Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years) men.
To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs <65 years old. Data for participants 65–74 vs ≥75 years old were also compared.
Data were from TRiUS (Testim Registry in the United States), which enrolled 849 hypogonadal men treated with Testim® 1% (50–100 mg testosterone gel/day) for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT), free testosterone (FT), and prostate-specific antigen (PSA) levels. Comparisons of parameters were made using Fisher’s exact test or analysis of variance. Nonparametric Spearman’s ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters.
Of the registry participants at baseline with available age information, 16% (133/845) were ≥65 years old. They were similar to men <65 years old in the duration of hypogonad-ism prior to enrollment (∼1 year), TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng/mL for ≥65 vs 1.14 ± 0.84 ng/mL for <65 years old, P = 0.1). Baseline values for the >75-year-old subcohort were not significantly different from subcohorts aged 65–74 years and <65 years.
Hypogonadal men ≥65 years old showed significant benefit from TRT over 12 months, similar to that found for hypogonadal men <65 years old. TRT was well tolerated in older patients, successfully increased testosterone level regardless of age, and did not significantly increase PSA levels in older men.
male hypogonadism; elderly; testosterone replacement therapy; testosterone gel; TRiUS registry; Testim
This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS).
RESEARCH DESIGN AND METHODS
The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12).
TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (>95%) were mild or moderate.
Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.
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.
androgens; androgenic agents; late-onset hypogonadism; testosterone replacement therapy
To examine the relationship between sex hormone–binding globulin (SHBG) and the metabolic syndrome (MetS) in pre-elderly and elderly men in China.
A cross-sectional study was done among 437 men, aged 45 to 94 years old. Early morning fasting sera were assayed for total testosterone (TT), SHBG and other biochemical markers. Free testosterone (FT) was calculated.
The SHBG level of the MetS group was significantly lower than those without MetS 35.70 (25.18, 47.10) nmol/L vs. 41.90 (31.80, 55.20) nmol/L; P < 0.001). As the number of MetS components increases, SHBG and TT levels became lower. SHBG correlated with age, as did TT and most of metabolic components. Body mass index (BMI), high density lipoprotein-cholesterol (HDL-C), triglyceride (TG), and TT remained independently associated with SHBG by multivariate regression analysis. In a logistic regression taking MetS as the dependent variable, SHBG (95% confidence interval (95% CI): 0.975−0.994, P = 0.018) and homeostasis model assessment for insulin resistance (HOMA-IR) (95%CI: 1.535−2.647, P < 0.001) were included in the final model.
Lower SHBG is independently associated with MetS among pre-elderly and elderly men. SHBG may be an independent predictor of MetS, but the mechanism of how SHBG is involved in MetS requires further studied.
Sex hormone–binding globulin; Metabolic Syndrome; Testosterone; Males
This study was conducted to investigate the effect of testosterone replacement treatment (TRT) in testosterone deficiency syndrome (TDS) patients with metabolic syndrome.
Materials and Methods
We reviewed the data of 200 men who were diagnosed with TDS and were undergoing TRT between August 2006 and August 2009. The 200 patients were divided into two groups (group 1: 71 patients with metabolic syndrome, group 2: 129 patients without metabolic syndrome) depending on metabolic syndrome, which was diagnosed according to the NCEP III criteria for Asians. Age, BMI (body mass index), waist circumference, serologic tests, AMS (the Aging Males' Symptoms scale), and IIEF (International Index of Erectile Function) were measured.
In group 1, waist circumference and fasting glucose were significantly decreased; hemoglobin and total testosterone were increased; and the somatovegetative scale score of the AMS, the total AMS score, the erectile function score of the IIEF, the overall satisfaction score of the IIEF, and the total IIEF score were significantly improved after TRT. On the other hand, in group 2, waist circumference, BMI, total cholesterol, LDL, and fasting glucose were significantly decreased; hemoglobin and total testosterone were increased; and the 2 subscale scores of the AMS (psychologic and somatovegetative), the total AMS score, all subscale scores of the IIEF, and the total IIEF score were significantly improved after TRT.
Overall, the patients who had TDS with metabolic syndrome showed less improvement in AMS, IIEF, and serum variables. Therefore, the correction of metabolic syndrome, such as diabetes, obesity, and hypertension, should be considered during TRT.
Hormone replacement therapy; Metabolic syndrome X; Testosterone
Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men.
Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT) treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.
hypogonadism; testosterone replacement therapy; erectile dysfunction; osteoporosis; cardiovascular disease
Obesity has become a major health problem. Testosterone plays a significant role in obesity, glucose homeostasis, and lipid metabolism. The metabolic syndrome is a clustering of risk factors predisposing to diabetes mellitus type 2, atherosclerosis, and cardiovascular morbidity and mortality. The main components of the syndrome are visceral obesity, insulin resistance, glucose intolerance, raised blood pressure and dyslipidemia (elevated triglycerides, low levels of high-density lipoprotein cholesterol), and a proinflammatory and thrombogenic state. Cross-sectional epidemiological studies have reported a direct correlation between plasma testosterone and insulin sensitivity, and low testosterone levels are associated with an increased risk of type 2 diabetes mellitus, dramatically illustrated by androgen deprivation in men with prostate carcinoma. Lower total testosterone and sex hormone-binding globulin (SHBG) predict a higher incidence of the metabolic syndrome. Administration of testosterone to hypogonadal men reverses part of the unfavorable risk profile for the development of diabetes and atherosclerosis.
Male hypogonadism, or testosterone deficiency syndrome (TDS), results from a failure of the testes to produce adequate androgen. Patients have low circulating testosterone in combination with clinical symptoms such as fatigue, erectile dysfunction, and body composition changes. The cause may be primary (genetic anomaly, Klinefelter’s syndrome) or secondary (defect in hypothalamus or pituitary), but often presents with the same symptomatology. In the older patient, androgen deficiency of the aging male (ADAM) is an important cause of secondary hypogonadism because testosterone levels decline progressively after age 40. Hypogonadal patients have alterations not only in sexual function and body composition, but also in cognition and metabolism. Regardless of etiology, hypogonadal patients who are both symptomatic and who have clinically significant alterations in laboratory values are candidates for treatment. The goal of hormone replacement therapy in these men is to restore hormone levels to the normal range and to alleviate symptoms suggestive of hormone deficiency. This can be accomplished in a variety of ways, although most commonly testosterone replacement therapy (TRT) is employed.
androgen deficiency; hypogonadism; testosterone deficiency syndrome; testosterone replacement
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.
Though the clinical significance of testosterone deficiency is becoming increasingly apparent, its prevalence in the general population remains unrecognised. A large web-based survey was undertaken over 3 years to study the scale of this missed diagnosis.
An online questionnaire giving the symptoms characterising testosterone deficiency syndrome (Aging Male Symptoms – AMS – scale) was set up on three web sites, together with questions about possible contributory factors. Results. Of over 10,000 men, mainly from the UK and USA, who responded, 80% had moderate or severe scores likely to benefit from testosterone replacement therapy (TRT). The average age was 52, but with many in their 40s when the diagnosis of ‘late onset hypogonadism’ is not generally considered. Other possible contributory factors to the high testosterone deficiency scores reported were obesity (29%), alcohol (17.3%), testicular problems such as mumps orchitis (11.4%), prostate problems (5.6%), urinary infection (5.2%) and diabetes 5.7%.
In this self-selected large international sample of men, there was a very high prevalence of scores which if clinically relevant would warrant a therapeutic trial of testosterone treatment. This study suggests that there are large numbers of men in the community whose testosterone deficiency is neither being diagnosed nor treated.
AMS questionnaire; web survey; testosterone deficiency; diagnosis; treatment; diabetes; alcohol; vasectomy
Late-onset hypogonadism (LOH) is a syndromic condition that has a well-recognized association with sexual and reproductive failure. LOH is frequently associated with chronic conditions including cardiovascular diseases (CVD), obesity, osteoporosis, HIV infection, renal failure, and obstructive pulmonary diseases. Despite this evidence, in patients with these conditions, LOH is still only rarely investigated and testosterone replacement therapy (TRT) rarely considered. In this paper, we critically reviewed the available evidence on LOH treatment focusing on possible risks and benefits. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. The fear of prostate cancer and the risk of erythrocytosis probably represent the main limitations of TRT in aging men. However, TRT in healthy older men in near physiological doses does not appear to incur serious adverse events, although regular monitoring of prostate-specific antigen and hematocrit levels is required. Available evidence also suggests that TRT might ameliorate central obesity and glycometabolic control in patients with metabolic syndrome and type 2 diabetes. In addition, TRT has been associated with an increase in bone mineral density in men with osteoporosis, with an improvement in lean body mass in subjects with human immunodeficiency virus infection or chronic obstructive pulmonary disease, as well as with peripheral oxygenation in patients with chronic kidney diseases. Despite this evidence, however, it should be recognized that the results of these trials were heterogeneous and limited by small sample sizes. Hence, further research is required regarding the long-term benefits and adverse effects of TRT in LOH.
