Plasma pterins and folate in late life depression: the Rotterdam Study

Tetrahydrobiopterin is a cofactor in the synthesis of monoamine neurotransmitters. High neopterin levels generally signal increased immune activation. Both pterins have been investigated in several small clinical studies of depressed patients with conflicting results. Therefore, we examined the relation of plasma biopterin and neopterin with depression in a population-based study. We also studied the association of pterins with folates in depressed persons as this vitamin is required for pterin biosynthesis. We screened 3884 adults aged 60 years and over for depressive symptoms. Screen positive subjects had a psychiatric interview to diagnose DSM-IV disorder. Plasma pterins and serum folate were determined in all persons with depressive symptoms (n=238) and randomly selected non-depressed persons (n=357). We found no association between the concentration of biopterin or neopterin with depressive symptoms or depressive disorders. However, in depressed persons the relation between pterins and folates was different than in the non-depressed, i.e. neopterin concentrations increased with folate levels in persons with depressive symptoms (0.09 per log(nmol/l folate); 95% CI=0.01, 0.18, P=0.03), but not in non-depressed persons (-0.07 per log(nmol/l folate); 95% CI=-0.17, 0.03, P=0.18). The interaction between depressive symptoms, folate and neopterin was significant (P=0.03). The study suggests that the relation between folate and pterins is altered in the depressed elderly.     

Serum concentrations of circulating thyroid hormones in a group of depressed men

Levels of circulating total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine TT3 and thyrotropin (TSH) were determined in 27 men with unipolar major depressive disorder ages 24-50, mean +/- SEM 36.9 +/- 2.9 years, and 38 healthy controls (HC) ages 20-50, mean +/- SEM 34.2 +/- 3.1 years. No significant differences were observed between HC and depressed men with regard to TT4 and FT4. Mean TT3 levels were lower, and mean TSH levels higher in depressed patients than in HC, p less than 0.05 for both, compatible with possible subclinical primary hypothyroidism in depressed patients. Consistent with this, an inverse correlation between basal TSH values and TT3 (r = -0.38, p less than 0.05) was noted in depressed but not in HC subjects.     

Increased incidence of diagnosed depressive illness in hypogonadal older men

CONTEXT: Age-associated hypogonadism (testosterone deficit) occurs in 30% of men after the age of 55; it is associated with decreased muscle mass, bone mineral density, and libido, and with anorexia, fatigue, and irritability. Although some of these symptoms overlap with those of depression, the association between the 2 disorders is unclear. OBJECTIVE: To determine if hypogonadal men have an increased incidence of depressive illness compared with eugonadal men. DESIGN: Historical cohort study using computerized medical records, followed by a manual medical record review. SETTING: Veterans Affairs Puget Sound Health Care System. PARTICIPANTS: Two hundred seventy-eight men 45 years and older, without prior diagnosed depressive illness and with consistently normal or low testosterone levels (total testosterone level < or =200 ng/dL [< or =6.94 nmol/L]; or free testosterone level < or =0.9 ng/dL [< or =0.03 nmol/L]) at baseline and during a 2-year follow-up period. MAIN OUTCOME MEASURES: Incidence of, and time to, a depression diagnosis. RESULTS: The 2-year incidence of diagnosed depressive illness was 21.7% in hypogonadal men vs 7.1% in others (chi2(1)=6.0, P=.01). A Kaplan-Meier survival analysis showed a significant difference between hypogonadal and eugonadal men in time to diagnosed depression (log-rank test chi2(1)=6.9, P=.008). We used Cox proportional hazards regression models to examine the association of hypogonadism and time to depression diagnosis, adjusting for age, race, number of clinic visits, alcohol use disorders, prostate cancer, and overall medical comorbidity. The unadjusted hazard ratio for depression with hypogonadism was 3.5 (95% confidence interval, 1.3-9.4) (P=.01). Controlling for all covariates, hypogonadism remained significantly associated with depression (adjusted hazard ratio, 4.2; 95% confidence interval, 1.5-12.0) (P=.008). CONCLUSIONS: Hypogonadal men showed an increased incidence of depressive illness and a shorter time to diagnosis of depression. Further prospective studies are needed to confirm these preliminary findings and to clarify the role of testosterone in the treatment of depressive illness in older men.     

