Baseline Total Testosterone Research Articles

Elevated LH predicts ischaemic heart disease events in older men: the Health in Men Study

Hypogonadism in men is associated with insulin resistance, elevations in pro-inflammatory cytokines and fibrinogen, and an atherogenic lipid profile. However, it is uncertain whether the age-related decline in testosterone is associated with ischaemic heart disease (IHD) events. To determine whether testosterone and its associated hormones, sex hormone-binding globulin (SHBG) and LH, predict IHD events in older men. Prospective cohort study. Between 2001 and 2004, 3637 community-dwelling men aged 70-88 years underwent a clinical assessment of cardiovascular risk factors and biochemical assessment of testosterone, SHBG and LH. Free testosterone was calculated using mass action equations. Participants were followed until December 2008 using electronic record linkage to capture IHD events (hospital admission or death). Mean follow-up was 5.1 years. During this period, 618 men (17.0%; 95% confidence interval (CI) 15.8, 18.3%) experienced an event, of which 160 were fatal. Men with higher baseline total or free testosterone levels experienced fewer IHD events (hazard ratio (HR)=0.89; 95% CI 0.82, 0.97 and HR=0.86; 95% CI 0.79, 0.94 for each one s.d. increase in total and free testosterone respectively). These associations were maintained after adjustment for age and waist:hip ratio but did not persist after adjustment for prevalent IHD or other cardiovascular risk factors. SHBG was not associated with IHD events. In contrast, higher LH levels were associated with reduced event-free survival in both univariate (HR=1.15; 95% CI 1.08, 1.22) and adjusted analyses (HR=1.08; 95% CI 1.01, 1.15). Dysregulation of the hypothalamic-pituitary-gonadal axis may be a risk factor for IHD. Further studies of men with either elevated LH or low testosterone are warranted.

Inverse association between total testosterone concentrations, incident hypertension and blood pressure

Background. Studies on the relationship between testosterone concentrations and blood pressure have yielded inconsistent results. Therefore, this study investigated the prospective association of total testosterone (TT) concentrations with risk of incident hypertension and blood pressure change in 1484 men aged 20–79 years.Methods. Data from the population-based Study of Health in Pomerania, Germany, were used. Serum TT concentrations, measured by chemiluminescent enzyme immunoassays, were categorised into age-specific quartiles. Generalised Estimating Equation (GEE) models, adjusted for age, waist circumference, physical activity, smoking and alcohol consumption were specified.Results. During a median follow-up time of 5.0 years, the prevalence of hypertension increased from 50.6% to 57.1%. TT concentrations were significantly lower in men with baseline and incident hypertension. Analyses revealed that men with baseline TT concentrations in the lowest quartile had an increased risk of incident hypertension (odds ratio (OR), 1.19 (95% CI, 1.10–1.28)) compared to men with higher TT concentrations. Furthermore, we found a significant inverse association of TT concentrations and blood pressure, showing that men with baseline TT concentrations in the lowest quartile showed the slightest change in systolic blood pressure (−6.01 mmHg), diastolic blood pressure (−2.11 mmHg) and pulse pressure (−3.98 mmHg). Sensitivity analyses in a subpopulation of men without antihypertensive medication confirmed these findings.Conclusion. These results show that low male TT concentrations are predictive of hypertension, suggesting TT as a potential biomarker of increased cardiovascular risk.

