Low Bioavailable Testosterone Levels Research Articles

Alcohol Consumption Is Associated with Hypogonadism and Decreased Sexual Function in Ghanaian Diabetics

Introduction: Alcohol usage has largely been seen as a risk factor for the development of sexual dysfunction as well as erectile dysfunction. Others have reported that prolonged alcohol usage and abuse is compatible with normal sexual function in the absence of endocrinological problems as well as hepatic dysfunction. About seventy five (75) percent of alcoholics have various sexual difficulties with improvements in sexual functions occurring after treatment of alcoholism and psychosexual therapy. It is evident from the various reports over the years that mild and occasional alcohol usage is not as much implicated in the causation of SD and its other forms as heavy, addictive or dependent alcohol usage. Alcohol usage has also long been linked to hypogonadism, testicular atrophy as well as leydig cell toxicity. Alcohol induced hypogonadism has been reported to resolve after withdrawal of alcohol use. Since both diabetes and alcohol usage have been strongly associated with both hypogonadism and sexual dysfunction, it is logical to expect that diabetics who frequently consume alcohol will have a worsened hypogonadal state and sexual function. This research therefore seeks to provide evidence of an association between alcohol consumption in diabetics and a worsened sexual dysfunction in comparison to diabetics who did not consume alcohol. Methods: Type II diabetic patients attending the Diabetic Clinic at the Maamobi General Hospital between the periods of January 2010 and March 2011 were consecutively recruited for this study. Diabetics with other known endocrinological diseases and physical disabilities were excluded from the study. Sexual function was assessed using the GRISS-M. Early morning fasting samples were used in lipid and testosterone profile assays. Results: Study participants who consumed alcohol recorded higher levels of triglycerides and LDL-Cholesterol. They also recorded significantly lower levels of bioavailable testosterone. Furthermore they also recorded higher scores for impotence, premature ejaculation, non-sensuality and infrequency but lower scores for avoidance and were about six times more likely to be infrequent in their sexual activity in comparison with those who did not consume alcohol. Conclusion: Alcohol consumption among diabetic males is associated with hypogonadism and has an impact on several domains of male sexual function. Diabetic males should be advised to avoid alcohol abuse in order to facilitate the management of diabetes associated sexual dysfunction.

Association between late-onset hypogonadism syndrome plus metabolic syndrome and prostate cancer and its aggressiveness

ObjectiveTo assess the relationship between prostate cancer (PC) and the presence of metabolic syndrome and late-onset hypogonadism (LOH) syndrome. Material and methodA retrospective study was conducted on 686 patients who underwent prostate biopsy. We analyzed the demographic variables, clinical data and biopsy results. To diagnose metabolic syndrome, we employed the criteria of the American Heart Association. For the diagnosis of LOH syndrome, we employed the Androgen Deficiency in the Aging Male questionnaire and testosterone levels (TT). We evaluated the relationship between free testosterone (FT) and bioavailable testosterone (BT) on one hand and PC and its aggressiveness on the other, as well as the usefulness of the TT to prostate specific antigen (TT/PSA) ratio in the PC diagnosis. ResultsThe patient's median age was 65 years. Metabolic syndrome is not associated with PC (39.4% vs. 35%; p=0.1) but is associated with a PC Gleason score>7 (50.4% vs. 29.44%; p=0.002). LOH, low FT and low BT are associated with an increased presence of PC (51% vs. 35%, p=0.02; 44.86% vs. 33.33%, p=0.03; and 46.46% vs. 33.08%, p=0.01, respectively) and with an increased probability of a PC Gleason score>7 (61.54% vs. 37.5%, p=0.02; 54.17% vs. 34.12%, p=0.02; 54.35% vs. 34.48%, p=0.02, respectively). Additionally, the median TT/PSA ratio was significantly lower in patients with positive biopsies (p=0.022). ConclusionsMetabolic syndrome was not associated with the probability of having PC but was associated with a PC Gleason score>7. Moreover, LOH syndrome had a higher percentage of PC and a greater presence of PC Gleason score>7, as did low levels of FT and low levels of BT.

