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Objectives: The beneficial effects of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH) on the body composition and metabolic outcomes are well-established. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". The aim of this study was to evaluate the effects of TRT on the levels of serum irisin in subjects with LOH.Study Design: A total 40 men with metabolic syndrome (MS) and LOH (measured serum testosterone concentration < 12 nmol/l). TRT with Testosterone Undecanoate (Nebido™) was performed at baseline and at week 6. Irisin serum concentration was determined at baseline and at week 18 by means of ELISA.Results: Circulating irisin was positively associated with serum testosterone (r = 0.283, p < 0.05). TRT has led to a statistically significant rise in circulating serum irisin levels (7.12 ± 0.76 mcg/ml versus 7.76 ± 0.75 mcg/ml; paired-samples t-test p < 0.001). ROC-analyses determined irisin to be predictive of treatment response (AUC = 0.741, p = 0.014).Conclusions: Irisin is positively associated with serum testosterone in a population of men with MS and LOH. TRT in these subjects has led to a significant improvement in associated clinical symptoms as well as to a significant rise in serum irisin levels. [ABSTRACT FROM AUTHOR]

Introduction: The best method for administering testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH) remains controversial. This study aimed to compare the efficacy and safety of a combined treatment (CT) involving intramuscular testosterone injection and testosterone ointment application [Glowmin® (GL)] with intramuscular injection monotherapy (IMIM).Materials and Methods: Patients were randomly assigned as follows: Group 1 received IMIM for 12 weeks and CT for 12 weeks and Group 2 received CT for 12 weeks and IMIM for 12 weeks. Patients were then asked about their treatment preferences: (A) IMIM, (B) a combination of IMIM and ointment, or (C) either A or B.Results: Patients (n = 43) completed the study without any adverse effects. No significant differences between each treatment period were found. In Group 1, most patients chose B (n = 13) while in Group 2, most chose A (n = 10). In each group, patients preferred the second treatment phase; however, statistical significance was not reached between A and B (Group 1, p = 0.11 and Group 2, p = 0.47, respectively).Conclusion: TRT by CT is compatible with TRT by IMIM. Patients who cannot continue TRT because of polycythemia from IMIM may be suited to CT. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH).Materials and methods: Thirty 18-month-old male Sprague-Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined.Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue.Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease. [ABSTRACT FROM AUTHOR]

Introduction: It is well known that there is a reduction of circadian rhythm in blood testosterone levels with aging. Our previous report revealed that 3 mg of short-acting testosterone ointment (Glowmin: GL) elevated serum testosterone levels to within the physiological range for 4-6 h. The aim of this study was to clarify the clinical efficacy and safety of GL used topically once every morning, to enhance the circadian rhythm of testosterone, for late-onset hypogonadism (LOH).Methods: A total of 61 LOH patients received 3 mg of GL topically once a day in the morning on scrotal skin for 24 weeks. The clinical efficacy of GL was evaluated by the aging males symptoms (AMS) scale, and blood sampling tests were measured before and after GL treatment.Results: Mean patients age was 55.3 ± 9.2 years old. Total AMS scores at 4, 12, and 24 weeks after GL treatments significantly decreased. The results of sub-analysis of AMS, including psychological, physical, and sexual factors also significantly improved after GL treatments. No severe adverse reactions or abnormal laboratory data were reported.Conclusions: This study shows that TRT for LOH with once daily GL treatment supports testosterone circadian rhythm and should be considered to be an effective and safe therapy for LOH. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis.Methods: From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n = 35) and control (n = 34) groups. The TRT group was administered 250 mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated.Results: At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0 ± 5.0 vs. 3.0 ± 3.2; p = .0434) and in adiponectin value (-0.90 ± 3.33 vs. 0.10 ± 2.04; p = .0192). There were no significant changes in other parameters.Conclusions: TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis. [ABSTRACT FROM AUTHOR]