Type 2 diabetes mellitus and testosterone: a meta-analysis study

Several studies suggest that type 2 diabetes mellitus (T2DM) is often associated with male hypogonadism. Despite the well-known link, the role of testosterone replacement therapy (TRT) in T2DM has not been completely clarified. The aim of the present study was to analyse systematically the relationship between androgen levels and T2DM by reviewing and meta-analysing available prospective and cross-sectional studies. In addition, a specific meta-analysis on the metabolic effects of TRT in available randomized clinical trials (RCTs) was performed. An extensive Medline search was performed including the following words: 'testosterone', 'type 2 diabetes mellitus' and 'males'. Of 742 retrieved articles, 37 were included in the study. In particular 28, 5 and 3 were cross-sectional, longitudinal and interventional studies, respectively. A further unpublished RCT was retrieved from http://www.clinicaltrials.gov. T2DM patients showed significantly lower testosterone plasma levels in comparison with non-diabetic individuals. Similar results were obtained when T2DM subjects with and without erectile dysfunction were analysed separately. Meta-regression analysis demonstrated that ageing reduced, while obesity increased, these differences. However, in a multiple regression model, after adjusting for age and body mass index (BMI), T2DM was still associated with lower total testosterone (TT) levels (adjusted r = -0.568; p < 0.0001). Analysis of longitudinal studies demonstrated that baseline TT was significantly lower among patients with incident diabetes in comparison with controls (HR = -2.08[-3.57;-0.59]; p < 0.001). Combining the results of RCTs, TRT was associated with a significant reduction in fasting plasma glucose, HbA1c, fat mass and triglycerides. Conversely, no significant difference was observed for total and high-density lipoprotein cholesterol, blood pressure and BMI. The meta-analysis of the available cross-sectional data suggests that T2DM can be considered independently associated with male hypogonadism. Although only few RCTs have been reported, TRT seems to improve glycometabolic control as well as fat mass in T2DM subjects.

Clomiphene citrate is effective in the treatment of the hypogonadal, subfertile male with body mass index (BMI) >25 kg/m 2

OBJECTIVE: BMI has been shown to be negatively correlated with total testosterone (TT) and bioavailable testosterone (BT) levels in infertile males. Clomiphene citrate (CC), a selective estrogen receptor modulator, is used in the empiric treatment of subfertile males to increase testosterone levels. We sought to study the efficacy of CC for treatment of subfertile males who are overweight (OW, BMI 25-29.9 kg/m2) or obese (OB, BMI>30 kg/m2). DESIGN: Prospective observational cohort study. MATERIALS AND METHODS: Hypogonadal patients were started on CC, and TT, BT and prostate specific antigen (PSA) levels were recorded at baseline and measured at 1, 3 and 5 months during therapy. Followup semen analysis or pregnancy status was recorded. Student's t-test was used to compare pre- and post-treatment biochemical parameters. RESULTS: The study included 20 men, mean age 32.9 ± 0.9(SEM). Lower mean baseline TT levels were seen in the OB group (n=12) compared to the OW group (n=8) (TT: 237 ± 20 vs 306 ± 26 ng/dl; p=0.053). Within 1 month of CC therapy, TT and BT were significantly increased in both groups (table 1). Levels remained significantly elevated for duration of therapy. PSA levels did not increase significantly after 3 month of CC therapy (p=0.17). 4 patients demonstrated improved sperm concentration and motility at 6 months and a total of 5 subjects achieved pregnancy.Table 1Baseline vs. 1 Month Post-CC TreatmentParameterBaseline1 monthP-valueTT ng/dL (OW)306 ± 26663 ± 56< 0.001BT ng/dL (OW)187 ± 16486 ± 55< 0.002TT ng/dL (OB)237 ± 20577 ± 52< 0.001BT ng/dL (OB)155 ± 13371 ± 42< 0.001Results reported as mean ± SEM. Open table in a new tab Results reported as mean ± SEM. CONCLUSION: Significant improvement in testosterone levels are seen with the use of CC in the treatment of the subfertile male with BMI>25 kg/m2. Subfertile men who are overweight or obese can benefit from treatment with CC in order to increase testosterone levels and potentially improve semen parameters.

