书目名称 | Testosterone | 副标题 | From Basic to Clinic | 编辑 | Alexandre Hohl | 视频video | http://file.papertrans.cn/904/903449/903449.mp4 | 概述 | Ethical focus on testosterone: discusses the public health issue of excessive testosterone use.Transgender: gives detailed information on trans men and testosterone use in this population.Multidiscipl | 图书封面 |  | 描述 | .Even though research on testosterone is increasing, there is still much controversy regarding its physiology and clinical use. This book provides a broad overview on testosterone, from its basic features to the most recent evidence of clinical applicability. In addition, specific conditions in which testosterone play a pivotal role are discussed in detail, such as hypogonadism, misuse and abuse, puberty, cardiovascular effects and testosterone therapy...The testes are vital organs for reproduction of the human species, besides being the main source of testosterone production in men. Although not essential for survival, these singular structures represent the essence of male biological function...Testosterone is the most important testicular androgen in men. Low serum testosterone levels are associated with cardiovascular morbidity, metabolic syndrome, type 2 diabetes mellitus, atherosclerosis, osteoporosis, sarcopenia, and mortality. Also, there is increasing evidencethat serum testosterone is a major biomarker status of men‘s health in general...Hypogonadism in a male refers to a decrease in one or both of the two major functions of the testes: sperm production or testosterone pr | 出版日期 | Book 2023Latest edition | 关键词 | Testosterone; Hypogonadism; Androgens; Anabolism; Hormones | 版次 | 2 | doi | https://doi.org/10.1007/978-3-031-31501-5 | isbn_softcover | 978-3-031-31503-9 | isbn_ebook | 978-3-031-31501-5 | copyright | The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerl |
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,The Cultural and Medical History of the Testes and Testosterone: From Antiquity to Modern Times, |
Eberhard Nieschlag,Susan Nieschlag |
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Abstract
Extirpation and transplantation of endocrine glands are among the earliest tools in experimental endocrinology. The testes, with their exposed position, are vulnerable and easily accessible to external manipulation, including trauma and forceful removal. Thus, the effects of testosterone and its absence as a consequence of loss of the testes became known quite early in the history of mankind. Castration, leading to a loss of virility and fertility, has been used over centuries for punishment of criminal acts and high treason, for the creation of obedient slaves and servants and for preserving the prepubertal soprano voices for musical entertainment. Although the testes were correctly identified as the source of androgenicity, attempts to use them in organotherapy can only have led to placebo effects. Testosterone itself was isolated only in 1935 and, since then, has been available as a powerful medication for the treatment of hypogonadism. Only recently did it become possible to produce injectable or transdermal testosterone preparations generating serum levels in the physiological range.
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,Androgen Receptor in Health and Disease, |
Alexandre Hohl,Marco Marcelli |
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Abstract
Testosterone and 5α–dihydrotestosterone acting through the androgen receptor (AR) direct virilization of the male fetus during embryogenesis, and the development of primary and secondary male sexual characteristics during puberty. During adulthood the AR signaling pathway is involved in maintaining the adult male phenotype, male reproduction, and functions of tissues such as bone and muscle..AR is a ligand activated transcription factor member of the nuclear receptor family of protein. It regulates transcription of a network of genes by recruiting coregulator complexes leading to chromatin reorganization, and histone modification at target genomic loci. Besides being involved with a spectrum of clinical conditions that include the syndromes of androgen insensitivity, a form of motor neuron disease known as spinal bulbar muscular atrophy and male infertility, abnormalities of AR signaling are also responsible for initiation, progression, and treatment resistance of prostate cancer..Thanks to the generation of transgenic animal models with conditional knock out of AR in a variety of target organs, it has been possible to recognize novel functions of AR signaling. Old and new aspects of AR physiopathology, together with emerging concepts on the role of AR signaling in females, breast cancer and polycystic ovarian disease, will be discussed in detail in this review.