Testosterone, androstenedione and dihydrotestosterone concentrations are elevated in female patients with major depression

Hyperactivity of the HPA-system in major depression is reflected by an increased secretion of adrenal hormones especially cortisol and dehydroepiandrosterone (DHEA). In women for whom androgenicity is associated with cardiovascular disorders the dominant source of androstenedione and testosterone secretion are the adrenal glands. To date, there is only sparse information about the regulation of androstenedione, testosterone and dihydrotestosterone (DHT) concentrations in women with severe major depression.Therefore, 11 pre- and postmenopausal, severely depressed, hypercortisolemic women (Hamilton Depression Scale, 31.3+/-5.9; age, 28-77 yrs; mean, 48. 1+/-18.1 yrs) and 11 age-matched healthy female controls (age, 24-81 yrs; mean, 47.9+/-21.5 yrs) underwent a 24 hour (h) blood sampling starting at 0800 h with 30-minute sampling intervals.By applying multivariate analysis of covariance with age as covariate, androstenedione, testosterone and DHT plasma levels at 0900 h show a trend for elevated concentrations in depressed women compared to controls (F(1,19)=2.7; P=0.057). Univariate F tests reveal a significant difference between the groups for androstenedione (4. 19+/-1.571 vs 2.584+/-1.257 nmol/l; P<0.05) testosterone (1.110+/-0. 278 vs 0.833+/-0.347 nmol/l; P<0.05) and DHT (0.656+/-0.207 vs 0. 483+/-0.242 nmol/l; P<0.05). Mean ACTH (16.4+/-10.4 vs 10.4+/-2.4 pmol/l; P=0.89), LH (13.5+/-11.8 vs 8.9+/-9.2 IU/l; P=0.12), FSH (35. 2+/-33.1 vs 31.3+/-35.7 IU/l; P=0.67) and estradiol (135.4+/-157.4 vs 82.2+/-85.1 pmol/l; P=0.20) plasma levels did not differ between patients and controls. Further, there was a trend towards an age related decline in testosterone secretion in healthy controls (r=-0. 24; P=0.08) which did not occur in depressed patients (r=0.17; P=0. 96), while the calculated ratio of DHEA to testosterone was similar in both groups (0.2+/-0.14 vs 0.13+/-0.7; P=0.21, unpaired t-test). In conclusion, androstenedione, testosterone and DHT concentrations all were increased in hypercortisolemic women with severe major depression. These findings are best explained as a consequence of an overstimulation of the adrenal glands through pituitary and hypothalamic sites of the HPA-system.     

Associations between sex steroid hormone levels and depressive symptoms in elderly men and women: results from the Health ABC study

INTRODUCTION: Sex steroid hormone levels decline with age and in some studies this decline has been linked with depressive symptoms. This study investigates the association between total testosterone, free testosterone, and DHEAS levels with depressive symptoms in a well-functioning elderly population. METHODS: Data are from 2855 well-functioning elderly men and women, 70-79 years of age, participating in the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression scale. Total testosterone, free testosterone, and DHEAS levels were assessed after an overnight fast. RESULTS: In men and women, DHEAS levels and depressive symptoms were inversely associated after adjustment for covariates (men: beta=-0.059, p=0.03, women: beta=-0.054, p=0.05). In addition, free testosterone levels in women, but not in men, were inversely associated with depressive symptoms (adjusted beta=-0.079, p=0.004). Men, but not women, in the lowest total testosterone quartile reported significantly more depressive symptoms than men in the other total testosterone quartiles (adjusted beta=-0.166, p=0.04). DISCUSSION: Our study is consistent with the idea that testosterone and DHEAS levels may play a role in mechanisms underlying depressive symptoms in old age.     

Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial

BACKGROUND: Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement. The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypogonadal men. METHOD: A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p = .02). CONCLUSION: In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.     

