In silico screening of potential agonists of a glucagon-like peptide-1 receptor among female sex hormone derivatives.

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that exerts its pleiotropic effects through a specific GLP-1 receptor (GLP-1R). The hormone-receptor complex might regulate glucose-dependent insulin secretion, and energy homeostasis; moreover, it could decrease inflammation and provide cardio- and neuroprotection. Additionally, the beneficial influence of GLP-1 on obesity in women might lead to improvement of their ovarian function. The links between metabolism and reproduction are tightly connected, and it is not surprising that different estrogen derivatives, estrogen-receptor modulator (SERM) and progestins used for gonadal and oncological disorders might influence carbohydrate and lipid metabolism. However, their possible influence on the GLP-1R has not been studied. The docking scores and top-ranked poses of raloxifene were much higher than those observed for other investigated SERMs and estradiol per se. Among different studied progestins, drospirenone showed slightly higher affinity to GLP-1R. Herein, the same data set of the drugs is evaluated by molecular dynamics (MD) simulations and compared with the obtained docking result. Notably, it is demonstrated that the used docking protocol and the applied MD calculations ranked the same ligand (raloxifene) as the best one. In the present study, raloxifene might exert an allosteric influence on GLP-1R signaling, which might contribute to potential beneficial effects on metabolism and weight regulation. However, further experimental and clinical studies are needed to reveal if the GLP-1R modulation has a real biological impact.Communicated by Ramaswamy H. Sarma.

Melatonin Receptor 1B and Corticosteroid Receptor Polymorphisms in Infertile Women with Implantation Failure and Miscarriages.

BACKGROUND: The development of assisted reproductive techniques has significantly improved fertility chances in many women, but recurrent implantation failure (RIF) and miscarriages (RM) might preclude successful pregnancy. Alterations in the intrinsic secretory patterns of melatonin and cortisol influence reproduction in humans, and imperfection of receptor - dependent signaling may additionally compromise the hormonal effects. Therefore, the present study aims to investigate the influence of certain melatonin and cortisol receptor polymorphisms in infertile women. METHODS: A total of 111 female infertile patients suffering from implantation failure and/or miscarriages were genotyped for MTNR1B rs1562444, MTNR1Brs10830962, GCCR rs41423247, and GCCR ER22/23EK variants. Additionally, 106 female volunteers were genotyped for the same polymorphisms. RESULTS: The allele and genotype distribution of the investigated polymorphisms did not differ between infertile women and the control group. Significantly more women with history of RIF have MTNR1B rs1562444 G-allele-containing genotypes in comparison to AA carriers (19.3% vs. 3.6%, p = 0.004). The minor allele of the ER22/23EK variant was more frequent in infertile patients with three or more unsuccessful implantation attempts than in other women (12.5% vs. 2.4%, p = 0.025). CONCLUSIONS: Melatonin receptor 1B polymorphisms might affect embryo implantation and early pregnancy loss, while their influence on late pregnancy complications needs further evaluation. The possible association between the cortisol receptor ER22/23EK variant and recurrent implantation failure might help to differentiate women who could benefit from corticosteroid treatment.

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS.

PURPOSE: Polycystic ovarian syndrome (PCOS) is a common heterogeneous condition with probably multifactorial genesis. Animal studies have proven the essential role of the sympathetic nervous system in the syndrome development, while human studies are still contradictory. The present study aims to investigate the possible influence of plasma-free metanephrine (MN), and normetanephrine (NMN), nerve growth factor (NGF), and renalase (RNL) on the hormonal and metabolic parameters in women with PCOS and healthy controls. METHODS: Fifty patients with PCOS and 30 healthy women participated in the study. The plasma-free MN and NMN, NGF, RNL, anti-Mullerian hormone (AMH), gonadotropin, androgen levels, and metabolic parameters were investigated. RESULTS: Plasma-free NMN and NGF concentrations were increased in PCOS individuals, while RNL levels were decreased compared to healthy volunteers. Increased plasma-free NMN (OR = 1.0213 [95%CI 1.0064-1.0364], p = 0.005) and NGF (OR = 1.0078 [95%CI 1.0001-1.0155], p = 0.046) but not MN or RNL levels were associated with a higher risk of PCOS after adjustment for age. Plasma-free NMN levels were positively associated with the LH (r = +0.253; p = 0.039). androstenedione (r = +0.265; p = 0.029), 17-OH progesterone (r = +0.285; p = 0.024), NGF (r = +0.320; p = 0.008), and AMH (r = +0.417; p < 0.001) concentrations of the investigated women. RNL levels were inversely related to the BMI (r = -0.245; p = 0.029), HOMA-IR (r = -0.250; p = 0.030), free testosterone (r = -0.303; p = 0.006) levels. systolic (r = -0.294; p = 0.008) and diastolic (r = -0.342; p = 0.002) blood pressure. CONCLUSIONS: Increased sympathetic noradrenergic activity and NGF synthesis might be related to the increased AMH and delta-4 androgen levels in a subgroup of PCOS patients. RNL levels might influence the metabolic status of PCOS patients. Further studies are needed to explore the significance of adrenal medullar and autonomic dysfunction for developing different PCOS phenotypes and their subsequent cardiovascular complications.