Effects of Testosterone Supplementation on Depressive Symptoms and Sexual Dysfunction in Hypogonadal Men with the Metabolic Syndrome

Low testosterone levels in men are associated with the metabolic syndrome (MetS) as well as with depressive symptoms, low vitality, and sexual dysfunction. To assess the effects of testosterone administration on these subjective symptoms, which have not extensively been studied in hypogonadal men with the MetS. The Beck Depression Inventory (BDI-IA), Aging Males' Symptoms (AMS) scale, and International Index of Erectile Function 5-item (IIEF-5) scale at baseline, 18 and 30 weeks were analysed using multilevel analysis. In a randomized, placebo-controlled, double-blind, phase III trial (ClinicalTrials.gov identifier: NCT00696748), 184 men suffering from both the MetS and hypogonadism were included. They were treated for 30 weeks with either parenteral testosterone undecanoate (TU; 1,000 mg IM TU, at baseline, and after 6 and 18 weeks; Nebido or placebo injections, 105 (92.9%) men receiving TU and 65 (91.5%) receiving placebo completed the 30-week trial. The 184 men were aged mean 52.1 years old (standard deviation [SD] 9.6; range 35-69), with a mean body mass index of 35.5 kg/m(2) (SD 6.7; range 25.1-54.8), and a mean total testosterone level of 8.0 nmol/L (SD 4.0). There were significant improvements in BDI-IA (mean difference vs. placebo after 30 weeks: -2.5 points; 95% confidence interval [CI]: -0.9; -4.1; P = 0.003), AMS (-7.4 points; 95% CI: -4.3; -10.5; P < 0.001), and IIEF-5 (+3.1 points; 95% CI: +1.8; +4.4; P < 0.001). The effects on the BDI-IA, AMS, and IIEF-5 were strongest in men with baseline total testosterone levels <7.7 mmol/L (i.e., median value). TU administration may improve depressive symptoms, aging male symptoms and sexual dysfunction in hypogonadal men with the MetS. The beneficial effects of testosterone were most evident in men with the lowest baseline total testosterone levels.

Variability in total testosterone levels in ageing men with symptoms of androgen deficiency

The aim of this study was to determine the variability in total testosterone (TT) levels in healthy, non-obese ageing men with symptoms of androgen deficiency. Men aged ≥55 years were recruited from the community. Morning TT levels were measured on four occasions in a 12-month period. In all, 96 men aged 62.7 ± 6.8 years were studied. Geometric mean values (95% confidence interval) of TT levels for the cohort at each time point were 14.5 (13.4-15.7), 14.6 (13.5-15.8), 15.5 (14.4-16.8) and 15.0 (13.9-16.2) nmol/L. The maximum intra-individual difference in TT between the four samples was 4.1 nmol/L (interquartile range: 2.9-6.4). Using the average of two baseline TT values reduces the maximum difference to 2.3 nmol/L (1.0-3.8). Only 1 of 25 men with a documented TT <10 nmol/L at baseline had TT levels <10 nmol/L at all subsequent time points. A single TT level is a reliable predictor of repeat measures taken within a 12-month period for a cohort of healthy ageing men with symptoms of androgen deficiency. However, given that the diagnostic criteria for androgen deficiency are, in part, predicated upon serum TT, there is sufficient intra-subject variability to warrant repeat sampling to confirm an initial low TT level. Using an average of two baseline TT values reduces this variability.

Association between sex steroids and cognition in elderly men

To examine the association of cognitive function with sex steroid and sex hormone binding globulin (SHBG) levels among elderly men. Prospective cohort study, The Osteoporotic Fractures in Men Study (MrOS), consisting of 5995 US community dwelling men of 65 years or older. One thousand six hundred and two men were chosen randomly from MrOS cohort for sex steroid level measurements by Mass Spectrometry (MS) at baseline. Two thousand six hundred and twenty-three MrOS participants with sex steroids measured using RIA were also examined. Baseline and follow-up (4.5 years later) performance on two cognitive tests: Trails B (executive function and motor speed) and 3MS (global cognitive function). Baseline total testosterone and oestradiol were measured by MS. Free testosterone (free-T) and free oestradiol (free-E) were calculated. SHBG was measured by radioimmunoassay. Data were analysed using linear regression. Baseline free-T and free-E levels were not associated with cognitive performance or change in cognition, following adjustment for age, education, race, health status and alcohol use. Baseline SHBG levels were inversely associated with follow-up trails B (P = 0.03) and 3MS performance (P = 0.02). Higher SHBG was associated with an increased risk of cognitive decline. Total sex steroid levels were not associated with cognitive performance. Despite large numbers of participants and rigorous sex steroid measurements, we did not observe an association between cognition and either testosterone or oestradiol levels. We conclude that endogenous sex steroids in the normal range are not related to executive function or global cognitive function in elderly men. High SHBG deserves further examination as a risk factor for cognitive decline.