Screening for depressive symptoms in the acute phase of stroke

Depressive symptoms can often be observed after stroke. We prospectively evaluated patients at a stroke unit in order to determine the occurrence and severity of depressive symptoms in the acute phase of stroke in 82 patients 7 +/- 2 days after admission to the stroke unit. Severity of stroke was evaluated by the Scandinavian and Orgogozo scales and the Barthel index. Severity of depressive symptoms was measured by the 13-item Beck scale. Mean age of the patients was 65.8 years. No gender difference was observed in the severity of stroke or depressive symptoms. DSM-IV criteria of adjustment disorder with depressed mood were fulfilled by 27% of the patients. In this group, stroke was significantly more severe by the Barthel, Orgogozo, and Scandinavian scales (p < 0.001). Whereas Beck score was at least 10 in 19.5%, severe depressive symptoms (Beck score > or = 15) occurred in less than 5% of patients with acute stroke. Those who could not walk by themselves or who were aphasic had significantly higher mean Beck scores (6.3 +/- 5.1 vs 2.4 +/- 3.1, p < 0.001, and 7.0 +/- 5.8 vs 3.4 +/- 3.9, p = 0.002). Significant correlation was found between the severity of stroke and that of the depressive symptoms (r = -0.56, -0.58, and -0.54 for the Scandinavian, Orgogozo, and Barthel scales, p < 0.001).     

Haemostatic abnormalities, cardiac involvement and serum tumor necrosis factor levels in X-linked dystrophic patients

Left ventricular thrombosis and systemic emboli have been demonstrated to complicate cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD). We investigated plasma levels of prothrombin fragment 1+2 (F1+2). thrombin-antithrombin III complex (TAT) and circulating levels of tumor necrosis factor-alpha (TNF-alpha), a procoagulant cytokine that has been shown to be elevated in patients with depressed cardiac function, in 20 patients with DMD and 12 patients with BMD as compared with 30 age-matched control subjects. Significantly elevated levels of F1+2 (DMD: 1.4+/-0.8 nmol/l; BMD: 1.8+/-0.8 nmol/l vs. controls: 0.7+/-0.2 nmol/l, p <0.01 and p <0.001, respectively), TAT complexes (DMD: 4.7+/-2.7 microg/l, BMD: 5+/-2.3 microg/l vs. controls: 1.6+/-0.5 microg/l, p <0.001) and TNF-alpha (54+/-9 vs. 25+/-7 pg/ml, p <0.001) were observed in patients with the dystrophic disease compared to control subjects. A significantly negative correlation was also found between F1+2 and TAT complexes and left ventricular ejection fraction (r = -0.65, p <0.0001; r = -0.80, p < 0.0001, respectively) and a positive correlation between F1+2 and TAT complexes and serum TNF-alpha levels (r = 0.67, p <0.0001; r = 0.70, p <0.0001, respectively). Our results indicate a hypercoagulable state in X-linked dystrophic patients. A possible relationship between haemostatic activation, left ventricular dysfunction and TNF-alpha system upregulation may be suggested.     

Bioavailable testosterone predicts a lower risk of Alzheimer's disease in older men

There is a paucity of data on the relationship between testosterone and Alzheimer's disease (AD) in older men. The objective of the present study was to investigate the effects of serum total testosterone (TT), bioavailable testosterone (BT), and sex hormone binding globulin (SHBG) levels on the subsequent risk of AD in nondemented Chinese older men. This was a one-year prospective cohort study. 153 ambulatory community-living nondemented Chinese older men, aged 55 years or over, were recruited and followed for one year. Morning serum TT, BT, and SHBG levels were measured at baseline. At one-year of followup, assessment for dementia and AD were performed. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. Overall, the mean age of the subjects was 72.7 (SD 6.9). 6.5% (n = 10) developed dementia (converters), all having AD. 93.5% (n = 143) did not develop dementia (non-converters). Logistic regression analysis for independent predictors of AD showed that the baseline serum BT level, systolic blood pressure (SBP) and ApoE "4 genotype were significant independent predictors, after adjustment for age, education, BMI, fasting plasma glucose, and serum HDLC levels. The baseline serum BT level predicted a reduced risk of AD (adjusted relative risk (RR) 0.22, 95% CI: 0.07-0.69)). Baseline SBP and ApoE "4 genotype but not SHBG were independent risk factors, with RRs of 1.04 and 5.04 respectively. In conclusion, the serum level of bioavailable testosterone in late life predicts a lower risk of future AD development in older men.     

