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.

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.

Evaluation of the isokinetic muscle strength, balance and anaerobic performance in patients with young male hypogonadism.

Hypogonadism is a clinical condition that occurs due to infrequent abnormalities in the hypothalamic-pituitary-gonadal (HPG) axis in adolescence. Symptoms include weakening of muscle and bone strength. 30 young male patients with congenital hypogonadotropic hypogonadism (CHH) and 20 healthy young males were included in the present study. Quadriceps and hamstring muscle strength, balance and anaerobic performance capacities of the study group were measured both before and six months after Testosterone replacement therapy (TRT). The strength of the extensor and flexor muscles of both legs showed a statistically significant increase in the isokinetic test values at 60(0)/sec and 180(0)/sec angular velocity (p < 0.05). When the parameters related to balance were investigated, a statistically significant difference was found for stability indices of left and right between pre-TRT and post-TRT (p = 0.001 for both comparisons). According to the patients' anaerobic performance measurement results, a statistically significant improvement (p < 0.001) was also found between pre-TRT and post-TRT values for each parameter. It was shown that TRT significantly increases muscle strength, balance, and anaerobic performance of patients with male CHH. As a result, we absolutely recommend the use of TRT in patients with male CHH.

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 between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy.

OBJECTIVES: Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. MATERIALS AND METHODS: Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). RESULTS: TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = -0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). CONCLUSION: TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.

Electrophysiological assessment of the autonomic nervous system in male patients with acromegaly.

BACKGROUND/AIMS: We aimed to electrophysiologically evaluate the autonomic function in acromegalic patients using sympathetic skin response (SSR) as a reflection of the sympathetic sudomotor activity and RR interval variation (RRIV) as an indicator of the cardiovagal autonomic function. METHODS: The study group consisted of 18 male acromegalics, and the control group was composed of 18 age- and sex-matched healthy subjects. Participants underwent SSR and RRIV tests. Beginning latencies and amplitudes of the median and tibial SSRs were compared among the groups. The RRIV values recorded at rest and during hyperventilation were compared among the patients and controls. RESULTS: Latencies of SSRs recorded from the palms (median) and soles (tibial) of acromegalics were significantly longer than in healthy subjects (p = 0.004, p < 0.001). The amplitude of SSR recorded from the sole (tibial) was significantly decreased (p = 0.028). The RRIVs obtained from acromegalics at rest and during hyperventilation were significantly decreased compared with those of controls (p < 0.001). The RRIVs obtained from controls prolonged significantly during hyperventilation (p < 0.001); however, in the acromegaly group, hyperventilation did not cause a significant change in RRIV (p = 0.983). CONCLUSIONS: The present study suggests that an autonomic dysfunction exists in patients with acromegaly. Dysautonomia in acromegalics may be documented by means of SSR and RRIV.

The relationship between ghrelin levels and insulin resistance in men with idiopathic hypogonadotrophic hypogonadism at diagnosis and after therapy.

INTRODUCTION: It has recently been shown that ghrelin affects energy balance and reproductive function, but the role of ghrelin in the pathogenesis of insulin resistance is unclear. Firstly to assess the interaction between insulin resistance and ghrelin levels in hypogonadal men, and then to show the effects of testosterone (T) therapy on insulin and ghrelin. MATERIAL AND METHODS: Twenty-four male patients newly diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) and 20 healthy male subjects were enrolled in this study. Ghrelin, insulin, glucose, total and free testosterone levels, HOMA-IR and QUICKI, and percentage of body fat mass were determined at baseline in all subjects and after therapy in hypogonadal men. RESULTS: When compared with control subjects, hypogonadal men had significantly lower total and free T concentrations, ghrelin levels, and QUICKI whereas they had significantly higher body fat mass and HOMA-IR score. Following T therapy, a significant increase in ghrelin and QUICKI, and a decrease in HOMA-IR score and body fat mass were demonstrated in hypogonadal men. Calculation of the Pearson coefficient showed that ghrelin concentrations in hypogonadal men were positively correlated with free and total testosterone and QUICKI, whereas they were negatively correlated with body fat mass and HOMA-IR. After six months of T therapy, these correlations were still observed. CONCLUSIONS: Our data supports the notion that ghrelin may constitute an important link between the regulation of reproduction and metabolic homeostasis.

