Serum Testosterone Levels and Symptom-Based Depression Subtypes in Men

The main objective of this preliminary study was to further clarify the association between testosterone (T) levels and depression by investigating symptom-based depression subtypes in a sample of 64 men. The data were taken from the ZInEP epidemiology survey. Gonadal hormones of a melancholic (n  = 25) and an atypical (n = 14) depression subtype, derived from latent class analysis, were compared with those of healthy controls (n  = 18). Serum T was assayed using an enzyme-linked immunosorbent assay procedure. Analysis of variance, analysis of covariance, non-parametrical tests, and generalized linear regression models were performed to examine group differences. The atypical depressive subtype showed significantly lower T levels compared with the melancholic depressives. While accumulative evidence indicates that, beyond psychosocial characteristics, the melancholic and atypical depressive subtypes are also distinguishable by biological correlates, the current study expanded this knowledge to include gonadal hormones. Further longitudinal research is warranted to disclose causality by linking the multiple processes in pathogenesis of depression.

Low serum testosterone and increased diastolic ocular perfusion pressure: a risk for retinal microvasculature

BACKGROUND Low levels of testosterone in men and changes in retinal microvascular calibre are both associated with hypertension and cardiovascular disease risk. Sex hormones are also associated with blood flow in microvascular beds which might be a key intermediate mechanism in the development of hypertension. Whether a direct association between endogenous testosterone and retinal microvascular calibre exists is currently unknown. We aimed to determine whether testosterone is independently associated with ocular perfusion via a possible association with retinal vascular calibre or whether it plays only a secondary role via its effect on blood pressure in a bi-ethnic male cohort. PROBANDS AND METHODS A total of 72 black and 81 white men (28-68 years of age) from the follow-up phase of the Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study were included in this sub-study. Ambulatory pulse pressure and intraocular perfusion pressures were obtained, while metabolic variables and testosterone were measured from fasting venous blood samples. Retinal vascular calibre was quantified from digital photographs using standardised protocols. RESULTS The black men revealed a poorer cardiometabolic profile and higher pulsatile pressure (>50 mm Hg), intraocular pressure and diastolic ocular perfusion pressure than the white men (p≤0.05). Only in the white men was free testosterone positively associated with retinal calibre, i.e. arterio-venular ratio and central retinal arterial calibre and inversely with central retinal venular calibre. These associations were not found in the black men, independent of whether pulse pressure and ocular perfusion pressure were part of the model. CONCLUSIONS These results suggest an independent, protective effect of testosterone on the retinal vasculature where an apparent vasodilatory response in the retinal resistance microvessels was observed in white men.

EMAS position statement: Testosterone replacement therapy in the aging male‏.

INTRODUCTION Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. AIMS The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. MATERIALS AND METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment.

Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity

Microbial exposures and sex hormones exert potent effects on autoimmune diseases, many of which are more prevalent in women. We demonstrate that early-life microbial exposures determine sex hormone levels and modify progression to autoimmunity in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D). Colonization by commensal microbes elevated serum testosterone and protected NOD males from T1D. Transfer of gut microbiota from adult males to immature females altered the recipient's microbiota, resulting in elevated testosterone and metabolomic changes, reduced islet inflammation and autoantibody production, and robust T1D protection. These effects were dependent on androgen receptor activity. Thus, the commensal microbial community alters sex hormone levels and regulates autoimmune disease fate in individuals with high genetic risk.

Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women

OBJECTIVE: Only a few studies have investigated variations of different markers for inflammatory processes during the physiological menstrual cycle. The results are conflicting, particularly concerning the correlation between the marker leptin and steroid hormones. The aim of the study was to investigate the inflammatory markers C-reactive protein (CRP) and leptin in the serum of healthy, normally ovulating women and to correlate these with each other and with the hormones of the gonadal axis. A cycle-dependence of the markers studied would imply an exact timing of the blood sampling for clinical needs. DESIGN: Observational study investigating the two inflammatory markers CRP and leptin in relation to the hormonal pattern of the gonadal axis during the normal cycle. METHODS: Ovulatory cycles of 36 healthy, young, normo-androgenic women, having a normal body mass index were evaluated. Serum concentrations of leptin and CRP, as well as of follicle-stimulating hormone, luteinising hormone, 17beta-oestradiol, progesterone, prolactin (PRL) and free testosterone were measured every 1-2 days during one full cycle. RESULTS: Serum levels of leptin and CRP behaved differently during ovulatory cycles, with higher concentrations for leptin only during certain phases. Significant correlations were found in the follicular phase between leptin and PRL and leptin and free testosterone. CONCLUSIONS: Leptin levels change during the menstrual cycle. Leptin levels are more stable on cycle days 1-5 than later in the cycle. For precise cycle-independent measurements, these fluctuations have to be taken into account. There is no similar cyclic pattern for CRP.