Changes in depressive symptoms and functional disability among community-dwelling depressive older adults

ABSTRACT Background: Previous studies have shown that the presence of depressive symptoms among older persons was evidently associated with subsequent physical and functional decline. However, few studies have directly examined the impact of changes in depressive symptoms or depressed mood on changes in functional ability. The present prospective study examined whether changes in the levels and remission of depressive symptoms were associated with changes in functional ability among community-living older persons who were treated for depressive symptoms in a primary care setting. Methods: Older persons aged 60 and above with depressive symptoms (N = 267) were followed up in a primary care treatment program over 12 months. Geriatric Depression Scale (GDS-15), and instrumental and basic activities of daily living (IADL and ADL) were measured at baseline and at 12-month follow-up. The associations of GDS change scores and conversion to non-depressed status with ADL and IADL change scores, controlling for baseline covariates including chronic medical comorbidity and Mini-Mental State Examination (MMSE), were examined in multiple regression analyses. Results: An improvement in GDS scores (baseline score minus 12-month score) was significantly associated with improvement (12-month score minus baseline score) in ADL (β = 0.355, p < 0.001) and IADL scores (β = 0.165, p = 0.018) after adjusting for baseline functional status, MMSE, chronic medical comorbidities, and other variables. In particular, conversion in GDS status to "non-depressive" state (GDS ≤4) was associated with an improvement in ADL change scores (β = 0.281, p = 0.019). Conclusion: In depressed older persons, an improvement in depressive symptoms was associated with improved functional ability.     

Association between social isolation and inflammatory markers in depressed and non-depressed individuals: results from the MONICA/KORA study

Introduction

Depressed individuals not only suffer from chronic low grade inflammation, but also exhibit an inflammatory hyper-responsiveness to acute stress. We investigate whether chronic stress also induces an exaggerated inflammatory response in individuals with increased depression features. As model for chronic stress, social isolation was chosen.

Methods

Interleukin (IL)-6 and hs-CRP levels were assessed in 1547 subjects (847 men and 700 women), derived from the population-based MONICA/KORA study. Standardized questionnaires were used to assess depressed mood (depression and exhaustion subscale) and social isolation (social network index). The relationship between the two inflammatory markers, social isolation and depressed mood was examined taking into account interactions social isolation × depressed mood using multivariable linear regression models, adjusted for age, BMI, smoking, alcohol, and physical activity. Analyses were performed in men and women separately.

Results

We observed a significant interaction between depressed mood and social isolation regarding IL-6 and hs-CRP, respectively in men (p-value = 0.02 for IL-6 and <0.01 for hs-CRP), evidencing a substantial synergistic effect of social isolation, and depressed mood on inflammatory responses. Furthermore, depressed and socially isolated men had highly significantly elevated IL-6 levels (geometric mean: 3.76 vs. 1.92 pg/ml, p-value <0.01) and heightened hs-CRP levels (geometric mean: 2.01 vs. 1.39 mg/l, p = 0.08) in comparison with non-depressed and socially integrated men. In women, no significant associations were seen.

Conclusion

The interaction of depressed mood and social isolation elicits a substantial synergistic impact on inflammatory markers in men, but not in depressed women.     

Fluoxetine treatment and testosterone levels.

BACKGROUND: Two published case studies have reported SRI/SNRI-associated low testosterone levels. Apathy and low testosterone, observed during venlafaxine treatment in one report, both resolved upon venlafaxine discontinuation. No studies have investigated the effect of chronic SRI treatment on human testosterone levels.As decreased testosterone has several negative health effects, we conducted a pilot study investigating the effect of fluoxetine treatment on testosterone levels. METHODS: Fourteen depressive disorder patients in good health (BDI = 15) were studied. In addition, 4 non-depressed patients were studied. Testosterone levels were drawn, and an apathy questionnaire (under development, not yet validated) was administered at intake.Fluoxetine was provided (10 mg/day for 7 days then 20 mg/day). To measure outcome, a follow-up testosterone level was drawn after 1 month's treatment. RESULTS: Eleven depressed, and 3 non-depressed, patients completed the study. While there were large differences-both increases and decreases-in some individuals' testosterone levels after fluoxetine treatment, for the study population as a whole, there was no relationship (depressed patients, p = 0.4; non-depressed patients, p 0.3) between fluoxetine treatment and testosterone levels.In patients with BDI = 20, testosterone levels at intake were highly associated with intake apathy levels (p = 0.0033). CONCLUSIONS: Further, larger, studies correlating changes in testosterone levels during SRI treatment with treatment response, apathy levels and possibly sexual dysfunction seem indicated.     