Prediction of testosterone response to human chorionic gonadotrophin in idiopathic hypogonadotropic hypogonadism patients.

In clinical practice, the human chorionic gonadotrophin (hCG) stimulation test is widely used to evaluate testicular function. Inhibin B, a gonadal peptide regulating follice-stimulating hormone (FSH) secretion, is an established marker of Sertoli cell function and spermatogenesis in adults. The aim of this study was to determine whether basal inhibin B levels are able to predict testosterone response to hCG in idiopathic hypogonadotropic hypogonadism (IHH) patients and to evaluate the correlation between inhibin B and gonadotropins in these patients and controls. Inhibin B (n=15) and other hormones (n=29) were measured in 29 patients with IHH and 32 controls. Inhibin B (n=8) and testosterone levels (n=25) before and after hCG stimulation were measured in 25 male patients with IHH by an immunoassay specific for inhibin B. Basal inhibin B was compared to the testosterone increase after hCG. There was a significant increase in inhibin B (22.6 +/- 9.8 vs 45.07 +/- 13 pg/mL; p=.005), free testosterone (2.92 +/- 0.55 vs. 7.9 +/- 1.5 pg/mL; p=.002), and total testosterone (69.0 +/- 15.9 vs. 184.9 +/- 44.1 ng/mL; p = .013) levels 72 hours after hCG injection. Inhibin B and the hCG-induced free testosterone and total testosterone increment correlated strongly (r=0.802, P<.001; r=0.793, P<.001, respectively). We conclude that basal inhibin B predicts the testosterone response to hCG in IHH patients and therefore gives reliable information about Leydig cell reserve. Furthermore, inhibin B levels show negative correlation with luteinizing hormone (LH) in control patients and positive correlation with FSH and LH in IHH patients. LH may effect inhibin B secretion. Further studies are necessary to define the physiology of inhibin B in human males.

Maprotiline induced weight gain in depressive disorder: changes in circulating ghrelin and adiponectin levels and insulin sensitivity.

Agents such as clozapine, olanzapine and mirtazapine frequently trigger an increase in body weight. Though the mechanisms have not been thoroughly clarified, recent studies indicate a role for ghrelin in regulation of appetite and weight gain. We investigated the relation of maprotiline induced weight gain to serum ghrelin and adiponectin levels, as well as insulin resistance in lean subjects with depressive disorder. A total of 40 male lean subjects with depressive disorder were treated with maprotiline (150 mg/day) for 30-days. Clinical data, fasting plasma glucose, lipids, insulin levels, serum ghrelin and adiponectin concentrations were determined before and after treatment. Insulin resistance was estimated using the homeostasis model assessment (HOMA) formula. After 30 days of treatment with maprotiline, mean body mass index increased significantly. Blood ghrelin and insulin levels and HOMA indexes increased, and adiponectin concentration decreased (p<0.001, for all) after the treatment period. Changes in ghrelin levels correlated neither of the parameters tested; whereas decrease in plasma adiponectin was associated with an increase in BMI (r=-0.671, p<0.001). In conclusion, the results indicate that treatment of lean patients with depressive disorder with maprotiline results in an increase in serum ghrelin and reduction in adiponectin levels. Weight gain due to maprotiline treatment may be related to its negative effects on the metabolic variables.

Transsphenoidal approaches to the pituitary: a progression in experience in a single centre.

BACKGROUND: Evolving of a single centre by means of different transsphenoidal approaches during the survey of methodological advances in pituitary surgery is presented. MATERIALS AND METHODS: Ninety-three consecutive patients with pituitary adenomas underwent transphenoidal pituitary operations at Gulhane Military Medical Academy from January 1996 to October 2007. Retrospective chart-based analysis of the surgical methods of transsphenoidal pituitary adenoma operations were done. Surgical methods were described. Outcomes and complications were presented. Attention is focused on the methodology of different surgical techniques of pituitary surgery. FINDINGS: During the evaluation period, 12 Sublabial approaches (1996-1998), 13 transseptal transsphenoidal approaches (1999-2000), 15 endonasal transsphenoidal approaches (2000-2004), 25 endoscopy assisted endonasal approaches (2002-2006) and 28 pure endoscopic endonasal approaches (2006-2007) were performed. CONCLUSIONS: Technologic advancements in endoscopy and gaining experience in pituitary surgery drives neurosurgeons toward less invasive approaches.