We investigated the correlation between highly sensitive C-reactive protein (hs-CRP) levels and erectile function, and assessed the clinical role of hs-CRP levels in men with late-onset hypogonadism (LOH) syndrome. For 77 participants, we assessed Sexual Health Inventory for men (SHIM) score, Aging Male Symptoms (AMS) score and International Prostate Symptom Score (IPSS). We also evaluated free testosterone (FT), hs-CRP, total cholesterol, triglyceride levels, high density lipoprotein cholesterol, hemoglobin A1c, body mass index, waist size and blood pressure. We attempted to identify parameters correlated with SHIM score and to determine the factors affecting cardiovascular risk based on hs-CRP levels. A Spearman rank correlation test revealed that age, AMS score, IPSS and hs-CRP levels were significantly correlated with SHIM score. Age-adjusted analysis revealed that hs-CRP and IPSS were the independent factors affecting SHIM score (r= -0.304 and -0.322, respectively). Seventeen patients belonged to the moderate to high risk group for cardiovascular disease, whereas the remaining 60 belonged to the low risk group. Age, FT value and SHIM score showed significant differences between the two groups. A multivariate regression analysis demonstrated that SHIM score was an independent factor affecting cardiovascular risk (OR: 0.796; 95%CI: 0.637-0.995). [ABSTRACT FROM AUTHOR]

Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males. [ABSTRACT FROM AUTHOR]

Late-onset hypogonadism (LOH) is a clinical syndrome characterized with aging and declined serum testosterone levels. Sexual symptoms are also essential for the diagnosis of LOH. Testosterone replacement therapy is used widely to treat LOH. However, the side effects of it should not be ignored, such as fluid retention, hypertension and spermatogenic suppression. Therefore, alternate treatment modalities have been pursued. Herbal medicines used widely in China have achieved satisfying results with little side effects. Nonetheless, there are few pharmacological researches on them. In this study, 24-month-old mice were used as LOH animal models to explore the pharmacological effects of a herbal medicine, saikokaryukotsuboreito (SKRBT), on serum testosterone levels and sexual functions. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein, a kind of rate-limiting enzyme of testosterone synthesis, was also examined. As a result, SKRBT improved the serum testosterone levels of these mice at a dose of 300 and 450 mg/kg. Multiple measures of sexual behavior were enhanced. The expression of StAR was also increased. Therefore, this study suggested that SKRBT can improve the serum testosterone levels by activating the expression of StAR and might be a viable option to treat sexual symptoms caused by LOH. [ABSTRACT FROM AUTHOR]

Late-onset hypogonadism (LOH) and depression contribute to cardiovascular disease (CVD) in male hemodialysis (HD) patients. Carnitine deficiency is frequently observed in HD patients, playing a role in CVD. We examined whether carnitine deficiency was independently associated with LOH and depression in these patients. Twenty-six male HD patients underwent determinations of serum levels of free carnitine and testosterone. Status of LOH and depression were evaluated by questionnaires using aging male symptoms' (AMS) scale and self-rating depression scale (SDS), respectively. Free carnitine and testosterone levels in male HD patients were significantly lower than those in age-matched healthy male subjects. Linear regression analysis showed that AMS scale was positively associated with SDS. Univariate regression analysis revealed that total carnitine (inversely), free carnitine (inversely) and HD duration were correlated with AMS scale. Multiple stepwise regression analysis revealed that free carnitine was an independent determinant of AMS scale. Furthermore, free carnitine was also independently correlated with SDS in male HD patients. This study demonstrated that decreased free carnitine levels were independently associated with AMS scale and SDS in male HD patients. The observations suggest that decreased free carnitine levels could be a marker and therapeutic target of LOH and depression in uremic men with HD. [ABSTRACT FROM AUTHOR]

Late-onset hypogonadism (LOH) is typically defined as the cluster of symptoms appearing in aging men and accompanied by a decrease in serum testosterone levels. The identification of a simple screening tool with a high level of sensitivity and specificity to predict LOH has remained a challenge. To identify men with LOH, a variety of self-administered questionnaires have been developed including The Saint Louis University Androgen Deficiency in the Aging Male (ADAM) Questionnaire, The Quantitative ADAM (qADAM) Questionnaire, The Aging Male Symptoms (AMS) rating scale, The Massachusetts Male Aging Study (MMAS) questionnaire and The New England Research Institutes (NERI) hypogonadism questionnaire. The applicability of these questionnaires in the clinical setting is debated because some of the symptoms associated with LOH could be attributed to the natural process of aging and comorbidities. The goal of this review is to compare the utility and the validity of the different LOH questionnaires. [ABSTRACT FROM AUTHOR]

