Emerging medication for the treatment of male hypogonadism.

INTRODUCTION: Male hypogonadism is characterized by inadequate production of Testosterone (T) (hypoandrogenism) and deficiencies in spermatogenesis. The main treatment of male hypogonadism is T replacement therapy (TRT), but for some of the patients, alternative drugs may be more suitable. AREAS COVERED: The available literature of T and alternative treatments for male hypogonadism are discussed. EXPERT OPINION: Transdermal application of T gels are the most commonly used route of T administration. Some oral T formulations are either associated with hepatic toxicity (i.e. methyltestosterone) or short half-lives that require multiple doses per day (i.e. oral testosterone undecanoate). Short acting, injectable T formulations are also available. If the patient prefers not to use daily drugs or short acting injectable formulations, depot formulations such as injectable testosterone undecanoate (TU) may be a good alternative. If the patient has hypogonadotropic hypogonadism and desires fertility or if he is adolescent, instead of TRT, gonadotropins can be started to stimulate testicular growth and spermatogenesis. In obese patients or for the patients having high risks for TRT, off label aromatase inhibitors (AI) and clomiphene citrate (CC), may be considered to stimulate LH, FSH and T levels. In patients with high prostate disease risk, selective androgen receptor modulators may be an alternative treatment but these latter treatments have not had high level evidence.

Endothelial dysfunction, insulin resistance and inflammation in congenital hypogonadism, and the effect of testosterone replacement.

Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p<0.001 for all) and lower TWEAK levels (p<0.001), compared to the healthy controls. After 5.56 ± 2.04 months of TRT, the patients had significantly elevated systolic blood pressures (p=0.01), body mass indexes and WC (p<0.001 and p=0.001 respectively) and decreased total and HDL cholesterol levels (p=0.032 and p<0.001 respectively). ADMA levels significantly increased (p=0.003), while the alterations in TWEAK, hsCRP and HOMA-IR were not significant. The results of the present study show that endothelial dysfunction, inflammation and insulin resistance are prevalent even in the very young subjects with CHH, who have no metabolic or cardiac problems at present. This increased cardiometabolic risk however, do not improve but even get worse after six months of TRT. Long term follow-up studies are warranted to investigate the unfavorable cardiometabolic effects of TRT.

Serum Pentraxin-3 Level in Patients Who Underwent Coronary Angiography and Relationship with Coronary Atherosclerosis.

OBJECTIVES: To evaluate the role of pentraxin-3 (PTX-3) in determining the presence and severity of coronary atherosclerosis in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: Ninety-five patients (77 males and 18 females) who underwent elective coronary angiography were enrolled in this study. Patients with heart failure, renal failure, diabetes and thyroid disease were excluded. The study population was divided into 3 groups: individuals with normal coronary arteries, patients with critical CAD (n = 35) and patients with noncritical CAD (n = 36). The association of PTX-3 levels with the presence and severity of CAD and the number of involved vessels were analyzed. RESULTS: The mean age was 53.40 ± 10.25 years. The PTX-3 levels were significantly higher in patients with CAD than without CAD (146.48 ± 48.52 vs. 109.83 ± 49.06 pg/ml, p < 0.001). A statistically significant difference was found among the 3 groups regarding the severity of CAD (165.66 ± 49.10, 127.83 ± 40.51 and 109.83 ± 49.06 pg/ml, p < 0.001, respectively). The serum PTX-3 levels in normal arteries were 110.4 ± 48.11 pg/ml, in single-vessel disease 132.35 ± 32.96 pg/ml, in 2-vessel disease 142.57 ± 55.88 pg/ml, in 3-vessel disease 156.07 ± 50.53 pg/ml, and in 3-vessel disease 160.50 ± 30.41 pg/ml. After adjusting for baseline confounders, older age (OR = 1.107, 95% CI = 1.027-1.193, p = 0.008) and higher PTX-3 levels (OR = 1.017, 95% CI = 1.003-1.032, p = 0.021) were detected as significant predictors for the presence of CAD. CONCLUSIONS: Higher PTX-3 levels were associated with the presence of CAD and its increased severity in clinically stable patients. Higher PTX-3 levels may be regarded as a novel diagnostic predictor and may offer therapeutic options in the clinic.

