Оценка тестостеронзаместительной терапии при реабилитации мужчин с нарушениями мочеиспускания после хирургического лечения ДГПЖ.

Introduction Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, diabetes, and cardiovascular disease. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome are considered. We hypothesized that men with testosterone deficiency will have high levels of CRP. Objective We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging and specifically attempted to determine if low androgen status is associated with a high inflammatory profile independent of comorbidities. Methods Male participants with serum TT level measured during two separate visits >3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL) and Triglyceride levels were collected via blood specimens. Comorbidity data were documented at each visit. Panel regression was used to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable for modeling. Results A total of 347 patients were included in this study (mean age = 69 ± 15, average follow up time = 6.7 ± 3.2 years). Participants had a median CRP level of 1.0 mg/dL and a median TT level of 446 ng/dL. On univariable analysis TT and HDL levels were associated with a decline in CRP, while BMI, congestive heart failure (CHF), Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP. On multivariable analysis, we found that increasing TT level was associated with a decline in CRP levels, independent of comorbidities (p = 0.018; Table 1). BMI was associated with a significant increase in CRP (p = 0.001, Table 1). Age, CHF, Diabetes, HDL, and Triglycerides were not significant predictors of CRP on multivariable analysis. Conclusions Lower levels of serum total testosterone are associated with an increased CRP in older men. Given the importance of CRP in pathogenesis of chronic disease, we highlight the potential benefits of restoring testosterone levels in older, hypogonadal men via TRT. Disclosure No.

Background: The use of testosterone replacement therapy (TRT) is widespread. Despite the positive changes, such as: an increase in testosterone levels, an improvement in erectile function and an increase in libido, it is possible to develop a negative manifestation — hyperestrogenism. To date, there are no studies assessing the prevalence of hyperestrogenism in the presence of TRT. Aim: To study the reliability of an increase in total testosterone and estradiol levels and changes in total weight, body mass index (BMI), waist circumference (WC) and hips (OB), depending on the type of TRT and hCG therapy. Materials and methods: For retrospective analysis, the medical records of patients with baseline testosterone deficiency and normal estradiol levels, who were prescribed TRT or hCG therapy, were selected. The patients were divided into 3 groups depending on the form of TRT and hCG therapy. The level of testosterone, estradiol, sex hormone binding globulin (SHBG), weight, OT, OB, BMI in each group was assessed 2 times — before the appointment of treatment and at different periods of treatment, for example, after 3–6–9 and 12 months. Most of the patients had a period of monitoring these parameters before the appointment of TRT or hCG therapy and after 6 months. Results: The increase in the levels of total testosterone and estradiol against the background of TRT in the total sample was 109.6% and 111.3%, respectively. In each group, increases in total testosterone and estradiol levels were significant, p ≤ 0.001. The level of total testosterone to physiological values increased only in the 2-nd group — reaching the average-normal, recommended levels, from 8.7 ± 0.5 (2.5) to 16 ± 2 (10). The maximum rises in total testosterone, as well as estradiol, were noted in the 1st group, from 9.5 ± 0.72 nmol / L (3) to 24.9 ± 2.7 nmol / L (11.62)) and with 24.19 ± 2 (8.5) to 58.1 ± 4 (18.1), respectively. TRT, like hCG therapy, promotes an increase in the level of estradiol, which was demonstrated in all groups, and not only in group 1-st: in group 2-nd from 28.1 ± 2.3 (11.3) to 55 ± 4 (20) and in the 3-rd group from 27.1 ± 2.5 (10.5) to 55.8 ± 4.6 (19.6). On average for the entire sample, from 26.6 ± 1.32 (10.2) to 56.2 ± 2.5 (19). Weight loss on TRT was significant only in the 2-nd group, and in all parameters — weight, BMI, waist and hip circumference. In the 3-rd group, BMI, WC and OB values also slightly decreased. In the 1-st group, the total weight slightly increased, while the BMI did not change, as did the OB value, and the OT value decreased slightly. Conclusion: TRT significantly increases the levels of total testosterone and estradiol, contributing to the normalization of testosterone levels, as in the 2-nd group, or the development of supraphysiological levels of total testosterone and hyperestrogenism, as in the 1st and 3-rd groups. Given that there is a strong belief that TRT leads to significant weight loss, our study confirmed this statement only in the 2-nd group.