The relationship between periodontal status and alkaline phosphatase levels in gingival crevicular fluid in men with hypergonadotropic hypogonadism.

PURPOSE: The aim of this preliminary study was to determine the possible relationship between alkaline phosphatase (ALP) levels in the gingival crevicular fluid (GCF) and periodontal disease in men with hypergonadotropic hypogonadism (HH). MATERIALS AND METHODS: A total of 41 patients were divided into four groups. 9 with HH and periodontitis (P/HH), 11 with HH and gingivitis (G/HH), 12 with systemically healthy and periodontally healthy (H/C) and 9 with systemically healthy and periodontitis (P/C). The clinical evaluation of patients was based on the following parameters; the plaque index (PI), gingival index (GI), probing depths (PD) and attachment level (AL). The levels of ALP in the GCF were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant difference could be detected in the mean clinical parameter data between the P/HH and P/C groups (p > 0.05). The periodontitis patients in both groups (P/C and P/HH) had higher mean probing depths than the H/C and G/HH patients (p < 0.001). The concentrations and total amounts of ALP in the GCF were significantly higher in both periodontitis groups compared to healthy and gingivitis groups (p < 0.01). The serum ALP levels were significantly higher in the P/HH group when compared to the other groups (p < 0.001). CONCLUSION: The findings of this study suggested that HH could be implicated as a contributing factor to the progress of periodontal disease.

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.

Periodontal status in men with hypergonadotropic hypogonadism: effects of testosterone deficiency.

BACKGROUND: The purpose of this clinical study was to evaluate the possible influence of testosterone hormone on common clinical measurements of periodontal disease in men with hypergonadotropic hypogonadism. METHODS: Twenty-four hypergonadotropic hypogonadal men (H) and 24 systemically healthy men (S) were divided into two groups as chronic periodontitis and clinically healthy controls after clinical examinations and radiographs. The H group consisted of 12 control (H/C) and 12 chronic periodontitis (H/P) patients, and the S group consisted of 12 control (S/C) and 12 chronic periodontitis (S/P) patients. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), and clinical attachment loss (CAL) scores were recorded. RESULTS: The mean of all clinical parameters (PI, GI, BOP, PD, and CAL) were significantly (P<0.05) higher in periodontitis groups (H/P and S/P) than controls (H/C and S/C). There were no significant differences in the PD and CAL scores between periodontitis groups (S/P and H/P). The mean of GI and BOP scores were statistically higher in the H/P group than the S/P group (P<0.05). There was a negative correlation between GI and free testosterone levels (r=-0.794; P<0.05). CONCLUSION: According to these results, serum testosterone levels may possibly influence periodontal disease in men, and testosterone may have an inhibitory effect on gingival inflammation.

Thyrotropinoma with Graves' disease detected by the fusion of indium-111 octreotide scintigraphy and pituitary magnetic resonance imaging.

Thyroid-stimulating hormone-secreting pituitary adenoma (TSHoma) is a rare benign endocrinological tumor which produces TSH in the pituitary gland. Herein, we presented a female patient having TSHoma with Graves' disease during and just after pregnancy that we found by indium-111 octreotide scintigraphy while investigating the patient for hyperthyroidism symptoms.

The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis.

OBJECTIVE: Fatty pancreas (FP) is related to obesity, and may have some clinical implications on glucose metabolism. The frequency and importance of FP in patients with nonalcoholic steatohepatitis (NASH) are not clear. This study aimed to investigate: the frequency of FP in patients with NASH, and its effects on serum glucose parameters. METHODS: FP was detected and graded by transabdominal ultrasonography (USG) in patients with biopsy-proven NASH and healthy controls. Body Mass Index and waist circumference were recorded, and serum lipids, fasting serum glucose, HbA1c, OGTT 2-h, insulin level, insulin resistance, type 2 diabetes mellitus (DM) and prediabetes rates were detected. RESULTS: Eighty-four subjects with NASH and 35 healthy controls were enrolled in the study. There was no FP in 41 (48.8%) of the NASH patients according to the study criteria. Forty-three of the NASH patients and 5 of the controls had different grades of fat in their pancreas (51.2% vs. 14%, p=0.001). The HbA1c and OGTT 2-h results were significantly higher in NASH patients with FP compared to those without FP (p=0.003 and p=0.018). The rates of both prediabetes and DM were also found to be significantly increased in NASH patients with FP (p=0.004). The mean waist circumference was higher in patients with FP (p=0.027). Grade of FP by USG showed no effect on study parameters in subgroup analysis. CONCLUSION: FP is common in patients with NASH and increases the rate of prediabetes and DM. The coexistence of both NASH and FP has a further impact on glucose metabolism and DM frequency.