Combined choroidal neovascularization and hypopituitarism in a patient with homozygous mutation in methylenetetrahydrofolate reductase gene.

We report a case of choroidal neovascularization (CNV) secondary to methylenetetrahydrofolate reductase (MTHFR) gene mutation in a 20-year-old male patient with hypopituitarism. Treatment with three consecutive injections of intravitreal ranibizumab (anti-vascular endothelial growth factor) resulted in significant improvement of the patient's vision and the appearance of the macula. A search of the literature produced no previously reported case of MTHFR gene mutation associated both CNV and possibly hypopituitarism. With hormone replacement therapy of hypopituitarism, acetyl salicylic acid 100 mg/day also was started. The patient was clinically stable both for CNV and other thromboembolic disorders over a 6-month follow-up and also 1-year follow-up period.

Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experience.

INTRODUCTION: The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH). SUBJECTS DESIGN AND METHODS: Seventy-seven never-treated patients with IHH and age and body mass index (BMI)-matched 42 healthy controls were analysed in a retrospective design. Twenty-eight patients were treated with testosterone esters (TE), 25 patients were treated with human chorionic gonadotropin (hCG) and 24 patients were treated with testosterone gel (TG). Biochemical parameters, tanner stages (TS) and TV were evaluated before and after 6 months of treatment. RESULTS: Pretreatment TV, TS and biochemical test results were similar among the three treatment subgroup. In the TE-treated group, BMI, haemoglobin, haematocrit, creatinine, triglyceride, total testosterone (TT), TS and TV increased, but HDL-cholesterol (C) and urea level decreased significantly. In the hCG-treated group, triglyceride level decreased, and luteinizing hormone level, TS and TV increased significantly. BMI, TT, TS and TV increased, and leucocyte count, total-C, HDL-C levels decreased significantly in the TG-treated patients. No treatment type resulted in any changes in insulin resistance markers. CONCLUSION: hCG treatment resulted in favourable effects particularly on TV and lipid parameters. When TV improvement is considered less important, TG treatment may be a better option for older patients with IHH because of its easy use, neutral effects on triglyceride, haemoglobin and haematocrit, and its beneficial effects on total cholesterol level.

Increase in subcutaneous adipose tissue and fat free mass in women with polycystic ovary syndrome is related to impaired insulin sensitivity.

OBJECTIVES: The present study was performed to search whether subcutaneous and whole body adipose tissue increase and they relate to measures of insulin sensitivity in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: 52 women with PCOS and 53 healthy controls, all with similar age and body mass index participated in the study. A skinfold caliper device was used to measure biceps, triceps, subscapular and suprailiac skinfold thickness (SFT). Mid-upper arm circumference (MUAC) was measured using a tape measure. Body fat distributions were determined by bioelectrical impedance analysis. Insulin resistance score was computed with the HOMA formula. Plasma adiponectin was measured by EIA. RESULTS: SFT in all defined areas, MUAC, total body and trunk fat free mass, and HOMA score were higher in women with PCOS compared with healthy women, while adiponectin level was significantly lower. SFT values correlated positively with HOMA score, and negatively with blood adiponectin level. Regression analysis indicated, SFT in triceps and supscapular areas, trunk fat mass, trunk fat ratio, fat free mass and trunk fat free mass values as the most powerful predictors of HOMA score. CONCLUSIONS: The present study showed that SFT in different body regions and fat-free tissue mass are increased in women with PCOS, with a significant relation to impaired insulin sensitivity.

Evaluation of sexual functional status and consistency of scales in patients with hypogonadotropic hypogonadism before and after testosterone replacement therapy: a single-center experience.