Abstract B113: Determinants of serum sex hormone binding globulin and testosterone in overweight and weight-reduced premenopausal women

Abstract Introduction: Epidemiological studies have linked androgens and low sex hormone binding globulin (SHBG) with increased risk for breast cancer in premenopausal women. Obesity and the metabolic complications associated with increased adiposity have been shown to mediate both of these factors. The purpose of this study was to determine whether weight reduction through caloric restriction (CR), CR + aerobic exercise (CR+AE) or CR + resistance training (CR+RT) modifies serum total testosterone, bioavailable testosterone and SHBG. Methods: Participants were 138 healthy, over weight (BMI 27–79) premenopausal women not taking oral contraceptives randomized to CR, CR+AE or CR+RT in order to achieve normal body weight (BMI&amp;lt;25). Results: All three groups significantly reduced BMI from baseline to follow-up. There was no significant difference in adjusted mean BMI among the groups following weight loss. All three groups significantly increased SHBG (p&amp;lt;0.0001) and significantly decreased bioavailable testosterone (p&amp;lt;0.0001) from baseline to follow up. With all participants combined there was significant decrease in total testosterone as well as in the CR group (p≤0.05 for both). There was no difference in adjusted mean total testosterone, bioavailable testosterone and SHBG concentrations among the three groups following weight loss. Multiple linear regression models revealed that 64% of the variance in baseline SHBG was explained by age, intra-abdominal fat, bioavailable testosterone, insulin, and high density lipoprotein (HDL). After adjusting for baseline SHBG, 81% of the variance was explained by age, free testosterone and HDL in the weight reduced state. Twenty-three percent of the variance in baseline total testosterone was explained by age, estradiol, norepinephrine, low density lipoprotein (LDL) and leptin. After adjusting for baseline total testosterone, 58% of the variance was explained by age, estradiol and leptin in the weight reduced state. Conclusions: Testosterone, bioavailable testosterone and SHBG are highly influenced by obesity and can be modified through weight loss. Weight loss through CR or in combination with exercise achieves similar effects on testosterone and SHBG concentrations. The determinants of serum total testosterone and SHBG are different in the overweight and weight reduced state. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B113.

P01-37 - Effects of testosterone supplementation on depressive symptoms in hypogonadal men with the metabolic syndrome: the Moscow study

IntroductionLow testosterone levels in men are associated with the metabolic syndrome (MetS) as well as with depressive symptoms, low vitality and sexual dysfunction.ObjectivesTo assess the effects of testosterone administration on these subjective symptoms, which have not extensively been studied in hypogonadal men with the MetS.MethodIn a randomized, placebo-controlled, double-blind, phase III trial, 184 men suffering from both the MetS and hypogonadism were included. They were treated for 30 weeks with either parenteral testosterone undecanoate (TU; 1000 mg IM testosterone undecanoate, at baseline, and after 6 and 18 weeks; Nebido®) or placebo injections. 105 (92.9%) men receiving TU and 65 (91.5%) receiving placebo completed the 30 week trial. The Beck Depression Inventory (BDI), Aging Males’ Symptoms (AMS) scale, and International Index of Erectile Function 5-item (IIEF-5) scale at baseline, 18 and 30 weeks were analysed using multilevel analysis.ResultsThe mean age was 52.1 years (range: 35-69), with a mean body mass index of 35.5 kg/m2 (SD 6.7), and a mean total testosterone level of 8.0 nmol/L (SD 4.0). There were significant improvements in BDI (mean difference vs. placebo after 30 weeks: -2.5 points; 95% confidence interval [CI]: -0.9;-4.1; P=0.003), AMS (-7.4 points; 95% CI: -4.3;-10.5; P&lt; 0.001), and IIEF-5 (+3.1 points; 95% CI: +1.8;+4.4; P&lt; 0.001). The effects were strongest in men with baseline total testosterone levels &lt; 7.7 mmol/L.ConclusionsTU administration may improve depressive symptoms, aging male symptoms and sexual dysfunction in hypogonadal men with the MetS.