Asociación del síndrome de hipogonadismo tardío y síndrome metabólico con el cáncer de próstata y su agresividad

ObjectiveTo assess the relationship between prostate cancer (PC) and the presence of metabolic syndrome and late-onset hypogonadism (LOH) syndrome. Material and methodA retrospective study was conducted on 686 patients who underwent prostate biopsy. We analysed the demographic variables, clinical data and biopsy results. To diagnose metabolic syndrome, we employed the criteria of the American Heart Association. For the diagnosis of LOH syndrome, we employed the Androgen Deficiency in the Aging Male questionnaire and testosterone levels (TT). We evaluated the relationship between free testosterone (FT) and bioavailable testosterone (BT) on one hand and PC and its aggressiveness on the other, as well as the usefulness of the TT to prostate specific antigen (TT/PSA) ratio in the PC diagnosis. ResultsThe patient's median age was 65 years. Metabolic syndrome is not associated with PC (39.4% vs. 35%; P=.1) but is associated with a PC Gleason score >7 (50.4% vs. 29.44%; P=.002). LOH, low FT and low BT are associated with an increased presence of PC (51% vs. 35%, P=.02; 44.86% vs. 33.33%, P=.03; and 46.46% vs. 33.08%, P=.01, respectively) and with an increased probability of a PC Gleason score >7 (61.54% vs. 37.5%, P=.02; 54.17% vs. 34.12%, P=.02; 54.35% vs. 34.48%, P=.02, respectively). Additionally, the median TT/PSA ratio was significantly lower in patients with positive biopsies (P=.022). ConclusionsMetabolic syndrome was not associated with the probability of having PC but was associated with a PC Gleason score >7. Moreover, LOH syndrome had a higher percentage of PC and a greater presence of PC Gleason scores >7, as did low levels of FT and low levels of BT.

Low circulating free and bioavailable testosterone levels as predictors of high-grade tumors in patients undergoing radical prostatectomy for localized prostate cancer

ObjectiveControversy exists regarding the propensity of hypogonadism and metabolic disorders to promote the development of high-risk prostate cancer (PCa). Our aim was to prospectively test whether preoperative circulating testosterone levels, obesity, and metabolic syndrome (MetS) were correlated with aggressive pathological features after radical prostatectomy (RP). Material and methodsOverall, 354 patients undergoing robot-assisted RP at our academic institution, between 2010 and 2013, to treat clinically localized PCa were included in this prospective study. Pelvic lymphadenectomy was performed in 116 (32.8%) patients and confirmed the absence of nodal metastases in all of them. Cardiovascular risk factors and body-mass index (BMI) were used to define MetS and obesity, respectively. Total testosterone (TT) levels were assessed using an immunoassay method, whereas bioavailable testosterone (BT) and free testosterone (FT) levels were estimated using Vermeulen׳s formula. Multivariate logistic regression analyses assessed independent predictors for postoperative aggressive pathological features (i.e., a pathological Gleason score [GS]≥7, extracapsular extension [ECE], seminal vesicle invasion [SVI], and positive surgical margins [PSM]) and GS upgrading. ResultsLow TT, BT, and FT levels were found in 54 (15.2%), 70 (19.8%), and 62 (17.5%) patients, respectively. Median BMI was 26.3kg/m2 (range: 17.4–43.9), and prevalence of MetS was 18.9%. Significantly higher rates of pathological GS≥7 were observed in groups with a low TT level (46.3% vs. 33.3%; P = 0.01), low BT level (44.3% vs. 33.1%; P<0.001), and low FT level (46.8% vs. 32.9%; P = 0.001). Multivariate analyses demonstrated that only low BT and FT levels were independent predictors of pathological GS≥7 (odds ratio [OR] = 1.76; P<0.001 and OR = 1.39; P<0.001, respectively) and GS upgrading (OR = 2.82; P<0.001 and OR = 1.71; P<0.001, respectively), but there was no significant correlation between low circulating testosterone levels and ECE, SVI, or PSM. Furthermore, BMI (OR = 1.28; P = 0.04) and MetS (OR = 1.19; P = 0.01) were only correlated with PSM. ConclusionHypogonadism, obesity, and MetS were not independent predictors of pathological GS ≥7, ECE, or SVI after RP. Our data suggest that only low BT and FT levels, which might logically result in an active androgen-depleted environment, were linked with high-grade PCa.

