Molly M. Shores

Testosterone Treatment and Mortality in Men with Low Testosterone Levels

CONTEXT 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. OBJECTIVE The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. DESIGN 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. SETTING The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. PATIENTS 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. MAIN OUTCOME MEASURE Total mortality in testosterone-treated compared with untreated men was measured. RESULTS 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 (P<0.0001) 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. CONCLUSIONS 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.

DSM-III-R personality disorders in a mood and anxiety disorders clinic: prevalence, comorbidity, and clinical correlates.

This study examined the prevalence, comorbidity, and clinical correlates of personality disorders in an outpatient sample (N = 352) with anxiety and depression. Subjects were diagnosed using the Structured Clinical Interview for DSM-III-R (SCID) on Axes I and II, and they also completed interview and self-report measures of symptoms. Subjects with a personality disorder were less likely to be married, more likely to be single or divorced, had lower family incomes, had more severe symptoms of both anxiety and depression, and had a greater number of lifetime Axis I diagnoses. Subjects with dysthymic and bipolar disorders were more likely, and subjects with panic disorder uncomplicated by agoraphobia were less likely to have a personality disorder compared to the rest of the sample. The most prevalent personality disorders were Avoidant, Obsessive-Compulsive, Paranoid, and Borderline. Paranoid co-occurred with Narcissistic, and Borderline co-occurred with Histrionic personality disorder significantly more often than chance and base rates would predict.

Short-term sertraline treatment suppresses sympathetic nervous system activity in healthy human subjects

Increased sympathetic nervous system (SNS) activity has been associated with stress, major depression, aging, and several medical conditions. This study assessed the effect of the selective serotonin reuptake inhibitor (SSRI), sertraline, on sympathetic nervous system (SNS) activity in healthy subjects. Twelve healthy volunteers participated in a double-blind, placebo-controlled, norepinephrine (NE) kinetic study, in which the effects of sertraline on SNS activity were ascertained by determining NE plasma concentrations and NE plasma appearance rates and clearance rates in sertraline or placebo conditions. Subjects received 50 mg of sertraline or placebo for two days and then one week later underwent the same protocol with the other drug. By single compartmental analysis, plasma NE appearance rates were significantly lower in the sertraline compared to the placebo condition (0.26+/-0.10 vs 0.40+/-0.23 microg/m(2)/min; P=0.04). Our study found that the net effect of short-term SSRI treatment is an apparent suppression of SNS activity as indicated by a decreased plasma NE appearance rate in the sertraline condition. If this preliminary finding can be extended to long-term treatment of patients, this could have significant therapeutic relevance for treating depression in elderly patients or those with cardiac disease, in which elevated SNS activity may exacerbate underlying medical conditions.

Low Testosterone Is Associated with Decreased Function and Increased Mortality Risk: A Preliminary Study of Men in a Geriatric Rehabilitation Unit

Objectives: To evaluate whether low testosterone levels are associated with greater depression or poorer function in a geriatric rehabilitation unit.

Testosterone, Dihydrotestosterone, and Incident Cardiovascular Disease and Mortality in the Cardiovascular Health Study

CONTEXT 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. OBJECTIVE The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality. DESIGN 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. MAIN OUTCOME The main outcomes were incident CVD and all-cause mortality. RESULTS 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). CONCLUSIONS 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.

The relationship between anxiety and depression: A clinical comparison of generalized anxiety disorder, dysthymic disorder, panic disorder, and major depressive disorder

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 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.

Tyrosine hydroxylase mRNA is increased in old age and norepinephrine uptake transporter mRNA is decreased in middle age in locus coeruleus of Brown-Norway rats.

In normal aging, cell loss occurs in the locus coeruleus (LC), the major noradrenergic nucleus in the brain. This study examined changes in the LC of aged rats by measuring mRNA expression for tyrosine hydroxylase (TH) and the norepinephrine uptake transporter (NET). TH and NET mRNA expression were measured by in situ hybridization in young, middle-aged and aged rats. It appears that in middle age, the transporter system responds initially to LC cell loss by decreasing NET mRNA expression. Then, with further aging and cell loss, TH mRNA expression increases which may potentially increase NE synthesis in the remaining neurons. These findings suggest that multiple regulatory components are used to maintain stable noradrenergic synaptic levels despite neuronal loss. Published by Elsevier Science B.V.

Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study

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.

Added Burden of Mental Disorders on Health Status Among Patients With Chronic Obstructive Pulmonary Disease

OBJECTIVE 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. METHOD 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 veterans version of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and the Shortness of Breath Questionnaire (SOBQ). RESULTS 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). CONCLUSIONS 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.

TESTOSTERONE, AGING AND SURVIVAL: BIOMARKER OR DEFICIENCY

Purpose of reviewThe purpose of this study is to review recent studies that examined the association of endogenous and exogenous testosterone and mortality in older men. Recent findingsOver 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. SummaryLow 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.