Introduction American Urological Association (AUA) guidelines for managing testosterone deficiency recommend that clinicians should consider measuring serum total testosterone levels in patients with specific medical conditions, even when typical signs or symptoms of testosterone deficiency are absent. One such condition is bone mineral density (BMD) loss, which has significant implications for overall health and wellness. Because this pathology is less common in men than women, it may be underdiagnosed or inadequately evaluated in male patients. Consequently, it remains unclear how frequently clinicians adhere to the AUA’s recommendation to assess testosterone levels in this context. Objective We aim to assess how often physicians utilize the AUA guidelines for testosterone deficiency in clinical practice when evaluating testosterone levels in men with low BMD. Methods Using the TriNetX database, we conducted a retrospective cohort analysis on men with no prior testosterone use aged ≥18 with low BMD on Dual-energy X-ray absorptiometry scan results or with a diagnosis of osteoporosis or osteopenia. The primary outcome was a documented serum testosterone level within 6 months after the low BMD diagnosis. Men were further stratified into low (<300) or normal (≥300 ng/dL) serum testosterone and assessed for subsequent testosterone replacement therapy (TRT). Results We identified 210,807 testosterone-naïve men with low BMD, of whom 17,275 (8.2%) had a testosterone level drawn within 6 months after the diagnosis of low BMD. Of those with a documented testosterone level, 8,866 (51.3%) had low serum testosterone. 47.9% of these men had a second testosterone level drawn within 12 months. This second testosterone level was also low in 74.7% of the cohort of patients. Only 3.5 % of these testosterone deficient men (314) were started on TRT in the next year. Conclusions Despite being recommended by AUA guidelines, few men diagnosed with BMD undergo serum testing for testosterone levels. While over half of those tested had low testosterone levels, many did not receive treatment. Further research should clarify the reason for these treatment gaps, as this may represent a group of men who may benefit from testosterone therapy. Disclosure No

Testosterone replacement therapy (TRT) has been used in millions of men worldwide to treat diminished libido and erectile dysfunction, and to improve strength and physical function. The estimated likelihood of adverse effects of long-term TRT is still essentially unknown, as overall high-quality evidence based upon prospective randomized trials to recommend for or against its use in most men with testosterone deficiency (TD) is lacking. Evidence to suggest that TRT increases cardiovascular morbidity and mortality risks is poor, as results vary across study populations and their baseline comorbidities. While TRT may increase serum prostate-specific antigen levels in some men, it often remains within clinically acceptable ranges, and has not been shown to increase the risk of prostate cancer. Current literature supports that TRT does not substantially worsen lower urinary tract symptoms, and may actually improve symptoms in some men. Limited evidence suggests that TRT may initially worsen obstructive sleep apnea in some men, but that this is not a longstanding effect. TRT may result in erythrocytosis in some men, however long-term studies have not reported significant adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms). Future research will require dedicated focus on evaluation of large, multiethnic cohorts of men through prospective trials to better elucidate both risk and hazard ratios of TRT as it relates to cardiovascular disease, prostate cancer, lower urinary tract symptoms, obstructive sleep apnea, erythrocytosis, and other to-be-determined theoretical risks in men both with and without cardiovascular risk equivalents.

BackgroundAtrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone.Methods and ResultsUsing data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score–weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post‐TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81–0.99, P=0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70–0.89, P=0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78– 1.0009, P=0.0675) in incidence of AF.ConclusionsThese novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF.

As men age, testosterone levels decline, and decreased testosterone levels are associated with increased risks of osteoporosis, metabolic syndrome, type 2 diabetes mellitus and mortality. Nevertheless, it is still uncertain whether reduced testosterone level is a cause of ill-health or a marker of pre-existing disease, as systemic illness lowers testosterone levels. Most circulating testosterone is bound to sex-hormone-binding globulin (SHBG) and albumin, whereas a small proportion circulates as free testosterone. Decreased SHBG level is associated with increased risks for insulin resistance and metabolic syndrome, although it would also be expected to be associated with increased free testosterone level. During male aging, total and free testosterone levels fall while SHBG level rises. Thus, associations between decreasing androgens and negative health outcomes might differ across men of various ages. Trials of testosterone therapy report benefits for body composition and BMD, but there are limited data on the effect of testosterone supplementation on cardiovascular risk. Whereas men who have androgen deficiency should be considered for testosterone therapy, the role of testosterone supplementation in older men who are not clearly hypogonadal requires further clarification. Further studies are also needed to establish whether the age-related decline in circulating testosterone level in men can be modified or prevented.