Recommendations on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men were first published by ISSAM in 2002 In 2005, and, in 2008, updated recommendations were published in the International Journal of Andrology, the Journal of Andrology, the Aging Male and European Urology. Towards discussions at the next ISSAM/ESSAM meeting in Moscow, 29 November 2013, we suggest the following update. [ABSTRACT FROM AUTHOR]

The Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging Male (ADAM) questionnaire have been widely used for screening men suspected of late-onset hypogonadism (LOH). We evaluated the consistency of the two questionnaires with sex hormone levels. A total of 985 men completed the two questionnaires, as well as an analysis of the serum levels of total testosterone (TT), bioavailable testosterone (BT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and sex hormone-binding globulin (SHBG). No correlation was observed between any hormone level and the psychological or somatic section of the AMS score, whereas the sexual section was correlated with the levels of FT, LH, FSH, SHBG and BT. Significant correlations were observed between the result of the two questionnaires and these hormone levels. When LOH was defined as TT < 300 ng/dl and FT < 5 ng/dl, the sensitivity and specificity of the AMS scale were 54.0% and 41.2% compared with 78.7% and 14.8% for the ADAM questionnaire. Several sex hormone levels correlated with the two questionnaires, but neither of these questionnaires had sufficient sensitivity and specificity. It is necessary to provide a new questionnaire applicable to the Chinese population to screening LOH. [ABSTRACT FROM AUTHOR]

The term 'late-onset hypogonadism (LOH)' is recommended to express the symptoms in middle-aged males with decreased testosterone. Although androgen replacement therapy (ART) might be an effective way to manage LOH, the risk of testosterone supplementation in elderly men is still concerned. On the other hand, to avoid adverse effects of ART, Kampo medicine (traditional Chinese-Japanese medicine) is often a first choice to treat LOH in Japan. However, their pharmacological studies are few. In this study, castrated mice was used as an LOH animal model for examining the pharmacological effects of a Kampo formula, saikokaryukotsuboreito (shortly SKRBT) on serum testosterone levels and seminal vesicles weights. Furthermore, an attempt to elucidate its pharmacological mechanism, inhibition of SKRBT and its components against aromatase were also examined with the enzyme-based assay. As a result, SKRBT improved significantly both the decline of serum testosterone levels and decrease of seminal vesicles weight of castrated mice at a dose of 125 mg/kg with a non dose-dependent manner. SKRBT and two components Scutellariae radix and Rhei rhizoma exhibited inhibitory activities with the IC50 values of 145, 29.2 and 29.7 µg/ml, respectively. These results suggested that the aromatase inhibitory activity of SKRBT may contribute, to a different extent, to the improvement of serum testosterone levels. [ABSTRACT FROM AUTHOR]

Introduction: The clinical significance of low to low-normal testosterone (T) levels in men remains debated. Aim: To analyze the effects of raising serum T on lean body mass (LBM), fat mass (FM), total body mass, and health-related quality-of-life (HRQoL). Methods: Randomized, double-blind, placebo-controlled study. Men, aged 50-80 years, with serum total T<15 nmol/L and bioavailable T < 6.68 nmol/L, and a Aging Males' Symptoms (AMS) total score >36, received 6 months treatment with transdermal 1% T gel (5-7.5 mg/day; n =183) or placebo gel ( n =179), followed by 12 months open-label with T in all. Results: After 6 months, LBM increased in T- treated patients by 1.28 ± 0.15 kg (mean ± SE) and FM decreased by 1.16 ± 0.16 kg, with minor changes with placebo (LBM +0.02 ± 0.10 kg and FM −0.14 ± 0.12 kg; all p < 0.001, T group vs. placebo). Changes were largely similar across subgroups of age, baseline total testosterone, and baseline BMI. Total HRQoL improved compared with placebo ( p < 0.05, T group vs. placebo). Conclusions: Six months 1% T gel improved body composition and HRQoL in symptomatic men with low to low-normal T, with further improvements over the following 12 months. [ABSTRACT FROM AUTHOR]

