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Aim. The purpose of this study was to examine various hormonal, biochemical and environmental factors (i.e., smoking and alcohol intake) and to investigate their possible correlation to the development of polycystic ovary syndrome (PCOS). The main objective was to evaluate the associations between hormonal profile and the antimüllerian hormone (AMH) levels in PCOS patients and their relation to environmental factors. Patients and Methods. In two gynecological clinics, 38 women with PCOS (defined according to the Rotterdam criteria) were enrolled and observed in relation to AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), Δ4-androstendione (Δ4-A), dehydroepiandrosterone sulfate (DHEA-S) and glucose plasma concentrations. Obesity, smoking and alcohol exposure were also studied. Results. AMH, T, Δ4-Α, DHEA-S, LH and FSH were increased in 76.3%, 50%, 31.8%, 23.7%, 21% and 18.4% of the patients, respectively. The LH/FSH ratio and glucose concentrations increased abnormally in 18.4% and 15.8% of the patients, respectively. AMH and T levels were both increased in 47.4% of the patients whereas both AMH and LH levels increased in 21% of the patients. Smoking, alcohol intake, obesity and glucose concentrations were not associated with AMH concentrations. On the contrary, high levels of T and LH were linked to higher levels of AMH. FSH concentrations were not increased in these patients. Conclusion. AMH is an important hormonal parameter for the diagnosis of PCOS. Larger clinical controlled studies are necessary in an effort to further investigate the inclusion of AMH measurement in the diagnostic criteria of PCOS. © 2017, Acta Endocrinologica Foundation. All rights reserved.

Background: Primary amenorrhea, oligomenorrhea and secondary amenorrhea are diagnosed commonly during adolescence. Weight aberrations are associated with menstrual disorders. Autoimmune thyroiditis is frequent during adolescence. In this study, the commonest clinical and hormonal characteristics of amenorrhea or oligomenorrhea during adolescence were investigated. Methods: In this cross-sectional study, one hundred and thirty-eight consecutive young patients presenting with amenorrhea or oligomenorrhea referred to an adolescent endocrinology and gynecology university clinic were studied. Clinical examination and an abdominal ultrasound were performed. Testosterone, free-testosterone, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, sex hormone binding globulin (SHBG), δ4-androstenedione (δ4A), free androgen index (FAI), insulin, glucose, thyroid stimulating hormone (TSH), total thyroxine (T4) (TT4), free T4 (FT4), total triiodothyronine (T3) (TT3) and free T3 (FT3). Concentrations were measured in blood samples. Results: Patients with primary and secondary amenorrhea presented more often with body mass index (BMI) < 18.5 and BMI > 25 kg/m2, respectively. BMI values correlated positively with insulin (r = 0.742) and glucose (r = 0.552) concentrations and negatively with glucose/insulin ratio values (r =-0.54); BMI values and insulin concentrations correlated positively with FAI values (r = 0.629 and r = 0.399, respectively). In all patients, BMI values correlated positively and negatively with free testosterone (r = 0.249) and SHBG (r =-0.24) concentrations, respectively. In patients with secondary amenorrhea insulin concentrations correlated negatively with SHBG concentrations (r =-0.75). In patients with oligomenorrhea BMI values correlated positively with insulin (r = 0.490) and TSH (r = 0.325) concentrations, and negatively with SHBG (r =-0.33) concentrations. Seventy-two percent, 21% and 7% of patients presented with TSH concentrations < 2.5 μIU/mL, between 2.5 μIU/mL, 4.5 μIU/mL and > 4.5 μIU/mL (subclinical hypothyroidism), respectively. Following the definition of polycystic ovary syndrome (PCOS) according to either the National Institutes of Health (NIH) criteria or those proposed in the literature by Carmina and his team, patients presented mainly with oligomenorrhea or secondary amenorrhea. There was good agreement between patients with amenorrhea or oligomenorrhea fulfilling both of the PCOS definition criteria employed. Conclusions: Among adolescent patients presenting with amenorrhea or oligomenorrhea for the first time those with low and high BMI present more often with primary and secondary amenorrhea, respectively. Obesity is involved in the development of hyperandrogenemia and hyperinsulinemia, particularly in PCOS patients. In these patients, subclinical hypothyroidism may be concealed and it should be investigated. These patients should be treated for abnormally increased or decreased BMI and be investigated for autoimmune thyroiditis.