Objective: This study aimed to investigate the frequency of sexual dysfunction and the effect of short-term testosterone replacement therapy on sexual functions in congenital hypogonadism patients. Furthermore, we sought to reveal the consistency of the self-report scales used for the diagnosis of sexual dysfunction and the relationship between biochemical parameters. Materials and methods: The study was conducted on 47 young male patients aged above 18 years who were diagnosed with hypogonadotropic hypogonadism. Short (IIEF-5) and long (IIEF-15) forms of the International Index of Erectile Function and Arizona Sexual Experiences Scale (ASEX) were applied before treatment under the supervision of a physician. The patients' blood pressure, height, and weight were measured, and their luteinizing hormone (LH), FSH, and total testosterone levels were recorded. Patients who started their treatments were called for a follow-up checkup after 6 months. Their blood pressure, height, and weight were measured by reapplying the ASEX, IIEF-5, and IIEF-15. In addition, their LH, FSH, and total testosterone levels in the biochemical tests were rerecorded. Results: In this study, the sexual dysfunction status of patients diagnosed with hypogonadotropic hypogonadism before and after treatment was evaluated using the ASEX, IIEF-15, and IIEF-5 scales. A decrease in sexual dysfunction was observed in all three scales after treatment compared with that before treatment. The IIEF-5 and IIEF-15 scales were found to be uncorrelated in terms of the pretreatment values but were correlated in terms of the post-treatment values. Although a correlation was observed between ASEX and IIEF- 5 before treatment, no correlation was detected between ASEX and IIEF-15. After the treatment, ASEX was found to be correlated with both IIEF-5 and IIEF-15. The results of the scales indicated the correlation in all categories, except the pretreatment results of the IIEF-15 scale. Conclusion: The results of the current study demonstrated a significant improvement in the sexual function of hypogonadism patients undergoing short-term testosterone therapy. The ASEX, IIEF-5, and IIEF-15 scales used in the diagnosis and follow-up of sexual dysfunction were useful for evaluating sexual functions in hypogonadotropic hypogonadism patients.

Increased frequency of anxiety, depression, quality of life and sexual life in young hypogonadotropic hypogonadal males and impacts of testosterone replacement therapy on these conditions.

Hypogonadotropic hypogonadism is defined as the failure in production of gonadal hormones, thus resulting in lower amounts of testosterone. Depression, anxiety and decreased quality of life are the most common psychopathological conditions in young hypogonadal men. The aim of the present study was to assess the still debated relationship with testosterone levels and psychological symptoms in young male patients with congenital hypogonadotropic hypogonadism (CHH). Thirty-nine young male patients with CHH and 40 age-matched healthy males were enrolled in the present study. The impact of testosterone replacement treatment (TRT) on the patients' anxiety and depression levels, sexual function and quality of life were assessed before and after 6 months of treatment using valid and reliable scales, including the Short Form-36 (SF-36), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Arizona Sexual Experiences (ASEX). Patients with CHH had significantly higher scores for BDI, BAI, and ASEX than the control subjects at baseline (p=0.011, p=0.036, p<0.001, respectively). The ASEX and BDI scores significantly improved after the TRT (p<0.001 for both), while the improvement in the BAI score was not statistically significant (p=0.135). When compared to the control group, treatment naïve hypogonadal patients had more severe symptoms of sexual dysfunction, anxiety, depression, and worse quality of life. After 6 months of TRT, we observed improvements in the above parameters, suggesting that low endogenous levels of testosterone might be related to the increased incidence of psychological symptoms.

The relationship of epicardial adipose tissue thickness to clinical and biochemical features in women with polycystic ovary syndrome.

The amount of epicardial adipose tissue (EAT), a component of body visceral adiposity, has been linked to the presence and severity of cardiovascular disease through multiple mechanisms. Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and subclinical inflammation, which participate in the mechanism of atherosclerosis. We searched if the patients with PCOS have increased EAT thickness (EATT), along with its relation to the measures of adiposity and insulin sensitivity. A total of 41 subjects with PCOS and 46 age and body mass index (BMI) matched healthy controls were enrolled. EAT was measured by echocardiography above the free wall of the right ventricle. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) formula, and plasma adiponectin level was measured by ELISA. Compared to healthy controls EATT and HOMA-IR score were significantly higher (p=0.0001 for both) while plasma adiponectin concentration was significantly lower (p=0.048) in women with PCOS. EATT correlated positively with total cholesterol, triglyceride, luteinizing hormone (LH) and negatively with sex hormon binding globuline (p<0.05 for all), whereas it displayed no correlation to plasma adiponectin level (p=0.924). Triglyceride level was the significant determinant of EATT in logistic regression analysis (p=0.035). Thickness of the EAT is increased in patients with PCOS in conjunction with hyperandrogenity. Prospective studies are required to identify the relation of EAT and cardiovascular risk in patients with PCOS.