Testosterone; Hypogonadism; Prostate; Diabetes mellitus; Erectile dysfunction
Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (≥65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21–0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.
sex hormone-binding globulin; hormonal dysregulation; insulin-like growth factor I; androgens
Metabolic syndrome and testosterone deficiency in men are closely Linked. Epidemiological studies have shown that Low testosterone Levels are associated with obesity, insulin resistance and an adverse Lipid profile in men. Conversely in men with metabolic syndrome and type 2 diabetes have a high prevalence of hypogonadism. Metabolic syndrome and Low testosterone status are both independently associated with increased all-cause and cardiovascular mortality. Observational and experimental data suggest that physiological replacement of testosterone produces improvement in insulin resistance, obesity, dyslipidae-mia and sexual dysfunction along with improved quality of Life. However, there are no Long-term interventional studies to assess the effect of testosterone replacement on mortality in men with Low testosterone Levels. This article reviews the observational and interventional clinical data in relation to testosterone and metabolic syndrome.
diabetes; insulin resistance; metabolic syndrome; obesity; testosterone deficiency
Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.
The effects of androgens on cardiovascular disease (CVD) risk in men remain unclear. To better characterize the relationship between androgens and HDL, we investigated the effects of testosterone replacement on HDL protein composition and serum HDL-mediated cholesterol efflux in hypogonadal men. Twenty-three older hypogonadal men (ages 51–83, baseline testosterone < 280 ng/dl) were administered replacement testosterone therapy (1% transdermal gel) with or without the 5α-reductase inhibitor dutasteride. At baseline and after three months of treatment, we determined fasting lipid concentrations, HDL protein composition, and the cholesterol efflux capacity of serum HDL. Testosterone replacement did not affect HDL cholesterol (HDL-C) concentrations but conferred significant increases in HDL-associated paraoxonase 1 (PON1) and fibrinogen α chain (FGA) (P = 0.022 and P = 0.023, respectively) and a decrease in apolipoprotein A-IV (apoA-IV) (P = 0.016). Exogenous testosterone did not affect the cholesterol efflux capacity of serum HDL. No differences were observed between men who received testosterone alone and those who also received dutasteride. Testosterone replacement in older hypogonadal men alters the protein composition of HDL but does not significantly change serum HDL-mediated cholesterol efflux. These effects appear independent of testosterone conversion to dihydrotestosterone. Further research is needed to determine how changes in HDL protein content affect CVD risk in men.
cardiovascular disease; lipoproteins; lipids; atherosclerosis; androgens
The indication for testosterone therapy in aging hypogonadal men without hypothalamic, pituitary, or testicular disease remains to be elucidated. The aim of this study was to investigate the effect of testosterone therapy on insulin sensitivity, substrate metabolism, body composition, and lipids in aging men with low normal bioavailable testosterone levels using a predefined cutoff level for bioavailable testosterone. A randomized, double-blinded, placebo-controlled study of testosterone treatment (gel) was done on 38 men, aged 60–78 years, with bioavailable testosterone <7.3 nmol/l and a waist circumference >94 cm. Insulin-stimulated glucose disposal (Rd) and substrate oxidation were assessed by euglycemic hyperinsulinemic clamps combined with indirect calorimetry. Lean body mass (LBM) and total fat mass (TFM) were measured by dual x-ray absorptiometry, and serum total testosterone was measured by tandem mass spectrometry. Bioavailable testosterone was calculated. Coefficients (b) represent the placebo-controlled mean effect of intervention. LBM (b = 1.9 kg, p = 0.003) increased while HDL–cholesterol (b = −0.12 mmol/l, p = 0.043) and TFM decreased (b = −1.2 kg, p = 0.038) in the testosterone group compared to placebo. Basal lipid oxidation (b = 5.65 mg/min/m2, p = 0.045) increased and basal glucose oxidation (b = −9.71 mg/min/m2, p = 0.046) decreased in response to testosterone therapy even when corrected for changes in LBM. No significant changes in insulin-stimulated Rd was observed (b = −0.01mg/min/m2, p = 0.92). Testosterone therapy increased muscle mass and lipid oxidation in aging men with low normal bioavailable testosterone levels; however, our data did not support an effect of testosterone on whole-body insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.
