Testosteron und erektile Dysfunktion

Primary hypogonadism represents a classic but rare cause of erectile dysfunction (ED) in men. Therapy with testosterone as monotherapy is therefore unlikely to cure ED in the typical ED patient. However, recent developments indicate a much greater role of testosterone in erectile function than has been supposed in the past. Serum testosterone levels decline in men with increasing age. Aging men might develop late-onset hypogonadism (LOH) associated with characteristic symptoms. Typical symptoms of LOH are represented by decreased libido and sexual function, osteoporosis, altered distribution of body fat, overall reduction in physical strength, and alterations in the general mood. Experimental and clinical studies over the last few years have also pointed out that hypogonadism results in characteristic alterations of the erectile tissue of the penis. These alterations might be reversible in response to hormone therapy with testosterone. Particularly testosterone might be a helpful supportive therapy in cases where PDE-5 antagonists have tended to lose their effectiveness on the erectile tissue in the treatment of ED.     

Dramatic improvement of penile venous leakage upon testosterone administration. A case report and review of literature

The main effect of testosterone was long-time assumed to be on sexual interest and, indirectly, on erectile function. Newer insights demonstrate that testosterone deficiency impairs the anatomical, ultrastructural, biological and physiological/functional substrate of penile erection, which can be, at least in part, restored by normalization of plasma testosterone levels. This is a report on a 56-year-old man suffering from diabetes mellitus type II and metabolic syndrome, who had complaints of a severe erectile dysfunction because of venous leakage, confirmed by pharmaco-cavernosography. He was also testosterone deficient (1.8 ng ml(-1)). Upon testosterone administration his erectile function improved dramatically. Repeated cavernosography no longer showed venous leakage.     

Hormonal supplementation and erectile dysfunction

The role of testosterone on sexual desire is well established. However, the effects of low testosterone levels in the pathophysiology of erectile mechanism in humans remains unclear. Recent evidence indicate that approximately 10-20% of men with erectile dysfunction (ED) have hormonal abnormalities, raising up to 35% over the age of sixty. It is now clear that sexual desire and erectile function in humans are both responsive to androgens, probably at different threshold values. In fact, different degrees of testosterone deficiency may determine a sequence of molecular penile events leading to reduced capacity of penile smooth muscle and endothelial cells of relaxation, without greatly affecting sexual desire. Also, androgens may directly control the expression and activity of phosphodiesterase type-5 in human corpus cavernosum. In some selected men with total testosterone below 10-13nmol/l and/or free testosterone below 200-250pmol/l, androgen supplementation may improve therapeutic efficacy of phosphodiesterase type-5 inhibitors. For ageing men with partial androgen deficiency (PADAM) who fail first-line oral treatments in whom androgens are not contraindicated, a combination of testosterone and phosphodiesterase type-5 inhibitors may be considered to improve erectile function and improve the quality of life.     

Can testosterone level be a good predictor of late‐onset hypogonadism?

Androgens are essential for the development and growth of the genitalia. They regulate the erectile physiology by multiple mechanisms. Several studies have examined associations among sex hormones' serum levels, erectile function and sex drive. We sought to identify a protocol for using testosterone in men with erectile dysfunction and late‐onset hypogonadism (LOH). During a 16‐month period, men with erectile dysfunction who presented to the andrology clinic were selected. They underwent a complete physical examination and filled out the International Index of Erectile Function‐5 questionnaire. Serum luteinising hormone (LH) and testosterone levels were evaluated. Patients received a single intramuscular injection of 250 mg testosterone. Thereafter, serum levels of LH and testosterone were measured 3 weeks later. The mean age was 53 years old. After treating patients with testosterone, 45 (94%) showed improvement in LOH symptoms including libido, loss of energy, irritability and quality of life. The mean International Index of Erectile Function was 9 and 13.1, prior to and after treatment respectively. Mean serum testosterone levels before and after treatment were 4.2 and 4.1 ng ml^?1 respectively (P = 0.849). Mean serum LH revealed a significant decrease after the study (P = 0.004) (6.12 and 5.1 ng ml^?1, before and after the study respectively). Our findings suggested that testosterone replacement therapy improves libido and LOH symptoms in individuals with almost normal or lower limit normal value of serum testosterone levels.     

