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BACKGROUND: Decline in serum androgens is common among older men and has been associated with cardiovascular disease, although its role in risk of atrial fibrillation (AF) has not been well defined. HYPOTHESIS: Low serum androgens are associated with an increased risk of AF. METHODS: We examined the prospective associations between testosterone, its more active metabolite dihydrotestosterone (DHT), and sex-hormone binding globulin (SHBG) with risk of AF among 1019 otherwise healthy men of average age 76.3±4.9 years in the Cardiovascular Health Study. RESULTS: After median follow-up of 9.5 years, 304 (30%) men developed AF. We detected a nonlinear association with risk of incident AF in both free and total DHT, in which subjects with the lowest levels had a higher risk of incident AF. After adjustment for demographics, clinical risk factors, left atrial diameter, and serum NT-proBNP levels, men with free DHT less than 0.16 ng/dL were at increased risk compared with men with higher levels (HR 1.48, CI 1.01–2.17, p

Over the past decade, there has been a substantial increase in the number of men who are treated with testosterone. Despite this increase in the use of testosterone, the risks of adverse cardiovascular events are unclear as meta-analyses have reported conflicting findings and no clinical studies have been large enough or long enough to adequately assess for cardiovascular risks. The goal of this paper is to review large prescription database studies of testosterone treatment and adverse cardiovascular events and mortality with the aim of providing some guidance for clinicians and researchers in this controversial area.

Background Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). Methods We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography–tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439). Results In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55–1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01–1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86–1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models. Conclusions In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.

Purpose Testosterone treatment of men with low testosterone is common and, although relatively short-term, has raised concern regarding an increased risk of prostate cancer (CaP). We investigated the association between modest-duration testosterone treatment and incident aggressive CaP. Materials and methods Retrospective inception cohort study of male Veterans aged 40 to 89 years with a laboratory-defined low testosterone measurement from 2002 to 2011 and recent prostate specific antigen (PSA) testing; excluding those with recent testosterone treatment, prostate or breast cancer, high PSA or prior prostate biopsy. Histologically-confirmed incident aggressive prostate cancer or any prostate cancer were the primary and secondary outcomes, respectively. Results Of the 147,593 men included, 58,617 were treated with testosterone. 313 aggressive CaPs were diagnosed, 190 among untreated men (incidence rate (IR) 0.57 per 1000 person years, 95% CI 0.49–0.65) and 123 among treated men (IR 0.58 per 1000 person years; 95% CI 0.48–0.69). After adjusting for age, race, hospitalization during year prior to cohort entry, geography, BMI, medical comorbidities, repeated testosterone and PSA testing, testosterone treatment was not associated with incident aggressive CaP (HR 0.89; 95% CI 0.70–1.13) or any CaP (HR 0.90; 95% CI 0.81–1.01). No association between cumulative testosterone dose or formulation and CaP was observed. Conclusions Among men with low testosterone levels and normal PSA, testosterone treatment was not associated with an increased risk of aggressive or any CaP. The clinical risks and benefits of testosterone treatment can only be fully addressed by large, longer-term randomized controlled trials.

Testosterone levels in men slowly decline with aging and also decline more abruptly due to medical illness or medications. Prescriptions for testosterone have increased dramatically over the past decade, since a testosterone-gel formulation was approved and since numerous studies reported an association between low serum testosterone and increased mortality. However, recent observational studies of testosterone treatment have reported conflicting results with some studies reporting decreased risks for mortality while others reported increased mortality risks with testosterone treatment. This paper will summarize recent studies of low serum testosterone and mortality and testosterone treatment and mortality and what the potential implications of these studies are for the clinician.

The purpose of this study is to review recent studies that examined the association of endogenous and exogenous testosterone and mortality in older men.Over the past several years, there has been a steep rise in testosterone prescriptions. The increased use of testosterone occurred in the context of several studies that reported an association between low serum testosterone and increased cardiovascular events and mortality. In contrast, recent studies have reported an association between testosterone treatment and adverse events. A testosterone treatment trial of mobility-impaired elderly men with prevalent cardiovascular disease was stopped due to increased cardiovascular events in the T-treated men and a meta-analysis reported increased cardiovascular events in T-treated men. In two recent large observational studies, testosterone treatment was associated with an increased risk for serious adverse cardiovascular events.Low testosterone is associated with mortality in multiple cohort studies; however, it is unclear if this is a causal association or due to low testosterone being a biomarker of poor health. Given recent reports of adverse outcomes associated with testosterone treatment, a conservative use of testosterone is warranted in men with cardiovascular disease who may be at greater risk for adverse outcomes.