Testosterone therapy; Insulin sensitivity; Substrate oxidation; Aging men
Low testosterone, with or without symptoms, reported in diabetic men in some studies. We investigated the prevalence of hypogonadism in Iranian type 2 diabetic men.
Materials and Methods:
Total testosterone (TT) and sex hormone binding globulin (SHBG) concentrations were measured in 247 diabetic men >30 years who had symptoms of androgen deficiency, according to ADAMs questionnaire. The correlation between some parameters and total, free and bioavailable testosterone levels was determined using Pearson correlation coefficient. Free and bioavailable testosterone were calculated by electronic calculator. Four patients were excluded because of high testosterone level, due to unreported androgen use. Overt hypogonadism was defined as total testosterone ≤8 nmol/l or calculated bioavailable testosterone (cBT)≤2.5 nmol/l and borderline hypogonadism was considered as TT 8-12 nmol/l or cBT 2.5-4nmol/l.
The mean and SD of age was 59 (9.3) years. The mean TT, calculated free testosterone (cFT), and cBT and SHBG levels were 4.81 (1.7) nmol/l, 0.11 (0.06) nmol/l, 2.42 (1.17) nmol/l and 36.15 (18.3) nmol/l, respectively. According to TT and cBT, overt hypogonadism observed in 7.4% and 61.6% of men, respectively, and the prevalence of borderline hypogonadism was 9.9% and 36%, respectively. cFT ≤0.16 nmol/l found in 227 diabetic men (96%). Hypogonadism (TT ≤12 nmol/l) was not correlated with obesity, smoking, age,duration of diabetes, blood pressure, and HbA1c.
Hypogonadism is highly prevalent in type 2 diabetes men.
Hypogonadism; male; Iran; prevalence; Type 2 diabetes mellitus
There is a high prevalence of hypogonadism in men with type 2 diabetes. This will lead to an increase in assessments of hypogonadism. Statins could potentially decrease testosterone levels by reducing the availability of cholesterol for androgen synthesis. We compared testosterone levels and hypogonadal symptoms with statin use in a cross-sectional study of 355 men with type 2 diabetes.
RESEARCH DESIGN AND METHODS
Total testosterone, sex hormone–binding globulin (SHBG), and estradiol were measured by an enzyme-linked immunosorbent assay. Bioavailable testosterone was measured by the modified ammonium sulfate precipitation method. Free testosterone was calculated using Vermeulen's formula. Symptoms of hypogonadism were assessed using the Androgen Deficiency in the Aging Male questionnaire.
Statins were associated with lower total testosterone (11.9 vs. 13.4 nmol/l, P = 0.006) and a trend toward lower SHBG (29.4 vs. 35.3 nmol/l, P = 0.034) compared with no treatment. Bioavailable testosterone, free testosterone, estradiol, and hypogonadal symptoms were not affected. Subanalysis showed that atorvastatin was associated with reduced total testosterone (11.4 vs. 13.4 nmol/l, P = 0.006) and a trend toward reduced SHBG (27.6 vs. 35.3 nmol/l, P = 0.022) compared with no treatment, and there was an apparent dose-response effect with the lowest levels of total testosterone seen in men treated with ≥20 mg atorvastatin (9.6 nmol/l, P = 0.017). Simvastatin use was not associated with significant reductions in testosterone or SHBG levels.
Assessing androgen status using total testosterone in men with type 2 diabetes treated with statins, particularly atorvastatin, may potentially lead to diagnostic error. Levels of bioavailable testosterone or free testosterone are recommended for the assessment of hypogonadism in this group if total testosterone levels are borderline.
Background: Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia, adverse clotting profiles, obesity, and insulin resistance. Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease.
Objective: This randomised single blind placebo controlled crossover study compared testosterone replacement therapy (Sustanon 100) with placebo in 10 men with ischaemic heart disease and hypogonadism.
Results: Baseline total testosterone and bioavailable testosterone were respectively 4.2 (0.5) nmol/l and 1.7 (0.4) nmol/l. After a month of testosterone, delta value analysis between testosterone and placebo phase showed that mean (SD) trough testosterone concentrations increased significantly by 4.8 (6.6) nmol/l (total testosterone) (p = 0.05) and 3.8 (4.5) nmol/l (bioavailable testosterone) (p = 0.025), time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 (54) seconds (p = 0.002), and mood scores assessed with validated questionnaires all improved. Compared with placebo, testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor α with delta values of −0.41 (0.54) mmol/l (p = 0.04) and −1.8 (2.4) pg/ml (p = 0.05) respectively.