Cardiovascular diseases and erectile dysfunction: the two faces of the coin of androgen deficiency

Traditionally, clinical conditions synonymous with the ageing male included cardiovascular disease (CVD), type 2 diabetes mellitus (DM) and sexual dysfunction, and were widely regarded as independent clinical entities. Over the last decade, interrelationship of clinical conditions has been convincingly demonstrated. Declining testosterone levels in the elderly, once regarded as an academic endocrinological question, appear to be central to the listed pathologies. It is now clear that erectile dysfunction is an expression of endothelial dysfunction. Testosterone deficiency is associated with an increased incidence of CVD and DM. The latter is often the sequel of the metabolic syndrome. Visceral obesity, a pivotal characteristic of the metabolic syndrome, suppresses the hypothalamic-pituitary-testicular axis leading to diminished testosterone production. Conversely, substantial androgen deficiency leads to signs and symptoms of metabolic syndrome. It is erroneous not to include testosterone measurements in the progress of the CVD, DM and erectile dysfunction. These conditions correlate strongly with testosterone deficiency.     

【特刊综述】迟发型性腺功能减退症：发病机制、诊断、和治疗的现有概念以及争议

尽管血清睾酮（T）受抑制在中老年男性中常见,但仅有一小部分人发展成伴有弥漫性（如勃起功能障碍）,生理性（如缺乏活力和虚弱）以及心理性（如抑郁）症状的真正的低雄激素综合征。这种综合征有多种称法,包括男性更年期或更年期,男人更年期和中老年男性部分雄激素缺乏。迟发型性腺功能减退症（LoH）最恰当地描述了这类综合征因而被普遍接受。在LOH中睾酮的降低是轻微的,因此性腺功能减退症可由原发性睾丸衰竭造成（睾酮水平低,黄体生成素水平高）,也可继发于下丘脑．垂体轴功能障碍（睾酮水平低,黄体生成素水平低或不正常）。后一种形式更常见,而且经常与超重／肥胖或慢性疾病相关（如2型糖尿病、代谢综合征、心脏病以及慢性阻塞性肺病、虚弱）。LOH诊断的问题是症状（在20％-40％随机男性中）和低水平的循环睾酮（占70岁以上的男性的20％）不相符。欧洲男性增龄研究（EMAs）近期为LOH定义了严格的诊断标准,包括同时存在可再生的低水平血清睾酮（总睾酮〈11nmol l-1且游离睾酮〈220pmol l-1）,以及性功能方面的三个症状（勃起功能障碍,性幻想和晨勃频次的减少）。以这个标准来看,仅有2％的40～80岁男性患有LOH。比之生理年龄本身,低水平睾酮的原因更常见的是肥胖,尤其是总体健康受损的那种。关于LOH是否需要治疗以及如何治疗的循证资料是非常稀缺的。最合理的方法是改变生活方式,降低体重以及对合并疾病进行有效治疗。雄激素替代治疗被广泛应用,但该法的真正疗效以及短期和长期的风险尚缺乏循证资料的支持。在这篇综述中,我们将总结迟发型性腺功能减退症的发病机制、诊断、和治疗的现有概念以及存在的争议。     

Recent perspectives on the age-related decline of testosterone

A pivotal question is whether the age-related decline of testosterone should be viewed as hypogonadism, i.e. a deficiency of testosterone manifesting itself by the signs and symptoms of insufficient androgen action and, in the best case, reversed by testosterone treatment. There is no clear dividing line between normal and subnormal blood testosterone levels for establishing with certainty whether a man is hypogonadal or not. Rather, symptoms accumulate gradually with decreasing testosterone level, with these levels of testosterone differing between individuals, while within a subject not all symptoms of testosterone deficiency will manifest themselves at the same blood testosterone level.