High plasma level of long Pentraxin 3 is associated with insulin resistance in women with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS. MATERIALS AND METHODS: Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. RESULTS: Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist-to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p < 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p < 0.05, for all). CONCLUSION: PTX3 level is increased in patients with PCOS in concordance with insulin resistance.

The effect of levothyroxine replacement therapy on lipid profile and oxidative stress parameters in patients with subclinical hypothyroid.

The purpose of this present study is to investigate the levels of oxidative stress parameters in patients with subclinical hypothyroidism (SH) and the effects of levothyroxine (LT4) replacement therapy on these parameters and lipid profile. At the beginning of the study blood samples were collected from the patients in order to analyse oxidative stress parameters, lipid profile and biochemical markers. After replacement therapy with LT4, in the third month, same tests were performed again. At the baseline superoxide dismutase (SOD) levels were found to be higher in SH patients, compared to the euthyroid group. After LT4 therapy, statistically significant decreases in SOD and catalase levels and increase in HDL-C levels were noticed. LT4 treatment was found to have positive effects on oxidative stress indicators and HDL-C levels.

The relationship between severity of coronary artery disease and plasma level of vascular endothelial growth factor.

OBJECTIVE: It has been known that ischemia or occlusion of coronary arteries in animal models increases the production of vascular endothelial growth factor (VEGF); however, little is known about the relationship between coronary artery disease and VEGF in humans. In this study, our aim was to evaluate the relationships between the degree of coronary occlusion and plasma VEGF level as well as other risk factors, including age, weight, arterial blood pressure, cholesterol, triglyceride, blood glucose, and high-sensitive C-reactive protein (hsCRP) in patients with established coronary artery disease. MATERIALS AND METHODS: Our study group consisted of 77 patients. Of these, 38 patients had normal coronary angiography (control group; group C) and 39 had abnormal angiography (17 critical lesion; group CL, 22 noncritical lesion; non-CL group). RESULTS: Plasma VEGF level was 116.95+/-30.12 pg/ml in the control group, 212.47+/-75.28 pg/ml in group CL, and 138.89+/-45.18 pg/ml in the non-CL group. Plasma VEGF level of group C was found to be lower than that of group CL (P<.05), but the difference between groups C and non-CL was insignificant (P>.05). However, logistic regression analysis showed that VEGF level of group CL was significantly higher (P<.001). There was a negative correlation between VEGF and haemoglobin (r=-0.58, P<.01), and positive correlation between VEGF and age (r=0.29, P<.04). There was no relationship between plasma VEGF level and other cardiac risk parameters. Group CL had a higher level of total and LDL-cholesterol levels. CONCLUSION: Increased plasma VEGF levels in patients with coronary artery disease may point that the coronary lesion is critical, and VEGF increase in patients with established coronary artery disease may be used as an indicator of the need for revascularization.

Assessment of geriatric predictors of adherence to Zoledronic acid treatment for osteoporosis: a prospective follow-up study.

Objectives Discontinuation of bisphosphonate treatment remains high even with the long acting parenteral options. Whether there are some unidentified causes of noncompliance more specific to aged individuals is unknown. The aim of this study was to investigate baseline predictors of adherence to Zoledronic acid (ZOL) infusions among non-demented older adults with osteoporosis. Methods Patients aged ≥ 65 years who received a first ever ZOL infusion for osteoporosis were prospectively enrolled. Risk factors for osteoporosis and fractures, comorbidities, geriatric assessment measures, including depression, and anticholinergic burden were determined at baseline. Adherence was defined as taking the next ZOL infusion at 12 months. Results A total of 187 participants were included (mean age: 75.7 ± 6.3 years, female: 77.5%). Adherence to the next ZOL infusion was 66.8% (n = 125). Non-adherent participants (n = 62, 33.2%) had significantly higher frequency of historical height decrease and depression at baseline. Poor adherence was associated with height decrease, presence of depression, and higher anticholinergic burden in univariate analysis. After adjustment for relevant confounders, fragility fracture history (OR: 0.38, 95%CI: 0.17-0.86, p = 0.020), depression (OR: 0.32, 95%CI: 0.12-0.82, p = 0.018), and higher anticholinergic burden (OR: 0.67, 95%CI: 0.49-0.93, p = 0.017) were the predictors of lower adherence to ZOL infusion. Conclusions The rate of adherence to the next ZOL infusion was still suboptimal among older women and men in this study. Past osteoporotic fractures, depression, and higher anticholinergic drug burden predicted poor ZOL adherence. It was a novel finding that drug-related anticholinergic side effects adversely influenced adherence to another medication without anticholinergic properties.