Can dysglycemia in OGTT be predicted by baseline parameters in patients with PCOS?

Background: Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the study: To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methods: The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. Results: Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. Conclusions: One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause.

The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT.

Multivariate Statistical Approach for Nephrines in Women with Obesity.

Catecholamines are physiological regulators of carbohydrate and lipid metabolism during stress, but their chronic influence on metabolic changes in obese patients is still not clarified. The present study aimed to establish the associations between the catecholamine metabolites and metabolic syndrome (MS) components in obese women as well as to reveal the possible hidden subgroups of patients through hierarchical cluster analysis and principal component analysis. The 24-h urine excretion of metanephrine and normetanephrine was investigated in 150 obese women (54 non diabetic without MS, 70 non-diabetic with MS and 26 with type 2 diabetes). The interrelations between carbohydrate disturbances, metabolic syndrome components and stress response hormones were studied. Exploratory data analysis was used to determine different patterns of similarities among the patients. Normetanephrine concentrations were significantly increased in postmenopausal patients and in women with morbid obesity, type 2 diabetes, and hypertension but not with prediabetes. Both metanephrine and normetanephrine levels were positively associated with glucose concentrations one hour after glucose load irrespectively of the insulin levels. The exploratory data analysis showed different risk subgroups among the investigated obese women. The development of predictive tools that include not only traditional metabolic risk factors, but also markers of stress response systems might help for specific risk estimation in obesity patients.

Membrane Melatonin Receptors Activated Cell Signaling in Physiology and Disease.

The pineal hormone melatonin has attracted great scientific interest since its discovery in 1958. Despite the enormous number of basic and clinical studies the exact role of melatonin in respect to human physiology remains elusive. In humans, two high-affinity receptors for melatonin, MT1 and MT2, belonging to the family of G protein-coupled receptors (GPCRs) have been cloned and identified. The two receptor types activate Gi proteins and MT2 couples additionally to Gq proteins to modulate intracellular events. The individual effects of MT1 and MT2 receptor activation in a variety of cells are complemented by their ability to form homo- and heterodimers, the functional relevance of which is yet to be confirmed. Recently, several melatonin receptor genetic polymorphisms were discovered and implicated in pathology-for instance in type 2 diabetes, autoimmune disease, and cancer. The circadian patterns of melatonin secretion, its pleiotropic effects depending on cell type and condition, and the already demonstrated cross-talks of melatonin receptors with other signal transduction pathways further contribute to the perplexity of research on the role of the pineal hormone in humans. In this review we try to summarize the current knowledge on the membrane melatonin receptor activated cell signaling in physiology and pathology and their relevance to certain disease conditions including cancer.

Prevalence and progression of carbohydrate disorders in patients with pheochromocytoma/paraganglioma: retrospective single-center study.

