男性青少年性腺功能减退症患者短期雄激素替代治疗对血脂和hsCRP水平的影响

目的 探讨性腺功能低减的青少年男性，短期雄激素替代治疗对血脂和超敏C反应蛋白（hsCRP）的影响。方法 本研究为前瞻性自身对照研究，共纳入33例性腺功能减退青少年男性。行短期（9个月）雄激素替代治疗，比较治疗前后血睾酮水平、第二性征发育程度、身高、握力、血红蛋白、血脂和hsCRP的差异。结果 （1）替代治疗后，睾酮水平明显升高，第二性征明显发育，身高、握力、血红蛋白显著增加（P值均〈0.05）；（2）短期雄激素替代治疗后，总胆固醇（TC），低密度脂蛋白（LDL-c），高密度脂蛋白（HDL-c）和甘油三酯（TG）部有所下降，但无统计学差异（P〉0．5）。超敏CRP显著下降（P=0.025）。结论 （1）性腺功能低减的青少年男性，短期雄激素替代治疗，可以促进第二性征发育，增加身高、握力和血红蛋白；（2）短期雄激素替代治疗，对血脂无显著性影响。但是，可以使hsCRP明显下降。     

衰老对老年男性性腺功能的影响及其机理

在衰老过程中有相当比例的男性随着年龄的增长出现性腺功能减退的症状和体征，并伴有血清睾酮水平降低，称为老年男性雄激素缺乏(ADAM)或部分雄激素缺乏(PADAM)或男性更年期(andropause)。与腹型肥胖、血脂异常、骨质疏松、肌肉容积缩小、肌力减退、勃起功能障碍和抑郁及认知功能减退等疾病的发生与男性性腺功能减退相关。而且，睾酮补充治疗使血清睾酮水平在正常范围内，可以明显改善性激素缺乏的临床表现。因此衰老对男性性腺功能的影响及其发生机理越来越受到关注。     

雄激素水平增龄变化对老年男性的影响

雄激素对机体的影响是多方面的。随着人体的衰老 ,雄激素水平会发生变化 ,这种变化对老年男性生理和心理会产生影响 ,如生殖功能、性功能、认知能力、情绪、骨骼肌肉等 ,老年男性雄激素水平的降低与临床表现之间的关系较为复杂 ,这方面的研究受很多因素的影响。对雄激素水平下降的老年男性可以给予激素替代治疗 ,但是也应对其副作用引起足够重视。     

利用腰围身高比预测有雄激素缺乏症的老年男性体内血清睾酮水平

老年男性血清睾酮的下降可能部分是由肥胖引起的,但是,还不能确定哪些肥胖相关的参数与睾酮水平最密切相关。我们研究过伴有雄激素缺乏症但健康状况良好的老年男性的年龄、肥胖和睾酮水平的关系。本研究中,我们从社区中募集了54岁以上无痛症或其他严重疾病的非吸烟男性做横向研究分析,测定身高,体重和腰围,并计算体质指数（BMI）和腰围身高比（WHt）。收集两个早上的血液样本,测量总睾酮,性激素结合球蛋白和促黄体激素。计算游离睾酮（cFT）。并对上述指标与肥胖参数之间的关系进行多元线性凹归分析。207名54-86岁之间的男性参与了此次研究。单因素分析结果表明腰围身高比与睾酮和游离睾酮的相关性明显高于体重和腰吲或体质指数。另外,对总睾酮和游离睾酮来说,体重和腰围以及身高都有重要意义（所有的P均小于0．05）,身高值中加入体重和腰围值后,导致体重和腰用以及身高的回归系数都增加了,其中腰围呈负相关,身高呈正相关。总之,腰围身高比是预测健康但有雄激素缺乏症的老年男性的睾酮和游离睾酮最好的体质指标。     

前列腺癌的间歇内分泌治疗

1941年，Huggins和Hodges发表了获得诺贝尔奖的有关雄激素去除对晚期前列腺癌作用的研究，开创了前列腺癌内分泌治疗的先河。前列腺癌的内分泌治疗包括联合内分泌治疗（CAB）、单独去势治疗、新辅助内分泌治疗（NHT）、辅助内分泌治疗（AHT）及间歇内分泌治疗（1AD）等，而前列腺癌经内分泌治疗后由激素依赖性转变为非激素依赖性，最终转化为激素不敏感性肿瘤，是前列腺癌患者癌特异性死亡的原因。近年来研究表明完全雄激素阻断并不能延长前列腺癌细胞进展到非雄激素依赖的时间，同时完全雄激素阻断带来患者生活质量的下降，如性欲低下，勃起功能障碍，疲劳，智力下降，心理障碍-精神抑郁，肌力降低，脂肪聚积，生理活动和整体活动能力降低，同时增加了患者的相关治疗费用。     