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,Physiology of Male Gonadotropic Axis and Disorders of Sex Development, |
Berenice Bilharinho Mendonca,Elaine Maria Frade Costa |
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Abstract
The hypothalamic-pituitary-testicular axis is activated at the third trimester of intrauterine life and in the neonatal period. Fetus testes differentiate by the end of the fifth embryonic weeks, before the gonadotrophs are functionally active. Therefore, GnRH deficiency does not affect male sexual differentiation..The 46,XY DSD are characterized by atypical or female external genitalia, caused by incomplete intrauterine masculinization, in the presence or absence of Müllerian structures. 46,XY DSD result from decreased production of testosterone, decreased conversion of testosterone into DHT or from impairment of their peripheral action. At histological analysis, testicular tissue in 46,XY DSD patients can be absent, partially or completely dysgenetic, or almost normal. Taking in account testosterone levels, the etiology of the 46,XY DSD can be classified into two large groups: low testosterone secretion and normal or high testosterone secretion..The majority of DSD patients present atypical genitalia and their sex assignment may be a complex procedure. The choice of male sex-of rearing in 46,XY babies with atypical genitalia is a challenge situation. The participation of a multidisciplinary team is essential in this process and the fast identification of a molecular defect causative of the disorder might collaborate in this decision.
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,Utility and Limitations in Measuring Testosterone, |
Mathis Grossmann |
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Abstract
Measurement of serum testosterone is essential to confirm a clinical suspicion of male androgen deficiency. Serum testosterone should be measured in the morning, in the fasted state in a medically stable patient without current or recent acute illness. A low serum testosterone should be confirmed. If the serum testosterone is repeatedly low, a tailored work-up is necessary to determine the cause of hypogonadism. Serum testosterone should be measured by a validated assay, and mass spectrometry-based assays are considered gold standard. While total testosterone is the primary measure to determine androgen status, in certain situations, measurement of sex hormone binding globulin and of free testosterone (ideally by gold standard equilibrium dialysis) can be helpful. In contrast, the utility of measuring the testosterone metabolites estradiol and dihydrotestosterone requires further research.
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,Male Puberty: What Is Normal and Abnormal?, |
David W. Hansen,John S. Fuqua |
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Abstract
Puberty is a pivotal time in an adolescent’s life. Knowing when puberty is precocious or delayed is important to correctly diagnose and treat abnormalities. Being able to appropriately check the progression of puberty is foundational for reaching the correct diagnosis. Precocious puberty is generally accepted as a testicular volume ≥4 mL prior to 9 years of age, and delayed puberty is a testicular volume <4 mL after 14 years of age. Causes of precocious puberty include both gonadotropin-dependent (central) and gonadotropin-independent (peripheral) etiologies, and treatment varies according to the etiology. Delayed puberty also has multiple causes, including primary gonadal abnormalities, such as testicular injury, and numerous causes of hypogonadotropic hypogonadism, both congenital and acquired. Constitutional delay of growth and puberty is a particularly common etiology of delayed puberty. It is usually benign, but affected boys may benefit from a short course of testosterone. Correctly ascertaining the etiology of delayed puberty will direct the appropriate therapy. While precocious or delayed puberty may be benign, some causes are very serious, making the need to understand this topic important for physicians.