Hypogonadism is a common condition which occurs more frequently in older men. It is characterized by low testosterone (T) and is associated with symptoms which are often nonspecific. A key symptom is low libido, but it can also be associated with erectile dysfunction, reduced muscle mass and strength, increased body fat, reduced bone mineral density and osteoporosis, reduced vitality, and depressed mood. Hypogonadism is linked with a variety of comorbid conditions including erectile dysfunction, metabolic syndrome, diabetes, obesity, and osteoporosis. However, the condition is often underdiagnosed. T supplementation in hypogonadism is associated with a range of benefits including improved sexual function, increased lean body mass and/or reduced fat mass, and improved bone mineral density. A variety of T supplementation formulations are available. Although there is no evidence of increased risk of initiating prostate cancer with T supplementation, it is contraindicated in men with prostate cancer. It is important that primary care physicians are aware of both the signs and symptoms of hypogonadism, the monitoring and testing that is required and the merits and advantages of the various T preparations to ensure optimal management of the condition with a treatment approach that best suits patients' needs. [ABSTRACT FROM AUTHOR]

Background: Despite being one of the relevant public health threats among ageing men, testosterone deficiency syndrome (TDS) is under-recognized and under-diagnosed. Objective: To assess current clinical practices of European physicians regarding diagnosis and management of TDS compared with current guidelines. Methods: Postal survey conducted June-November 2008 in France, Germany, Italy and Spain among urologists, endocrinologists and general practitioners to collect information regarding knowledge of TDS. Results: Among 801 respondents, the majority of endocrinologists and urologists had received training on TDS, either initially or as part of continuous medical education. TDS was recognized by 86.5% of physicians as a true clinical entity, and estimated the prevalence at 10-15% of the male population; 73.5% considered that symptoms and a low level of testosterone were required for diagnosis. Treatment preferences were quarterly intramuscular injections (26.3% of physicians), percutaneous gels (23.9%), matrix patch (21.2%), semi-monthly injections (15.4%) and oral therapy (13.4%). Adverse effects of testosterone replacement therapy, such as benign prostatic hyperplasia and prostate cancer, were a concern for physicians. Conclusions: TDS management appeared to be close to that recommended in international guidelines. Signs and symptoms of testosterone deficiency were fairly well known, but some diagnostic and treatment variations were observed. [ABSTRACT FROM AUTHOR]

In aging men, serum endogenous testosterone is inversely associated with common carotid intima-media thickness (IMT) and directly with beneficial plasma lipid levels; however, the relationship to endothelial function is poorly characterized. We examined the association between serum testosterone and endothelium-dependent brachial artery flow-mediated dilatation (FMD) in middle-aged to elderly men. A group of 83 men aged 40-69 years (mean 55.9 ± 7.5 [SD]) with andropausal symptoms were studied. We measured their serum lipids, testosterone, luteinizing hormone, mean carotid IMT and brachial artery FMD by high resolution B-mode ultrasound. Brachial FMD correlated inversely with vessel diameter ( r == −0.38, p == 0.0004), alcohol consumption ( r == −0.22, p == 0.047) and serum testosterone ( r == −0.27, p == 0.01), but not with luteinizing hormone. In multivariate analysis, FMD was explained by testosterone ( β == −0.17, p == 0.0226), high density lipoprotein cholesterol ( β == 4.17, p == 0.0312) and vessel diameter ( β == −4.37, p < 0.0001) when adjusted for age, body mass index, triglycerides, blood pressure, carotid IMT, smoking, alcohol consumption, cardiovascular diseases and use of lipid lowering medication (HMG-CoA reductase inhibitors). In middle-aged to elderly men, there is an inverse correlation between serum testosterone and brachial FMD. These data suggest that testosterone may have an adverse effect on systemic endothelial function. [ABSTRACT FROM AUTHOR]

Introduction. Patients with late onset hypogonadism (LOH) also suffered from lower urinary tract symptoms (LUTS) and LOH symptoms. The objects of this study are to evaluate the efficacy of testosterone replace therapy (TRT) by testosterone ointment (Glowmin: GL) for LUTS in LOH patients. Methods. The Aging Male Symptom (AMS) scale, Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36), International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) were obtained from patients with LOH. A total of 41 patients with LOH have been treated with TRT using 6 mg/day of GL for 3 months. Serum free testosterone levels (FT) and these four scores were compared before and after TRT. Results. Serum FT levels and the scores for the four parameters of AMS, six of eight domains in SF-36, IIEF-5 and total IPSS improved significantly after 3 months TRT. In addition, all IPSS domains also improved significantly, and voiding disturbance seems to have improved more than storage disturbance ( P = 0.0280 vs. 0.0483). Conclusion. TRT by administration of GL is considered to be effective in the improvement of not only ED and LOH symptoms, but also LUTS (especially voiding disturbance) of patients with LOH. [ABSTRACT FROM AUTHOR]