The diagnosis of late onset hypogonadism (LOH) and, certainly, the decision to provide androgen treatment must be made with caution, taking the specific increment of symptoms in relation to testosterone levels into account. The various symptoms of LOH might start at various concentrations of androgens. With a given plasma testosterone level, some complaints might be present and others not. This has also been confirmed in studies establishing symptom-specific thresholds of androgen levels.

Symptoms of LOH do not manifest themselves at uniform threshold values of testosterone. Therefore, symptoms of testosterone deficiency are not uniformly and predictably related to blood testosterone values, which may lead to different diagnostic criteria for testosterone deficiency. So, the conclusion seems inevitable that the clinical manifestations of hypogonadism are multifactorially determined and that the diagnosis should not only depend on the measurement of testosterone but a proper assessment should comprise somatic and psychological aspects in addition to measurement of testosterone.     

Testosteronsubstitutionstherapie beim Prostatakarzinom

After the fourth decade of life the total testosterone level in men decreases continually. If clinical symptoms, such as decreased libido or erectile dysfunction are combined with a decreased serum testosterone level this is known as late onset hypogonadism (LOH) or partial androgen deficiency in the aging male (PADAM). In such cases testosterone substitution therapy is indicated. One important question is how to treat patients suffering from LOH but also have prostate cancer which was treated curatively in the past? Only relatively little data are available with small numbers of patients which show that testosterone substitution therapy is possible without an increased risk of a relapse in cases of cured prostate cancer. If the patient was cured it does not matter if radical prostatectomy or radiation therapy was used. It is mandatory that patients are well-informed about substitution therapy and that regular surveillance and controls are carried out during the therapy. For patients who still have prostate cancer which has not yet been treated or not yet cured decisions on whether the benefit of the testosterone replacement is greater than the potential risk of a progress of the disease have to be made on an individual case-specific basis.     

Testosterone and Erection: Practical Management for the Patient with Erectile Dysfunction

Although erectile dysfunction (ED) and testosterone deficiency syndrome are two independently distributed disorders, there is a degree of overlap between them. Testosterone replacement therapy, either alone or combined with other treatments such as a phosphodiesterase type 5 (PDE5) inhibitor, may therefore be useful in some men with ED. Corrective treatment of ED includes sex therapy, risk factor modification, chronic usage of PDE5 inhibitors, and testosterone replacement. Studies have shown that testosterone replacement in men with hypogonadism improves libido and erectile function in a significant proportion of cases. If corrective treatment fails or is not indicated, symptomatic treatments such as oral PDE5 inhibitors or intraurethral/intracavernous therapy are available. PDE5 inhibitors are an excellent first-line choice, although a significant proportion of men still fail to respond to monotherapy. Testosterone deficiency may be overlooked in some men with ED and, because this may be associated with lower expression of PDE5 in the penis, it could result in failure of PDE5 inhibitor therapy. Recent recommendations, therefore, suggest the need for combination therapy in some patients. In conclusion, all men presenting with ED should have their testosterone levels checked, and testosterone replacement should be considered in those with low levels. Testosterone replacement should also be considered in hypogonadal men with ED not responding to PDE5 inhibitors. If erections remain insufficient after 3 mo, a combination of testosterone and a PDE5 inhibitor may be beneficial.     

Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone

Until a decade ago the ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus, lower urinary tract symptoms and erectile dysfunction (ED), were regarded as distinct diagnostic/therapeutic entities but there is a growing awareness that these entities are not disparate and, to improve the health of the ageing male, require an integral approach. There is an inter-dependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower-than-normal testosterone levels. A new concept of the role of testosterone in male physiology suggests that testosterone plays also a significant role in the development and maintenance of bone and muscle mass and is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but exerts also essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. Treatment of testosterone deficiency is to become part and parcel of this approach.     

