Psychologically and biochemically assessed stress in a follow-up study of long-term unemployed

Abstract

It has been suggested that psychological stress is one of the reasons for the high morbidity among unemployed people in Western countries. The same may apply to the well-documented high mortality. It would be expected that increased levels of biological stress would be found in these people. In the present study a sample of 310 long-term unemployed people from Norway was followed for 2 years. Psychologcal stress was assessed by medical examination and by the psychometric tests GHQ-28 and HSCL-30, the latter compared with a reference population of employed people. Serum levels of cortisol, prolactin and testosterone, together with immunoglobulins IgA, IgG and IgM, were compared with working controls. The unemployed had a high level of psychological distress at the first examination, the sanie for men and women. At the 2-year follow up distress was reduced by re-employment. This fits the ‘causation hypothesis' which explains the high distress level as caused by unemployment. The other direction of causation, ‘the selection hypothesis', assuming that distressed persons have an increased chance of continuous unemployment, was also confirmed in the present study. As for biological stress, significant differences were not found between the unemployment, the re-employed and the working controls.     

Could gonadal and adrenal androgen deficiencies contribute to the depressive symptoms in men with systolic heart failure?

Background: Testosterone (TT) and dehydroepiandrosterone sulphate (DHEAS) are neurosteroids and their deficiencies constitute the hormone risk factors promoting the development of depression in elderly otherwise healthy men. We investigated the link between hypogonadism and depression in accordance with age and concomitant diseases in men with systolic HF using the novel scale previously dedicated for elderly population.

Methods: We analysed the prevalence of depression and severity of depressive symptoms in population of 226 men with systolic HF (40–80 years) compared to 379 healthy peers. The severity of depression was assessed using the Polish long version of Geriatric Depression Scale (GDS).

Results: In men aged 40–59 years the severity of depressive symptoms was greater in NYHA classes III–IV compared to NYHA classes I–II and reference group. In men aged 60–80 years depressive symptoms were more severe in NYHA class III-IV compared to controls (all p?≤?0.001). In multivariate logistic regression model in men aged 40–59 years advanced NYHA class was associated with higher prevalence of mild depression (OR?=?2.14, 95%CI: 1.07–4.29) and chronic obstructive pulmonary disease (COPD) with higher prevalence of severe depression (OR?=?69.1, 95%CI: 2.11–2264.3). In men aged 60–80 years advanced NYHA class and TT deficiency were related to higher prevalence of mild depression (respectively: OR?=?2.9, 95%CI: 1.3–6.4; OR?=?3.6, 95%CI: 1.2–10.63).

Conclusion: TT deficiency, COPD and advanced NYHA class were associated with higher prevalence of depression in men with systolic HF.     

Total testosterone levels are correlated to metabolic syndrome components

Introduction: Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin. Some studies suggest a possible link between low total testosterone (TT) levels and the presence of MetS.

Aim: To analyze the strength and independence of associations between TT and MetS components in non-diabetic men.

Methods: In this cross-sectional study, 143 non-diabetic men older than 40 were analyzed.

Main outcomes measure: Blood samples were collected to evaluate metabolic profile and TT levels. MetS was defined as the presence of three or more of the following characteristics: fasting blood glucose levels?≥?100?mg/dL, triglyceride?≥?150?mg/dL, HDL-c??102?cm.

Results: Mean age of the study population was 61.5?±?8.61 years old. MetS was present in 47.9% of the individuals. Thirty-four men had low TT and MetS was observed in 23 (70%) against 50 (46%) in those with normal TT (≥?300?ng/dL) (OR 4.94, p?p?=?0.03) and HDL-c (Beta: 0.19; p?=?0.04) remained significantly correlated with TT levels.

Conclusions: Low TT levels were associated with MetS diagnosis. Abdominal obesity was the MetS component independently correlated to low TT levels.     

Endocrine markers during a job intervention

An intervention consisting of a thorough examination of the psychological worksite problems and a follow-up with feedback and recommendations was made in four different office worksites. One of the sites («active» group) was more organizational change-oriented than the others («passive» group). The course was followed before, three times during the 3 months of the intervention, and 4 months after the end of it, by means of three endocrine plasma markers: cortisol, prolactin and testosterone. In both study groups the prolactin levels increased in women during the starting phase of the intervention, whereas in men prolactin levels remained stable with a tendency (p=0.06) towards lowered prolactin levels during the end phase of the intervention in the active group. Cortisol levels increased markedly in the passive group and tended to decrease in the active group during the intervention (two-way interaction p=0.003), particularly in men. These findings may be indicative of feelings of uneasiness. Testosterone increased in the active group only, particularly at the beginning of the intervention and particularly in women, and also increased in a non-intervention control group. Testosterone levels are associated with anabolic activity. An increase may be indicative of a «placebo effect» of the intervention. Testosterone changes were still clearly observable after 4 months.     