选择性雄激素受体调节剂治疗迟发性男性性腺功能低下症

几种睾酮制剂用于治疗老年男性性腺功能减退。这些疗法在其便利性、灵活性、区域供应和费用等方面有区别,但有共同的药代动力学基础,同时缺乏长期安全性数据。简洁和成本较低的基于药代动力学的注册临床试验使得开发改善性的治疗迟发性性腺功能减退的新疗法的商业动机减少了。在前列腺、头发、皮肤受雄激素缺乏影响的患者中,选择性雄激素受体调节剂已被证明可以提供合成代谢的好处。（目前,选择性雄激素受体调节剂的临床进展集中在有限定身体功能的临床终点的急性肌肉萎缩和低体重）。在具有有益的药理、理想的药代动力学的选择性雄激素受体调节剂应用于治疗迟发性男性性腺功能低下症前,其在男性性腺功能低下治疗中关于临床缺陷的更清晰的监管是必须的。     

雄激素缺乏与老年疾病的关系

睾酮作为一种主要由男性睾丸分泌的雄性激素,除具有刺激生殖器官生长发育,维持生精和正常性欲等作用外,还有促进蛋白质生物合成,促进肌肉和骨骼的生长等许多重要的生理作用.睾酮水平随着年龄的老化、睾丸功能的减退出现不同程度的减低,随之带来一系列病理生理变化及临床症状.因此,研究雄激素缺乏与疾病的关系具有重要的临床意义.     

雄激素和雄激素受体与老年男性颈动脉内膜中层厚度的相关研究

目的 探讨老年男性颈动脉内膜中层厚度与雄激素和雄激素受体水平变化的相关性. 方法 入组老年男性89例,根据颈动脉内膜中层厚度分为内膜正常组、内膜增厚组、斑块形成组、管腔狭窄组,采用化学发光法检测血清中黄体生成素、卵泡刺激素、总睾酮和雌二醇.使用流式细胞技术测定外周淋巴细胞内雄激素受体水平. 结果 与内膜正常组比较,内膜增厚组VLDL-c显著升高;斑块形成组HDL-c显著降低,LDL-c显著增加;管腔狭窄组收缩压、舒张压和LDL-c均显著增加.老年男性中斑块形成组和管腔狭窄组与内膜正常组比较总睾酮水平和雄激素受体荧光强度明显下降. 结论 老年男性颈动脉内膜中层厚度的增加伴随着总睾酮和雄激素受体水平明显降低.雄激素受体水平的下降可能与动脉粥样硬化的发生发展相关.     

雄激素受体在睾丸内的分布及与生精调节的关系

睾丸间质细胞合成和分泌的雄激素主要有睾酮（testosterone，T）、双氢睾酮。（dihydrotestosterone，DHT）、脱氢异雄酮（dehydroisoandrosterone，DHIA）和雄烯二酮（androstenedione）。在各种雄激素中，双氢睾酮的生物活性最强，睾酮次之。雄激素的作用广泛，在雄激素的诱导下，含有Y染色体的胚胎向男性化方面分化，促进内生殖器发育，而双氢睾酮则主要刺激外生殖器的发育。     

组蛋白去甲基化酶在前列腺癌中的作用研究进展

前列腺癌是一种常见的老年男性恶性疾病,在西方国家发病率位居恶性肿瘤首位。前列腺癌的生长是雄激素依赖性的,晚期前列腺癌抗雄激素治疗有效,但雄激素去势治疗一段时间后,大多数最终发展为雄激素非依赖性前列腺癌或去势抵抗性前列腺癌（CRPC）阶段。组蛋白修饰是基因转录调节控制组织细胞发育分化的关键分子机制。     

Frailty and its relationship to late onset hypogonadism

The vulnerable health status usually preceding the onset of overt disability is often referred to as frailty. A stringent definition is elusive, but it may be viewed as a physiological syndrome, characterised by decreased reserve and diminished resistance to stressors, resulting from cumulative decline across multiple physiological systems and causing vulnerability to adverse outcomes. Many elements of frailty are related to the neurological system, metabolism, joints, bones and muscles. Central to frailty is the dramatic decline in muscle mass and strength with ageing. Therefore, sarcopenia seems to be the major determinant of frailty.