To retrospectively review hypogonadal men receiving testosterone replacement therapy (TRT), and evaluate the changes in prostate-specific antigen (PSA) levels over an extended period, and thus evaluate the occurrence of prostate cancer, as a primary concern in treating late-onset hypogonadism (LOH) is the potential increased risk of prostate cancer; we also recorded the cardiovascular effects of TRT. In all, 81 hypogonadal men (mean age 56.8 years) were followed for a mean (range) of 33.8 (6-144) months after starting TRT. All men had a normal baseline PSA level before TRT and had routine laboratory investigations, including measurements of body mass index (BMI), haematocrit, lipid profile, and liver function tests (LFTs). Testosterone and PSA levels were assessed every 6-12 months. Patients with a biopsy-confirmed or recent history of prostatitis before treatment were excluded. TRT was discontinued in men who developed prostate cancer. Before and 36 months after treatment the total testosterone levels were 241.1 and 379.8 ng/dL (P < 0.05), respectively. Four men (4.9%) developed prostate cancer at a mean (range) of 32.5 (22-41) months after starting TRT. In men without prostate cancer (95.1%), PSA levels did not increase significantly at 1-year intervals for 5 years. There was no statistical difference in PSA level change from baseline to 36 months when patients without prostate cancer were stratified into groups according to age (< or =50, 55-65 and > or =70 years). In men with prostate cancer there was an increase in mean PSA level from baseline to 18 months of 1.8 ng/mL, and to 36 months of 3.2 ng/mL (P < 0.05). Total cholesterol improved from 203.8 to 166.6 mg/dL (P < 0.05) after 36 months of TRT; the BMI, haematocrit and LFTs did not change significantly. LOH is an increasingly prevalent disease characterized by a symptomatically low testosterone level, and TRT is effective in normalizing serum testosterone levels, providing a beneficial cardiovascular effect, and improving sexual function and overall quality of life. PSA levels remain stable after normalization of testosterone for > or =5 years, prostate cancer can be effectively diagnosed and treated in men taking TRT, and the incidence of prostate cancer among men with LOH on TRT is no greater than that in the general population.

Polymorphic GGC repeats in the androgen receptor (AR) gene can alter transactivation of androgen-responsive genes and increase the risk of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We investigated the association between GGC repeat length, testosterone levels and the risk of developing PCa and BPH in a population from southern Brazil. A sample comprising 130 PCa, 126 BPH and 88 control patients was evaluated. DNA was extracted from leukocytes and the AR gene was analyzed by fragment analysis. The hazard ratio (HR) was estimated. GGC mean length was not different between the three study groups. The risk of developing PCa in individuals with GGC > 19 was 3.300 (95 %CI 1.385-7.874) higher when compared to the GGC ≤ 19 group (p = 0.007). The risk of developing PCa and BPH in individuals with total testosterone levels <4 ng/mL was 2.799 (95 % CI 1.362-5.754). (p = 0.005) and 2.786 (95 % CI 1.470-5.280) (p = 0.002), respectively. Total testosterone levels in patients with GGC > 19 were significantly lower when compared to patients in the GGC ≤ 19 group. Our data suggest that the presence of a high number of polymorphic GGC repeats in the AR gene is associated with an increased risk of developing PCa and BPH, and that lower testosterone levels also increase the risk of developing these diseases.

Bulbomembranous Urethral Strictures Repair After Surgical Treatment of Benign Prostatic Hyperplasia. Experience From a Latin American Referral Centre

Objectives:Age related decline in sex hormone levels has been associated with decreased muscle mass, bone density, and changes in metabolism in both males and females[1-3]. Although the effect of estrogen levels on tendon size and architecture has been studied in females [4,5], the influence of testosterone levels on tendons in males is unknown. The purpose of the present study was to retrospectively compare free testosterone (FT) and total testosterone (TT) level in males diagnosed with Achilles tendon rupture and healthy normal historical data as a means of evaluating if decreased sex hormone level is a risk factor for tendon injury. We hypothesized males diagnosed with Achilles tendon ruptures will have lower FTand TT levels than age-matched normal levels in the literature.Methods:22 males diagnosed with Achilles injury that had their FT (nmol/L) and TT (nmol/L) levels measured as part of their initial clinical evaluation were retrospectively identified. The FT and TT levels of these injured men were directly compared to age matched historical data [5-7]. The mean FT and TT levels, and 95% confidence intervals were then compared. The difference of means was reported as statistically significant if the confidence interval for the difference in means test did not include zero.Results:Six males age 24-33, ten age 34-43, four age 44-53 and two males age 54-63 had FT and TT levels recorded as part of their care. For each age group, the mean FT and TT levels of males with Achilles tendon rupture were lower than the respective age-matched normal controls reported in the literature. Males in their 30s, 40s and 50s had statistically significant lower FT and TT levels compared to normal controls in the literature (Figure 1a, b, * indicates difference of means test statistically significant, P<0.05). The variability in males in the 20s, and the smaller sample size in our case cohort did not allow us to detect differences for males in third decade of life. Males between age 34-43 had largest difference in means compared to historical data.Conclusion:Our study showed the average FT and TT levels of males with Achilles tendon rupture were lower than corresponding age-matched historical data for each age group. Males in their 30s, 40s and 50s had statistically significant lower FT and TT levels compared to normal controls in the literature. Past studies have shown there is an increased incidence of Achilles tendon rupture for males during this same decade of life [8]. Overall, we believe our findings suggest low hormone levels maybe associated with the risk of Achilles tendon rupture. The main limitation of this retrospective study design is fact that the FT and TT levels were not redrawn to account for the impact of injury on these hormone levels. Future studies will be repeated with larger sample size, and include albumin and sex-binding globulin levels to help adjust for other biological factors that may influence these measures. Cited1.Tenover. Testosterone and the aging male. Journal of andrology, 1997. 2. Clarke. Archives of biochemistry and biophysics, 2010. 3.Figueroa. The journals of gerontology. Series A, Biological sciences and medical sciences, 2003 4.Cook.Scandinavian journal of medicine & science in sports, 2007. 5.Finni. Journal of applied physiology, 2009 6.Mohr.Clinical endocrinology, 2005. 7.Vermeulen.The Journal of clinical endocrinology and metabolism, 1996. 8. Halmenschlager. International urology and nephrology, 2012.