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,Gynecomastia, |
Alexandre Hohl,Marcelo Fernando Ronsoni,Simone van de Sande Lee |
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Abstract
Gynecomastia is a benign proliferation of glandular tissue in the male breast. It can be unilateral or, more commonly, bilateral and often asymmetrical (Billa et al., Andrology 9: 1444, 2021)..A recent study observed a 32.3% prevalence of gynecomastia among 1877 men undergoing CT scans during the coronavirus pandemic (Aslan et al., Eur J Breast Health 17(2):173–179, 2021). Its prevalence was also studied in different populations and three main peaks were found throughout life: 60–90% of newborns, approximately 50% of pubescent and young adults and 24–65% of the elderly. The wide variation in prevalence is due, in part, to differences in the definition of gynecomastia. In some studies, the condition was diagnosed if the breast diameter was ≥0.5 cm on palpation, while in others, the minimum diameter of breast glandular tissue required was ≥2 cm (Braunstein, J Clin Endocrinol Metab 105(10):e3810–e3811, 2020; Kanakis et al., Andrology 7(6):778–793, 2019)..Most cases are asymptomatic and self-limiting, but when persistent, they can be associated with important psychosocial consequences, including depression, anxiety, eating disorders, body dissatisfaction, and low self-esteem (Ordaz and Thompson, Body Image 15:141–148, 2015; Baumgarten and Dabaja, Curr Urol Rep 19(7):46, 2018).
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,Hypogonadotropic and Hypergonadotropic Hypogonadism, |
Prativa Rajbhandari,Jerry Sanghun Han,Christina Wang,Ronald Swerdloff |
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Abstract
Male hypogonadism is a clinical syndrome that results from failure of the testes to produce physiological levels of testosterone and inadequate spermatogenesis due to disruption at one or more levels of the hypothalamic-pituitary-testis axis. Testosterone deficiencies arising from diseases affecting the hypothalamus/pituitary are associated with low gonadotropins (both LH and FSH) and is termed hypogonadotropic hypogonadism, whereas testicular disorders are associated usually with elevated gonadotropins and are termed hypergonadotropic hypogonadism. Diagnosis of hypogonadism can sometimes be difficult given that the symptoms and signs are nonspecific and can vary depending on age, comorbid illness, severity, and duration of hypogonadism. A thorough medical history, physical examination, and laboratory tests are required to determine the etiology.
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,Functional Hypogonadism: Diabetes Mellitus, Obesity, Metabolic Syndrome, and Testosterone, |
Ricardo Martins da Rocha Meirelles |
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Abstract
Low blood testosterone levels are found more frequently in patients with type 2 diabetes mellitus, obesity, and metabolic syndrome than in the general population, as shown by epidemiological studies. All these conditions are associated with insulin resistance, and there is a two-way relationship between them, and low testosterone levels: not only the metabolic disorder can lead to hypogonadism, but also testosterone deficiency can contribute to type 2 diabetes mellitus, obesity, and metabolic syndrome. Besides the sexual symptoms of loss of libido, erectile dysfunction, and absence of morning erections, low testosterone levels are associated with an increase in adipose tissue and a decrease in muscle mass, not only because testosterone induces differentiation of pluripotent mesenchymal cells into myocytes and inhibit conversion into adipocytes, but also low testosterone levels favor incorporation of triglycerides in fat cells due to inhibition of lipoprotein lipase activity. Most of the deaths in type 2 diabetes, obesity, and metabolic syndrome are due to cardiovascular diseases, and there is an increase of these disorders in men with low testosterone levels. There is consistent scientific evidence that testosterone replacement in hypogonadal patients can lessen the risk factors for cardiovascular diseases and decrease mortality. On the other hand, functional hypogonadism can be reversed by weight loss and better control of diabetes. The few studies that link testosterone replacement to an increase in cardiovascular death present methodological severe issues and are not confirmed by a careful meta-analysis.