Association of serum androgen concentrations with cardiovascular risk factors in elderly male patients with chronic systolic heart failure in China

Objective: To survey the serum androgen concentrations and investigate the relationship between androgen levels and cardiovascular risk factors in elderly male patients with chronic systolic heart failure (HF) in China.Methods: 106 consecutive male patients hospitalized for chronic systolic HF aged from 60 to 87 were enrolled. About 400 healthy age-matched men were compared as a control group. Total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured. Differences of androgen levels between HF patients and healthy men were determined by t-test and associations of androgen with cardiovascular risk factors were evaluated by partial correlations analyses.Results: Compared with healthy men, TT, FT and DHEAS levels in patients with HF decreased, whereas SHBG level increased significantly (both p < 0.01). TT was negatively correlated with TC, TG and DBP (p < 0.05), FT was negatively correlated with TC, LDL-C and DBP (p < 0.05). SHBG correlated with BMI and smoking history positively (p < 0.05).Conclusions: Level of bio-available testosterone decreased with advancing age, especially in men with HF. Men with low levels of bio-available testosterone had worse profiles of cardiovascular risk factors. Treatment of HF is still challenging and testosterone supplementation therapy may be an effective therapeutic option.

Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy

Objective. Recent studies show an inverse relationship between testosterone levels and prostate cancer (PCa). The usefulness of hormonal patterns in PCa diagnosis is controversial. This study aimed to determine the relationship between hormonal patterns and PCa, and to find a cut-off point of hormone levels to assess PCa risk. Material and methods. A prospective analysis was undertaken of 279 patients referred for first or second prostate biopsy in the Hospital Clínic Barcelona from November 2006 to May 2009. The indication for prostate biopsy was suspicion of PCa based on the results of digital rectal examination (DRE) and/or elevation of serum prostate-specific antigen (PSA). Screening was carried out with a 5+5-core transrectal ultrasound-guided prostate biopsy. Age, prostate volume, DRE (normal or abnormal), biopsy findings (normal or report of PCa), PSA, free-to-total PSA, PSA density, testosterone and sex hormone-binding globulin (SHBG) were also prospectively recorded. Free and bioavailable testosterone were calculated using Vermeulen's formula. Results. In the multivariate analysis, abnormal DRE [odds ratio (OR = 5.46, p < 0.001], SHBG levels ≥ 66.25 nmol/l [OR = 3.27; 95% confidence interval (CI) 1.52 to 7.04, p < 0.002] and bioavailable testosterone levels ≤ 104 ng/dl (OR = 4.92, 95% CI 1.78 to 13.59, p = 0.002) were related to the diagnosis of prostate adenocarcinoma. Age, free testosterone, PSA, testosterone, PSA/testosterone, PSA/free testosterone and PSA/bioavailable testosterone were not related to PCa diagnosis. Conclusions. Low bioavailable testosterone levels and high SHBG levels were related to a 4.9- and 3.2-fold risk of detection of PCa on prostate biopsy owing to PSA elevation or abnormal DRE. This fact may be useful in the clinical scenario in counselling patients at risk for PCa.

