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Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality, and also affect quality of life. The ESPRIT study (Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy) is a 6-month, multinational, open label, observational study in hypogonadal men being treated with transdermal AndroGel in usual daily clinical practice; 1,700-2,400 patients will be enrolled in Canada, Germany, Central and Eastern Europe, Russia and the Middle East. The main objective will be to evaluate the effect of AndroGel on symptoms of hypogonadism and quality of life as assessed by the Aging Males' Symptoms scale. Further objectives include evaluating the effect and time to onset of improvement in erectile dysfunction and libido/sexual desire (International Index of Erectile Function), fatigue (Multi-dimensional Fatigue Index) and body composition (waist circumference, body mass index). Subgroup analyses will be performed: <50 years versus > or = 50 years; absence versus presence of metabolic syndrome. The safety of AndroGel will also be assessed. The study population will consist of newly diagnosed hypogonadal men (age > or = 18 years), in whom testosterone deficiency has been confirmed by clinical features and biochemical tests according to international guidelines, who are currently being prescribed AndroGel (testosterone 1% gel, starting dose 50 mg testosterone per day).
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PMID:Rationale, design and methods of the ESPRIT study: Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy, in hypogonadal men. 1857 63

Testosterone replacement therapy (TRT) can have significant beneficial effects in the appropriate hypogonadal male patient. Testosterone deficiency is common in primary care practice and recognition of the signs and symptoms of this abnormality will allow physicians to choose appropriate interventions. The symptoms of clinical hypogonadism include muscle weakness, fatigue, mood changes and a reduced libido. Signs include a reduced muscle mass, osteoporosis, anemia and increased adiposity. While routine screening for testosterone deficiency, determination of testosterone levels in high risk populations, including obesity and diabetes, will help the clinician direct TRT to the patients most likely to benefit from therapy. In this article the syndrome of male hypogonadism is discussed, together with therapeutic choices available to the primary care physician.
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PMID:Testosterone replacement therapy for the primary care physician. 1870 68

Hypogonadism is a common condition, especially among older men, but often goes undiagnosed and untreated. It can be associated with a number of signs and symptoms that affect health and quality of life, including feelings of low energy and fatigue; decreased sex drive and performance; decreased muscle mass and strength; decreased bone mineral density; and increased body fat, particularly abdominal fat, a putative risk factor for metabolic syndrome and type 2 diabetes mellitus. The evidence supporting testosterone replacement therapy (TRT) in improving these and related conditions is strong and consistent for body composition and sexual function; moderately consistent for bone mineral density; inconsistent for insulin sensitivity, glycemic control, and lipid profiles; and weak and inconsistent for mood and cognitive function. The concern of some physicians about the potential for TRT to stimulate prostate cancer is not supported by decades of data accumulated to date, though studies of longer duration (eg, 10 years or more) would be even more convincing. Other research needs are discussed. As the front line of health care delivery, primary care physicians need to be vigilant in diagnosing and treating symptomatic hypogonadism. Based on current guidelines, we recommend assessing testosterone levels when an adult man exhibits signs of hypogonadism, and as part of normal medical screening in men starting at age 40 to 50 years, to establish a baseline. A physician should discuss the possibility of TRT with symptomatic patients who have a serum total testosterone level < 300 ng/dL. If TRT is initiated, a patient's response and adverse events should be assessed every 3 to 6 months, and therapy adjusted accordingly.
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PMID:Testosterone replacement therapy in hypogonadal men: assessing benefits, risks, and best practices. 1882 32

A specialized clinic for middle-aged and elderly hypogonadal men was established in our institution five years ago. A retrospective study of the 511 patients who attended our clinic during this period was conducted and the issues involved in treating these patients were identified. The patients' age distribution, symptoms, serum testosterone values, treatment, and course were examined. The patients' mean age was 54.0 years (range, 35 to 74 years); approximately half of the patients were in their fifties. Most patients complained of decline in libido, general fatigue, and erectile dysfunction. The patients' mean serum free testosterone was 9.28 pg/ml; 40.3% of patients had a serum free testosterone value of less than 8.5 pg/ml, which is the threshold value for the initiation of androgen replacement therapy (ART) in Japan. ART was given to 220 (43.1%) patients, and it was considered effective in 100. It appears that male climacteric disorder and late-onset hypogonadism have become commonly recognized in Japan. There will be an increasing need for specialized clinics for such men in the future.
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PMID:[Analysis of the statues of patients visiting our specialized clinic for hypogonadal men: 5-year experience]. 1930 13