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,Male Hypogonadism and Aging: An Update, |
Pedro Iglesias,Alberto Núñez,Juan J. Díez |
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Abstract
Male hypogonadism can be defined as a functional testicular deficiency involving insufficient testosterone (T) synthesis and impaired spermatogenesis. This disorder can develop at any time of life and is usually accompanied by different clinical manifestations. In all cases, the biochemical marker is a low circulating T. A progressive decrease in serum T with age has been reported in several epidemiological studies, and reduced serum T concentrations are a common finding in older men. This decrease in T may be accompanied by clinical signs and symptoms such as decreased libido, impotence, decreased body hair growth, reduced muscle mass, fatigue, and decreased bone mass, among others. This condition has been defined as androgen deficiency in the elderly male, andropause, late-onset hypogonadism (LOH) or functional hypogonadism. An inverse relationship has also been reported between T deficiency and cardiovascular (CV) morbidity and all-cause and CV mortality in elderly men. Androgen treatment with T would only be indicated in elderly men with symptoms and signs of hypogonadism after excluding contraindications, such as breast or prostate cancer. In this review we update different aspects of the definition, epidemiology, clinical presentation, and therapeutic options related to androgen deficiency in the elderly male.
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,Male Hypogonadism and Traumatic Brain Injury, |
Alexandre Hohl,Roger Walz |
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Abstract
Traumatic brain injury (TBI) is a worldwide public health problem that mainly affects young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults, as well as a tremendous resource burden on the health and wellness sector. Hormonal dysfunction is highly prevalent during the acute phase of severe TBI, but it can also occur many years after the trauma. In particular, the investigation of the gonadotropic axis may be relevant in young men with a previous history of TBI and signs and symptoms of male hypogonadism.
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,Male Hypogonadism and Fertility, |
Kareim Khalafalla,Rodrigo L. Pagani,Samuel J. Ohlander,Craig S. Niederberger |
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Abstract
An increase in public awareness and direct-to-consumer marketing has led to an increase in the number of men seeking evaluation for hypogonadism. Whether due to the physiological dependence of spermatogenesis on an intact hypothalamic pituitary hormonal axis or due to the repercussions of suppressive hypogonadal treatments on semen parameters, male hypogonadism is tightly associated with infertility. Proper assessment and management of the hypogonadal male necessitates an evaluation for the underlying etiology along with a thorough discussion on the underlying goals of therapy, including current and future reproductive potential. Therapy to address the underlying hypogonadal symptoms ought to take into consideration the reproductive implications, and, when appropriate, alternatives to exogenous testosterone therapy should be utilized to allow for the preservation or optimization of fertility potential.
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,Anabolic Steroid-Induced Hypogonadism, |
Alexandre Hohl,Simone van de Sande Lee,Marcelo Fernando Ronsoni |
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Abstract
The abuse of anabolic-androgenic steroids (AAS) with the aim of increasing muscle mass and strength is increasing among men, currently configuring a public health problem. One consequence is suppression of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in hypogonadism after withdrawal. Severity usually depends on the type of AAS, dose, and duration of use, and may be persistent and even irreversible. AAS-induced hypogonadism management involves establishing a trusting relationship between the patient and the physician, discontinuing the use of AAS, in addition to the judicious use of medications such as testosterone replacement therapy (TRT), selective estrogen receptor modulators (SERM), and human chorionic gonadotropin (hCG). The literature on the subject is still scarce, and more studies are needed for a better understanding of the aspects that involve AAS abuse, to enable prevention actions and the adequate management of adverse effects.
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,Testosterone Therapy: Oral Androgens, |
Svetlana Kalinchenko,Igor Tyuzikov,George Mskhalaya,Yulia Tishova |
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Abstract
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,Testosterone Therapy: Transdermal Androgens, |
Jonas Čeponis,Fiona Yuen,Ronald S. Swerdloff,Christina Wang |
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Abstract
Transdermal testosterone administration delivers testosterone on the intact skin surface through a patch or a permeable membrane or directly on the skin as a gel or lotion. The . serves as a depot allowing small doses of testosterone to pass into systemic circulation thus achieving sustained “steady state” serum testosterone levels. There is usually a gradual rise in serum testosterone within the first few hours after application and followed by levels within the physiological adult male range for 24 h. In some preparations depending on the time of application serum testosterone profile mimics normal circadian variation observed in healthy younger men. Transdermal testosterone avoids first-pass metabolism by the liver and has less effects on the lipoprotein. For many hypogonadal men transdermal testosterone is an attractive user-controlled and non-invasive way of testosterone replacement. The main problems of transdermal gels/lotions are the secondary exposure of testosterone through skin transfer to women and children on close skin contact and large skin surface area of application. Precautions such as washing and wearing clothing covering the application area will prevent transfer. Users learn to overcome these issues and transdermal testosterone is the most popular method of androgen replacement in some countries such as the USA.