The effect of androgen deprivation therapy on CD4/CD8 T cells in HIV-negative patients receiving definitive 3D radiation treatment for their prostate carcinoma: Final report of a prospective study

11056 Background: CD4 and CD8 T cells play critical roles in human immunity. The aim of this prospective study is to explore the correlation of the absolute CD4/CD8 T cell counts and total testosterone in patients receiving androgen deprivation therapy (ADT) with goserelin acetate and definitive radiation treatment (RT) for their prostate cancer. Methods: Thirty-four HIV-negative patients were included in this study between June 2006 and January 2007. All patients had a baseline total testosterone level (T), PSA, CD4 and CD8 T cell counts. CD4/8 T cells count was measured using flow cytometry. All patients received 6 months of ADT prior to (baseline) and during RT to the prostate. Subsequent blood samples were taken at 2, 8, 12 and 24 months. Blood samples were taken between 8–10 am to control for diurnal variations in CD4/CD8 T cell counts and T levels. To study the correlation of T with CD4/8 T cell changes, the Spearman correlation coefficient was calculated. The study was approved by the appropriate Ethics Committee. Results: Median age for the study patients was 68 years. At baseline, median testosterone level was 350 ng/dL, median CD4 T cell count was 1055 mm3, and median CD8 T cell count was 644 mm3. None of the patients received anti-androgens. At two months, testosterone was at the castrate and subnormal levels in 85% and 100% of the patients, respectively. The lower testosterone levels resulted in significant reduction of CD4 and CD8 T cell counts at 2, 8, 12 and 24 months compared to baseline counts. This effect was more pronounced for CD4 T cells at all time points (p=&lt;0.02). At 24 months, when total testosterone levels were increasing, CD4 and CD8 T cell counts were also following these upward trends. The seen correlation between lower testosterone and decline in CD4 and CD8 T cells was only statistically significant in older patients (&gt;65 years) and was not associated with significant decline in total white blood cell counts. Conclusions: CD4/CD8 T cell counts are sensitive to changes in total testosterone levels. Lower testosterone levels negatively affecting CD4/CD8 T cells counts at all study time points. Since CD4/CD8 T cells play major roles in cellular immunity, further studies are warranted No significant financial relationships to disclose.

Testosterone Improves Erectile Function in Hypogonadal Patients With Venous Leakage

The goal of this study was to assess the therapeutic benefits of long-acting testosterone therapy in hypogonadal patients with erectile dysfunction (ED). We recruited 29 patients with ED, ranging in age from 32 to 65 years (mean +/- SD, 47 +/- 9.7 years), with low plasma testosterone, who did not respond to phosphodiesterase type 5 inhibitor therapy. To evaluate penile arterial and venous blood flow, we employed duplex Doppler ultrasonography. For confirmation of diagnosis of venous leakage, pharmacocavernosography was carried out in 9 patients and magnetic resonance imaging with intracavernous contrast enhancement was carried out in 8 patients. All patients were treated with 1000 mg injectable testosterone undecanoate on day 1, followed by another injection after 6 weeks and every 3 months thereafter, in accordance with Nebido therapy protocol. Plasma testosterone levels were determined in all patients at baseline and after 18 and 30 weeks of testosterone treatment. The International Index of Erectile Function (IIEF-5) was administered at baseline and after 18 and 30 weeks of testosterone treatment. At baseline total testosterone ranged from 7 to 11.8 nmol/L (200 to 345 ng/dL) in 25 patients. Eighteen and 30 weeks after testosterone treatment, the mean testosterone plasma levels were 18 and 21.5 nmol/L (520 and 625 ng/dL), respectively. After 18 and 30 weeks of testosterone treatment, 20 out of the 29 patients demonstrated marked improvement in erectile function domain, as assessed by the IIEF-5. This was also associated with diminution of venous leakage. We suggest that, in hypogonadal men with ED, testosterone therapy improves erectile function in patients with ED and venous leakage.