A 59-year-old male was referred to our hospital with chief complaints of general fatigue and muscle stiffness of the shoulders. His hormonal data were total testosterone 0.05 ng/ml (normal: 2.01-7.5 ng/ml), free testosterone less than 0.6 pg/ml, leuteinizing hormone (LH) 1.1 mIU/ml (2.2-8.4 mIU/ml), follicle stimulating hormone (FSH) 2.4 mIU/ml (1.8-12 mIU/ml) and prolactin (PRL) 13.1 ng/ml (4.3-13.7 ng/ml). Though both his genital stage and pubic hair stage were Tanner V, his testis volume was 12 ml on the right and 10 ml on the left. A gonadotropin releasing hormone (GnRH) stimulation test revealed low responses of LH and FSH. Magnetic resonance imaging of the head revealed pituitary tumor (15 mm). Our diagnosis was acquired hypogonadtropic-hypogonadism-related pituitary tumor. Transsphenoidal hypophysectomy was performed and pathological diagnosis revealed epidermoid cyst. Three months after the operation, his total testosterone was elevated to 1.17 ng/ml and his complaints were improved.
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PMID:[Male hypogonadotropic hypogonadism (MHH) outpatient with testosterone deficiency syndrome: a case report]. 1930 17

Gonadotrophic axis dysfunction is commonly observed in HIV-infected patients. The pathogenesis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, decreased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunction. In HIV-infected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonadotrophic axis associated with HIV infection and its treatment.
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PMID:[Gonadotrophic axis dysfunction in men with HIV-infection/aids]. 2012 51

There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue. Diagnosis of the condition requires the presence of low serum testosterone levels and the presence of hypogonadal symptoms. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Restoration of testosterone levels to the normal range improves libido, sexual function, and mood; reduces fat body mass; increases lean body mass; and improves bone mineral density. Testosterone treatment is contraindicated in subjects with prostate cancer or benign prostate hyperplasia and risks of treatment are perceived to be high by many physicians. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment.
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PMID:A practical guide to male hypogonadism in the primary care setting. 2051 42

Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free-testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life.
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PMID:Male hypogonadism associated with advanced cancer: a systematic review. 2054 64

A 41-year-old man presented with left optic neuritis (ON) without evidence of other autoimmune disease or hormonal imbalance. MRI showed enlargement of the left optic nerve but no sellar lesion. The patient recovered after steroid therapy but later developed right ON and required treatment again. Follow-up MRI revealed an ill-defined, enlarging sellar lesion with enhancement extending into the right cavernous sinus, and the patient developed symptoms of fatigue and loss of libido. Hormonal studies revealed hypogonadism and hypocortisolism. All laboratory investigation for autoimmune and infectious diseases remained negative. A transsphenoidal biopsy of the lesion revealed lymphocytic hypophysitis. The concomitant development of lymphocytic hypophysitis and optic neuritis suggests a common and likely autoimmune etiology. Visual loss in patients with LYH can sometimes be due to ON rather than compression of the optic apparatus, with significant implications for treatment strategies.
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PMID:Lymphocytic hypophysitis in a patient presenting with sequential episodes of optic neuritis. 2067 77

Adolescent female athletes are at increased risk for low bone mineral density (BMD) secondary to exercise-induced hypogonadism. Of particular concern is that the adolescent years are also a critical time for bone accrual, and deficits incurred during this period could lead to suboptimal peak bone mass acquisition and subsequent fracture risk in later life. Although weight-bearing exercise is typically associated with an increase in BMD, amenorrheic athletes have lower BMD than eumenorrheic athletes and nonathletic controls as a consequence of low energy availability and subsequent hypogonadism. It is important to recognize that critical interactions exist between net energy availability and the hypothalamo-pituitary-gonadal (H-P-G) axis that are key to the development of a hypogonadal state when energy intake cannot keep pace with expenditure. While the link between energy availability and gonadtotropin pulsatility patterns is well established, the actual metabolic signals that link the two are less clear. Decreased energy availability in athletes is associated with decreases in fat mass, and alterations in adipokines (such as leptin and adiponectin) and fat-regulated hormones (such as ghrelin and peptide YY). These hormones impact the H-P-G axis in animal models, and it is possible that in athletes alterations in fat-related hormones signal the state of energy availability to the hypothalamus and contribute to suppression of gonadotropin pulsatility, hypothalamic amenorrhea and consequent decreased BMD. A better understanding of pathways linking low energy availability with functional hypothalamic amenorrhea and low BMD is critical for the development of future therapeutic strategies addressing these issues in amenorrheic athletes.
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PMID:Influence of ghrelin and adipocytokines on bone mineral density in adolescent female athletes with amenorrhea and eumenorrheic athletes. 2095 63


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