SummaryObjective Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men. Design Cohort study. Participants Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010. Measurements Adjudicated ischaemic stroke. Results Among 1032 men (mean age 76, range 66–97), followed for a median of 10 years, 114 had an incident ischaemic stroke. Total T and free T were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke (P = 0·006) in analyses adjusted for stroke risk factors. The lowest risk of stroke was at DHT levels of 50-75 ng/dl, with greater risk of stroke at DHT levels above 75 ng/dl or below 50 ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischaemic stroke with HR 0·77 (95% CI, 0·61, 0·98) per standard deviation in analyses adjusted for stroke risk factors. Conclusions Dihydrotestosterone had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify whether there is an optimal androgen range associated with the least risk of adverse outcomes in elderly men.

Although sex hormone-binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, in older adults, whose glycemic pathophysiology differs from younger adults.To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men.In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men free of diabetes and cardiovascular disease in the Cardiovascular Health Study in 1994.Insulin resistance estimated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity estimated by the Gutt index in 1996, and incident diabetes (n = 112) ascertained over a mean follow-up of 9.8 years.In linear regression models adjusted for demographics, alcohol consumption, current smoking, body mass index, and other androgens, SHBG [HOMA-IR 0.30 units lower per doubling; 95% confidence interval (CI), 0.08 to 0.52; P = 0.01] and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI, 0.06 to 0.30; P = 0.01), but not free T (P = 0.33), were inversely associated with insulin resistance. In corresponding Cox proportional hazards models, total DHT was again inversely associated with risk of diabetes (adjusted hazard ratio per doubling, 0.69; 95% CI, 0.52 to 0.92; P = 0.01), but SHBG (hazard ratio, 1.09; 95% CI, 0.74 to 1.59; P = 0.66) and free T (hazard ratio, 1.15; 95% CI, 0.92 to 1.43; P = 0.23) were not.Among older men, higher levels of DHT were inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, whereas levels of T were not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.

Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this.The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality.In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection.The main outcomes were incident CVD and all-cause mortality.Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P.002 and P = .04, respectively) and all-cause mortality (P.001 for both).In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.

Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known.The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels.This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori.The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers.Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [≤250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005.Total mortality in testosterone-treated compared with untreated men was measured.Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (P0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42-0.88; P = 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease.In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.

Patients with chronic obstructive pulmonary disease (COPD) and comorbid mental disorders are known to have worse health status. The association between these variables remains complex and poorly understood. We sought to better understand the association between COPD severity, mental disorders (depression/anxiety), and health status.This cross-sectional study compared participants without COPD or with mild COPD (n = 162) to those with moderate (n = 25), severe (n = 38), and very severe (n = 26) COPD. We recruited participants from a primary care and a pulmonary clinic at a veterans affairs medical center between July 2001 until September 2002. We used the Patient Health Questionnaire to screen for depression and anxiety and the Posttraumatic Stress Disorder Checklist to screen for posttraumatic stress disorder. Health status was assessed with the veteran's version of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and the Shortness of Breath Questionnaire (SOBQ).COPD severity was associated with worse physical status and dyspnea as measured by the SF-36 physical component summary and the SOBQ but was not associated with worse mental status as measured by the SF-36 mental component summary. At each level of COPD severity, participants with mental disorders had worse health status and dyspnea as measured by the SF-36 physical component summary, mental component summary, and SOBQ. Significant linear trends with COPD severity were associated with increased prevalence of any depressive disorder, major depressive disorder, and nonpanic/non-PTSD anxiety disorders (all tests for linear trend, P.01).Independent of COPD severity, comorbid mental disorders were associated with worse health status and dyspnea. Studies are needed to determine whether patients with comorbid mental disorders may have more significant improvement in physical symptoms and functioning if providers focus more on psychiatric conditions.