Serum testosterone and bioavailable testosterone correlate with age and body size in hypogonadal men treated with testosterone undecanoate (1000 mg IM – Nebido®)

To investigate the loading regimen for intramuscular (IM) testosterone undecanoate (Nebido) to determine whether testosterone and bioavailable testosterone levels achieved correlate with age or body size of subjects studied. Retrospective observational study of testosterone naïve patients and patients previously treated with an alternative testosterone therapy. 51 hypogonadal men (35, 68.6% secondary hypogonadism). 8 (16%) had not previously received testosterone therapy. Patients received an IM injection of Nebido (1000 mg) at baseline and a second injection after 6 weeks. Serum was assayed at baseline and 18 weeks after commencing Nebido for total testosterone (TT) and SHBG. Bioavailable testosterone was calculated (cBioT) using TT and SHBG. Measurements were taken for weight, body mass index (BMI) and body surface area (BSA). Baseline TT (mean 11.5 nmol/l, range 0.3-54.8) increased by 50% after commencing Nebido (17.2 nmol/l (5.4-32.8), P = 0.0001). 75% of subjects had a TT within the reference range (8.0-25.0 nmol/l). Subjects with primary hypogonadism had a higher 18-week TT [20.9 nmol/l (9.8-32.8) vs. 15.5 (5.4-32.6), P = 0.02] and SHBG [39.2 nmol/l (11-82) vs. 25.7 (9.0-60.0), P = 0.003] although the cBioT was not significantly different [4.9 nmol/l (2.9-7.3) vs. 4.2 (2.0-7.9), P = 0.12]. The 18-week TT positively correlated with age (R = 0.36, P = 0.01) and negatively correlated with weight (R = -0.38, P = 0.006), BMI (R = -0.42, P = 0.002) and BSA (R =-0.38, P = 0.007). Similarly cBioT correlated with age (R = 0.28, P = 0.04), weight (R = -0.29, P = 0.03), BMI (R = -0.30, P = 0.03) and BSA (R = -0.27, P = 0.05). Age (t = 2.04, P = 0.05) and baseline testosterone (t = -9.26, P < 0.0001) were independent variables of the increase in TT at 18 weeks. This starting regimen is simple and provides the majority of men with a TT within the reference range. Age and baseline TT are independent variables of the increase in TT with IM testosterone undecanoate. At week 18 age and body size correlated with the cBioT and TT and this may then be used to estimate dosing frequency for this therapy.

The Association of Testosterone Levels with Overall Sleep Quality, Sleep Architecture, and Sleep-Disordered Breathing

Little is known about the association of low endogenous testosterone levels and abnormal sleep patterns in older men, although pharmacological doses of testosterone are associated with increased severity of sleep apnea and other sleep disturbances. The objective of the study was to examine the association between serum testosterone levels with objectively measured sleep characteristics. This was a cohort study. Community-dwelling men aged 65 yr or older from six clinical centers in the United States participated in the study. A total of 1312 men had baseline total testosterone levels measured in 2000-2002, followed 3.4 yr later by 72-h (minimum) actigraphy and one-night in-home polysomnography to assess sleep duration, sleep fragmentation, and sleep apnea. Analyses were performed by quartile of total testosterone and categorically defined low vs. higher total testosterone (<250 ng/dl vs. > or =250 ng/dl). Lifestyle and body size were covariates. Total testosterone levels were unrelated to age or duration of sleep. Men with lower testosterone levels had lower sleep efficiency, with increased nocturnal awakenings and less time in slow-wave sleep as well as a higher apnea-hypopnea index and more sleep time with O(2) saturation levels below 90%. Low testosterone levels were associated with overweight, and all significant associations were attenuated or absent after adjusting for body mass index or waist circumference. In a post hoc analysis in men with higher body mass index (>27 kg/m2), testosterone was significantly associated with more periods awake after sleep onset and lower sleep efficiency. Low total testosterone levels are associated with less healthy sleep in older men. This association is largely explained by adiposity. Clinical trials are necessary to determine whether body weight acts directly or indirectly (via low testosterone) in the causal pathway for sleep-disordered breathing in older men.