BACKGROUND: Carbohydrate disorders are the most frequent metabolic disorders, affecting a significant proportion of patients with pheochromocytoma. OBJECTIVE: A retrospective study assessed the prevalence and progression of carbohydrate disorders in 204 patients (92 men, 112 women) with histologically proven pheochromocytoma diagnosed in a single specialized tertiary center during a 40-year period (1978-2017). One hundred were followed-up after tumor removal. RESULTS: Carbohydrate disorders were diagnosed in 49.5% of cases: 30.4% with diabetes and, 19.1% prediabetes. Subjects with carbohydrate disorders had significantly greater age at diagnosis and higher 24-hour urine metanephrine and normetanephrine concentrations than those with normal glucose tolerance. One-third of patients with diabetes achieved good glycemic control under oral treatment (54% on metformin monotherapy). One-third of patients overall required preoperative insulin treatment. Postoperative follow-up (100 patients; 5-year mean duration) showed reduced prevalence of diabetes (13% vs. 33%; P=0.0007) and prediabetes (12% vs. 24%; P=0.027). Almost 60% of subjects initially diagnosed with carbohydrate disorders recovered normal glucose tolerance after surgery; these subjects had significantly higher preoperative urine metanephrine/normetanephrine levels than those with persistent diabetes/prediabetes. Correlation analysis revealed a moderate negative relationship between urine metanephrine/normetanephrine concentration and the outcome of the carbohydrate disorders (Spearmen's Rho=-0.507; P=0.013). There was no significant difference according to pre- or postoperative prevalence of obesity (15% vs. 16%; P=0.845) or dyslipidemia (46% vs. 39%; P=0.316). CONCLUSIONS: Carbohydrate disorders affect approximately 50% of pheochromocytoma patients; 30% develop overt diabetes, which may be the only clinical manifestation in some rare cases. Pheochromocytoma-related diabetes is more likely to affect patients with predominant adrenaline secretion. It is often easy to control and usually requires oral antidiabetic treatment. Reversibility of carbohydrate disorders depend on severity, preoperative metanephrine level, age and weight.

Familial Hypercholesterolaemia in a Bulgarian Population of Patients with Dyslipidaemia and Diabetes: An Observational Study.

INTRODUCTION: Patients with diabetes and familial hypercholesterolaemia (FH) are at very high risk of cardiovascular events, but rates of FH detection are very low in most countries, including Bulgaria. Given the lack of relevant data in the literature, we conducted a retrospective observational study to (1) identify individuals with previously undiagnosed FH among patients being treated at Bulgarian diabetes centres, and (2) gain insight into current management and attainment of low-density lipoprotein cholesterol (LDL-C) goals in such patients. METHODS: From a database of diabetes centres across Bulgaria we retrieved medical records from patients aged ≥ 18 years with type 1/2 diabetes mellitus (T1DM/T2DM) who were being treated with insulin/insulin analogues, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors. Patients with FH (Dutch Lipid Clinic Network score ≥ 3) were identified, and their data analyzed (lipid-modifying therapy (LMT), diabetes treatment, cardiovascular events and glycaemic and lipid parameters). RESULTS: A total of 450 diabetic patients with FH (92.0% with T2DM; 52.4% receiving insulin/insulin analogues) were included in the analysis. LMT consisted of statin monotherapy (86% of patients; 18% receiving high-intensity statin monotherapy), statin-based combination therapy (13%) or fenofibrate (< 1%). Median LDL-C was 4.4 mmol/L. Although 30% of patients had a glycated haemoglobin level of ≤ 7%, only one patient (< 1%) achieved the LDL-C target recommended in 2016 European guidelines for very high-risk patients (< 1.8 mmol/L). Previous cardiovascular events were documented in 40% of patients. CONCLUSION: To our knowledge, this is the first study to specifically explore lipid target achievement in diabetic patients with FH. In this preselected Bulgarian population, < 1% of patients achieved the 2016 European guideline-defined LDL-C target. These data highlight the importance of identifying FH in diabetic patients as early as possible so that they can receive appropriate treatment.

Causes and Metabolic Consequences of Gynecomastia in Adult Patients.