Hand preference in humans is associated with testosterone levels and androgen receptor gene polymorphism

Exposure of the central nervous system to androgens during the early developmental period has been proposed to play a role in the establishment of hand preference in males. Existing data, however, are inconclusive. In the present investigation, handedness was assessed in a large sample of left-, mixed-, and right-handed men (N=180) using a standardized handedness inventory. Saliva sampling was used to assay levels of bioavailable testosterone and DNA genotyping was carried out to quantify AR-CAG repeat length, a genetic marker of the capacity of the androgen receptor to respond to testosterone. Strongly left-handed males were found to have lower levels of bioavailable testosterone than right-handed males, while males with mixed handedness exhibited a weaker androgen receptor, but no significant difference from right-handers in circulating testosterone levels. These findings support the view that testosterone could play a role in the development of hand preference in males. Furthermore, because the AR gene lies on the X chromosome, it provides a potential theoretical bridge to genetic theories of handedness that postulate the existence of an X-linked locus important in the establishment of hand preference.

Increased medial temporal lobe and striatal grey-matter volume in a rare disorder of androgen excess: a voxel-based morphometry (VBM) study

Major questions remain about how sex hormones influence human brain development and cognition. Studies in humans and animals suggest a strong impact of androgen on the structure and function of the medial temporal lobe (MTL) and striatum. Using voxel-based morphometry (DARTEL), we compared MTL and striatal structures in 13 [mean age (±S.D.) 12.7±3.2 yr, mean bone age 14.8±3.2 yr] boys with familial male precocious puberty (FMPP), characterized by early excess androgen secretion, and 39 healthy age-matched boys (mean age 14.3±2.5 yr). The FMPP group showed significantly larger grey-matter volume (GMV) in parahippocampal and fusiform gyri as well as putamen relative to controls. By comparison, larger GMV for controls relative to patients was only apparent in the precentral gyrus. Exploratory regression analyses that examined the impact of age on the current findings revealed a significant increase of GMV in the putamen with age in patients suffering from excess androgen but not in controls. Finally, current levels of free testosterone were obtained in the patient group. Analyses revealed a significant negative association indicating that FMPP boys with low levels of bioavailable testosterone exhibited high GMV in the bilateral striatum. The findings suggest a critical influence of androgen on human brain development and are discussed in relation to male-dominant psychiatric childhood disorders.

Effects of Transdermal Testosterone on Bone and Muscle in Older Men with Low Bioavailable Testosterone Levels, Low Bone Mass, and Physical Frailty

To investigate the effects of testosterone supplementation on bone, body composition, muscle, physical function, and safety in older men. Double-blind, randomized, placebo-controlled trial. A major medical institution. One hundred thirty-one men (mean age 77.1 +/- 7.6) with low testosterone, history of fracture, or bone mineral density (BMD) T-score less than -2.0 and frailty. Participants received 5 mg/d of testosterone or placebo for 12 to 24 months; all received calcium (1500 mg/d diet and supplement) and cholecalciferol (1,000 IU/d). BMD of hip, lumbar spine, and mid-radius; body composition; sex hormones, calcium-regulating hormones; bone turnover markers; strength; physical performance; and safety parameters. Ninety-nine men (75.6%) completed 12 months, and 62 (47.3%) completed end therapy (mean 23 months; range 16-24 months for 62 who completed therapy). Study adherence was 54%, with 40% of subjects maintaining 70% or greater adherence. Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL, respectively, in the treatment group. BMD on testosterone increased 1.4% at the femoral neck and 3.2% at the lumbar spine (P=.005) and decreased 1.3% at the mid-radius (P<.001). There was an increase in lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance. There were no differences in safety parameters. Older, frail men receiving testosterone replacement increased testosterone levels and had favorable changes in body composition, modest changes in axial BMD, and no substantial changes in physical function.