Testosterone replacement therapy for late-onset hypogonadism: current trends in Korea

Testosterone levels in men older than 40 years can decrease at a rate of 1%-2% per year, and reports show that more than 50% of 80-year-old men have testosterone levels consistent with hypogonadism. Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms of serum testosterone deficiency. In recent decades, the concept of LOH in ageing men has become familiar in European countries and the United States. It is also a topic of interest and debate throughout Korea. However, most of the data regarding advantages or disadvantages of testosterone replacement therapy (TRT) as treatment for LOH have been primarily obtained from studies on Western populations; therefore, studies of the effects of TRT in Asian men, who may have different serum testosterone compared to Western men, are needed. TRT is commonly prescribed in Korea, despite the paucity of studies on the effects of TRT in Asian populations. Data from various TRT studies based on Korean have shown its efficacy in increasing serum testosterone levels and improving subjective symptoms as assessed by questionnaires. Currently, patches and short-acting intramuscular injections are displaced by gels and long-acting formulations. However, to prevent overdiagnosis and overtreatment, indication for TRT should include both low testosterone levels and symptoms and signs of hypogonadism.     

The ageing penis

Epidemiological reports have demonstrated the determinant role that age plays in the pathophysiological mechanism of an erection. The atherosclerosis of the penis and its ischaemia that occurs with ageing impacts directly on the intracavernous structures and the erectile physiologic function. The effects of testosterone on libido and sexual behaviour are well established but its function in the erectile mechanism remains unclear. In the animals, testosterone deficiency seems to provoke a decrease in smooth muscle content and nitric oxide (NO) production. In human, testosterone seems to affect the central system rather than the peripheral mechanism of an erection. The role of ischaemia and the decrease in testosterone in the mechanism of erectile dysfunction are reviewed.     

The efficacy of testosterone ointment (Glowmin) treatment for late-onset-hypogonadism (LOH) patients according to LOH severity

The most basic treatment for late-onset hypogonadism (LOH) is hormone replacment therapy (HRT). In Japan, intra-muscular injection of testosterone (T) has been used for LOH treatment as HRT. Testosterone ointment (Glowmin) has been available for HRT from 1965 as an over-the-counter drug, and the profile of serum T levels and efficacy of testosterone ointment for LOH patients has been reported. In this study, we analyzed the relationship between the efficacy of testosterone ointment and LOH severity. Fifty LOH patients were treated with 6 mg of testosterone ointment per day. After 12 weeks of treatment, they were divided into 2 groups according to the severity of their LOH, serum total T and free T levels, measured by such means as total aging males' symptoms (AMS) score. The improvements of total AMS score, international index of erectile function 5 score and MOS 36-Item Short-Form Health Survey (SF-36) score were observed and analysis of variation was performed. Results showed that the symptoms in the more severe patients had a total AMS score improvement in 4 domains, AMS (psychological), SF-36 body pain (BP), social function (SF), role-emotion, compared to patients with slight LOH. While patients with normal serum T levels felt BP improvement as opposed to patients with low serum T levels, there was no significant difference in the other domains. In conclusion, testosterone ointment is considered to be effective in improving several elements of AMS and SF-36 in patients with a high AMS score.     

睾酮替代治疗雄激素缺乏ED患者65个月1例报告及文献复习

目的:通过对1例雄激素缺乏的ED患者行65个月的睾酮替代治疗观察,探讨长期睾酮替代治疗的可行性及雄激素缺乏ED的机制,为其合理治疗提供参考。方法:跟踪1例雄激素缺乏的ED患者应用睾酮替代治疗65个月的治疗效果、IIEF-5评分,雄激素变化,PSA、Hb及RBC变化及长期应用睾酮的不良反应监测,并结合相关文献进行分析。结果:46岁男性,IIEF评分7分,在未治疗前血清总睾酮(TT)2.79 ng/ml,反复多次应用多种PDE5抑制剂均无效,诊断为LOH,予以睾酮替代疗法,补充十一酸睾酮胶囊,开始2周80 mg,2次/日,后改为40 mg,2次/日,2个月后TT正常达3.45 ng/ml,体能、焦虑等症状明显好转,但是性功能无明显改善,予以PDE5抑制剂按需服用,感觉应用有效,IIEF评分21分,坚持联合用药45个月后停用PDE5抑制剂,单用睾酮替代治疗18个月,阴茎勃起坚挺,性功能满意,IIEF评分21分,定期复查性激素水平、PSA和血常规未见明显异常。结论:睾酮替代治疗可以改善PDE5抑制剂治疗雄激素缺乏的ED的效果,长期睾酮治疗雄激素缺乏症是安全、有效的。     