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,Testosterone Therapy: Injectable Androgens, |
Aksam Yassin |
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Abstract
Testosterone formulations have been available to patients since the 1930s but have proven less than ideal. Conventional injectable testosterone esters have been used as testosterone replacement but generate supraphysiological testosterone concentrations shortly after injection followed by a rapid decline, becoming subphysiological in the days before the next injection. These rapid fluctuations in plasma testosterone are subjectively experienced as disagreeable. Available since 2004, testosterone undecanoate is an injectable testosterone preparation with a considerably better pharmacokinetic profile. After two initial injections with a 6-week interval, the following intervals between injections are usually 12 weeks, amounting to a total of four injections per year. Plasma testosterone concentrations with this preparation are nearly always in the range of normal men, so are its metabolic products estradiol and dihydrotestosterone. Testosterone undecanoate, like other testosterone preparations, reverses the effects of hypogonadism on bone and muscle and significantly improves metabolic parameters and sexual functions, without the “roller coaster” effects of traditional testosterone injections. Other adverse effects, such as polycythemia and disturbed lipid profiles, have not been observed. Although some studies suggest a link between injectable testosterone and comorbidities such as prostate cancer, diabetes, and cardiovascular disease, conflicting data highlight the need for longer-term better controlled, randomized studies. Even though testosterone undecanoate stands out as a valuable contribution to the treatment options of androgen deficiency, a number of alternative therapies such as selective androgen receptor modulators are under development proving, from preliminary studies, as competitive testosterone replacement options.
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,Benefits and Adverse Events of Testosterone Therapy, |
Elaine Maria Frade Costa,Lorena Guimarães Lima Amato,Leticia Ferreira Gontijo Silveira |
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Abstract
Testosterone plays an essential role in several aspects of men’s health. The main indication for testosterone treatment is in men with confirmed diagnosis of hypogonadism, signs of androgen deficiency, and low serum testosterone levels. Other possible indications include constitutional delay of growth and puberty, men with sexual dysfunction, female-to-male transsexual persons, androgen deficiency in the aging male, hypogonadism secondary to drugs, and chronic illness. Common drug-related adverse events include increase in hematocrit, acne, breast tenderness, gynecomastia, and exogenous testosterone can lead to a state of transitory infertility. It is not recommended to start testosterone replacement therapy in men with untreated severe obstructive sleep apnea or with benign prostatic hypertrophy. The effects of testosterone on lipid metabolism and cardiovascular risk remain uncertain. In each situation the testosterone replacement brings specific benefits but the overall goals of therapy are to establish and maintain secondary sexual characteristics, sexual function, sense of well-being, and to improve body composition, muscle mass and strength, bone mineral density, and quality of life.
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,Testosterone and Sexual Function, |
Giovanni Corona,Giulia Rastrelli,Simona Ferri,Alessandra Sforza,Mario Maggi |
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Abstract
Much evidence has documented that testosterone (T) plays a crucial role in regulating male sexual function acting either at central or peripheral level. Sexual symptoms and in particular, erectile dysfunction and reduced frequency of sexual thoughts and sleep-related erections represents the most specific symptoms associated with hypogonadism in adulthood. Some evidence suggests that sex is actually an excellent way to boost T levels in milder forms of hypogonadism. In particular, it has been reported that sexual inertia resets the reproductive axis to a lower activity, somehow inducing a secondary hypogonadism, characterized by a reduced LH bioactivity. T replacement therapy (TTh) is able to improve all aspects of male sexual function and should be considered the first line treatment in ED patients with overt hypogonadism. However, TTh as mono-therapy might not be sufficient in complicated subjects. In these cases a combination therapy with phosphodiesterase type V inhibitors may improve the outcome. In young uncomplicated individuals with milder forms of hypogonadism, the restoration of normal sexual function, however, obtained might improve T levels.