The Brave New World of Function-Promoting Anabolic Therapies: Testosterone and Frailty

Physical function is an excellent marker of an individual’s health (1). Limitations in physical function are an important public health problem because of their high prevalence and their association with adverse health outcomes, including the increased risk of disability, poor quality of life, hospitalization, and mortality (2, 3). In the USA alone, 12–14% of the noninstitutionalized population—approximately 35–38 million people—have a disability due to a chronic health condition (4). For people over age 65 yr, 35 to 40% experience activity limitations or disability. Because the U.S. population is aging, the percentage of population aged 65 yr or over will increase from 12% in 2000 to 20% in 2030—to more than 69 million. The number of people 85 or older is expected to grow from 3 million (2.1%) to 6.2 million (3.4%) in the United States alone. The majority of individuals who reach this age will experience some limitation in function (4, 5). The costs of support services, lost productivity associated with disabling conditions, and the impact of disability on an individual’s quality of life will have enormous societal consequences (6). Currently, the practicing physicians have few therapeutic choices for the treatment of older individuals with functional limitations and physical disability. Exercise, physical rehabilitation, and behavioral modalities have had limited impact at a population level. Therefore, there is growing need for developing pharmacological function promoting therapies for the treatment of functional limitations. It has become apparent that a small number of intersecting signaling pathways are crucial for regulating muscle growth through their effects on ribosomal protein translation (AkT/mammalian target of rapamycin pathway), mesenchymal progenitor cell differentiation (Wnt and Smad signaling), and muscle protein degradation (ubiquitin-proteasome pathway and the FoXo family of transcription factors). Pharmacophores that selectively modulate these signaling pathways, such as androgens, myostatin antagonists, and GH/IGF-I mimetics are being explored for their potential as function-promoting anabolic therapies; of these, androgens are the farthest along in development. The idea that androgens have anabolic effects on the skeletal muscle is not new. Athletes and recreational body builders who abuse androgens do so because of the widely held perception that androgens increase muscle mass, muscle strength, and athletic performance. However, systematic investigations of androgens as function-promoting therapies have been limited largely to the past 15 yr (7). Epidemiological studies have shown that circulating testosterone levels are associated with skeletal muscle mass, muscle strength, and self-reported as well as performancebased measures of physical function (8–10). Cawthon et al. (11) reported in a recent issue of the Journal that low levels of bioavailable testosterone in men participating in the Osteoporotic Fractures in Men Study (MrOS) were associated independently with worse frailty status. In longitudinal analysis, the men in the lowest quartile of bioavailable testosterone levels had approximately 1.5-fold higher odds of greater frailty status 4.1 yr later (11). However, neither total nor free testosterone levels were associated with frailty status. Mohr et al. (12) in a separate analysis of the data from the Massachusetts Male Aging Study (MMAS) also found no significant association of

Sex Steroid Hormone Concentrations and Risk of Death in US Men

The association of sex hormone levels with mortality over a median of 16 years of follow-up was evaluated in a prospective cohort study. The study included 1,114 US men who participated in phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey Mortality Study and had no history of cardiovascular disease or cancer at baseline. Multivariable adjusted hazard ratios for all-cause mortality associated with a decrease in hormone concentration equal to the difference between the 90th and 10th percentiles of the sex hormone distributions were estimated by using proportional hazards regression. The hazard ratios associated with low free testosterone and low bioavailable testosterone levels were 1.43 (95% confidence interval (CI): 1.09, 1.87) and 1.52 (95% CI: 1.15, 2.02), respectively, for follow-up between baseline and year 9; they were 0.94 (95% CI: 0.51, 1.72) and 0.98 (95% CI: 0.56, 1.72), respectively, for follow-up between year 9 and year 18. Men with low free and bioavailable testosterone levels may have a higher risk of mortality within 9 years of hormone measurement. Future studies should be conducted to fully characterize the association of low free and bioavailable testosterone concentrations and mortality in men and to describe the mechanism underlying the association.