Effects of androgen replacement therapy on cornea and tear function in men with idiopathic hypogonadotropic hypogonadism.

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) is an endocrine disorder defined with the presence of typical clinical signs and symptoms plus laboratory confirmation of serum testosterone (T) levels lower than 300 ng/dl. Androgen replacement therapy (ART) is the first-step treatment of male IHH. To date, no clinical trial, which investigates the changes on corneal structure and tear function, of systemic ART in men have been published. The objective of this study was to investigate the effects of ART on cornea and tear function in patients with IHH. MATERIALS AND METHODS: This prospective, interventional study was conducted at the Gulhane Military Medical Academy, Ankara, Turkey, a tertiary referral military hospital. Thirty-four eyes of 17 men with IHH patients were evaluated with Schirmer I test, ultrasound pachymeter, applanation tonometer and confocal microscopy. A Testosterone compound (Sustanon® 250 mg) was administered by intramuscular injection in the course of a 3-week period to induce puberty, and human chorionic gonadotropin (Pregnyl® 5000 IU) was administered twice weekly for 3 months to induce fertility. The patients were re-evaluated at the third month of the treatment. Main Outcome Measures were Schirmer score, central corneal thickness (CCT), intraocular pressure (IOP), endothelial cell density, coefficient of variation and cell shape. RESULTS: Schirmer scores showed similar results after the treatment compared to pre-treatment levels (p = 0.14). There was no statistically significant difference in CCT and IOP compared to baseline data (p = 0.96, p = 0.73, respectively), and no significant differences were found in corneal endothelial cell density, percentage of cell size variability or hexagonality (p = 0.83, p = 0.58, p = 0.64, respectively). CONCLUSIONS: This is the first study that investigates the effects of ART on corneal structure and tear function in men. ART seems to have no short-term effects on corneal structure and tear function. Further publications of larger, long-term and controlled studies are needed.

Diurnal leptin secretion is intact in male hypogonadotropic hypogonadism and is not influenced by exogenous gonadotropins.

Circulating leptin shows a pulsatile secretory pattern along with a nocturnal rise. We have previously shown that circulating leptin concentrations are high in males with untreated idiopathic hypogonadotropic hypogonadism (IHH). However, circadian leptin secretion in IHH before and after gonadotropin treatment is not known. Thus, we studied 14 adult males with IHH who had no history of previous hormonal therapy, and 12 age- and body mass index-matched healthy men. Plasma leptin concentrations were measured with 1-h intervals for 24 h before and 6 months after gonadotropin treatment. The 24-h mean leptin concentration showed a significant decrease, from 11.78 +/- 1.908 microg/liter at baseline to 10.85 +/- 1.939 microg/liter after 6 months of therapy (z = 3.107; P = 0.002). Before and after treatment, 24-h mean leptin concentrations were also significantly higher in the patient group when compared with controls (4.275 +/- 0.711 microg/liter) (z = 5.938; P = 0.0001). Hourly leptin levels demonstrated a diurnal pattern in hypogonadal patients, a surge in the midday, and a peak just after midnight, and this pattern did not differ before and after treatment. We observed a similar diurnal pattern in the control subjects too. Leptin levels were negatively and significantly correlated with free testosterone and total testosterone levels both before (r = -0.656, P = 0.011; and r = -0.639, P = 0.014, respectively) and after (r = -0.537, P = 0.048; and r = -0.563, P = 0.036, respectively) gonadotropin administration. Our observations suggest that the diurnal rhythm of leptin is intact in males with IHH, and short-term gonadotropin treatment does not effect its diurnal rhythm. Moreover, testosterone produced under the influence of the gonadotropin treatment led to decreases in the leptin levels.

