Can the administration of testosterone to men with late-onset hypogonadism be discontinued?

Over the last decade, in addition to the classical forms of hypogonadism attributable to defects in testicular steroidogenesis (primary hypogonadism) or defects of the hypothalamo–pituitary unit (secondary hypogonadism), a new form has been defined: late-onset hypogonadism (LOH). LOH is partially based on the ageing process of the hypothalamo–pituitary–testicular axis leading to a diminution of the efficacy of testicular steroidogenesis, but a more significant determinant of decline in testosterone levels with ageing is disease and, in particular, the so-called metabolic syndrome. The main components of the metabolic syndrome are abdominal obesity, insulin resistance, hypertension and dyslipidaemia and these components are, in principle, remediable. Administration of testosterone to elderly men with the metabolic syndrome and hypogonadal values of testosterone leads to an improvement in the components of the metabolic syndrome which, in turn, could lead to an improvement in the own testicular hormone production eventually obviating the need for testosterone administration. There is very limited experience with this approach but this strategy deserves further exploration.     

Treatment for late-onset hypogonadism: the current situation in Japan

Prevention of age-related disability has become very important because the number of people aged 60 years and older is increasing rapidly. Androgen levels decrease with aging and this plays many physiologic roles in various organs. Late-onset hypogonadism (LOH) has received widespread attention in the last few years. LOH symptoms include sexual dysfunction and depression, and the first-line treatment should be hormone replacement therapy (HRT), by which several symptoms of LOH are improved. Although several types of testosterone preparations are available worldwide, the testosterone preparations available in Japan are limited. For this reason, the Clinical Practice Manual for LOH, authored by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male, recommends HRT with testosterone enanthate, human chorionic gonadotropin (hCG) and ‘Glowmin’, a short-acting testosterone ointment produced in Japan. In this review, we summarize the efficacy of HRT for LOH symptoms and introduce hCG and Glowmin therapy according to the Clinical Practice Manual. However, several studies, including our own, have shown that LOH symptoms are not always related to serum testosterone concentration. Thus, HRT is not adequate as the only treatment option for LOH because eugonadal men with symptoms of LOH comprise 30% of the general population. We discuss the efficacy of Japanese herbal medicines, which have been used for treatment of the menopause and several psychological disorders, particularly in the treatment of eugonadal patients with symptoms of LOH.     

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.     

十一酸睾酮治疗迟发性性腺功能低下的研究进展

随着老年化社会的到来,迟发性性腺功能低下的患者人数也逐渐增加。治疗迟发性性腺功能低下的方法也多种多样,而十一酸睾酮作为治疗迟发性性腺功能低下的主要药物,获得明显效果。本文就十一酸睾酮治疗迟发性性腺功能低下的研究进展作一综述。     

The characteristics of late-onset hypogonadism, its prevalence, symptoms, and diagnosis

With aging in most but not all men

• Total testosterone levels decline

• Even more so free testosterone levels

• This is associated with symptoms of testosterone deficiency, not only of sexual functioning but also of bone density, muscle mass and metabolic risk factor for cardiovascular disease and diabetes

• The diagnosis is based both on clinical symptoms and on laboratory measurements, more so of free testosterone than of total testosterone.

• Treatment with testosterone is acceptably safe provided established guidelines are adhered to

他达拉非对中老年男性LOH患者T、IIEF及SEP影响的临床研究

目的:观察他达拉非联合安特尔治疗中老年男性迟发性性腺功能低下(LOH)的临床疗效。方法:选择125例中老年男性LOH患者随机分为两组,治疗组65例使用他达拉非加十一酸睾酮治疗,对照组60例使用十一酸睾酮胶囊治疗。分别记录治疗前及治疗后4周时的总睾酮(T)、国际勃起功能指数评分(IIEF)、患者性生活日记(SEP)等的变化。结果:治疗后2组T、IIEF及SEP评分均有不同程度改善,与治疗前比较,差异均有统计学意义(P<0.05);治疗组T、IIEF及SEP评分改善更为显著,与对照组比较,差异均有统计学意义(P<0.05)。结论:使用他达拉非联合十一酸睾酮胶囊,可较好地改善中老年男性患者T、IIEF及SEP分数,提高患者性生活满意度及自信心,具有比单纯补充睾酮更好的综合疗效。     