Bioavailable Testosterone Should be Used for the Determination of Androgen Levels in Infertile Men

We determined the relationship between total testosterone and bioavailable testosterone in men presenting with infertility. In addition, the effects of body mass index and age on testosterone levels were examined. To determine if total testosterone measurements are an accurate reflection of tissue available testosterone in infertile men, levels of total testosterone were compared to bioavailable testosterone levels. Males presenting with infertility were studied. A total of 73 patients underwent complete history and physical examination. Serum levels of total testosterone and bioavailable testosterone were measured as a morning sample in all patients. Patients were classified as having low, normal or high levels of total or bioavailable testosterone. To determine the effect of obesity, patient weight was converted to body mass index for analysis. Of 73 patients evaluated 34 (47%) had low total testosterone levels while only 19 (26%) had low bioavailable testosterone levels. The discrepancy between total testosterone and bioavailable testosterone was even greater in men older than 40 years with 10 of 17 (59%) having low total testosterone levels and 8 (80%) having normal bioavailable testosterone levels. Body mass index negatively correlated with total testosterone and bioavailable testosterone levels. Testosterone status should be determined by the measurement of bioavailable testosterone when evaluating infertile males.

Hormone profiles, body mass index and aging male symptoms: results of the Androx Vienna Municipality study

Aging in the male is accompanied by steroid hormonal decline, and men may develop symptoms associated with hypogonadism. Increased awareness of ‘andropause’ in recent years has led to greater demand for hormonal assessments, resulting in a rising burden for health economics. We conducted a cross-sectional study to define men at risk for hypogonadism, in whom further hormonal investigation should be performed.We examined 664 blue-collar workers aged 40–60 years at their workplace and determined hormonal status and body mass index (BMI). Men with an abnormal urogenital status and those on medication that might affect endocrine status were excluded from the study. All participants completed the validated Aging Male Symptom (AMS) questionnaire and obtained scores for psychological symptoms, somatovegetative symptoms, and sexual symptoms.Multiple logistic regression analyses revealed a significantly increased risk (represented by the odds ratio) of psychological symptoms for men with low levels of testosterone and/or bioavailable testosterone (BAT). Increased BMI as well as low testosterone levels and/or low BAT levels raised the risk of somatovegetative symptoms. Each decrease of BAT by 1 ng/ml caused an approximately 1.8-fold increase of the risk (odds ratio = 1.832, p = 0.005). Additional independent risk factors were increased age and low luteinizing hormone (LH) level. Men aged 55 years with BMI > 28 kg/m2 and with somatovegetative symptoms and moderate or severe psychological symptoms had a 7.2-fold increase in the risk of a BAT level < 1.5 ng/ml compared to men without these risk factors (p < 0.001). Sensitivity and specificity were 75% and 71%, respectively.The AMS score combined with age and BMI provides an easy and convenient method to identify men with probable androgen deficiency who require hormonal assessment.

BIO-AVAILABLE TESTOSTERONE LEVELS FALL ACUTELY FOLLOWING MYOCARDIAL INFARCTION IN MEN: ASSOCIATION WITH FIBRINOLYTIC FACTORS