725 Objective: This study compared the quality of end-of-life care between veterans with and without schizophrenia who died of cancer in the northwestern United States. Methods: In this cross-sectional study, medical records of 60 veterans with schizophrenia and 196 with no major mental illness who died of cancer were compared on hospice enrollment, palliative and life-sustaining interventions, advance directives, and site of death. Results: Among veterans with schizophrenia, 58% had an advance directive, 73% received an opiate before hospice enrollment, 63% had a physician order to forgo cardiopulmonary resuscitation, 55% were hospice enrolled, and 27% died in the hospital. Schizophrenia patients had longer hospice stays (107±144 versus 63±96 days, p=.05) and more physician orders for life-sustaining treatment (15% versus 5%, p=.006) compared with veterans without mental illness. Conclusions: On most measures, veterans with schizophrenia who died of cancer received comparable or better endof-life care than veterans without mental illness. (Psychiatric Services 61:725–728, 2010) T he goals of palliative care are relief of suffering and improvement in quality of life for patients facing life-threatening illness. Such improvements are made through prevention, assessment, and treatment of pain and other symptoms and the provision of psychological, emotional, and spiritual support (1). Palliative care is patient and family centered and emphasizes patient autonomy and advance planning for care. By 2003, 25% of U.S. hospitals sponsored a palliative care program (2). Patients become eligible for palliative care delivered by a hospice organization at the point they are expected to have less than six months of remaining life. The primary goals of hospice care are comfort and preservation of quality of life; cure of the terminal illness is no longer being pursued. Hospice care is delivered by an interdisciplinary cadre of physicians, nurses, social workers, and chaplains. Most often care is in patients’ homes, but it also occurs in long-term care settings and, rarely, in inpatient hospice units. Although originally developed as an approach for patients with advanced cancer, currently over half of hospice enrollees in the United States have noncancer diagnoses. In 2007, 39% of all decedents in the United States were hospice enrolled before death (3). Hospice and palliative care are intu

This study examined the relationship between the chronic disorders, generalized anxiety disorder (GAD) and dysthymic disorder (DD), and the more acute disorders, panic disorder (PD) and major depressive disorders, panic disorder (PD) and major depressive disorder (MDD) in 110 psychiatric outpatients with diagnoses of either PD, MDD, GAD, or DD. Pure, mixed, and early-/late-onset forms of the chronic disorders were compared with each other and then with PD and MDD on clinical measures and psychiatric history. Minimal differences were found between pure GAD and mixed GAD or between pure DD and mixed DD. The chronic disorders, DD and GAD, had distinct clinical symptom profiles when compared with each other and appeared more closely related to their parent disorders than to each other. However, despite these similarities, there were significant differences between DD and MDD in contrast to the minimal differences between GAD and PD, providing less support for GAD as a valid diagnostic category separate from PD. Comparisons of early-/late-onset DD and GAD showed more severe symptoms in late-onset DD, in contrast to more severe symptoms in early-onset GAD. These varying patterns of symptom severity may warrant study for further syndromal delineation.

Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans.We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. A low testosterone level was a total testosterone level of less than 250 ng/dL (8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (0.03 nmol/L). Men were classified as having a low testosterone level (166 [19.3%]), an equivocal testosterone level (equal number of low and normal levels) (240 [28.0%]), or a normal testosterone level (452 [52.7%]). The risk for all-cause mortality was estimated using Cox proportional hazards regression models, adjusting for demographic and clinical covariates over a follow-up of up to 8 years.Mortality in men with normal testosterone levels was 20.1% (95% confidence interval [CI], 16.2%-24.1%) vs 24.6% (95% CI, 19.2%-30.0%) in men with equivocal testosterone levels and 34.9% (95% CI, 28.5%-41.4%) in men with low testosterone levels. After adjusting for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34-2.63; P.001) while equivocal testosterone levels were not significantly different from normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a sensitivity analysis, men who died within the first year (50 [5.8%]) were excluded to minimize the effect of acute illness, and low testosterone levels continued to be associated with elevated mortality.Low testosterone levels were associated with increased mortality in male veterans. Further prospective studies are needed to examine the association between low testosterone levels and mortality.