Effect of testosterone on E1S-sulfatase activity in non-malignant and cancerous breast cells in vitro

INTRODUCTION: Testosterone (T) is a therapeutic option for women with hypoactive sexual desire disorder. T may have an impact on the mammary gland by altering local estrogen synthesis. The aim of the present study was to measure the effect of T on estrone-sulfate (E1S)-sulfatase (STS) expression, and activity using hormone-dependent BC cells with high and low aggressive potential (BT-474, MCF-7), and HBL-100 as a breast cell line of non-malignant origin. METHODS: Cells were incubated in RPMI 1640 medium containing 5% steroid-depleted fetal calf serum for 3d, and subsequently incubated in absence or presence of T alone, and combined with anastrozole (A) at 10(-8)M, and 10(-6)M at 37 degrees C for either 24h or directly in cell extracts ("direct"). STS protein expression was measured by dot-blot (immunoblotting), and STS, HSD17B1 and HSD17B2 mRNA levels by quantitative RT-PCR. STS activity was evaluated by incubating homogenized breast cells with [(3)H]-E1S and separating the products E1, and E2 by thin layer chromatography. RESULTS: Basal STS mRNA expression did not reveal group differences. However, STS mRNA was decreased by T+A in MCF-7 cells. 17HSDB1 expression was decreased by T+A in BT-474 cells, and 17HSDB2 expression was decreased by A and T+A treatment in MCF-7 cells. Basal and T treated STS protein expression was significantly higher in malignant compared to non-malignant breast cells. However, T did not induce significant intra-cell line differences. Similarly, basal and T treated STS activity was significantly higher in highly malignant compared to non-malignant breast cells. Regardless of cell lines, T slightly decreased STS activity after "direct" incubation, but led to an increase of local estrogen formation after 24h which was attenuated, and partly reversed by A, respectively. CONCLUSIONS: The more aggressive the breast cell line, the higher the local estrogen formation. The transition from normal to malignant seems to be accompanied by an altered autoregulation. The given local endocrine milieu seems to be essential for response to T.

Aromatase deficiency caused by a novel P450arom gene mutation: impact of absent estrogen production on serum gonadotropin concentration in a boy.

We identified a new point mutation in the CYP19 gene responsible for aromatase (P450arom) deficiency in a 46,XY male infant with unremarkable clinical findings at birth. This boy is homozygote for a 1-bp (C) deletion in exon 5 of the aromatase gene causing a frame-shift mutation. The frame-shift results in a prematurely terminated protein that is inactive due to the absence of the functional regions of the enzyme. Aromatase deficiency was suspected prenatally because of the severe virilization of the mother during the early pregnancy, and the diagnosis was confirmed shortly after birth. Four weeks after birth, the baby boy showed extremely low levels of serum estrogens, but had a normal level of serum free testosterone; in comparison with the high serum concentration of androstenedione at birth, a striking decrease occurred by 4 weeks postnatally. We previously reported elevated basal and stimulated FSH levels in a female infant with aromatase deficiency in the first year of life. In contrast, in the male infant, basal FSH and peak FSH levels after standard GnRH stimulation tests were normal. This finding suggests that the contribution of estrogen to the hypothalamic-pituitary gonadotropin-gonadal feedback mechanism is different in boys and girls during infancy and early childhood. In normal girls, serum estradiol concentrations strongly correlate with circulating inhibin levels, and thus, low inhibin levels may contribute to the striking elevation of FSH in young girls with aromatase deficiency. In contrast, estradiol levels are physiologically about a 7-fold lower in boys than in girls, and serum inhibin levels remain elevated even though levels of FSH, LH, and testosterone are decreased.

Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

BACKGROUND Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. METHODS Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. RESULTS The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; p<0.05). CONCLUSIONS An interdependence between acute mental stress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels.

Hyperglycaemia but not hyperlipidaemia decreases serum amylase and increases neutrophils in the exocrine pancreas of cats

The goal of the study was to determine whether hyperglycaemia or hyperlipidaemia causes pancreatitis in cats and to assess the effect of excess serum glucose and lipids on amylase and lipase activity. Ten-day hyperglycaemic and hyperlipidaemic clamps were carried out in five and six healthy cats, respectively. Ten healthy cats received saline and served as controls. The activity of amylase was below the normal range in 4 of 5 hyperglycaemic cats by day 10. The activity of lipase did not vary in any of the cats. Samples of exocrine pancreas were normal on histological examination, but the number of tissue neutrophils was increased in hyperglycaemic cats (P<0.05). In a retrospective study 14 of 40 (35%) cats with naturally occurring diabetes mellitus had amylase activities below the reference range at the time of admission. Amylase activities normalised within 1 week of insulin therapy and subsequent glycaemic control. Lipase activity was increased in 26 of 40 (65%) diabetic cats and remained elevated despite glycaemic control. In conclusion, hyperglycaemia, but not hyperlipidaemia, increases pancreatic neutrophils in cats. However, because the histological morphology of the exocrine pancreas was normal, hyperglycaemia may play only a minor role in the pathogenesis of pancreatitis. Low amylase activities in diabetic cats may reflect an imbalance in glucose metabolism rather than pancreatitis.