BACKGROUND: Gynecomastia (GM) is a benign enlargement of male breast due to glandular tissue proliferation. GM is a symptom of systemic or local hormonal disturbances, which could be associated with functional changes or pathological conditions. However, the long-lasting steroid imbalance in men with GM might exert negative influence on their metabolic health. METHODS: A total of 110 adult men with symptomatic GM were included in the present retrospective cross-sectional study. Anthropometric, metabolic, and hormonal data of the patients were collected. RESULTS: In almost 64% of GM patients, the underlying pathological condition was identified. Moreover, the development of GM was among the primary symptoms leading to the proper diagnosis in more than 40% of hypogonadal patients. The prevalence of metabolic syndrome (MS) was 53%; the highest prevalence of MS was found in patients with medication-induced GM and in the hypogonadal patients, whereas the lowest prevalence was observed in men with idiopathic postpubertal GM despite the similar degree of obesity. The lower testosterone levels were associated with more unfavorable lipid profile in the GM patients. CONCLUSION: The development of GM in adults might be an important symptom of an underlying gonadal disease. Moreover, it could be associated with an increased risk of metabolic disturbances. Our results support the need of detailed laboratory and hormonal investigations in patients with GM including targeted screening for metabolic disturbances. Further longitudinal studies are needed to evaluate the long-term consequences of sex hormones imbalance on cardiovascular morbidity and mortality in adults with GM.

Standardised data collection for clinical follow-up and assessment of outcomes in differences of sex development (DSD): recommendations from the COST action DSDnet.

The treatment and care of individuals who have a difference of sex development (DSD) have been revised over the past two decades and new guidelines have been published. In order to study the impact of treatments and new forms of management in these rare and heterogeneous conditions, standardised assessment procedures across centres are needed. Diagnostic work-up and detailed genital phenotyping are crucial at first assessment. DSDs may affect general health, have associated features or lead to comorbidities which may only be observed through lifelong follow-up. The impact of medical treatments and surgical (non-) interventions warrants special attention in the context of critical review of current and future care. It is equally important to explore gender development early and refer to specialised services if needed. DSDs and the medical, psychological, cultural and familial ways of dealing with it may affect self-perception, self-esteem, and psychosexual function. Therefore, psychosocial support has become one of the cornerstones in the multidisciplinary management of DSD, but its impact remains to be assessed. Careful clinical evaluation and pooled data reporting in a global DSD registry will allow linking genetic, metabolomic, phenotypic and psychological data. For this purpose, our group of clinical experts and patient and parent representatives designed a template for structured longitudinal follow-up. In this paper, we explain the rationale behind the selection of the dataset. This tool provides guidance to professionals caring for individuals with a DSD and their families. At the same time, it collects the data needed for answering unsolved questions of patients, clinicians, and researchers. Ultimately, outcomes for defined subgroups of rare DSD conditions should be studied through large collaborative endeavours using a common protocol.

Long-term follow-up of a female patient with non-classical 11ß-hydroxylase deficiency and two novel mutations in CYP11B1.

11ß-Hydroxylase deficiency is the second most common enzyme disorder after 21-hydroxylase deficiency causing congenital adrenal hyperplasia (CAH11ß). In females, the clinical phenotype of CAH11ß classic forms is associated with ambiguous genitalia, virilization and hypertension, while most common complaints in milder non-classic forms include hirsutism, acne, menstrual disturbances, and infertility. Herein, we present clinical and genetic characteristics of an adult woman with 11ß-hydroxylase deficiency, hypertension and infertility; she has been followed up from her first pregnancy to her early menopause. Genetic analyses of the patient revealed a compound-heterozygosity due to two variants in the CYP11B1 gene p.Val316Met and p.Asp480ThrfsTer2. Both mutations have not been previously reported as pathogenic in the literature. Emerging questions concerning the clinical management, fertility potential, mineral corticoid abnormalities and perimenopausal transition in patients with non-classic CAH11ß have also been briefly discussed. The presented case of an adult woman with CAH11ß shows that the proper diagnosis and close monitoring of patients with different CAH forms might ensure good therapy adherence and successful fertility.

Caring for individuals with a difference of sex development (DSD): a Consensus Statement.

The term differences of sex development (DSDs; also known as disorders of sex development) refers to a heterogeneous group of congenital conditions affecting human sex determination and differentiation. Several reports highlighting suboptimal physical and psychosexual outcomes in individuals who have a DSD led to a radical revision of nomenclature and management a decade ago. Whereas the resulting recommendations for holistic, multidisciplinary care seem to have been implemented rapidly in specialized paediatric services around the world, adolescents often experience difficulties in finding access to expert adult care and gradually or abruptly cease medical follow-up. Many adults with a DSD have health-related questions that remain unanswered owing to a lack of evidence pertaining to the natural evolution of the various conditions in later life stages. This Consensus Statement, developed by a European multidisciplinary group of experts, including patient representatives, summarizes evidence-based and experience-based recommendations for lifelong care and data collection in individuals with a DSD across ages and highlights clinical research priorities. By doing so, we hope to contribute to improving understanding and management of these conditions by involved medical professionals. In addition, we hope to give impetus to multicentre studies that will shed light on outcomes and comorbidities of DSD conditions across the lifespan.