Thyroid dysfunction is the commonest endocrine disorder in pregnancy apart from diabetes. Thyroid hormones are essential for fetal brain development in the embryonic phase. Maternal thyroid dysfunction during pregnancy may have significant adverse maternal and fetal outcomes such as preterm delivery, preeclampsia, miscarriage and low birth weight. In this review we discuss the effect of thyroid disease on pregnancy and the current evidence on the management of different thyroid conditions in pregnancy and postpartum to improve fetal and neonatal outcomes, with special reference to existing guidelines on the topic which we dissect, critique and compare with each other. Overt hypothyroidism and hyperthyroidism should be treated appropriately in pregnancy, aiming to maintain euthyroidism. Subclinical hypothyroidism is often pragmatically treated with levothyroxine, although it has not been definitively proven whether this alters maternal or fetal outcomes. Subclinical hyperthyroidism does not usually require treatment and the possibility of non-thyroidal illness or gestational thyrotoxicosis should be considered. Autoimmune thyroid diseases tend to improve during pregnancy but commonly flare-up or emerge in the post-partum period. Accordingly, thyroid auto-antibodies tend to decrease with pregnancy progression. Postpartum thyroiditis should be managed based on the clinical symptoms rather than abnormal biochemical results. © 2016 The Authors

Studies in postmenopausal women have identified sclerostin as a strong candidate for mediating estrogen effects on the skeleton. The effects of estradiol on sclerostin and Dickkopf-1 in younger women remain unclear. The main purpose of this study is to investigate the impact of estradiol and gonadotrophins fluctuations during the menstrual cycle on circulating sclerostin and Dickkopf-1 levels and the possible relationship of sclerostin and Dickkopf-1 with changes in N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links. Fourteen healthy premenopausal Caucasian women, with regular menses, aged 33.6 ± 4.5 years participated. After the first day of menstruation and every-other-day up to the next menses, fasting serum estradiol, luteinizing hormone, follicle-stimulating hormone, sclerostin, Dickkopf-1, N-terminal propeptide of type 1 collagen, and C-telopeptide of collagen cross-links levels were measured in peripheral blood. Participants completed dietary questionnaires and the International physical activity questionnaire during the cycle. Neither sclerostin nor Dickkopf-1 levels changed significantly across the menstrual cycle (p = 0.18 and p = 0.39, respectively), while N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links levels presented cyclic variation (p < 0.001 and p = 0.004, respectively). Baseline sclerostin (29.23 ± 10.62 pmol/L) positively correlated with N-terminal propeptide of type 1 collagen (r = 0.71, p < 0.01) and C-telopeptide of collagen cross-links (r = 0.63, p < 0.05), while Dickkopf-1 (4.82 ± 2.23 pmol/L) correlated positively with N-terminal propeptide of type 1 collagen (r = 0.56, p < 0.05). Mid-cycle E2 levels presented significant negative association with the percent decrease of C-telopeptide of collagen cross-links at all-time points during the luteal period (r = −0.60 to −0.68, p < 0.05–0.01). Circulating sclerostin and Dickkopf-1 levels do not change across the menstrual cycle and do not demonstrate any relationship with estradiol in premenopausal women. Further investigation is needed concerning the role of sclerostin and Dickkopf-1 on bone turnover in young estrogen-sufficient women. © 2016, Springer Science+Business Media New York.

A 43-year-old woman, previously misdiagnosed as having primary hyperthyroidism and treated with antithyroid drugs, presented to us with overt hyperthyroidism, high levels of thyroid hormones and elevated thyroid-stimulating hormone (TSH). Μagnetic resonance imaging (MRI) revealed a pituitary microadenoma extending suprasellarly. The patient responded favorably to initial treatment with somatostatin analogs for 2 years but due to the escape phenomenon, TSH levels escalated and hyperthyroidism relapsed. Transsphenoidal adenomectomy was applied but recurrence was again observed due to incomplete tumor removal. Gamma knife radiosurgery was finally employed 5.5 years ago, resulting in complete disease remission without evidence of long-term complications to date. Thyrotropin-secreting adenomas (TSHomas) are rare with an estimated prevalence of about one case per million. We retrieved from the literature 14 cases of TSHomas treated by gamma knife radiosurgery and compared the outcomes. Our results demonstrate the efficacy and safety of gamma knife radiosurgery for achieving remission in most of the cases, suggesting validation of this technique as an effective treatment option for the management of recurrent TSHomas. © 2016, Hellenic Endocrine Society. All rights reserved.