Neuropeptide Y acts within the rat testis to inhibit testosterone secretion

The factors that influence Leydig cell activity currently include peptides such as neuropeptide Y (NPY). In this work we investigated the ability of this compound, injected directly into the testes of adult male rats, to alter testosterone (T) release into the general circulation. At a 5μg/kg dose administered 1h prior to challenge with human chorionic gonadotropin (hCG, 1.0 U/kg, iv), NPY significantly (P<0.01) blunted the T response to this gonadotropin. The inhibitory effect of NPY was observed in animals pretreated with an antagonist to gonadotropin-releasing hormone or not, indicating that the decrease in plasma T found was most likely independent of pituitary luteinizing hormone. However, testicular levels of steroidogenic acute regulatory (STAR) protein or translocator protein (TSPO) in the Leydig cells did not exhibit consistent changes, which suggested that other mechanisms mediated the blunted T response to hCG. We therefore used autoradiography and immunohistochemistry methodologies to identify NPY receptors in the testes, and found them primarily located on blood vessels. Competition studies further identified these receptors as being Y(1), a subtype previously reported to modulate the vasoconstrictor effect of NPY. The absence of significant changes in STAR and TSPO levels, as well as the absence of Y(1) receptors on Leydig cells, suggest that NPY-induced decreases in T release is unlikely to represent a direct effect of NPY on these cells. Rather, the very high expression levels of Y(1) found in testicular vessels supports the concept that NPY may alter gonadal activity, at least in part, through local vascular impairment of gonadotropin delivery to, and/or blunted T secretion from, Leydig cells.

Influence of total and specific IgE, serum tryptase, and age on severity of allergic reactions to Hymenoptera stings

The aim of this study was to analyze the influence of total serum IgE and other potential risk factors on severity of systemic allergic Hymenoptera sting reactions.

Determination of voriconazole in human serum and plasma by micellar electrokinetic chromatography

The micellar electrokinetic capillary chromatography (MEKC) separation and analysis of voriconazole and UK 115794 (internal standard) were examined and an assay for determination of voriconazole in human plasma and serum was developed. The MEKC medium comprises a 2:15 (v/v) mixture of methanol and a pH 9.3 buffer composed of 5mM Na(2)B(4)O(7), 7 mM Na(2)HPO(4) and 54 mM SDS. Sample preparation is based upon liquid/liquid extraction with ethylacetate and dichloromethane (75%/25%) at physiological pH. Using this approach with 250 microl serum or plasma and reconstitution of the dried extract into 100 microl of a buffer composed of 0.5mM Na(2)B(4)O(7) and 0.7 mM Na(2)HPO(4) (pH 9.3), the detection and quantitation limits were determined to be 0.1 and 0.2 microg/ml, respectively, a sensitivity that is suitable for therapeutic drug monitoring of voriconazole (provisional therapeutic range: 1-6 microg/ml) in human plasma and serum samples. The method was validated and compared to an HPLC method, showing excellent agreement between the two for a set of 91 samples that stemmed from patients being treated with voriconazole. The MEKC assay is also demonstrated to be suitable to explore pharmacokinetic data of voriconazole.

LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum

Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT, MiPT, DMT, and 5MeO-DMT are contained in the tryptamine group, BZP, MDBP, TFMPP, mCPP, and MeOPP in the piperazine group. Using an Applied Biosystems LC-MS/MS API 365 TurboIonSpray it is possible to identify all 35 substances. After addition of internal standards and mixed-mode solid-phase extraction the analytes are separated using a Synergi Polar RP column and gradient elution with 1 mM ammonium formate and methanol/0.1% formic acid as mobile phases A and B. Data acquisition is performed in MRM mode with positive electro spray ionization. The assay is selective for all tested substances. Limits of detection were determined by analyzing S/N-ratios and are between 1.0 and 5.0 ng/mL. Matrix effects lie between 65% and 118%, extraction efficiencies range from 72% to 90%.

Can S-100B serum protein help to save cranial CT resources in a peripheral trauma centre? A study and consensus paper

Cranial CT (CCT) is the gold standard to rule out traumatic brain injury. The serum level of the protein S-100B has recently been proposed as promising marker of traumatic brain injury. We prospectively investigated whether it might be a reliable tool for CCT triage in mild brain injury at a peripheral trauma centre with limited CT resources.