Several components of the frailty syndrome are related to the physiological actions of testosterone. Testosterone also has effects on psychological functioning. Testosterone (or its aromatisation product oestradiol) is required for the maintenance of bone mineral density. Testosterone also stimulates red blood cell formation.

Testosterone thus has a profound effect on body composition. A significant characteristic of ageing and a factor in frailty is the loss of muscle mass and the increase in fat mass. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, thus reversing the development of a downward spiral of loss of muscle mass and increase in fat mass. Skeletal muscles of older men are as responsive to the anabolic effects of testosterone as those of younger men, indicating that age as such should not be an impediment to elderly men benefiting from the anabolic effects of testosterone. So, while frailty is obviously a complex syndrome, some elements are androgen-associated and these may improve in men with subnormal testosterone levels.     

Musculoskeletal Frailty: A Geriatric Syndrome at the Core of Fracture Occurrence in Older Age

A progressive decline in physiologic reserves inevitably occurs with ageing. Frailty results from reaching a threshold of decline across multiple organ systems. By consequence, frail elderly experience an excess vulnerability to stressors and are at high risk for functional deficits and comorbid disorders, possibly leading to institutionalization, hospitalization and death. The phenotype of frailty is referred to as the frailty syndrome and is widely recognized in geriatric medical practice. Although frailty affects both musculoskeletal and nonmusculoskeletal systems, sarcopenia, which is defined as age-related loss of muscle mass and strength, constitutes one of the main determinants of fracture risk in older age and one of the main components of the clinical frailty syndrome. As a result, operational definitions of frailty and therapeutic strategies in older patients tend to focus on the consequences of sarcopenia.     

Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery

According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation- equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on Pub Med and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia- the loss of muscle mass- is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patient's peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the preoperative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and longterm outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepatopancreatico-biliary resections.     

Frailty and sarcopenia: definitions and outcome parameters

An operational definition of musculoskeletal decline in older people is needed to allow development of interventions for prevention or treatment, as was developed for the treatment of osteoporosis. Frailty and sarcopenia are linked, but distinct, correlates of musculoskeletal aging that have many causes, including age-related changes in body composition, inflammation, and hormonal imbalance. With the emergence of a number of exciting candidate therapies to retard the loss of muscle mass with aging, the derivation of a consensual definition of sarcopenia and physical frailty becomes an urgent priority. Although several consensual definitions have been proposed, these require clinical validation. An operational definition, which might provide a threshold for treatment/trial inclusion, should incorporate a loss of muscle mass as well as evidence of a decrease in muscle strength and/or physical activity. Evidence is required for a link between improvements in the measures of muscle strength and/or physical activity and clinical outcomes to allow development of interventions to improve clinical outcomes in frail older patients.     

Developing Consensus Criteria for Sarcopenia: An Update

Sarcopenia, the age‐related loss of muscle mass and strength, is a major cause of impaired physical function, which contributes to mobility disability, falls and hospitalizations in older adults. Lower muscle mass and strength are also associated with lower bone mineral density and greater risk for osteoporotic fractures. Thus, identification of sarcopenia could be important for fracture prevention as it may help improve fracture risk assessment, and muscle mass and strength can be improved with exercise, even among the frailest older adults. Unfortunately, there are no consensus diagnostic criteria for sarcopenia. Consequently there is no guidance to help clinicians identify older adults with clinically meaningful low muscle mass or weakness. Further, development of novel sarcopenia therapies is hindered not only due to the difficulty in identifying participants for clinical trials, and but also because there are no validated, clinically appropriate endpoints for assessment of treatment efficacy. There is currently a major push to establish a consensus definition of sarcopenia, and recent work holds promise that this goal may be within reach. This article discusses the evolution of the definition of sarcopenia, and focuses on the latest recommended diagnostic criteria proposed by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. While these empirically‐based cut‐points for clinically important low muscle mass and weakness are a significant step forward for the sarcopenia field, important questions remain to be answered before consensus diagnostic criteria can be definitively established. Ongoing work to refine sarcopenia criteria will further advance the field and bring this important contributor to falls, fractures and disability into the mainstream of clinical care and ultimately lead to better quality of life with aging. © 2015 American Society for Bone and Mineral Research.     