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,Testosterone Therapy and Prostate Cancer, |
Ernani Luis Rhoden,Daniel de Freitas G. Soares,Abraham Morgentaler |
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Abstract
While the benefits of testosterone therapy are well documented with regard to the clinical signs and symptoms of testosterone deficiency, there is still a fear among the medical community that testosterone therapy could be a stimulus for the emergence of prostate cancer (PCa) or promote its progression. However, the evidence shows that testosterone(T) appears to have limited stimulatory effects on the prostate. Several studies suggest that testosterone stimulates the growth of prostatic neoplasia only at very low concentrations, and variations in the endogenous testosterone levels within the physiological range or above do not appear to influence prostate growth or function, as measured by markers such as prostate-specific antigen. The recognition of the finite ability of androgens to stimulate prostate growth, called the saturation model, has led to important changes in medical practice, especially with regard to consideration of testosterone therapy for men with a history of prostate cancer. Recent clinical experiences in men with PCa have suggested that T therapy is not as risky as once believed. Studies regarding testosterone administration in hypogonadal men after PCa treatment have shown no evidence of worse oncologic prognosis. Even in patients in active surveillance protocols, testosterone has been administrated with no modification of oncological outcomes, suggesting that T therapy is safe when correctly indicated and strictly monitored.
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,Testosterone and Cardiovascular Effects, |
Bu B. Yeap |
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Abstract
As men grow older, circulating testosterone (T) declines while the prevalence of ill-health increases. T is metabolised by 5α-reductase (SRD5A2) to dihydrotestosterone (DHT, a more potent androgen) and by aromatase (CYP19A1) to estradiol (E2, an oestrogen). In a large study of men aged 40–69 years, circulating T concentrations were not associated with risk of incident cardiovascular events. However, lower circulating T has been associated with higher incidence of cardiovascular events in older men. Higher T or higher DHT concentrations are independent predictors for reduced incidence of stroke in older men, and higher DHT was independently associated with reduced mortality from ischaemic heart disease. The impact of exogenous T treatment in this context remains controversial. One randomised controlled trial (RCT) of T in older men with limited mobility reported an increase in cardiovascular adverse events associated with T. Another comparable study in frail or intermediate-frail older men found no such signal. The US Testosterone Trials (T Trials) found that T therapy in older men with low baseline T moderately improved sexual function, with no excess of cardiovascular adverse events. However, a sub-study of the T Trials reported an increase in coronary atheroma volume in testosterone treated men. A recent large RCT Testosterone for the Prevention of Type 2 Diabetes Mellitus in high-risk men (T4DM) randomised 1007 men with impaired glucose tolerance or newly diagnosed type 2 diabetes to 2 years of testosterone treatment on a background of a lifestyle program. This showed a 40% reduction in the risk of type 2 diabetes after 2 years, with no signal for adverse cardiovascular events. Meta-analyses of T RCTs have generally not shown an association with cardiovascular adverse events. Retrospective analyses of health or insurance and prescription databases possess major methodological limitations including lack of randomisation and other sources of bias and confounding. Such studies have shown conflicting results: some associated T prescriptions with increased risk of CVD events, while more associated T use with lower risk of CVD events or lower mortality. Thus, further studies are warranted to clarify the effects of T treatment on the cardiovascular system. Men who are androgen deficient due to disease of the hypothalamus, pituitary, or testes should be considered for T replacement therapy, while additional research is needed to clarify the role of T supplementation to preserve health in men with low-normal circulating T in the absence of pathological hypogonadism.
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