Diagnosis of hypogonadism in patients treated with low energy shock wave therapy for erectile dysfunction: a narrative review

Several methods of treatment of erectile dysfunction (ED) are offered with low energy shock-wave therapy (LESWT) gaining increasing attention. Reports have documented that LESWT stimulates tissue neovascularization, proliferation and differentiation of endothelial cells, and production of nitric oxide - all can improve the condition of erectile tissue. However, the overall and sexual condition of men deteriorates with age which is linked with a constant decrease in testosterone concentration. A higher risk of sexual health disorders and reduced physical fitness correlates with a testosterone concentration of <12 nmol/L. Such patients may require testosterone replacement therapy. We conducted a target literature review to investigate whether testosterone concentration is taken into account in studies on the use of LESWT in the treatment of ED. We found that most studies did not provide any information on testosterone status. Only 8 of 25 studies examined showed values of testosterone concentrations. Only one of these analyses checked the relationship between the efficacy of LESWT and testosterone concentration. As a result, meta-analyses published to date may not show the full value of LESWT in the treatment of ED. We conclude that in the light of the significant role testosterone plays in the process of an erection and the mechanism of LESWT action, it can be recommended to examine testosterone concentration and to diagnose hypogonadism during the qualification of patients to studies on LESWT efficacy. Moreover, the effectiveness of LESWT in relation to the current testosterone concentration should also be further investigated.     

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.     

Men's health in primary care: an emerging paradigm of sexual function and cardiometabolic risk

An office evaluation of men's health in primary care requires a thorough understanding of the implications of male sexual dysfunctions, hypogonadism, and cardiometabolic risk stratification and aggressive risk management. The paradigm of the men's health office visit in primary care is the recognition and assessment of male sexual dysfunction, specifically erectile dysfunction, and its value as a signal of overall cardiometabolic health, including the emerging evidence linking low testosterone and the metabolic syndrome. Indeed, erectile dysfunction may now be thought of as a harbinger of cardiovascular clinical events and other systemic vascular diseases in some men.     

Efficiency of intracavernosal alprostadil and oral clomiphene citrate combination treatment in penile vasculogenic erectile dysfunction patients accompanied by late-onset hypogonadism

In this study, the efficiency of intracavernosal alprostadil + oral clomiphene citrate (CC) treatment in late-onset hypogonadism (LOH) accompanied by penile vasculogenic erectile dysfunction (PVED) in patients irresponsive to phosphodiesterase type 5 inhibitor treatment was evaluated. A total of 31 patients with concurrent PVED and LOH were included in the study. The patients were given intracavernosal alprostadil (10–20 μg) and oral CC (50 mg) every day for 12 weeks. Before and after treatment, a 15-question International Index of Erectile Function (IIEF-15) questionnaire, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP)2 and SEP3 levels were analysed, and follicle stimulating hormone (FSH), luteinising hormone (LH), total testosterone and prostate-specific antigen (PSA) levels were measured. In all, 41.9% of patients had pure arterial deficiency, 19.3% had pure venous deficiency, and 38.7% had arterial + venous (mixed) deficiency. A significant increase was detected in total testosterone, FSH, LH and PSA values after treatment when compared to values before treatment (p < .001, p < .001, p < .001 and p = .034 respectively). A significant recovery was observed in IIEF-15 subscores, EHS and SEP2-SEP3 results. In PVED patients accompanied by LOH, intracavernosal alprostadil and oral CC combination is an efficient, low cost, safely applicable and tolerable treatment.     