Evaluation of sexual functional status and consistency of scales in patients with hypogonadotropic hypogonadism before and after testosterone replacement therapy: a single-center experience

ABSTRACT Objective: This study aimed to investigate the frequency of sexual dysfunction and the effect of short-term testosterone replacement therapy on sexual functions in congenital hypogonadism patients. Furthermore, we sought to reveal the consistency of the self-report scales used for the diagnosis of sexual dysfunction and the relationship between biochemical parameters. Materials and methods: The study was conducted on 47 young male patients aged above 18 years who were diagnosed with hypogonadotropic hypogonadism. Short (IIEF-5) and long (IIEF-15) forms of the International Index of Erectile Function and Arizona Sexual Experiences Scale (ASEX) were applied before treatment under the supervision of a physician. The patients' blood pressure, height, and weight were measured, and their luteinizing hormone (LH), FSH, and total testosterone levels were recorded. Patients who started their treatments were called for a follow-up checkup after 6 months. Their blood pressure, height, and weight were measured by reapplying the ASEX, IIEF-5, and IIEF-15. In addition, their LH, FSH, and total testosterone levels in the biochemical tests were rerecorded. Results: In this study, the sexual dysfunction status of patients diagnosed with hypogonadotropic hypogonadism before and after treatment was evaluated using the ASEX, IIEF-15, and IIEF-5 scales. A decrease in sexual dysfunction was observed in all three scales after treatment compared with that before treatment. The IIEF-5 and IIEF-15 scales were found to be uncorrelated in terms of the pretreatment values but were correlated in terms of the post-treatment values. Although a correlation was observed between ASEX and IIEF-5 before treatment, no correlation was detected between ASEX and IIEF-15. After the treatment, ASEX was found to be correlated with both IIEF-5 and IIEF-15. The results of the scales indicated the correlation in all categories, except the pretreatment results of the IIEF-15 scale. Conclusion: The results of the current study demonstrated a significant improvement in the sexual function of hypogonadism patients undergoing short-term testosterone therapy. The ASEX, IIEF-5, and IIEF-15 scales used in the diagnosis and follow-up of sexual dysfunction were useful for evaluating sexual functions in hypogonadotropic hypogonadism patients.

Increased Endothelial Dysfunction and Insulin Resistance in Patients with Klinefelter Syndrome.

BACKGROUND AND OBJECTIVE: Patients with Klinefelter Syndrome (KS) have increased cardiometabolic risk however the pathogenesis is not clear. We investigated the presence of endothelial dysfunction, insulin resistance and inflammation in an unconfounded population of KS. METHODS: A total of 32 patients with KS (mean age 21.59 ± 1.66 years) and 33 healthy control subjects (mean age: 22.15 ± 1.03 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), homeostatic model assessment of insulin resistance (HOMA-IR) index and highsensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: The patients had higher Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), insulin, HOMA-IR and ADMA levels (p < 0.001 for all) and lower High Density Lipoprotein Cholesterol (HDL-C) and total testosterone levels (p=0.002 and p<0.001, respectively), compared to the healthy controls. Total testosterone levels were significantly negatively correlated to ADMA (r = - 0.479, p < 0,001), hs-CRP (r = -0.291, p = 0.034) and positively correlated to HDL-C (r = 0.429, p = 0.001) levels. The multivariate analysis has shown that total testosterone (ß = -0.412, p = 0.001) and TG (ß = 0.332, p = 0.009) levels were the significant independent determinants of the plasma ADMA levels. CONCLUSION: The results of the present study show that endothelial dysfunction and insulin resistance are prevalent even in the very young subjects with KS, who have no metabolic or cardiac problems at present. Also, hypogonadism seems to play an important role for increased cardiometabolic risk in patients with KS.