New Territory for an Old Disease: 5-Alpha-Reductase Type 2 Deficiency in Bulgaria.

Disorders/differences of sexual development (DSD) are a group of conditions, some of which can be clinically indistinguishable mainly due to their phenotypic variability. Defining the molecular basis of their wide spectrum is still in progress. The diagnosis of 5-alpha-reductase type 2 (5α-reductase-2) deficiency is difficult especially in newborns and pre-pubertal individuals, and as a result its frequency might be underestimated. In the present study, we describe the clinical characteristics and molecular defects in 3 nonrelated 5α-reductase-2 deficiency patients of Bulgarian descent. Sequencing analysis revealed the mutations p.Y188CfsX9 and p.G196S, and MLPA analysis showed a deletion of exon 1 in the SRD5A2 gene. The observed genetic substitutions were not detected in 76 additionally screened unrelated controls, but a heterozygous healthy carrier of the p.R171S mutation was found. This is the first study on the molecular basis of 5α-reductase-2 deficiency in Bulgaria. It suggests that the carrier frequency of mutations in the SRD5A2 gene might be noteworthy worldwide. There is no correlation between cultural aspects, location, and/or population size and the number of different mutations in SRD5A2 detected, and more efforts should be made to determine the prevalence of this condition in different geographic areas. Our study supports the importance of genetic testing in 46,XY DSD patients, especially in countries or regions where 5α-reductase-2 deficiency has not been reported so far.

Influence of the body weight on the onset and progression of puberty in boys.

BACKGROUND: Unlike in girls, the data on the relationship between pubertal development and body weight in boys are controversial. METHODS: We measured the height, body weight, body mass index (BMI), pubic hair stages, testicular volume, penis length and circumference of 4030 boys, aged between 7 and 19 years. According to their body weight, the investigated children and adolescents were divided in four groups at each age: underweight boys (BMI <12th percentile), boys with normal weight (12th-84.99th percentile), overweight boys (85th-94.99th percentile) and boys with obesity (BMI ≥95th percentile), and their data were compared. RESULTS: The onset of puberty occurred when the boys' weight gained 40.33±9.03 kg (median 39.00) and BMI was 18.62±3.12 kg/m2 (median 17.80), whereas the late stage was reached at weight of 62.44±10.39 kg (median 61.00) and BMI 21.47±2.84 kg/m2 (median 21.20). Earlier maturing boys were heavier than their coevals, whereas underweight boys developed puberty later. CONCLUSIONS: The onset and progression of puberty in boys are in a significant positive relationship with weight and BMI. Moreover, in the overweight boys pubertal development begins and comes to the late stage earlier in comparison with normal weight children, whereas in those who are underweight a delay at every stage of the development is observed.

A Novel SRY Gene Mutation p.F109L in a 46,XY Female with Complete Gonadal Dysgenesis.

46,XY complete gonadal dysgenesis (CGD) is a disorder of sexual development that can result from different mutations in genes associated with sex determination. Patients are phenotypically females, and the disease is often diagnosed in late adolescence because of delayed puberty. Here, we present the clinical and molecular data of a 46,XY female CGD patient with gonadoblastoma with dysgerminoma and incidentally found inherited thrombophilia. The clinical significance of the described de novo SRY gene mutation c.325T>C (p.F109L) is discussed. This case report supports the critical role of the HGM domain in the SRY gene and the need of a multidisciplinary approach for CGD patients.

Does an Association between the Idiopathic Left-Sided Varicocele and Eye Colour Exist?