Low testosterone levels predict incident depressive illness in older men: effects of age and medical morbidity

OBJECTIVE: Prior studies found that chronic low testosterone levels are associated with an increased risk of depression. We investigated whether low testosterone levels in older men predict depressive illness over 2 years, while controlling for age and medical morbidity. METHOD: Participants were 748 men, aged 50 years or older, without prior ICD-9-diagnosed depressive illness, with a testosterone level obtained between 1995 and 1997. Measures were age, mean total testosterone levels (low: < or = 2.5 ng/mL), medical morbidity, and incidence and time to depressive illness. RESULTS: Men with low testosterone levels had a greater 2-year incidence of depressive illness (18.5% vs. 10.4%, df = 1, p = .006) and a shorter time to onset of depressive illness (log-rank chi(2) = 8.1, df = 1, p = .004). The unadjusted hazard ratio (HR) for depressive illness in men with low testosterone levels was 1.9 (95% confidence interval [CI] = 1.2 to 3.0, p = .005). After adjustment for age and medical morbidity, men with low testosterone levels continued to have a shorter time to depressive illness (adjusted HR = 2.1; 95% CI = 1.3 to 3.2, p = .002). Due to a significant interaction between age and medical morbidity, we conducted stratified Cox regression analyses and found that low testosterone levels and high medical morbidity or an age of 50 to 65 years were associated with increased depressive illness (p = .002). CONCLUSION: Low testosterone levels are associated with an earlier onset and greater incidence of depressive illness. Men with low testosterone levels who had high medical morbidity or were aged 50 to 65 years had an increased risk for depressive illness. Further prospective studies are needed to examine the role of testosterone in depressive illness in older men.     

The Association between Online Gaming, Social Phobia, and Depression: an Internet Survey

ABSTRACT: OBJECTIVE: Online gaming technology has developed rapidly within the past decade, and its related problems have received increasing attention. However, there are few studies on the psychiatric symptoms associated with excessive use of online games. The aim of this study is to investigate the characteristics of online gamers, and the association between online gaming hours, social phobia, and depression using an internet survey. METHODS: An online questionnaire was designed and posted on a popular online game websites, inviting the online gamers to participate the survey. The content of the questionnaire included demographic data, profiles of internet usage and online gaming, and self-rating scales of Depression and Somatic Symptoms Scale (DSSS), Social Phobia Inventory (SPIN), and Chen Internet Addiction Scale (CIAS). RESULTS: A total of 722 online gamers with a mean age of 21.8 +/- 4.9 years completed the online survey within one month. 601 (83.2 %) participants were male, and 121 (16.8 %) were female. The mean weekly online gaming time was 28.2 +/- 19.7 hours, which positively associated with history of online gaming (r=0.245, p<0.001), total DSSS (r=0.210, p<0.001), SPIN (r=0.150, p<0.001), and CIAS (r=0.290, p<0.001) scores. The female players had a shorter history of online gaming (6.0+/-3.1 vs. 7.2+/-3.6 years, p=0.001) and shorter weekly online gaming hours (23.2+/-17.0 vs. 29.2+/-20.2 hours, p=0.002), but had higher DSSS (13.0+/-9.3 vs. 10.9+/-9.7, p=0.032) and SPIN (22.8+/-14.3 vs. 19.6+/-13.5, p=0.019) scores than the male players. The linear regression model showed that higher DSSS scores were associated with female gender, higher SPIN scores, higher CIAS scores, and longer weekly online gaming hours, with controlling for age and years of education. CONCLUSION: The online gamers with longer weekly gaming hours tended to have a longer history of online gaming, and more severe depressive, social phobic, and internet addiction symptoms. Female online gamers had fewer weekly online gaming hours and a shorter previous online gaming history, but tended to have more severe somatic, pain, and social phobic symptoms. The predictors for depression were higher social phobic symptom, higher internet addiction symptoms, longer online gaming hours, and female gender.     