Effect of testosterone replacement therapy on vitamin D and FGF-23 levels in congenital hypogonadism.

INTRODUCTION: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. MATERIAL AND METHODS: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. RESULTS: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p<0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). CONCLUSIONS: The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.

Add on Exenatide Treatment is Beneficial in Poorly Controlled Obese Type 2 Diabetics under Intensive Insulin Regimens.

Background: Intensive insulin treatment is bothersome in obese patients with type 2 diabetes mellitus. High insulin dosages further increase weight gain and the risk of hypoglycemia. Glucagon like peptide-1 receptor agonists decrease the insulin need, cause weight loss and reduce the risk of hypoglycemia. There is limited data about the effect of exenatide on obese diabetics under intensive insulin regimens. Methods: This retrospective case series report the clinical outcomes of 23 obese (13 morbidly obese) patients with uncontrolled type 2 diabetes mellitus (Age=59±10.44 years, body mass index 41.1±6.8 kg/m2, HbA1c 9.9±1.5%), under high dose (94.1±39.6 unit) intensive insulin. Exenatide twice daily was added for a mean follow-up period of 11.22±7.01 (3-30) months. Intensive insulin regimens were continued in 7 patients while the others were switched to basal insulin during the follow-up. Results: During the follow-up, mean HbA1c levels of the patients significantly improved (p=0.019), along with the significant decrease in body mass index and the total insulin need (p<0.001 for both). Baseline insulin dosages were significantly higher in the intensive regimen group (p=0.013) while other demographical and clinical characteristics were similar. No significant difference was present between the groups regarding the alterations of HbA1c, body mass index and the reduction in total insulin dosages. Conclusion: Add on exenatide appears to be a rational treatment modality in uncontrolled obese patients with type 2 diabetes mellitus despite intensive insulin regimens. Further prospective randomized studies with longer follow-up periods are recommended.

Visceral adiposity index and triglyceride/high-density lipoprotein cholesterol ratio in hypogonadism.

BACKGROUND: Cardiometabolic risk is high in patients with hypogonadism. Visceral adiposity index (VAI) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio are the practical markers of atherosclerosis and insulin resistance and independent predictors of cardiaovascular risk. To date, no study has evaluated VAI levels and TG/HDL-C ratio in hypogonadism. SUBJECTS AND METHODS: A total of 112 patients with congenital hypogonadotrophic hypogonadism (CHH) (mean age, 21.7 ± 2.06 years) and 124 healthy subjects (mean age, 21.5 ± 1.27 years) were enrolled. The demographic parameters, VAI, TG/HDL-C ratio, asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured for all participants. RESULTS: The patients had higher total cholesterol (p = 0.04), waist circumference, triglycerides, insulin, and HOMA-IR levels (p = 0.001 for all) than the healthy subjects. VAI and ADMA and TG/HDL-C levels were also higher in patients than in healthy subjects (p < 0.001 for all). VAI was weakly correlated with ADMA (r = 0.27, p = 0.015), HOMA-IR (r = 0.22, p = 0.006), hs-CRP (r = 0.19, p = 0.04), and total testosterone (r = -0.21, p = 0.009) levels, whereas TG/HDL-C ratio was weakly correlated weakly with ADMA (r = 0.30, p = 0.003), HOMA-IR (r = 0.22, p = 0.006), and total testosterone (r = -0.16, p = 0.03) levels. Neither VAI nor TG/HDL-C ratio determined ADMA, HOMA-IR, and hs-CRP levels. CONCLUSIONS: The results of this study demonstrate that patients with hypogonadism have elevated VAI and TG/HDL-C ratio. These values are significantly correlated with the surrogate markers of endothelial dysfunction, inflammation, and insulin resistance. However, the predictive roles of VAI and TG/HDL-C ratio are not significant. Prospective follow-up studies are warranted to clarify the role of VAI and TG/HDL-C ratio in predicting cardiometabolic risk in patients with hypogonadism.