The possible interrelation between male reproductive disorders and iris pigmentation is poorly understood. We have found a link between eye colour and the existence of adolescent varicocele. Therefore, we aimed to extend our investigation on the relationship between the eye colour and varicocele in adult men. 231 andrology outpatients from Caucasian origin were included in the study. The presence of varicocele, sperm disturbances, and the iris pigment of the patients were investigated. Left-sided varicocele was found in 93 adults. In the group of light-eyed men the prevalence of varicocele was significantly lower than among the dark-eyed men (15% versus 59.5%, P < 0.001). No associations were found between the eye colour and disturbances in semen parameters in males with varicocele (P = 0.419) and in those without varicocele (P = 0.586). The present results in adult men suggest that the prevalence of varicocele could be associated with the iris pigment. A possible genetic linkage between the eye colour and the susceptibility to some disorders like varicocele could not be excluded. However, the iris pigmentation seems not to have a direct relationship with the sperm disturbances.

Androgen receptor (CAG)n polymorphism and androgen levels in women with systemic lupus erythematosus and healthy controls.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects mainly females. Therefore, interrelations between the reproductive and immune system have been assumed. Considering the complex influence of hormones and receptors, we aimed to investigate the influence of androgens and androgen receptor (AR) polymorphism in women with SLE. One hundred and sixteen patients and 44 healthy women were investigated. Testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulphate (DHEAS) concentrations and AR (CAG)n polymorphism were determined. SLE patients had significantly lower levels of total and free testosterone and DHEAS in comparison with the controls. No differences in the CAG repeat length between the groups were established. Women with two alleles carrying more than 22 CAG repeats had significantly higher levels of SHBG (101.51 ± 61.81 vs. 69.22 ± 45.93 nmol/l, p = 0.015) and DHEAS (3.11 ± 2.65 vs. 2.11 ± 3.06 µmol/l, p = 0.007) and a tendency to higher testosterone concentrations (2.35 ± 2.10 vs. 1.71 ± 1.70 nmol/l, p = 0.056) in comparison with other women. The CAG repeat length in the relatively longer (CAG)n allele was inversely related to the Systemic Lupus International Collaborating Clinics/ACR index (r = -0.258, p = 0.009). In conclusion, the androgen receptor (CAG)n polymorphism is not related to the development of SLE, but it could modulate the severity of the lupus chronic damages as well as the androgen levels in women.

Decreased daily melatonin levels in women with systemic lupus erythematosus - a short report.

BACKGROUND: The neuroendocrine system is known to influence immunity, but the precise interactions between different hormones and autoimmune disorders remain obscure. AIMS: The present study aimed to investigate the role of daily serum melatonin concentrations in the development of systemic lupus erythematosus (SLE) in women. STUDY DESIGN: Case-control study. METHODS: One-hundred and eleven SLE female patients and 46 healthy women were included in the study. Daily serum melatonin levels were investigated in all participants. RESULTS: SLE patients showed significantly lower daily melatonin levels in comparison to healthy women during the short photoperiod (17.75±7.13 pg/mL [16.05] vs. 21.63±6.60 pg/mL [20.10], p=0.012). Hormone concentrations were inversely related to the SLE activity index (SLEDAI) (r= -0.268, p=0.004), but they did not correlate to any particular American College Rheumatology (ACR) criterion (p>0.05 for all). CONCLUSION: Daily melatonin levels were decreased in women with systemic lupus erythematosus and correlated inversely to the activity of the autoimmune disease. Further studies are needed to clarify the importance of the pineal and extrapineal melatonin secretion in patients with systemic lupus erythematosus as well as the interrelations between hormones and autoimmunity.

Sperm disturbances in metabolic syndrome: what we actually know.

Evaluation of: Lotti F, Corona G, Degli Innocenti S et al. Seminal, ultrasound and psychobiological parameters correlate with metabolic syndrome in male members of infertile couples. Andrology 1(2), 229-239 (2013). Male hypogonadism is considered a fundamental component of metabolic syndrome (MetS), but the data concerning sperm quality in men with MetS are still scarce. The role of MetS in male fertility is poorly investigated owing to the fact that the prevalence of metabolic syndrome increases with age and peaks at the time when reproductive plans of couples are already accomplished. However, the worldwide trend towards a younger age of MetS development, owing to the increase in obesity, and the tendency for reproduction later in life could aggravate the influence of the metabolic disturbances on male reproduction. The present article is an important step in the study of the interrelations between MetS and subfertility.