Adult-onset testosterone deficiency (TD) in men is diagnosed by the finding of low serum testosterone levels and recognised, associated symptoms. The condition has high prevalence in men over 50 years of age, particularly those with type 2 diabetes (T2DM). Accumulating data show adult-onset TD is associated with increased mortality risk. We review the literature and consider the evidence suggesting testosterone therapy (TTh) reduces mortality, especially in men with T2DM. We previously reported that in the Burntwood Lichfield Atherstone Sutton Coldfield Tamworth (BLAST) study screened cohort of men with adult-onset TD and T2DM adult-onset TD was associated with increased mortality with TTh decreasing this higher mortality. The data hinted that the effect was greater in older men. We confirmed this observation with statistical analyses to study the effect of age on the association between adult-onset TD and mortality; Cox regression analysis demonstrated that the reduced risk (hazard ratio: 0.61, 95% CI: 0.38–0.96) following TTh was restricted to men above the median age of 65.89 years. Finally, we speculate on putative mechanisms that may mediate these associations. Heterogeneity in men with adult-onset TD is expected in view of its definition of low testosterone levels together with associated clinical phenotypes that are not always directly related. Many of these classifying phenotypes are associated with increased mortality. Thus, it is perhaps possible that mechanism(s) of all-cause mortality reduction following TTh is via the impact on these associated phenotypes such as the metabolic syndrome (MetS), hyperglycaemia, hypertension, dyslipidaemia, low haematocrit, sex hormone binding levels, erectile dysfunction, etc. We propose that further research studying the effect of TTh takes heterogeneity into account.

Testosterone Therapy and Obstructive Sleep Apnea: Is There a Real Connection?

Mechanisms of testosterone deficiency-related endothelial dysfunction: Invited commentary for the Hellenic Journal of Cardiology on: Tsikas et al. “Associations between asymmetric dimethylarginine, nitrite-dependent renal carbonic anhydrase activity and plasma testosterone levels in hypogonadal men”

There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke. We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3. In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.

Introduction/ObjectiveTransurethral resection of the prostate (TURP) is a gold treatment method in older men who develop lower urinary tract symptoms (LUTS) which are caused by benign prostatic hyperplasia (BPH) and benign prostatic obstruction (BPO). The objective of the study was to assess the impact of BPH surgical treatment with TURP method on the quality of life, as a consequence of urinary symptoms.Material and methodsThe research material was based on 40 patients who, due to BPH, were treated with the method of transurethral resection. International Prostate Symptom Score (IPSS) was used in the research i.e. question Nº 8 that relates to the quality of life, as a consequence of the urinary symptoms. The criteria for the patients to be selected for this type of BPH surgical treatment were good general status of the patient, age under 80, the weight of benign prostatic gland hyperplasia tissue 30–80 grams, postvoid residual urine (PVR) higher than 150 ml, IPSS value >19 points, and Index of Quality of Life (IQL) values > 3 points. All patients, first preoperatively, and then postoperatively, gave answers to IPSS IQL in time intervals of 4, 8 and 12 weeks.ResultsDifference testing of IQL arithmetic means (AM) between results before the operation, then during the first, second and third checkup was performed with the t-test and Wilcoxon test of equivalent pairs, and has shown that there is a highly statistically significant difference between preoperative values and the values during all the postoperative checkups. Taking into consideration the age subgroups (20 patients between 59 and 69 years and 20 patients between 70 and 80 years), difference testing of arithmetic means between results before the operation and first, second and third checkup, isolated, for each age subgroup, was carried out. It has demonstrated that there is a statistically significant difference between preoperative values and values during all postoperative checkups. Difference testing of arithmetic means between the stated age groups has also been conducted. The t-test and Mann-Whitney test have been used for this purpose and have shown that there is no statistically significant difference between preoperative test results and the results during all postoperative checkups.ConclusionThe quality of life, as a consequence of urinary symptoms, has significantly improved after the BPH treatment with TURP method. The impact of TURP on the quality of life is not related to age i.e. TURP is equally efficient regardless of patient’s age.