Aim: The aim of this study was to determine the potential therapeutic benefit of a single administration of a GnRH analogue in premenopausal women presenting large functional ovarian cysts (FOCs) (diameter > five cm). Materials and Methods: Fifty-one patients (median age 37.4 years) diagnosed with ovarian cysts, presumed benign based on transvaginal and/or transabdominal ultrasound, were divided in three study groups. Patients of group A received no medication whereas patients of groups B and C were treated with a single administration of a GnRH analogue and combined oral contraceptives, respectively. Patients were re-examined after a three-month period. Three of the 51 patients were lost in follow-up or stopped the treatment. Results: Complete resolution of the ovarian cysts was observed in eight (50%), 14 (70%), and eight (67%) patients of groups A, B, and C, respectively. No side effects were observed in either of the three groups. The positive therapeutic effect in group B did not reach statistical significance compared with the two other groups (p > 0.05). Conclusion: A new option of treating large FOCS through a single-dose of a GnRH analogue is proposed and should be carefully considered. Further research is needed in order to evaluate GnRH analogues as an alternative treatment.

Purpose: The aim of this study was to estimate the prevalence, to evaluate the characteristics of the metabolic syndrome (MetS) in Greek women with polycystic ovary syndrome (PCOS) and to investigate the correlation of MetS with body mass index (BMI). Methods: In a prospective controlled study, 230 Greek female patients with PCOS and 155 age-matched healthy controls were enrolled. Diagnosis of PCOS was based on the revised criteria of Rotterdam. Both groups were examined for MetS. Diagnosis of MetS was based on the revised criteria of International Diabetes Federation (IDF). Results: The prevalence of the MetS was 12.6 %, nearly sevenfold higher than the controls. Elevated fasting plasma glucose (7.0 vs. 1.9 %) and elevated triglycerides (10.4 vs. 3.2 %) were more frequent in the PCOS cohort (p

Objective: Preterm birth is a major cause of neonatal morbidity and mortality in the developed world. In order to better understand the pathophysiological pathway of this condition, the role of genetic factors and/or inflammation-associated molecules, as well as of socioeconomic parameters, is therefore under intense investigation. The purpose of this review study was to examine the potential role of maternal serum relaxin levels in the etiology of preterm birth.Methods: Electronic databases (Pubmed, Embase, Cochrane Library) were searched for previously published research studies that investigated the biological role of relaxin and the mechanisms in which this hormone is involved during pregnancy and labor.Results: It is evident that while relaxin is an essential endometrial/decidual angiogentic factor playing a vital role in maternal accommodation of pregnancy, elevated levels of this hormone could well be associated with preterm birth.Conclusions: There are strong indications that maternal serum hyperrelaxinemia correlates with an increased risk of preterm birth. © 2014 Informa UK Ltd.

The cytokine granulocyte colony-stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate hematopoietic stem cell mobilization, myelopoiesis, and the production and activation of neutrophils. In response to exercise-induced muscle damage, G-CSF is increased in circulation and G-CSFR has recently been identified in skeletal muscle cells. While G-CSF/G-CSFR activation mediates pro- and anti-inflammatory responses, our understanding of the role and regulation in the muscle is limited. The aim of this study was to investigate, in vitro and in vivo, the role and regulation of G-CSF and G-CSFR in skeletal muscle under conditions of muscle inflammation and damage. First, C2C12 myotubes were treated with lipopolysaccharide (LPS) with and without G-CSF to determine if G-CSF modulates the inflammatory response. Second, the regulation of G-CSF and its receptor was measured following eccentric exercise-induced muscle damage and the expression levels we investigated for redox sensitivity by administering the antioxidant N-acetylcysteine (NAC). LPS stimulation of C2C12 myotubes resulted in increases in G-CSF, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNFα) messenger RNA (mRNA) and an increase in G-CSF, IL-6, and MCP-1 release from C2C12 myotubes. The addition of G-CSF following LPS stimulation of C2C12 myotubes increased IL-6 mRNA and cytokine release into the media, however it did not affect MCP-1 or TNFα. Following eccentric exercise-induced muscle damage in humans, G-CSF levels were either marginally increased in circulation or remain unaltered in skeletal muscle. Similarly, G-CSFR levels remained unchanged in response to damaging exercise and G-CSF/G-CSFR did not change in response to NAC. Collectively, these findings suggest that G-CSF may cooperate with IL-6 and potentially promote muscle regeneration in vitro, whereas in vivo aseptic inflammation induced by exercise did not change G-CSF and G-CSFR responses. These observations suggest that different models of inflammation produce a different G-CSF response. Copyright 2015, Mary Ann Liebert, Inc.

