasing cardiovascular and ED risk.     

Significance of hypogonadism in erectile dysfunction

To review the role and significance of hypogonadism, defined as a low testosterone (T) level, in erectile dysfunction (ED). Review of literature. Serum T is below 3 ng/ml in 12% of ED patients, including 4% before and 15% after the age of 50. Replacement studies in men with severe hypogonadism demonstrate that sexual desire and arousal, as well as the frequency of sexual activity and spontaneous erections are clearly T-dependant. Psychic erections are partly T-dependant. The effects of T upon sexual function are dose-dependant up to a threshold level that is consistent within an individual, but markedly variable between individuals, ranging from 2 to 4.5 ng/ml. More evidence is required to confirm a significant impact of T on the intrapenile vascular mechanisms of erections in men as it is the case in animals. No convincing association of T with ED has been found in epidemiological studies. As concerns clinical experience, although a meta-analysis of the randomized controlled trials established that T therapy consistently restores erectile function in young hypogonadal patients with T below 3.46 ng/ml, the effects of this treatment have been mostly disappointing when used alone in older patients consulting for ED who are subsequently diagnosed to have hypogonadism following routine T measurement. These poor results may probably be explained by the high prevalence of co-morbidities, and by the fact that ED itself may induce hypogonadism. Combination therapy with T and PDE5 inhibitor (PDE5I) may be effective in the hypogonadal ED patients when T therapy alone fails. However, more evidence is required to confirm the hypothesis that a minimum level of T is required for a complete effect of PDE5I in certain men, since a PDE5I was able to restore complete erections in severely hypogonadal men. Though a low T level is not always the only cause of ED in hypogonadal ED patients, there are important benefits in screening for hypogonadism in ED. A low T level justifies a 3 month trial of T therapy, before combining a PDE5I if T therapy alone fails     

Testosterone and prostate cancer: an historical perspective on a modern myth

OBJECTIVES: To review the historical origins and current evidence for the belief that testosterone (T) causes prostate cancer (pCA) growth. METHODS: Review of the historical literature regarding T administration and pCA, as well as more recent studies investigating the relationship of T and pCA. RESULTS: In 1941 Huggins and Hodges reported that marked reductions in T by castration or estrogen treatment caused metastatic pCA to regress, and administration of exogenous T caused pCA to grow. Remarkably, this latter conclusion was based on results from only one patient. Multiple subsequent reports revealed no pCA progression with T administration, and some men even experienced subjective improvement, such as resolution of bone pain. More recent data have shown no apparent increase in pCA rates in clinical trials of T supplementation in normal men or men at increased risk for pCA, no relationship of pCA risk with serum T levels in multiple longitudinal studies, and no reduced risk of pCA in men with low T. The apparent paradox in which castration causes pCA to regress yet higher T fails to cause pCA to grow is resolved by a saturation model, in which maximal stimulation of pCA is reached at relatively low levels of T. CONCLUSIONS: This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of T and pCA that may be clinically and scientifically rewarding.     

睾酮与男性骨质疏松

男性骨质疏松的病因是多方面的 ,雄激素水平下降是很重要的一个因素。雄激素不仅在获得骨峰值及维持骨量中起重要作用 ,雄激素水平下降与随增龄而发生的骨丢失关系也很密切。雄激素通过雄激素受体影响成骨细胞功能 ,各种局部因子起调节作用。老年人部分睾酮替代治疗可提高骨密度 ,但其利弊需进一步观察。同时雌激素在男性骨质疏松中所起作用开始受到关注     

阳萎治疗的选择与评价

３２５例阳萎患者采用多种治疗方法，观察其疗效进行比较与评价。口服药物总显效率仅为１５％。静脉性阳萎手术无期疗效仅２８．１％，动脉性阳萎无期疗效为５０％。自我海绵体内注射前列腺素Ｅ１（ＰＧＥ１）２５例，均可达到较满意性交，无副作用，无期疗效尚需观察。真空缩窄装置适用于老年或血管病变严重者，口服药物适用于轻度阳萎患者。ＰＧＥ１自我注射见效快，常可使部分患者免除手术之苦，已成为阳萎治疗的重要手术并可同时     

