scholarly journals Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency

2006 ◽  
Vol 189 (3) ◽  
pp. 595-604 ◽  
Author(s):  
J J Corrales ◽  
M Almeida ◽  
R Burgo ◽  
M T Mories ◽  
J M Miralles ◽  
...  

Androgens are considered to have immunomodulatory effects but their cellular mechanisms of action remain largely unknown. In the present study we prospectively analyzed the serial effects of androgen-replacement therapy on both the distribution of peripheral blood lymphocytes, monocytes and dendritic cells as well as on the production of interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNFα) inflammatory cytokines by circulating monocytes and CD33 myeloid, CD16 and plasmacytoid dendritic cell subsets, the most potent antigen-presenting cells (APCs) in type-2 diabetic men with partial androgen deficiency. Analyses were performed before therapy and at 1, 3, 6 and 12 months after treatment with 150 mg testosterone enanthate every 2 weeks in a group of 13 type-2 diabetic men. Our results show for the first time that testosterone-replacement therapy is associated with a reduction or complete abrogation of spontaneous ex vivo production of IL-1β, IL-6 and TNFα by APCs. Meanwhile, the in vitro production of inflammatory cytokines by these cells after stimulation with lipopolysaccharide plus recombinant human interferon-γ remained unchanged, suggesting that APCs preserve their constitutive machinery to produce inflammatory cytokines under androgen treatment. These results confirm and extend previous observations about the anti-inflammatory effects of androgen therapy on APCs in a new, previously unexplored model of androgen deficiency; namely, aging type-2 diabetic men. A decreased production of inflammatory cytokines by APCs might have important consequences for sex differences in susceptibility to autoimmune diseases, inflammatory response to injury and atheromatosis.

Author(s):  
Volodymyr Pankiv ◽  
Tetyana Yuzvenko ◽  
Nazarii Kobyliak ◽  
Ivan Pankiv

Background: In men with low levels of testosterone in the blood, it is believed that the symptoms can be regarded as an association between testosterone deficiency syndrome and related comorbidities. Aim: to investigate the effectiveness of testosterone therapy in patients with type 2 diabetes (T2D) and androgen deficiency. Materials and methods: Testosterone replacement therapy was carried out in 26 men with T2D and clinically or laboratory-confirmed androgen deficiency. The age of the subjects ranged from 35 to 69 years old. Laboratory studies included determinations of the concentration of the hormones estradiol, luteinizing hormone (LH), and prostate-specific antigen (PSA). The observation period was 9 months. Results: The average level of total blood testosterone in the subjects before treatment was 9.4 mol/l and was likely lower than that of the control group (19.3 ± 1.6 nmol/l). The levels of total testosterone in the subjects ranged from 3.9 nmol/l to 10.7 nmol/l, and hormone levels measuring less than 8.0 nmol/l were observed in only 11 patients. After a course of testosterone replacement therapy, a stabilization in total testosterone levels at the level of reference values (as compared to the start of treatment) was observed in the blood of men with T2D after 9 months of observation and the administration of the fourth injection (16.83 ± 0.75 nmol/l). Conclusion: The use of long-acting injectable testosterone undecanoate leads to normalization of total testosterone levels in the blood of men with T2D and androgen deficiency, and LH levels in these patients are unlikely to change.


2021 ◽  
Vol 37 (5) ◽  
pp. 20-26
Author(s):  
P. S. Popov ◽  
I. A. Kournikova ◽  
V. I. Torshin ◽  
N. N. Malyutina

Objective. To assess the state of lipid metabolism indicators and predict cardiovascular risk in patients with secondary (acquired) hypogonadism on the background of androgen replacement therapy. Testosterone replacement therapy is often used in modern medicine for diagnosed androgen deficiency in patients of any age group. There are quite a lot of publications devoted to diagnosis and treatment, but the effectiveness and safety of any therapy is determined by several factors, of which two were considered in the presented study dose-dependent effect and compliance. Material and methods. Sixty two patients aged 30 to 52 years with androgen deficiency and a low risk of developing cardiovascular diseases were examined according to the Princeton Consensus criteria. Patients were divided into groups depending on the severity of androgen deficiency and the duration of therapy. Complaints, objective status, muscle strength, daily blood pressure and heart rate monitoring data, lipidogram and sex hormone indicators were evaluated. Results. The obtained data suggest that androgen replacement therapy in doses that lead to an increase in the level of testosterone in the blood above the upper limit of reference values had a negative impact on the lipid spectrum and increased cardiovascular risk for this group of patients. Conclusions. The analyzed approach to therapy of androgen deficiency should provide an individual adjustment of dosage on the background of determining the target blood testosterone level.


2004 ◽  
Vol 286 (3) ◽  
pp. E449-E455 ◽  
Author(s):  
Andrew N. Carley ◽  
Lisa M. Semeniuk ◽  
Yakhin Shimoni ◽  
Ellen Aasum ◽  
Terje S. Larsen ◽  
...  

Hearts from insulin-resistant type 2 diabetic db/db mice exhibit features of a diabetic cardiomyopathy with altered metabolism of exogenous substrates and reduced contractile performance. Therefore, the effect of chronic oral administration of 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (COOH), a novel ligand for peroxisome proliferator-activated receptor-γ that produces insulin sensitization, to db/db mice (30 mg/kg for 6 wk) on cardiac function was assessed. COOH treatment reduced blood glucose from 27 mM in untreated db/db mice to a normal level of 10 mM. Insulin-stimulated glucose uptake was enhanced in cardiomyocytes from COOH-treated db/db hearts. Working perfused hearts from COOH-treated db/db mice demonstrated metabolic changes with enhanced glucose oxidation and decreased palmitate oxidation. However, COOH treatment did not improve contractile performance assessed with ex vivo perfused hearts and in vivo by echocardiography. The reduced outward K+ currents in diabetic cardiomyocytes were still attenuated after COOH. Metabolic changes in COOH-treated db/db hearts are most likely indirect, secondary to changes in supply of exogenous substrates in vivo and insulin sensitization.


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