Testosterone in men's health: a new role for an old hormone

Testosterone is an anabolic hormone with a wide range of beneficial effects on men's health. A considerable body of evidence suggests that testosterone (T) deficiency contributes to the onset and/or progression of type 2 diabetes mellitus (T2D), insulin resistance (IR), metabolic syndrome (MetS), cardiovascular disease (CVD), and erectile dysfunction (ED). Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Low testosterone also produces adverse effects on cardiovascular health. Androgen deficiency is associated with increased levels of total cholesterol, low density lipoprotein (LDL), increased production of pro-inflammatory factors, increased thickness of the arterial wall, and contributes to endothelial dysfunction. Testosterone therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and hemoglobin A1c levels. Testosterone supplementation restores arterial vaso-reactivity, reduces pro-inflammatory cytokines, total cholesterol, and triglyceride levels and improves endothelial function and high density lipoprotein (HDL) levels. The therapeutic role of testosterone in men's health, however, remains a hotly debated issue for a number of reasons, including the purported risk of prostate cancer. In view of the emerging evidence suggesting that androgen deficiency is a risk factor for MetS, T2D, IR, CVD, and ED, androgen replacement therapy in hypogonadal men may potentially reduce the risk for these pathologies.     

Intramuscular testosterone undecanoate for the treatment of male hypogonadism–review of recent data

Androgen preparations are indicated for the treatment of male hypogonadism. The re-establishment of normal testosterone (T) levels in hypogonadal men has been shown to result in improved libido, erectile quality and mood and to have positive effects on body composition and other parameters. Several treatment options exist for hypogonadal patients; the most commonly used include injectable intramuscular testosterone esters such as testosterone enanthate administered at intervals of 2–3 weeks, which often leads to temporary fluctuations in serum testosterone levels. A novel injectable testosterone ester, testosterone undecanoate (TU), is as effective and safe as the standard injectable formulation and requires only four injections per year in long-term treatment while maintaining serum T levels within the physiological range. Recent data confirm the safety and efficacy of long-term TU therapy in patients treated over a period of up to 7.5 years and show the positive impact of testosterone on the cavernosal tissues that are pathologically altered due to androgen deficiency in an animal model and in humans. Men with erectile dysfunction and low serum testosterone may benefit from testosterone administration and the combination of phosphodiesterase 5-inhibitors and testosterone may be indicated in men who do not respond sufficiently to testosterone alone.     

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.     

老年男性勃起功能及迟发性性腺功能减退症状与下尿路症状严重性的关系

本文旨在研究土耳其爱琴海地区的老年男性下尿路症状（LUTSs）、勃起功能障碍（ED）和有症状的迟发性性腺功能减退症（SLOH）三者间的关系。符合以下标准的500名男性患者被纳入该研究：40周岁以上；过去6个月内有稳定的性关系；在六个泌尿外科诊所之一进行过就诊登记。每位患者均行血清PSA、睾酮水平及尿流率的检测，并填写国际前列腺症状评分和生活质量评分（IPSS-QoL）量表、国际勃起功能指数（IIEF）问卷和老年男性症状（AMS）量表。在所有的研究对象中，23．9％的患者有轻度LUTSs，53．3％有中度LUTSS，22．8％有重度LUTSS。每组间总睾酮水平无明显差异。除此之外，69．6％的病人患有ED，且ED的发生率与LUTS严重性呈正相关。71．2％的患者出现SLOH（AMS〉27），且IPSS评分越高，严重的性腺功能减退症状的发生率也越高。相关性分析显示以上三种问卷分数之间有显著关联。总之，LUTS严重性是ED和SLOH的非年龄依赖性危险因素，LUTS严重性和SLOH症状之间似乎有显著的相关性，但还需要从病因学和生物学角度进行深入阐明。     

Survey for late-onset hypogonadism among old and middle-aged males in Shanghai communities

This study sought to investigate late-onset hypogonadism (LOH) in old and middle-aged males in Shanghai communities, using symptom score evaluation systems and measurements of sex hormone levels. One thousand cases of males aged 40-70 years were investigated. The aging male symptoms (AMS) scale and androgen deficiency in aging males (ADAM) questionnaire were used at the beginning of the investigation, followed by measurement of the sex hormone-related factors (total testosterone (TT), free testosterone (fT), sex hormone-binding globulin (SHBG) and bioavailability of testosterone (Bio-T)). There were 977 valid questionnaires. The LOH-positive rates shown by AMS and ADAM were 59.88% and 84.65%, respectively; values increased with the age of the patients. There were 946 results related to sex hormone measurements, which showed the following results: TT was not related to aging (P>0.05); levels of SHBG increased with age; and fT and Bio-T decreased with age. There was a significant difference in fT between LOH-positive and LOH-negative patients, as shown by the ADAM. In summary, TT levels were not related to aging, even though SHBG did increase while fT and Bio-T decreased with aging. Clinically, the diagnosis of LOH cannot be based on serum TT level.     