Carotid intima-media thickness in late-onset major depressive disorder

BACKGROUND: This study explored whether patients with late-onset major depressive disorder showed higher carotid artery intima-medium thickness (IMT) and investigated the relationship between the IMT and white matter hyperintensities on magnetic resonance imaging (MRI) among patients. METHODS: Fourteen elderly patients with late-onset major depressive disorder from a psychiatric outpatient clinic and 11 non-depressed controls received a comprehensive psychiatric assessment, ultrasound IMT measurements of the carotid arteries, and cerebral MRI. RESULTS: The carotid IMT was higher in the patient group vs the control group (1.26 +/- 0.30 vs 1.00 +/- 0.20 mm; t = 2.40, p < 0.03). The difference was more apparent in the common carotid artery (1.20 +/- 0.32 vs 0.97 +/- 0.13 mm; t = 2.31, p < 0.04). There was a high correlation (r = 0.55, p < 0.05) between the carotid IMT and white matter hyperintensities among patients with late-onset major depressive disorder. CONCLUSION: Results of this study suggest that atherosclerosis represented by the carotid IMT contributes to the development of late-onset major depressive disorder. The findings support the vascular depression hypothesis.     

Serum testosterone levels in bipolar and unipolar depressed female patients and the role of medication status

Abstract

Objective: to compare testosterone levels between female depressed patients and female bipolar patients.

Methods: Sixty-one female patients with major depressive disorder (MDD) (n?=?23) or bipolar disorder (BD) (n?=?38) between 18 and 45?years old were included in the study. Participants were evaluated during a depressive or manic episode with the Hamilton depression rating scale (HDRS) or Young mania rating scale (YMRS), respectively. No patients in the MDD group were taken valproate while in the BD group 14 (36.84%) were taken valproate. Total testosterone (TT) and free testosterone (FT) levels were quantified during the early follicular phase of the cycle, with radioimmunoassay or solid phase enzyme-linked immunoassay. Data were collected from May 2016 to February 2017.

Results: Mean TT serum levels were significantly higher in BD patients in comparison to MDD patients. Although age and diagnosis were related to TT levels, however when we added valproate use in the analysis, only the relation between TT and valproate use remained significant.

Conclusions: In this sample, TT levels were related to valproate use in patients with BD. More studies regarding the role of testosterone in affective symptoms should be conducted to clarify the relation between testosterone, affective disorders, and medication.

• Keypoints

• We observed that testosterone levels were significant higher in bipolar women compared to women with MDD.

• The use of valproate could be associated with the testosterone levels in female patients with BD.

• Evaluation of women suffering BD should include a testosterone levels determination, particularly when they are taking valproate.

     

Testosterone therapy in men with Parkinson disease: results of the TEST-PD Study

BACKGROUND: Testosterone deficiency has been reported in patients with Parkinson disease (PD), Alzheimer disease, and Huntington disease. It is not known whether testosterone therapy (TT) in men with borderline hypogonadism and neurodegenerative diseases will be of substantial benefit. Previously, we reported that testosterone deficiency is more common in patients with PD compared with age-matched control subjects, and we also reported in 2 small open-label studies that some nonmotor symptoms responded favorably to TT. OBJECTIVE: To define the effects of TT on nonmotor and motor symptoms in men with PD and probable testosterone deficiency. DESIGN: Double-masked, placebo-controlled, parallel-group, single-center trial. PATIENTS: Two experimental groups: patients with PD who were receiving either TT or placebo. INTERVENTIONS: Participants received either the study drug by intramuscular injection (200 mg/mL of testosterone enanthate every 2 weeks for 8 weeks) or placebo (isotonic sodium chloride solution injections). In patients in each group, the testosterone serum concentration was obtained at each study visit. During 2 study visits, testosterone levels were blindly evaluated and the intramuscular testosterone dose was increased by 200 mg/mL if the free testosterone value failed to double from the baseline value. MAIN OUTCOME MEASURES: The primary outcome variable was the St Louis Testosterone Deficiency Questionnaire, and secondary outcome measures included measures of mood, cognition, fatigue, motor function, and frequency of adverse events. At the end of the double-blind phase, all patients were offered open-label TT and were followed up after 3 and 6 months. RESULTS: Fifteen patients in the placebo group (mean age, 69.9 years), receiving a mean total levodopa equivalent dose of 924 mg/d, had a baseline free testosterone level of 47.91 pg/mL, compared with 15 patients in the TT group (mean age, 66.7 years), receiving an average total levodopa equivalent dose of 734 mg/d, who had a baseline free testosterone level of 63.49 pg/mL. Testosterone was generally well tolerated. More subjects in the TT group experienced lower extremity edema (40% vs 20%). In 2 patients, 1 in each group, prostate-specific antigen levels were elevated from baseline. The improvement in the TT group compared with the placebo group (1.7 vs 1.1) on the St Louis Testosterone Deficiency Scale was not statistically significant. In addition, there were no significant differences in motor and nonmotor features of PD between the 2 groups, although a few subscales showed improvements (Hopkins Verbal Learning Test, P<.04; and Backward Visual Span subtrial, P<.03). However, long-term open-label TT resulted in delayed but sustained improvement in subjects in the TT group who continued to receive treatment (n = 6) compared with subjects in the placebo group who elected not to receive TT (n = 3). CONCLUSIONS: Testosterone therapy was generally well tolerated in elderly men with PD and probable testosterone deficiency. While there was no significant difference in the motor and nonmotor scales between the TT and placebo groups at the end of 8 weeks compared with baseline, this may be due to several study limitations, including small sample size, a strong placebo effect with intramuscular therapy, and short follow-up that did not allow measurement of delayed effects of TT in some subjects. Until more definitive studies are reported, practitioners should be particularly cautious in treatment of low testosterone concentrations in men with PD and borderline testosterone deficiency, and careful consideration should be given to the risks vs the benefits of TT.     