Weapons of penile smooth muscle destruction: Androgen deficiency promotes accumulation of adipocytes in the corpus cavernosum

In men with erectile dysfunction, venous leakage is a common condition among non-responders to medical management and is attributed to penile smooth muscle atrophy. Androgens play a role in regulating trabecular smooth muscle growth and function. Further, androgens stimulate differentiation of progenitor cells into smooth muscle cells and inhibit their differentiation into adipocytes. We postulate that androgens exert a direct effect on penile tissue to maintain erectile function, and that androgen deficiency produces metabolic and structural imbalances in the corpus cavernosum, resulting in venous leakage and erectile dysfunction. To date, research efforts on the mechanisms by which androgens regulate penile erectile physiology have mainly focused on investigating the role of the NO/cGMP pathway. However, androgen-dependent mechanisms that regulate tissue remodeling have been poorly defined. Characterization of the molecular and cellular mechanisms by which androgens regulate corpus cavernosum structural and functional integrity would provide significant gains in knowledge and understanding of an important pathogenic process. In this review, we discuss the potential role of androgen in maintaining differentiation of progenitor cells into smooth muscle lineage and inhibition of differentiation into adipocytes. Androgen deficiency promotes differentiation into adipogenic lineage, and accumulation of adipocytes in the corpus cavernosum may contribute to erectile dysfunction.     

Testosterone therapy - what,when and to whom?

Testosterone therapy has been used for more than 60 years in the treatment of male hypogonadism. The classical forms of hypogonadism are comprised of primary testicular failure or insufficient testicular stimulation due to the lack of pituitary gonadotropins. Typical causes of primary hypogonadism are Klinefelter's syndrome, anorchia or acquired disturbances of testicular function. Secondary hypogonadism is characterized by insufficient production of pituitary gonadotropins, due either to pituitary failure or defects at the hypothalamic level. It is unequivocally accepted in clinical practice that any male with inadequately low testosterone production for his age will require androgen therapy. In addition to the classical forms of hypogonadism, the past decade of research has clearly demonstrated that, with increasing age, many men will suffer from decreasing testosterone production. About 15-25% of men over the age of 50 years will experience serum testosterone levels well below the threshold considered normal for men between 20 and 40 years of age. Studies substituting testosterone in elderly men with low serum testosterone have shown that men with clinical symptoms identical to the symptomatology of classical hypogonadism will benefit most from such therapy. Therefore, it is the general consensus to treat men with age-related hypogonadism only when clinical symptoms are present that can be potentially corrected by testosterone administration. Until recently, intramuscular injections of esters, such as testosterone enanthate, have been the mainstay of testosterone therapy. The introduction of testosterone patches has not challenged this approach, since many users of patches suffer from moderate to severe skin reactions. Some oral testosterone formulations have proven to be problematic, as absorption can be variable, bioavailability is frequently poor, due to the first-pass effect of the liver, and frequent administration is often required<citeref rid="b1"><emph>¹</emph></citeref>. Oral testosterone undecanoate avoids, at least partially, the first-pass effect of the liver. However, plasma testosterone levels generally undergo large fluctuations<citeref rid="b2"><emph>²</emph></citeref>. The large fluctuations in serum testosterone levels caused by conventional intramuscular injections result in unsatisfactory shifts in mood and sexual function in some men, which, combined with the frequency of injections, make the intramuscular mode of delivery far from ideal. Recently, a hydroalcoholic gel containing 1% testosterone has proven to be as efficient as a testosterone patch, but with fewer side-effects and a higher grade of patient satisfaction<citeref rid="b3"><emph>³</emph></citeref>^-<citeref rid="b4"></citeref><citeref rid="b5"><emph>⁵</emph></citeref>. Doses of 50-100 mg gel applied once daily on the skin deliver sufficient amounts of testosterone to restore normal hormonal values and correct the signs and symptoms of hypogonadism. The gel has been shown to be effective and successful in patients in the United States, who have benefited from its availability for almost 3 years. In the near future, intramuscular injections of testosterone undecanoate will become commercially available. Such injections have a very favorable pharmacokinetic profile, with one injection every 3 months maintaining serum testosterone well within the normal range. In phase III studies, intramuscular testosterone undecanoate proved to be as efficient as testosterone enanthate, with only one-quarter of the number of injections required and more stable serum testosterone levels. Thus, the new application modes - hydroalcoholic gel (for example, Testogel®, Schering AG, Germany) and intramuscular testosterone undecanoate (Nebido®, Schering AG, Germany) - appear to be the methods of choice in the near future, one being very suitable for hormone therapy in elderly men, the other for long-term substitution in classical forms of hypogonadism.     