Conclusion: Testosterone replacement therapy in hypogonadal men delays time to ischaemia, improves mood, and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor α.
Data about metabolic syndrome (MetS) in children is limited in China. We aimed to assess the prevalence of MetS related components, and their association with obesity. Data were collected as part of a representative study on MetS among 19593 children, aged 6–18 years old in Beijing. General obesity was assessed by body mass index (BMI) and central obesity by waist circumference. Finger capillary blood tests were used to assess triglyceride (TG), total cholesterol (TC) and impaired fasting glucose (IFG). Vein blood samples were collected from a subsample of 3814 children aged 10–18 years to classify MetS. MetS was defined according to the International Diabetes Federation 2007 definition. The associations between MetS related components and the degree and type of obesity were tested using logistic regression models. The prevalence of overweight, obesity, high blood pressure, elevated TG, TC and IFG were13.6%, 5.8%, 8.5%, 8.8%, 1.2% and 2.5%, respectively. Compared with normal weight children, overweight and obese children were more likely to have other MetS related components. In the subsample of 3814 children aged 10–18 years, the prevalence of MetS was much higher in obese subjects than in their normal weight counterparts (27.6% vs. 0.2%). Children with both general and central obesity had the highest prevalence of MetS. Compared with normal weight children, overweight and obese children were more likely to have MetS (overweight: OR = 67.33, 95%CI = 21.32–212.61; obesity: OR = 249.99, 95% CI = 79.51–785.98). Prevalence of MetS related components has reached high level among Beijing children who were overweight or obese. The association between metabolic disorders and obesity was strong.
Late-onset hypogonadism (LOH) has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone (T) levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T (different thresholds), sexual parameters, medical history data (delayed puberty, pituitary disease or cryptorchidism) and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.
late-onset hypogonadism (LOH); male hypogonadism; testosterone; sexual dysfunction
Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood.
The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use.
Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women.
Aging; Testosterone; Skeletal Muscle; Men; Women
Effect of parenteral testosterone esters administration on bone-mineral density (BMD) and bone turnover in young age onset male hypogonadism is not studied in Indian subjects.
To prospectively study the effect of short-term (6 months) replacement therapy with parenteral testosterone enanthate-propionate combination on BMD and bone turnover markers in hypogonadal adult patients.
Settings and Design:
Prospective, tertiary care academic center.
Materials and Methods:
Thirteen young, otherwise healthy hypogonadal males (age 25.5 ± 4.9 yrs, serum testosterone 2.56 ± 4.29 nmol/l) were subjected to BMD measurements (DXA) and estimation of urinary Crosslaps™ and serum osteocalcin at baseline. Twelve healthy age and BMI-matched males served as controls for BMD measurements. The hypogonadal patients were administered parenteral testosterone esters (as mixed enanthate and propionate) 250 mg i.m. every 2-3 weeks, and prospectively followed for 6 months. BMD and bone markers were studied at the end of 6 months.
Statistical Analysis Used:
Mann-Whitney nonparametric test, paired t-test and Pearson's test of two-tail significance.
At baseline, BMD was significantly lower in hypogonadal males as compared to that in controls. With testosterone replacement, there was significant improvement in BMD, both at trabecular and cortical sites, There was a decline in bone turnover with treatment (Ur Crosslaps™:creatinine ratio: pretreatment 72.8 ± 40.4, post-treatment 35.5 ± 23.8 μg/mmol, P = 0.098; serum osteocalcin: pre-treatment 41.0 ± 16.8, post-treatment 31.7 ± 2.1 ng/ml, P = 0.393).
Short-term parenteral testosterone replacement significantly improves BMD at the hip, lumbar spine and forearm in hypogonadal young males.
C-terminal telopeptide; collagen-Crosslaps™; osteocalcin
Some men presenting with diffuse musculoskeletal pain have testosterone values below the normal range for their age. While scant evidence suggests that functional status in such men may improve with testosterone replacement therapy, there are currently no published studies evaluating a potential correlation between diffuse musculoskeletal pain and male hypogonadism. In a cohort of 45 hypogonadal men with diffuse musculoskeletal pain we found a negative correlation between the duration of pain in years and baseline total testosterone values. Although advancing age would theoretically predispose individuals to lower testosterone concentrations, age was not independently associated with baseline testosterone values, nor were any other variables we examined. At this time generalised screening of gonadal function for such men is not indicated. A prospective study would more clearly evaluate a potential relationship between diffuse musculoskeletal pain and testosterone values in men and might determine if testosterone replacement leads to any measurable improvement.