老年男性的睾酮替代疗法

男性正常衰老过程伴随血清睾酮水平下降 ,但是尚不清楚它是否将导致许多男性的睾酮缺乏症。过去 10年中 ,越来越多的研究兴趣转向确认对那些睾酮缺乏的老年男性采用睾酮替代疗法 (TRT)是否有助于阻止或逆转衰老的某些方面。TRT有益效应相关的主要雄性激素靶器官包括 :骨、肌肉、脂肪组织、心血管系统和脑。与此同时 ,TRT对靶器官 (如前列腺 )的潜在不良反应仍需评估。本文的目的是总结有关老年男性TRT问题的最新认识。     

阴茎勃起功能障碍诊断方法探讨

目的　探讨阴茎勃起功能障碍 (ED)的诊断方法。　方法　对 186例阴茎勃起功能障碍患者分别采取国际勃起功能评分 (IIEF 5 )、阴茎海绵体注射 (ICI)试验、血清性激素 (LH、T、PRL和E2 )测定、阴茎彩色双功能超声、阴茎海绵体造影及球海绵体肌反射潜伏时间等检查。　结果　有186、71、2 8、4 5、2 1和 17例患者分别接受了上述检查 ,诊断心理性ED 4 6例 ,动脉性ED 6例 ,静脉性ED 15例 ,内分泌性ED 3例 ,神经性ED 3例 ,混合性ED 10例 ,原因不明 10 3例。　结论　ED是高度个性化疾病 ,针对患者不同情况采取相应的诊断方法 ,有利于选择高效、经济、安全的治疗方法。     

Testosterone and the Prostate: The Evidence So Far

It has traditionally been accepted that testosterone substitution in men with testosterone deficiency syndrome has the potential to harm the prostate. This theory originates from 1941 and is based on data presented for only two patients, one of whom had already been castrated. A review of the current peer-reviewed medical literature, however, has proved inconclusive. Whilst there is clear evidence that a reduction in serum testosterone to castration concentrations is able to reduce levels of prostate-specific antigen and delay the progression of established prostate cancer, it is difficult to prove the converse. Recent studies have shown that testosterone replacement has little effect on prostate tissue androgen levels and cellular function, whilst in men with prostate cancer, low serum testosterone levels were reported to be associated with the presence of extraprostatic cancer. Nevertheless, it is clear that the two classical contraindications for the administration of testosterone, that is, suspected or histologically proven prostate cancer and symptomatic benign prostatic hyperplasia, must be carefully respected.     

原发性精索静脉曲张与阴茎勃起功能障碍的相关性探讨

目的 了解原发性精索静脉曲张与阴茎勃起功能障碍的关系.方法 以527例原发性精索静脉曲张患者为研究对象,全部原发性精索静脉曲张患者均接受手术治疗,搜集手术前后精索静脉曲张的临床资料和国际勃起功能指数-5(IIEF-5)问卷调查结果.结果 国际勃起功能指数-5(IIEF-5)分值随原发性精索静脉曲张术后治愈而升高.原发性精索静脉曲张疗效满意,合并的勃起功能障碍病情好转.结论 原发性精索静脉曲张很可能是勃起功能障碍的危险因素,其继发的心理因素,也可以成为勃起功能障碍的心理病因之一.原发性精索静脉曲张的治疗,可以改善阴茎勃起功能障碍的病情.

Abstract：

Objectives To understand the relationship between Varicocele( VC ) and erectile dysfunction (ED). Methods 527 patients with VC were investigated by International Index of Erectile Function - 5 ( IIEF-5) before and 6 months after surgery. All patients were treated with operation for Varicocele. Results The prevalonce of Erectile dysfunction in patients with varicocele decreased after the varicocele been treated. The treatment of varicoeele was satisfying, the state of erectile dysfunction turn for the better. Conclusions Varicocele probably is one of the risk factor in erectile dysfunction. The treatment of varicocele can improve the state of erectile dysfunction.     