Zoledronic Acid Use and Risk of Cognitive Decline among Elderly Women and Men with Osteoporosis.

OBJECTIVES: Bisphosphonates are the first line treatment options in the prevention and treatment of osteoporosis among elderly women or men. Age associated cognitive decline may increase due to adverse effects of medications. The aim of the present study was to observe the course of cognitive skills in elderly subjects treated with a bisphosphonate. MATERIALS AND METHODS: This prospective study enrolled 120 community-dwelling, non-demented women and men with osteoporosis aged 65 and older who were treated with first-ever zoledronic acid. Mini mental state examination (MMSE) was measured along with geriatric depression scale (GDS) measurement, clock drawing test (CDT), and other clinical and laboratory evaluations that could affect cognition at baseline and 12 months. The primary outcome was at least one point decrease in the final MMSE score at one year. RESULTS: Scores of MMSE (28.29±2.17 and 28.23±2.37, p=0.681), GDS (3.24±2.88 and 2.96±2.88, p=0.062) and CDT (3.69±0.68 and 3.75±0.60, p=0.268) did not change after zoledronic acid infusion at one year. Education in years and presence of newly started medicines with anticholinergic properties was independently associated with at least one point reduction in MMSE score [odds ratio: 3.07 (%95 confidence interval: 1.00-9.44)]. CONCLUSION: Among elderly woman and men with osteoporosis, cognitive functions remained stable 12 months after the administration of first-ever zoledronic acid.

Comparison of estimated GFR equations based on serum cystatin C alone and in combination with serum creatinine in patients with coronary artery disease.

OBJECTIVE: Several new equations (GFRCKD-EPI-cr, GFRCKD-EPI-CysC, GFRCKD-EPI Cr+CysC) are used for the calculation of estimated GFR (eGFR) to evaluate renal function. These equations explicitly demonstrate the association of coronary artery disease (CAD) and severe renal impairment cases. However, these equations are considered insufficient to explain the relation with normal or mildly impaired eGFR and CAD. Our hypothesis was to indicate the inversely proportional relationship of eGFR values, calculated by the different equations, with the presence of CAD in patients with normal or mildly impaired renal function. METHODS: Eighty-eight patients who underwent elective coronary angiographic intervention were enrolled into the study. The study population was divided into two groups based on angiographic documents: patients with normal coronary arteries (CAD-) and patients with CAD (CAD +). These patients were stable and decided to implement angiography for the purpose of suspicion about CAD and control. Since it is thought that eGFR equations based on creatinine are inadequate to determine chronic kidney disease (CKD) and overestimate CKD diagnosis, cystatin C-based equations are considered an alternative. Due to the potential effects of inflammatory events of the markers used in equations, patients with diabetes mellitus, severe CKD, and inflammatory bowel disease were excluded from the study. RESULTS: The average age of all participants was 51.93±9.31 (32-65 years); 80.7% (n=71) was male. A statistical difference was found between the CAD (-) group and the CAD (+) group in terms of the variables of age (45.46±8.48 vs. 54.95±8.11, p<0.001), gender (67.9% vs. 86.7%, male, p=0.037), cystatin C values (1.37±0.34 vs. 0.85±0.39, p<0.001), and GFR equations defined by the Chronic Kidney Disease Epidemiology: GFRCKD-EPI-cr (85.86±14.20 vs. 79.45±10.25, p=0.018), GFRCKD-EPI-CysC (58.61±21.87 vs. 100.82±32.00, p<0.001), and GFRCKD-EPI Cr+CysC (68.29±13.49 vs. 90.75±18.34, p<0.001). After adjustment of the variables in multiple regression analyses, only age (OR, 1.199; 95% CI, 1.077 to 1.335, p=0.001), gender (OR, 8.252; 95% CI, 0.223 to 55.659, p=0.030), and the GFRCKD-EPI-CysC equation (OR, 1.059; 95% CI, 1.028 to 1.090, p<0.001) were detected as predictors for presence of CAD. CONCLUSION: GFR equations based on cystatin C or combined with creatinine may have superiority to GFR equations based on creatinine alone in CAD patients. However, the impact of different variables on the GFRCKD-EPI-CysC equation should not be ignored in specific groups, such as CAD.