浙江省一农村社区迟发性性腺功能减退症的调查研究

目的:调查乡村中老年男性迟发性性腺功能减退症(LOH)的流行病学情况。方法:2012年4～10月在浙江省嘉兴市嘉善县魏塘乡村采用年龄分层抽样选取996例40～80岁的中老年男性进行中老年男子雄激素缺乏(ADAM)、老年男子症状(AMS)和国际勃起功能问卷-5(IIEF-5)调查,同时测定血清中总睾酮(TT)、性激素结合球蛋白(SHBG)及白蛋白(ALB)水平,Vermeulen公式计算游离睾酮(cFT)及生物可利用睾酮(Bio-T)水平,超声检测前列腺、睾丸体积。结果:研究对象年龄(56.22±8.82)岁,ADAM及AMS筛查LOH的患病率分别为62.86%和23.05%;ED阳性率为68.83%,SHBG、LH、cFT及Bio-T筛查LOH各组之间存在统计学差异。结论:浙江省嘉善县魏塘乡村中老年男性LOH筛查率较国内其他报告(特别是大中城市)LOH筛查率低,ED患病率接近。城乡中老年LOH患病率有差别,值得进一步研究。     

Testosteronsubstitutionstherapie beim Prostatakarzinom

During the male 40s total testosterone levels decrease continuously. If clinical symptoms like decreasing libido, erectile dysfunction, osteoporosis, altered distribution of body fat, reduction in physical strength, or alterations in psychological mood are combined with a decreased serum testosterone level late-onset hypogonadism (LOH) is obvious. Before the substitution of testosterone is initiated, it is essential to exclude prostate cancer because the progress of prostate cancer depends on androgens. The question is now how to treat patients who suffer from androgen deficiency but have cured prostate cancer in their history? Concerning this there are only a few studies with a small number of patients which show that testosterone substitution therapy is possible without an increased risk for recurrence of prostate cancer. As long as the patient was cured it does not matter if he underwent a radical prostatectomy or brachytherapy. Absolutely necessary is that the patient is well informed about the therapy and regularly controlled during the therapy.     

Recognising late-onset hypogonadism: a difficult task for sexual health care

Late-onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with advancing age and characterised by typical symptoms together with a deficiency in serum testosterone levels. Identification of LOH-related symptoms and signs is, therefore, essential for suspecting this condition. We investigated a specific association between indicative signs and symptoms of androgen deficiency and its biochemical correlates (total T below 12 and/or 8 nmol/l) in a large series (2817) of patients consulting our Sexual Dysfunction Unit. In addition, a systematic review of the literature using Medline (1969 to March 2009) was also performed. We found that although structured interviews, such as ANDROTEST or other self-reported questionnaires, might help physicians to familiarise themselves with hypogonadal symptoms and suspect LOH, LOH-related symptoms and signs are rather non-specific, as they are also characteristic of the ageing process per se. We confirmed that an accurate focused clinical history (inquiring about cryptorchidism, pituitary diseases and delayed puberty) can be very informative about the presence of LOH. In addition, sex life-related performances (libido, erection and ejaculation) and attitudes (masturbation and extra-marital affairs) might also provide insights. Clinical signs, such as testis volume, penile blood flow and the presence of the metabolic syndrome, can also raise the suspicion of LOH: an increased waist circumference increases the risk of having LOH by a factor of 3. Although a clinical evaluation is mandatory in suspecting LOH, it is our opinion that the determination of total testosterone is essential in confirming the diagnosis and/or in starting any substitutive therapy.     