The effect of acute myocardial infarction on plasma levels of testosterone in men is unclear. No previous studies have evaluated the bio-available fraction of testosterone. Low plasma testosterone levels have been associated with several risk factors for myocardial infarction, including an unfavorable fibrinolytic profile. In a prospective, case control study, we examined changes in plasma levels of sex hormones, including bio-available testosterone, in patients with acute myocardial infarction and in control subjects. In addition, changes in hormone levels in patients were compared with alterations in the fibrinolytic profile. Thirty male patients admitted with chest pain were studied. Twenty two had acute myocardial infarction and eight had non-specific chest pain. Plasma levels of total and bio-available testosterone, 17β-estradiol, sex hormone binding globulin and insulin were measured at baseline and throughout admission. In addition, fibrinolytic factors (plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen) were measured in patients who received fibrinolysis. Height and weight, and the subsequent development of heart failure or myocardial dysfunction were also recorded. Patients had lower levels of bio-available testosterone (2.07±0.75 nmol/L vs. 5.3±1.7 nmol/L, p<0.05) and higher levels of 17β-estradiol (87.9±39.5 pmol/L vs. 48.1±18.4 pmol/L, p<0.001) than controls. Total and bio-available testosterone levels fell acutely following myocardial infarction (11.9±3.8 nmol/L to 9.7±3.3 nmol/L, p<0.05; 1.95±0.76 nmol/L to 1.55±0.67 nmol/L, p<0.05). This reduction was associated with elevation of PAI-1 activity and reduction of tPA activity, independent of changes in plasma insulin levels. Patients with lower baseline levels of testosterone and higher levels of 17β-estradiol had a relatively pro-thrombotic fibrinolytic profile and increased risk of complications. In conclusion, total and bio-available levels of testosterone fall following acute myocardial infarction in men, in association with adverse changes in fibrinolytic profile. It is not clear whether this association represents a direct effect of testosterone on thrombotic tendency but warrants further investigation.

Bone turnover markers and sex hormones in men with idiopathic osteoporosis.

In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention. We determined various biochemical parameters of bone metabolism and sex hormones in 31 men with idiopathic osteoporosis and 35 age matched control subjects. In the men with osteoporosis, a significantly increased urinary excretion of deoxypyridinoline (5.3 +/- 0.2 vs. 4.6 +/- 0.2 nmol mmol-1 creatinine; P = 0.033) in addition to increased serum levels of the c-terminal telopeptide of type I collagen (2677 +/- 230 vs. 2058 +/- 153 pmol; P = 0.037) were found. While parameters of bone formation were not significantly different in the patients and controls, serum bone sialoprotein levels were significantly decreased in the patients (3.7 +/- 0.8 vs. 12.4 +/- 4.0 ng mL-1; P = 0.021). Moreover, in men with idiopathic osteoporosis, lower levels of estradiol (91.3 +/- 5.8 vs. 114.6 +/- 7.8 pmol L-1; P = 0.044), higher levels of sex hormone binding globulin (31.5 +/- 3.1 vs. 24.2 +/- 1.4 nmol L-1; P = 0.034) and a decreased free androgen index (42.6 +/- 5.2 vs. 56.4 +/- 5.9; P = 0.016) were seen. Serum estradiol levels correlated negatively with several parameters of bone resorption. In men with idiopathic osteoporosis, bone resorption is increased and exceeds bone formation. The excessive bone resorption seen in idiopathic male osteoporosis may be due to decreased estradiol levels and low levels of bioavailable testosterone.

Validation of a screening questionnaire for androgen deficiency in aging males

It is now well established that testosterone levels decline with age. What has not been established is whether the decline in testosterone is associated with a symptom complex. This study examined whether certain symptoms are more commonly present in males with low bioavailable testosterone (BT) levels. These were used to evaluate a questionnaire for androgen deficiency in aging males (ADAM). The validity of the ADAM questionnaire to screen for low BT was tested in 316 Canadian physicians aged 40 to 62 years. Low BT levels were present in 25% of this population. None had elevated luteinizing hormone (LH) levels. The ADAM questionnaire had 88% sensitivity and 60% specificity. When the questionnaire was administered twice 2 to 4 weeks apart to 10 men, it was determined that the coefficient of variation was 11.5%. In a second study of 34 ADAM-positive patients, 37% of those with clearly normal BT levels demonstrated some evidence of dysphoria. Finally, in 21 patients who were treated with testosterone, improvement on the ADAM questionnaire was demonstrated in 18 (P .002). These data support the concept of a symptom complex associated with low BT levels in aging males. In addition, the ADAM questionnaire appears to be a reasonable screening questionnaire to detect androgen deficiency in males over 40 years of age.