Testosterone and erectile dysfunction

Aging is associated with a decline in several important health factors in men, including libido. Serum testosterone concentrations also decrease with age, and many age-related clinical features are closely associated with androgen deficiency, including erectile function (ED). Approximately 70% of ED is of organic origin, with the major risk factors being diabetes mellitus, hypercholesterolemia, smoking and chronic medical illnesses. These are also established risk factors for atherosclerosis, which is the predominant predisposing factor of vasculogenic ED. The introduction of phosphodiasterase-5 (PDE-5) inhibitors for the treatment of ED made a significant impact both in terms of clinical efficacy, and increasing the awareness of the condition. In spite of this, some patients fail to respond to PDE-5 inhibitors alone. Both animal and clinical studies indicate that testosterone therapy improves both erectile function and the response to PDE-5 inhibitors in patients with ED and hypogonadism. Indeed, interventional studies demonstrate that testosterone replacement therapy improves erectile function in hypogonadal men who have previously failed to respond to PDE-5 inhibitors alone. Furthermore, it has been demonstrated that the full therapeutic potential of PDE5 inhibitors will only become manifest in a eugonadal state. Recent studies have demonstrated a close relationship between testosterone and ED and suggest that testosterone therapy may be a valuable option for an increasing number of affected men. European guidelines recommend that all men presenting with ED should have their testosterone concentrations measured.     

勃起功能障碍阴茎血流动力学研究

目的 探讨勃起功能障碍(erectile dysfunction,ED)的病因诊断。方法 130例ED患者通过阴茎海绵体内应用血管活性药物,进行阴茎海绵体血流动力学和海绵体造影检查。观察并记录阴茎一肱动脉血压指数(penile brachial index,PBI)、海绵体内压(intracavermous pressure,ICP)、维持灌流率(maintenance flow rate,MFR),海绵体内压跌差(pressure loss change,PLC)等项指标及阴茎静脉血管形态。结果 130例ED中有39例为静脉漏,其中15例为动脉血供不足伴静脉漏。海绵体造影显示28例为单纯背深静脉漏,其余11例为背深静脉复合阴茎脚静脉漏。结论 阴茎血流动力学检测可作为ED病因诊断的有效方法。     

Androgen therapy in the aging male

The world population is expanding rapidly; at the same time, life expectancy is increasing, and fertility rates are decreasing. Due to these facts, it is expected that the biggest increases of population growth will occur in the aging population. In the aging male, endocrine changes and a decline in endocrine function involve tissue responsiveness as well as reduced secretory output from peripheral glands and alterations in the central mechanism controlling the temporal organization of hormonal release. The latter are likely to be responsible for the dampened circadian hormonal and non-hormonal rhythms. These are in part responsible for the age-dependent decrease of the peripheral levels of testosterone, dehydroepiandrosterone (DHEA), the thyroid hormones, growth hormone (GH), IGF1 and melatonin. These hormonal changes, which develop in most men at about the age of 50, are in part responsible for endocrine deficiencies of some older men. One of the best-studied endocrine deficiencies is late-onset hypogonadism. This is a syndrome characterized by adverse effects on multiple organ systems and decreased quality of life, associated with advancing age and characterized by signs and symptoms of hypogonadism and a deficiency in serum androgen levels with or without a decreased genomic sensitivity to androgens. In cases of endocrine deficiencies, traditional endocrinology aims to replace the missing hormone or hormones with substitutes. It has been demonstrated that interventions such as hormone therapies may favorably influence some of the pathological conditions in aging men by preventing the preventable and delaying the inevitable. A comprehensive medical, psycho-social and life-style history, a physical examination and laboratory testing are essential for the diagnosis and management of late-onset hypogonadism. Acute, chronic or inter-current diseases must be taken into consideration prior to initiating any hormonal substitution therapy. In the era of evidence-based medicine, we have to acknowledge that data on testosterone therapy (HT) in the aging male is mostly circumstantial, based on experience in the treatment of transitional or chronic hypogonadism in young men resulting from disease or experiments of nature. However, over the past several years prospective studies on testosterone therapy in the aging male were performed and shown to be beneficial for certain older men in preventing or delaying some aspects of aging. Recommendations for algorithms for the diagnosis of late-onset hypogonadism and monitoring therapy for safety and efficacy are the subject of this paper.