Testosterone supplementation for hypogonadal men by the nasal route

Although multiple forms of testosterone replacement therapy are available to treat hypogonadism, none is ideal. This article reports on the pharmacokinetics of an innovative nasal formulation of testosterone in hypogonadal men. The first study was undertaken in eight men with a baseline total testosterone (TT) of 130.8 ± 87.4 ng/dL and examined the pharmacokinetics of nasal testosterone given in a single dose of 7.6 mg, 15.2 mg or 22.8 mg, respectively. The second study examined the pharmacokinetics of nasal testosterone (7.6 mg) given either twice or three times a day in 21 severely hypogonadal men (baseline TT in 20 patients <50 ng/dL, in one patient 152 ng/dL) for 14 days. The steady-state concentration of testosterone was within the normal range in all treatment groups, but only in the 3-times-a-day group was the 95% confidence interval completely within the physiological range. The average DHT level did not exceed the upper range of normal. The clinical global visual analogue scale improved in the whole group receiving testosterone (p < 0.001). All adverse events in both studies were of mild to moderate intensity and were evaluated as unlikely or not related to the administered study drug. No patients dropped out during treatment.Comparison with the normal circadian rhythm by computer modelling suggests that nasal testosterone can be used to mimic the normal diurnal pattern in eugonadal men. Thus, nasal testosterone can be administered safely to humans in doses that approximate serum concentrations in the normal physiological range.

Testosterone Supplementation in Older Men

The progressive decline in testosterone levels as men age has led to suggestions that physical, functional, or cognitive benefits could accrue from testosterone supplementation later in life. In a double-blind Dutch study, 237 healthy men (mean age, 67) with low-normal circulating testosterone levels (mean baseline total testosterone level, 308 ng/dL) were randomly assigned to …

The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes

Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. Leptin, adiponectin, resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. At baseline, leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r=-0.68; P=0.002) and bioavailable testosterone levels (r=-0.73; P=0.007). CRP levels also correlated significantly with total testosterone levels (r=-0.59; P=0.01). Testosterone treatment reduced leptin (-7141.9 +/- 1461.8 pg/ml; P=0.0001) and adiponectin levels (-2075.8 +/- 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-alpha, IL-6 or CRP levels were observed. Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH BASELINE TESTOSTERONE LEVELS IN BORDERLINE HYPOGONADAL AGING MEN.

Background Obstructive sleep apnea (OSA) becomes more prevalent as men aging. In fact, age is the number one predictor for obstructive sleep apnea. At the same time, serum testosterone level decreases about 50% from age 30 to 80. Some previous studies have demonstrated a link between obstructive sleep apnea and testosterone supplement therapy. However, it has not been determined whether at baseline, obstructive sleep apnea is associated with serum testosterone level. Methods Twenty-eight older men between the ages of 60 to 80 with borderline hypogonadism were enrolled in this study. Apnea-hypopnea index (AHI), baseline total serum testosterone level, age, BMI, neck size, and LDL level were evaluated. Study subjects were divided into those with obstructive sleep apnea (AHI ≥ 10) and a non-sleep apnea group (AHI Results At baseline, baseline serum testosterone levels (288 ± 48ng/dL) were significantly different (p = .001) between the obstructive sleep apnea group (n = 14) and the non-sleep apnea group (n = 14). Also, the AHI (17 ± 3) was inversely correlated with serum testosterone (r2= .20, p = .02). No other risk factors, including age (67 ± 6), BMI (29 ± 4 kg/m2), neck size (16 ± 1 inches), and LDL levels (103 ± 26 mg/dL), were significantly different between the two groups (p = ns). Conclusions In borderline hypogonadal aging men, baseline serum testosterone levels can be a predictor for the risk of obstructive sleep apnea.