Clinical experiences with testosterone therapy: prostate safety

Due to a decrease in Leydig cell function, a considerable proportion of men over 50 years of age will develop hypogonadism. Consequently, loss of libido and several other testosterone-dependent symptoms may become evident. When decreased levels of biologically available testosterone are found, and corresponding symptoms are present, these men could be eligible for testosterone substitution therapy. Testosterone treatment in testosterone-deprived men has been shown to improve general well-being, osteoporosis, muscle atrophy, libido and - if present - anemia. Despite these positive effects, testosterone treatment has to be performed with caution. Although it has not been proven that elevation of the serum testosterone level to the normal range results in a greater risk of developing prostate cancer, the effects of testosterone on a prostate cancer already present are well established. Several studies have demonstrated that testosterone treatment does not result in a significant increase in serum levels of prostate-specific antigen (PSA) or prostate volume. The long-term effects, however, are currently unknown. For these reasons, testosterone treatment should be performed only when the presence of prostate cancer is unlikely; i.e. when PSA levels are within normal limits and digital rectal examination does not reveal any suspicious findings. These examinations may still miss some small prostate cancers that could be promoted by testosterone treatment. The determination of PSA levels under testosterone treatment is necessary every 3 months, at least for the first year. Steadily rising PSA levels require immediate cessation of testosterone administration and the initiation of further diagnostic procedures (prostate biopsy), to rule out prostate cancer.     

Psychologically and biochemically assessed stress in a follow-up study of long-term unemployed

It has been suggested that psychological stress is one of the reasons for the high morbidity among unemployed people in Western countries. The same may apply to the well-documented high mortality. It would be expected that increased levels of biological stress would be found in these people. In the present study a sample of 310 long-term unemployed people from Norway was followed for 2 years. Psychologcal stress was assessed by medical examination and by the psychometric tests GHQ-28 and HSCL-30, the latter compared with a reference population of employed people. Serum levels of cortisol, prolactin and testosterone, together with immunoglobulins IgA, IgG and IgM, were compared with working controls. The unemployed had a high level of psychological distress at the first examination, the sanie for men and women. At the 2-year follow up distress was reduced by re-employment. This fits the 'causation hypothesis' which explains the high distress level as caused by unemployment. The other direction of causation, 'the selection hypothesis', assuming that distressed persons have an increased chance of continuous unemployment, was also confirmed in the present study. As for biological stress, significant differences were not found between the unemployment, the re-employed and the working controls.     

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

Background.?Studies on the relationship between testosterone concentrations and blood pressure have yielded inconsistent results. Therefore, this study investigated the prospective association of total testosterone (TT) concentrations with risk of incident hypertension and blood pressure change in 1484 men aged 20–79 years.

Methods.?Data from the population-based Study of Health in Pomerania, Germany, were used. Serum TT concentrations, measured by chemiluminescent enzyme immunoassays, were categorised into age-specific quartiles. Generalised Estimating Equation (GEE) models, adjusted for age, waist circumference, physical activity, smoking and alcohol consumption were specified.

Results.?During a median follow-up time of 5.0 years, the prevalence of hypertension increased from 50.6% to 57.1%. TT concentrations were significantly lower in men with baseline and incident hypertension. Analyses revealed that men with baseline TT concentrations in the lowest quartile had an increased risk of incident hypertension (odds ratio (OR), 1.19 (95% CI, 1.10–1.28)) compared to men with higher TT concentrations. Furthermore, we found a significant inverse association of TT concentrations and blood pressure, showing that men with baseline TT concentrations in the lowest quartile showed the slightest change in systolic blood pressure (?6.01?mmHg), diastolic blood pressure (?2.11?mmHg) and pulse pressure (?3.98?mmHg). Sensitivity analyses in a subpopulation of men without antihypertensive medication confirmed these findings.

Conclusion.?These results show that low male TT concentrations are predictive of hypertension, suggesting TT as a potential biomarker of increased cardiovascular risk.     

Testosterone replacement therapy improves erythrocyte membrane lipid composition in hypogonadal men

Aim: The aim of this study was to investigate the effects of testosterone replacement therapy (TRT) on erythrocyte membrane (EM) lipid composition and physico-chemical properties in hypogonadal men. Methods: EM isolated from three patients before and after TRT with injectable testosterone undecanoate or testosterone gel were used for analysis of the phospholipid and fatty acid composition, cholesterol/phospholipid ratio, membrane fluidity, ceramide level and enzyme acivities responsible for sphingomyelin metabolism. Results: TRT induced increase of phosphatidylethanolamine (PE) in the EMs and sphingomyelin. Reduction of the relative content of the saturated palmitic and stearic fatty acids and a slight increase of different unsaturated fatty acids was observed in phosphatidylcholine (PC). TRT also induced decrease of the cholesterol/total phospholipids ratio and fluidization of the EM. Discussion: The TRT induced increase of PE content and the reduction of saturation in the PC acyl chains induced alterations in the structure of EM could result in higher flexibility of the erythrocytes. The increase of the SM-metabolizing enzyme neutral sphingomyelinase, which regulates the content of ceramide in membranes has a possible impact on the SM signaling pathway. Conclusion: We presume that the observed effect of TRT on the composition and fluidity of the EM contributes for improvement of blood rheology and may diminish the thrombosis risk. Larger studies are needed to confirm the findings of this pilot study.