Determinants of bone density in healthy older men with low testosterone levels.

Osteoporosis is a significant problem in older men, 30% of all hip fractures occur in men and the mortality rate following hip fracture exceeds that of women. Testosterone is thought to be important in the development of peak bone mass hut its role in age-related bone loss is not established. The purpose of this study was to define the predictors of bone mass ill healthy older men with low testosterone levels but without symptomatic osteoporosis. Eighty-three community-dwelling white men, aged more than 65 years old, selected for low bioavailable testosterone levels (< or = 4.44 nmol/l) participated in a cross-sectional study located at a university general clinical research center. Sex hormone concentrations and markers of bone turnover were assayed in serum and urine. Risk factors for osteoporosis and physical activity were ascertained by physical examination and questionnaire, including the Physical Activity Scale in the Elderly (PASE) questionnaire. Bone mineral densities of the femoral neck (FN BMD), spine, and whole body were measured by dual x-ray absorptiometry. Lower extremity muscle strength (1 repetition maximum) was measured using a leg press machine. Mean bone mineral density values were 0.93 +/- 0.14 g/cm2 for femoral neck, 1.31 +/- 0.23 g/cm2 for spine, and 1.22 +/- 0.12 g/cm2 for whole body. Thirty-one of the 82 subjects (37%) had t scores < -1 and 12 of 82 subjects (15%) had t scores < -2.5 at the femoral neck. Multiple linear regression analysis demonstrated that bioavailable testosterone, body mass index (BMI), and PASE scores were positively correlated with, and significant predictors of, femoral neck BMD, accounting for 34.4% of the variance in FN BMD (F = 10.10, p = .001). Examining each variable independently, bioavailable testosterone accounted for 20.7%, physical activity score for 9.0%, and BMI for 6.5% of FN BMD. Using analysis of variance, mean values for FN BMD were significantly different between men grouped by tertile of bioavailable testosterone (F = 6.192, p = .003). FN BMD mean values were 0.86 +/- 0.14 g/cm2 for the lowest tertile, 0.94 +/- 0.16 for the middle tertile, and 0.99 +/- 0.14 for the highest tertile. Markers of bone turnover were inversely correlated, and strength directly correlated with BMD, but did not contribute to the multiple regression model. Fifty-two percent of older men with low bioavailable testosterone levels had BMD levels below the young adult normal range and are likely at an increased risk of fracture. Bioavailable testosterone, BMI, and physical activity scores were significant determinants of FN BMD in these men. These variables are potentially modifiable and, therefore, amenable to intervention. Hence, our results suggest the need for testosterone replacement and physical activity intervention trials in men at risk for osteoporotic fractures.

Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study.

A cross-sectional population-based study examined the association between endogenous sex hormones and depressed mood in community-dwelling older men. Participants included 856 men, ages 50-89 yr, who attended a clinic visit between 1984-87. Total and bioavailable testosterone, total and bioavailable estradiol, and dihydrotestosterone levels were measured by radioimmunoassay in an endocrinology research laboratory. Depressed mood was assessed with the Beck Depression Inventory (BDI). Levels of bioavailable testosterone and bioavailable estradiol decreased with age, but total testosterone, dihydrotestosterone, and total estradiol did not. BDI scores increased with age. Low bioavailable testosterone levels and high BDI scores were associated with weight loss and lack of physical activity, but not with cigarette smoking or alcohol intake. By linear regression or quartile analysis the BDI score was significantly and inversely associated with bioavailable testosterone (both Ps = 0.007), independent of age, weight change, and physical activity; similar associations were seen for dihydrotestosterone (P = 0.048 and P = 0.09, respectively). Bioavailable testosterone levels were 17% lower for the 25 men with categorically defined depression than levels observed in all other men (P = 0.01). Neither total nor bioavailable estradiol was associated with depressed mood. These results suggest that testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone. A clinical trial is necessary to test this hypothesis.