Purpose: To compare the outcomes of embryos selected via time lapse monitoring (TLM) versus those selected with conventional methods of selection in subfertile women undergoing ICSI. Methods: The study population (239 women) was classified into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2 (conventional monitoring). Groups were compared according to the clinical and ICSI cycle characteristics and reproductive outcomes, while transfers were performed at day 2 or 3. Subgroup analyses were performed, in women of both groups according to age and clinical parameters, and in embryos of Group 1 based on their cellular events. Results: There was a statistically significant difference between the two study groups with regard to the outcome parameters, favoring Group 1 and especially in women >40 years of age. No differences were found in subgroup analyses in participants of both groups, regarding the stimulation protocol used, number of the oocytes retrieved and type of subfertility, while in Group 1 the percentages of “in range” cellular events were higher in certain divisions in ages 35–40, non-smokers, and the GnRH-agonist group, and in embryos that resulted in pregnancy. Conclusion: Morphokinetic parameters of early embryo development via TLM are related to the characteristics of subfertile patients and associated with ICSI outcomes. © 2015, Springer Science+Business Media New York.

Postmenopausal hyperandrogenism is a state of relative or absolute androgen excess originating from either the adrenals and/or the ovaries, clinically manifested as the appearance and/or increase in terminal hair growth or the development of symptoms/signs of virilization. In either settings, physicians need to evaluate such patients and exclude the presence of the relatively rare but potentially life-threatening underlying tumorous causes, particularly adrenal androgen-secreting tumors. It has been suggested that the rapidity of onset along with severity of symptom and the degree of androgen excess followed by relevant imaging studies may suffice to identify the source of excessive androgen secretion. However, up to date, there is no consensus regarding specific clinical and hormonal indices and/or imaging modalities required for diagnostic certainty. This is particularly relevant as the aging population is increasing and more cases of postmenopausal women with clinical/biochemical evidence of hyperandrogenism may become apparent. Furthermore, the long-term sequels of nontumorous hyperandrogenism in postmenopausal women in respect to cardiovascular morbidity and mortality still remain unsettled. This review delineates the etiology and pathophysiology of relative and absolute androgen excess in postmenopausal women. Also, it attempts to unravel distinctive clinical features along with specific hormonal cut-off levels and/or appropriate imaging modalities for the facilitation of the differential diagnosis and the identification of potential long-term sequels. © 2015 European Society of Endocrinology Printed in Great Britain.

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2mg 17β-estradiol/1mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4mg/dl versus 40.1mg/dl, p=0.019) while lowering TG (166mg/dl versus 109mg/dl, p=0.026) and AIP (0.24 versus 0.04, p=0.007). No changes were noted in TC and LDL (215.7mg/dl versus 192.25mg/dl and 87.46mg/dl versus 76.35mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05ng/ml versus 2.20ng/ml, p=0.002) and E-selectin (73.98ng/ml versus 56.73ng/ml, p=0.004). No change was observed in Thrombomodulin and vWf (11.76ng/ml versus 13.90ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p=0.003), while only carotid bulb IMT decreased significantly (0.65mm versus 0.60mm, p=0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype. © 2014 Informa UK Ltd. All rights reserved.

The pharmacotherapy of obesity has historically recorded an overall poor safety and efficacy profile largely because of the complex mechanisms involved in the pathophysiology of obesity. It is hoped that a better understanding of the regulation of body weight will lead us to the development of effective and safer drugs. Recent advances in our understanding of the regulation of energy homeostasis has allowed the design of novel anti-obesity drugs targeting specific molecules crucial for the modulation of energy balance, including drugs that induce satiety, modulate nutrient absorption or influence metabolism or lipogenesis. Almost a decade after the Food and Drug Administration approved the first weight loss medication, it recently approved two novel anti-obesity drugs Belviq (lorcaserin) and Qsymia (topiramate and phentermine), thus signalling the beginning of a new era in the pharmacotherapy of obesity. It is believed that the next generation of weight-loss drugs will be based on combination treatments with gut hormones in a manner that mimics the changes underlying surgically induced weight loss thus introducing the so called 'bariatric pharmacotherapy'. An in-depth understanding of the interrelated physiological and behavioural effects of these new molecules together with the development of new treatment paradigms is needed so that future disappointments in the field of obesity pharmacotherapy may be avoided.