抑郁症伴或不伴糖尿病患者过夜小剂量地塞米松抑制试验的对照研究

目的 探讨下丘脑-垂体-肾上腺轴(HPA)功能异常在抑郁症患者伴发的糖尿病发病机制中的意义.方法 首次诊断为糖尿病的抑郁症患者(病例组)、正常血糖稳态的抑郁症患者(对照组)各40例,于药物治疗前测定空腹血糖、糖负荷后2 h血糖,并行过夜小剂量(1 mg)地塞米松抑制试验.结果 (1)病例组抑制前8:00、16:00及...     

Short-term patterns of pulsatile luteinizing hormone secretion do not differ between male-to-female transsexuals and heterosexual men

This study tested whether there is a difference in the pulsatile LH secretion between male-to-female transsexuals and eugonadal heterosexual men. The mean serum LH concentrations, the LH pulse frequency, and the LH pulse amplitude were compared between a group of eight male-to-female transsexuals and a group of 22 heterosexual men. Blood samples for LH determinations were collected every 10 min for seven hours. 17-beta-estradiol and testosterone were measured at the beginning of each test. There were no significant differences between the heterosexual and transsexual group in LH pulse frequency (3.9 +/- 1.3 vs. 3.9 +/- 1.7), LH pulse amplitude (3.7 +/- 1.3 U/l vs. 3.0 +/- 0.5 U/l), mean serum LH concentration (5.2 +/- 1.4 U/l vs. 5.4 +/- 1.1 U/l), 17-beta-estradiol (0.07 +/- 0.01 nmol/l vs. 0.08 +/- 0.02 nmol/l), or testosterone (22.9 +/- 3.7 nmol/l vs. 21.8 +/- 8.0 nmol/l). We conclude that the pulsatile release characteristics of LH do not allow a distinction between eugonadal heterosexual men and eugonadal male-to-female transsexuals.     

Judgement of the hypothalamic-pituitary-adrenocortical function in psychiatric patients by betamethasone-induced cortisol suppressibility

Summary Betamethasone induced cortisol suppressibility was examined in 62 drug free consecutively admitted psychiatric inpatients. Betamethasone was choosen instead of the commonly used dexamethasone, because its double half-life compared to dexamethasone and its higher tissue availability. After a base-line evaluation with blood samples drawn at 8 a.m., 4 p.m., and 11 p.m., 0.5 mg or 1.0 mg betamethasone was given orally at 11 p.m. Postbetamethasone cortisol as well as betamethasone blood levels were then measured at the same time points as on the baseline day. In the groups receiving 1.0 mg betamethasone non-depressed patients had significantly (p<0.05) lower postbetamethasone cortisol levels than depressed patients for each time point measured whereas 0.5 mg betamethasone did not differentiate depressed from non-depressed patients. Patients with other depressions like schizoaffective psychosis -depressive subtype- or organic brain syndrome with depressive symptomatology demonstrated similar postbetamethasone cortisol profiles as the group of patients with major depression. Betamethasone plasma concentrations differed significantly (p< 0.001) with respect to the oral dosage with higher values for the 1.0 mg betamethasone groups.