The Age Related Decrease in Testosterone is Significantly Exacerbated in Obese Men With the Metabolic Syndrome. What are the Implications for the Relatively High Incidence of Erectile Dysfunction Observed in These Men?

We examined pooled baseline data from 2 lipid treatment studies to evaluate the relationship among total serum testosterone levels, obesity and the metabolic syndrome in aging men. Baseline total serum testosterone, lipid, glycemic and anthropometric data were obtained from 864 men (mean age 52 years) participating in 2 lipid treatment studies. Inclusion criteria for the 2 studies included low-density lipoprotein cholesterol 130 to 160 mg/dl and triglycerides 350 mg/dl or less. For all patients as well as the nonmetabolic syndrome and the metabolic syndrome cohorts, testosterone decreased with increasing body mass index (p < 0.0001 for Pearson correlation coefficient in all 3 cohorts). Mean baseline total serum testosterone levels in obese and severely obese aging men with the metabolic syndrome were around 150 and 300 ng/dl, respectively, less than that in aging, lean men with no metabolic syndrome. The relative contributions of each of the individual National Cholesterol Education Program Adult Treatment Panel III components of the metabolic syndrome to low serum testosterone in aging men was examined using multiple linear regression modeling. Based on these analyses the presence of diabetes or fasting serum glucose greater than 110 mg/dl, body mass index 30 kg/m or greater, and triglycerides 150 mg/dl or greater each appeared to have a clinically relevant association with low serum testosterone. This study demonstrated that aging men with obesity and the metabolic syndrome have a significant decrease in total serum testosterone levels compared to aging, metabolically healthy men. These data suggest that the well established association between erectile dysfunction and pre-diabetes/diabetes (particularly in obese pre-diabetic/diabetic patients) may involve a hormonal component.

The Metabolic Syndrome and Smoking in Relation to Hypogonadism in Middle-Aged Men: A Prospective Cohort Study

In men, hypoandrogenism is associated with features of the metabolic syndrome. It is not known whether men with the metabolic syndrome are at a higher risk of developing hypogonadism. We therefore assessed whether the metabolic syndrome predicts development of hypogonadism 11 yr later in 651 middle-aged Finnish men participating in a population-based cohort study. Men with the metabolic syndrome at baseline as defined by the World Health Organization (n = 114, 20%) had a 2.6-fold increased risk of developing hypogonadism as defined by total testosterone levels less than 11 nmol/liter at the 11-yr follow-up independent of age, smoking, and other potential confounders. Further adjustment for body mass index (OR, 2.0; 95% CI, 1.1-3.8) or baseline total testosterone levels (OR, 1.9; 95% CI, 1.0-3.4) attenuated the association. The association of the metabolic syndrome with hypogonadism as defined by calculated free testosterone levels less than 225 pmol/liter was similar, but weaker. The adjusted decrease in testosterone concentrations during the 11-yr follow-up was also greater in men with than without the metabolic syndrome. Smokers had a nonsignificantly lower risk of developing hypogonadism during follow-up, whereas a decrease in smoking increased the risk of hypogonadism. The metabolic syndrome predisposes to development of hypogonadism in middle-aged men. Prevention of abdominal obesity and the accompanying metabolic syndrome in middle age may decrease the risk of hypogonadism in men, especially in those who quit smoking.

Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men.

To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men. Prospective observational study. Second-generation Japanese-American males enrolled in a community-based population study. At baseline, 110 men received a 75g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutaneous fat areas (SCF). After 7.5y, IAF increased by a mean of 8.0 cm2 (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r= -0.26, P= 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/l] = -107.13, P = 0.003). In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type 2 diabetes mellitus.