Quality of Life in Sarcopenia and Frailty

The reduced muscle mass and impaired muscle performance that define sarcopenia in older individuals are associated with increased risk of physical limitation and a variety of chronic diseases. They may also contribute to clinical frailty. A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities. This review and report of an expert meeting presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarizes QoL concepts and specificities in older populations and examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability, argues that a disease-specific QoL instrument for sarcopenia/frailty would be an asset for future research, and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade-off study could be appropriate.     

Impact of obesity on hypogonadism in the andropause

Obesity is an issue that is increasingly affecting ageing men. With ageing, there is a decline in androgens as well. There are implications for the health of ageing men as a result of hypogonadism. Overall, there seems to be an inverse relationship between body mass index and testosterone levels, as is also demonstrated in our cross-sectional study. Obesity seems to depress the production of testosterone. It has been hypothesized that there is increased aromatization of testosterone to oestradiol and alteration of the hypothalamic-pituitary-adrenal axis in obese older men. Some hormones can affect obesity in ageing men including leptin, insulin, dehydroepiandrostenedione and growth hormone. The relationship of obesity to these hormones in ageing men will be reviewed. Testosterone replacement in ageing men can alter body composition whereby fat is exchanged for muscle. These studies will also be reviewed. Further studies in this field are recommended to evaluate long-term benefits and risks.     

Testosterone replacement therapy in older adult men

Serum testosterone levels decline slowly with normal ageing in men and, although all men are not destined to become hypogonadal as they age, the prevalence of androgen deficiency in the older male is not insignificant. Over the past several decades, there has been an increasing interest in evaluating whether testosterone therapy (male HRT) might be beneficial for certain older men in preventing or reversing some aspects of ageing. The major androgen target organs of interest with regard to beneficial effects of male HRT include bone, muscle, adipose tissue, the cardiovascular system and the central nervous system (libido and aspects of mood). At the same time, potential adverse effects of male HRT on target organs such as the prostate continue to be evaluated. It is the purpose of this review to summarize the information to date with regard to testosterone replacement therapy in the older man and to discuss areas where more research and clinical information need to be forthcoming. Hormonal replacement therapy (HRT) for post-menopausal women has been studied and discussed for many years. The idea of male HRT, however, is a relatively recent development, with increasing interest in this area occurring only over the past two decades. Reasons for this nascent enthusiasm include burgeoning evidence that testosterone levels decline with normal male ageing (and with age-associated diseases) and an interest in preventing age-related dysfunction and prolonging quality life among an ever increasing population of older adults. The decline in testosterone with age often parallels unfavourable changes in organs upon which androgens act and the goal of male HRT would be to prevent, stabilize or even reverse some of these detrimental target-organ changes.     

Sarcopenia: etiology, clinical consequences, intervention, and assessment

The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence.     

Association between speed of sound of calcaneal bone assessed by quantitative ultrasound and sarcopenia in a general older adult population: A cross-sectional study

BackgroundLower calcaneal speed of sound may be related to sarcopenia because sarcopenia and osteopenia/osteoporosis show a linked relationship in older adults. The purpose of this study is to clarify whether the speed of sound of calcaneal bone assessed by quantitative ultrasound is associated with sarcopenia in a community-dwelling older adult population.MethodsThis was a cross-sectional observational study. The participants in the study were recruited from a group of individuals who had registered for an annual town-sponsored medical check-up. The inclusion criteria for participation in the study were (1) aged older than 40 years, (2) living independently, and (3) able to walk without assistance. Those who had nursing care insurance were excluded. Four hundred sixty-seven residents (182 men, 285 women) were registered in the study. Demographic information, fall history, muscle mass index, grip strength, and gait speed were assessed. The speed of sound through the calcaneal bone was evaluated using a CM-200 sonometer. The assessment for sarcopenia is based on the recommendations of the Asian Working Group for Sarcopenia.ResultsSpeed of sound was positively correlated with muscle mass index and gait speed in men, and was positively correlated with grip strength and gait speed in women, when adjusted for age and body mass index. In a multivariate logistic regression analysis adjusted for age and sex and other confounders, speed of sound was independently related with lower gait speed and sarcopenia in women. Speed of sound under 1470.5 m/sec had discriminated for sarcopenia in females.ConclusionWe propose that the speed of sound of calcaneal bone may be used to screen for sarcopenia in women. Sarcopenia should be considered if the speed of sound value is less than 1470.5 m/s in older women.