Increased oxidative stress and hypozincemia in male obesity.

OBJECTIVES: Antioxidants protect an organism from the detrimental effects of free radicals via scavenging or inhibiting their formation. Alterations in the levels of antioxidants and several essential trace elements in the plasma and various tissues of ob/ob mice have been reported previously. The aim of this study was to investigate oxidative status and trace elements in obese individuals. DESIGN AND METHODS: Seventy-six obese men (body mass index (BMI) > 30 kg/m(2)) and 24 healthy, age-matched male control volunteers were enrolled in the study. Fasting plasma insulin, glucose, triglyceride (TG), total cholesterol, VLDL, and HDL levels, erythrocyte glutathione peroxidase (GSH-Px) and copper zinc-superoxide dismutase (CuZn-SOD) activities, and erythrocyte thiobarbituric acid reactive substances (TBARS) levels were measured in both groups. Erythrocyte copper (Cu), zinc (Zn) and iron (Fe) levels were also measured. RESULTS: We found that the mean Cu and Fe levels in obese individuals were not significantly different than those in the control group, whereas the mean Zn levels were significantly lower than those of the control group (p = 0.023). The mean erythrocyte CuZn-SOD and GSH-Px levels in obese individuals were significantly lower than those in controls (p = 0.001) whereas erythrocyte TBARS levels were significantly higher (p = 0.001) than those of the control group. CONCLUSION: We conclude that male obesity is associated with defective antioxidant status and hypozincemia, which may have implications in the development of obesity related health problems.

Voice changes after androgen therapy for hypogonadotrophic hypogonadism.

OBJECTIVES/HYPOTHESIS: Males with isolated hypogonadotropic hypogonadism (IHH) fail to undergo normal sexual development, including the lack of masculinization of the larynx. The objective of this study was to measure the mean vocal fundamental frequency (MF0) in IHH patients and determine the impact of androgen treatment. An additional aim was to compare the MF0 between IHH patients and controls. STUDY DESIGN: Prospective observational study. METHODS: Twenty-four patients with IHH were identified along with 30 normal males and females. Voice recordings were obtained on all subjects. Androgen therapy was administered to the IHH patients. The MF0 and serum sex hormone levels were measured before treatment and at intervals during therapy. These results were compared with the pretreatment data within the IHH group. Voice parameters were also compared between the pre- and posttreatment IHH patients and the normal males and females. RESULTS: The MF0 in untreated IHH patients was 229 +/- 41 Hz. This was intermediate between the normal male (150 +/- 22 Hz, P < .001) and normal female patients (256 +/- 29 Hz, P < .01). After treatment, the MF0 in the IHH group decreased to 173 +/- 30 Hz (P < .0001); indeed, their posttreatment MF0 approached that of normal males (P < .08). Serum hormone levels responded to the injected testosterone, but these levels did not directly correlate with MF0. CONCLUSIONS: MF0 in IHH patients is intermediate between normal male and female levels. After treatment with testosterone, these values approach the range of normal males. This prospective study details the impact of androgens on the larynx and vocal function in patients with IHH.

Evaluation of central neuropathy in type II diabetes mellitus by multimodal evoked potentials.

The electrophysiological results in 51 patients with diabetes mellitus type II were compared with those in 30 age and sex matched healthy control subjects. Peripheral and cortical latencies of median and tibial somatosensory evoked potentials (SEP), bilateral I-III and I-V interpeak latencies (IPL) of brainstem auditory evoked potentials (BAEP), bilateral P100 latency of visual evoked potentials (VEP) and bilateral cortical latency and central motor conduction time of motor evoked potentials (MEP) were evaluated. We observed prolonged latencies suggestive of central neuropathy in DM type II. It has been shown that most of the electrophysiological parameters in patients with DM type II correlate with the duration of the disease, some of them with the age of the patient, and few of them with the onset of the disease. To our knowledge, there is no correlation between the electrophysiological parameters and the level of glycemia or the degree of metabolic control. We conclude that central and peripheral neuropathies in DM are related to the duration of the disease and not to the degree of hyperglycemia and metabolic control.