Introduction. Elderly men are bothered by lower urinary tract complaints designated as lower urinary tract symptoms (LUTS). In epidemiological studies LUTS appears strongly associated with erectile dysfunction, and also with metabolic syndrome. LUTS occurs at an age at which plasma testosterone levels decline, in some men to hypogonadal values. Objectives. This pilot study tested whether testosterone administration to elderly men complaining of LUTS and whose plasma testosterone levels are below normal, might alleviate LUTS. Methods. Group 1 (n = 10) received treatment with testosterone gel (50 mg) daily for three months; group 2 (n = 20) received treatment with injections of testosterone undecanoate 1000 mg for 26 weeks. Results. Upon these interventions, plasma testosterone increased to the normal range. Symptoms of LUTS, measured by the International Prostate Symptoms Score, improved significantly, and also scores of the Aging Males' Symptoms scale and international index of erectile function improved. There were no untoward effects on the prostate over this period of time of the study. Conclusion. Testosterone administration improved symptoms of LUTS in men with late-onset hypogonadism. The mechanism of action is as yet not understood, but it may be connected with or parallel with the effects of testosterone on penile tissues in hypogonadal men, such as on nitric oxide and phosphodiesterase. [ABSTRACT FROM AUTHOR]

The decline, with aging, in serum concentrations of biologically active forms of testosterone in men is an indisputable fact and some men will eventually develop symptoms of late-onset hypogonadism (LOH) with its clinical consequences. LOH reduces quality of life and may pose important risk factors for frailty, changes in body composition, cardiovascular disease, sexual dysfunction and osteoporosis. Testosterone supplementation in cases of LOH will restore serum testosterone levels into the physiologic range; will restore metabolic parameters to the eugonadal state, increase muscle mass, strength, and function; maintaine or improve BMD reducing fracture risk; will improve neuropsychological function (cognition and mood); libido and sexual functioning; and enhance quality of life. The ultimate goals, however, are to maintain or regain a high quality of life, to reduce disability, to compress major illnesses into a narrow age range and to add life to years. To achieve these goals men must also adjust their lifestyle to optimize dietary habits, as well as to exercise and to abstain from smoking life-long. Monitoring these patients is a shared responsibility that cannot be taken lightly. The physician must emphasize to the patient the need for periodic evaluations and the patient must agree to comply with these requirements. The physician's evaluation should include an assessment of the clinical response and monitoring must be tailored to the indications and individual needs of the patient. [ABSTRACT FROM AUTHOR]

Prescription sales for testosterone products have substantially increased over the last several years reflecting the growing awareness of physicians for the potential benefits of testosterone replacement therapy in men with hypogonadism. Indiscriminate administration of testosterone poses a risk and has to be deprecated. Testosterone supplementation to treat late-onset hypogonadism (LOH), a term for androgen deficiency in elderly men, is still controversially discussed mainly due to a lack of large, controlled clinical trials on efficacy and safety. To provide guidance for physicians primarily dealing with aging men, ISSAM is periodically updating and publishing its recommendations as new data become available [Morales A, Lunenfeld B. International Society for the Study of the Aging Male. Investigation, treatment and monitoring of late-onset hypogonadism in males. Official recommendations of ISSAM. International Society for the Study of the Aging Male. Aging Male 2002;5:74–86 and Morales A, Lunenfeld B. Androgen replacement therapy in aging men with secondary hypogonadism. Draft recommendations for endorsement by ISSAM. Aging Male 2001;4:1]. Following a panel discussion at the 4th ISSAM Congress in Prague in February 2004, the International Society of Andrology (ISA), the International Society for the Study of the Aging Male (ISSAM) and the European Association of Urology (EAU) revised existing recommendations on the definition, diagnosis and management of LOH. The recommendations are based on the currently available scientific data on androgen supplementation therapy and should be regarded as provisional until larger-scale, long-term studies are available. While certainly not intending to be exhaustive, this review will highlight some relevant background information and provide the underlying scientific rationale for the ISA, ISSAM and EAU recommendations on LOH published in this issue. [ABSTRACT FROM AUTHOR]