Lower urinary-tract symptoms and testosterone in elderly men

OBJECTIVES: The objective was to examine the effects of testosterone administration on symptom scores of lower urinary tract symptoms (LUTS). METHODS: The literatures on the epidemiological association between the metabolic syndrome, erectile failure and (LUTS) were reviewed. RESULTS: In men with the metabolic syndrome and erectile failure, often lower-than-normal testosterone levels are found. This is less clear for men with LUTS, but the relationship between testosterone and LUTS might be indirect and based on the association of the metabolic syndrome with an overactivity of autonomic nervous system. This overactivity may play a key role in increasing the severity of LUTS above an intrinsic basal intensity that is determined by the genitourinary factors in aging men. Androgen receptors are present in the epithelium of the urethra and the bladder. Testosterone may play a role in the reflex activity of the autonomic nervous system in the pelvis, or may interact with postsynaptic non-genomic receptors suppressing detrusor activity. Human neurons in the wall of the bladder contain nitric oxide synthase. Similar to the penis, testosterone has an impact on nitric oxide synthase. CONCLUSIONS: Some studies investigating the effects of normalizing testosterone levels in elderly men have found a positive effect on variables of the metabolic syndrome and, simultaneously, on scores of the International Prostate Symptoms Score (IPSS) which is worthy of further investigation in randomized, controlled and sufficiently powered clinical trials.     

A survey on relative frequency of metabolic syndrome and testosterone deficiency in men with erectile dysfunction

Purpose

Erectile dysfunction (ED) is a common male sexual dysfunction and affects the individual??s physical and psychological well-being. It has been classified as organic and psychogenic. Men with low testosterone levels have an increased risk of ED. On the other hand, direct detrimental effect of metabolic syndrome on the endothelium, smooth muscle and nerves of the vascular system of the penis is what causes ED to develop in men with metabolic syndrome. Therefore, it is supposed that a large number of men with erectile dysfunction are patients who have ED, metabolic syndrome and testosterone deficiency as a triad. The aim of this study is determining relative frequencies of metabolic syndrome and testosterone deficiency in a group of men with ED.

Methods

Men suffering from ED who were referred to a certain private urology clinic between 22.11.2009 and 22.9.2010 were evaluated for metabolic syndrome criteria; their morning free testosterone levels were measured, and then the related questionnaires were filled out.

Results

Of 241 men with ED, the relative frequency of metabolic syndrome was 41.5%, of testosterone deficiency was 36.5% and of metabolic syndrome in combination with testosterone deficiency was 19.5%.

Conclusion

The relative frequencies of metabolic syndrome and testosterone deficiency in men with ED seem to be significant, and it is the time that we should evaluate ED not as a disease but as a presentation of multiple underlying pathologies which needs medical attention to general health.     

How to optimise treatment of erectile dysfunction above and beyond the beneficial effects of a phosphodiesterase type 5 inhibitor

The introduction in 1998 of the phosphodiesterase type 5 (PDE-5) inhibitors has changed the landscape of diagnosis and, in particular, the treatment of erectile dysfunction (ED). It has paved the road for a more profound insight into ED. ED and other ailments of elderly men, such as atherosclerosis, hypertension, diabetes mellitus and lower urinary tract symptoms were usually regarded as distinct diagnostic/therapeutic entities, but there is growing evidence that they are interrelated and are factors in ED. To optimise the treatment of ED, an integral approach to the health of the ageing male is required. There is an interdependence between the metabolic syndrome, ED and patterns of testosterone in ageing men. The main features of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia, significant factors in the aetiology of erectile function. The metabolic syndrome is associated with lower-than-normal testosterone levels. Testosterone is a determinant of glucose homeostasis and lipid metabolism. Testosterone is not only a factor in libido but also exerts essential effects on the anatomical and physiological substrate of penile erection. With these recent insights, the health problems of elderly men must be placed in a context that allows an integral approach. While PDE-5 inhibitors are the mainstay of treatment of men with ED, treatment of testosterone deficiency is becoming part and parcel of a new approach to both ED and the metabolic syndrome. The diagnostic work-up of ED should comprise measurement of plasma testosterone. If proven deficient, treatment with testosterone is indicated.