Assessment of possible effects for testosterone replacement therapy in men with symptomatic late-onset hypogonadism

We herein report clinical assessments of efficacy and side effects of T replacement therapy (TRT) in men with late-onset hypogonadism (LOH). The study included 56 patients who were diagnosed with LOH and treated with TRT for at least 6 months at our institution. Age, ageing male symptom (AMS) scale, and androgen decline in the ageing male (ADAM) questionnaires were examined. Fasting blood samples were analysed for sex hormones, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), red blood cell count (RBC), haemoglobin (Hb), haematocrit (Ht), and prostate-specific antigen (PSA). Total and psychological symptoms scores were measured by the AMS scale and the ADAM questionnaire score, demonstrating that the sum of positive responses to the questions were significantly improved after TRT (P < 0.05). TC, HDL, and LDL cholesterol, TG, AST, ALT, γ-GTP, RBC, Hb, Ht, and PSA were not significantly different between before and after TRT. Although TRT for men with LOH may cause favorable changes in psychological conditions, it may not have effects on lipid metabolism, liver function, RBC, and PSA level.     

Varicocele is associated with hypogonadism and impaired erectile function: a prospective comparative study

We conducted this prospective comparative study to examine the hypothesis that varicocele was associated with hypogonadism and impaired erectile function as reflected in International Index of Erectile Function‐5 (IIEF‐5) scores as well as nocturnal penile tumescence and rigidity (NPTR) parameters. From December 2014 to December 2015, a total of 130 males with varicocele complaining of infertility or scrotal discomfort and 130 age‐matched healthy males chosen from volunteer healthy hospital staff as controls were recruited in this study. Serum testosterone (TT) levels and IIEF‐5 scores as well as NPTR parameters were evaluated and compared between varicocele and control subjects. All participants were further grouped into hypogonadism based on the cut‐off value 300 ng/dL. A total of 45 of 130 patients were identified as hypogonadism, while it was not found in control subjects. A multivariate logistic regression with likelihood ratio test revealed that TT levels as well as grade III and II varicocele posed significant indicators for hypogonadism occurrence (chi‐square of likelihood ratio = 12.40, df = 3, p < .01). Furthermore, TT levels and infertility duration were associated with IIEF‐5 scores in a multivariate linear regression analysis (adjusted R² = 0.545). In conclusion, the correlation of grade III and II varicocele with an increased risk of hypogonadism was confirmed in this study and an impaired erectile function correlated with TT levels and infertility duration was also observed.     

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.     

Lifestyle/dietary recommendations for erectile dysfunction and female sexual dysfunction

Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction.     

北京市社区中老年男性性功能调查报告:BPC-BPH研究结果

目的 调查北京市社区中老年男性性欲低下、勃起功能障碍(ED)、射精障碍的患病情况.方法 采用分层多阶段整群不等比例随机抽样方法选择北京市15个社区1656名年龄≥50岁男性作为调查对象,分别记录国际勃起功能问卷(IIEF-5)评分及男性性功能问卷(O'Leary 1995),应用χ~2检验分析结果.结果 符合标准的调查对象共1644人.年龄50～93(64.5±9.8)岁.平均IIEF-5(9.4±8.6)分.以IIEF-5评分0～21诊断为ED,总ED患病率90.45%,性欲低下60.04%,射精障碍38.81%.各年龄组(10岁/组)间ED、性欲低下、射精障碍患病率差异有统计学意义(P＜0.0001),各年龄组间不同程度ED患病率差异有统计学意义(P＜0.0001).趋势检验表明随年龄增加,ED、性欲低下、射精障碍患病率逐渐增加(Z=10.1,P＜0.0001),与年龄呈正相关性.结论 随年龄增加ED、性欲低下、射精障碍的患病率逐渐增加.ED患病率最高.