In this report, we propose an intervention capable of improving IVF outcomes in subfertile women with poor ovarian response. This intervention derives from anecdotal data and observations in our daily practice, but most importantly from trials on experimental models and subfertile women with Polycystic Ovarian Syndrome (PCOS). Our hypothesis suggests that transvaginal induction of trauma to the ovary in the cycle preceding IVF should benefit poor ovarian responders and their lowered pregnancy rates by increasing - at least - the number of retrieved oocytes during oocyte retrieval. Up-to-the minute data show that, via this means, there is a unique response of the ovarian surface epithelium and stroma to the induced trauma. The potential pathways of this beneficial response involve an improvement of the raised gonadotrophins to act either through the mechanical reduction of the size of the ovary or through alterations of the hormonal profile by lowering LH, inhibin and local androgen concentrations through hypothalamic-pituitary axis feedbacks, the induction of increased blood flow to the ovaries, a differentiated local immune reaction and a non-elucidated as yet role of reactive oxygen species. In this report, we also describe the technique and the associated possible negative points while we try to point out the needed research steps to ensure its efficiency before it enters daily clinical practice. © 2014 Elsevier Ltd.

Immunoreactive CRH (IrCRH) is produced locally in experimentally induced and spontaneous inflammation, where it exerts autocrine or paracrine proinflammatory effects. In addition, CRH is secreted by the human placenta, rat Leydig cells, and rat and human ovaries, where it may participate in the inflammatory processes of ovulation and luteolysis, and/or the regulation of steroidogenesis. Finally, CRH is secreted in vitro by cultured human epithelial and decidualized stromal endometrial cells. To investigate the presence of CRH in human endometrium in vivo, we examined this tissue immunohistochemically and by extraction/RIA using a polyclonal, highly specific antirat/human CRH antibody. Endometrial biopsies from 33 women, aged 23-43 yr (median age, 33.5 yr), were performed by linear endometrial curettage for diagnostic purposes at different stages of the cycle. Intense IrCRH staining was localized in the cytoplasm of cells of the endometrial glands in all samples examined. IrCRH was also found in endometrial stromal cells exhibiting decidual reaction and in local immune accessory cells. The mobility of the endometrial IrCRH molecule was similar to that of r/hCRH in reverse phase high pressure liquid chromatography. The presence of CRH in the endometrium, and more specifically in the glandular epithelium, during the proliferative and secretory phases of the menstrual cycle together with its known proinflammatory properties, suggest that this neuropeptide might participate in the inflammatory-like phenomena of endometrial physiology, such as menstrual shedding, surface epithelium repair, and/or implantation of the blastocyst. The presence of CRH in decidualized stromal cells is in accordance with its previously reported production by in vitro decidualized cultured endometrial stromal cells as well as by the placental decidua.

Sarcoidosis is an autoimmune disease, and hypothalamic-pituitary-adrenal (HPA) axis activity is blunted in autoimmunity. Exercise stimulates the HPA axis, and we hypothesized that in sarcoidosis patients responses to treadmill exercise would be reduced. Hence, we studied 44 sarcoidosis patients [27 untreated (age, mean ± SD, 42 ± 2 years, 12 males, 15 females) and 17 dexamethasone treated (age, 46 ± 4 years, 7 males, 10 females)] and 20 healthy controls (40 ± 5 years old, 9 males, 11 females). Blood samples were drawn before, at peak (exhaustion), and 15 min after treadmill exercise for adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor (TNF), interleukin-1β (IL-1β) and IL-6 measurements. At peak, plasma ACTH (pg/ml) was increased in untreated (mean ± SE, ΔACTH = 162.8 ± 29.9) and treated (ΔACTH = 123.3 ± 48.1) patients and controls (ΔACTH = 112.3 ± 41.7). Post-exercise, cortisol (ng/ml) was increased (p < 0.05) in untreated patients (Δcortisol = 48.4 ± 14.7) and controls (Δcortisol = 46.0 ± 15.9), but not significantly in treated patients (Δcortisol = 1.43 ± 2.56). At baseline, serum IL-6 (pg/ml) and TNF (pg/ml) were higher in untreated (3.02 ± 0.54 and 3.89 ± 0.72) and treated (1.75 ± 0.33 and 2.16 ± 1.00) patients, respectively, than in controls (0.80 ± 0.66 and 1.58 ± 0.32). At peak exercise, IL-6 was increased in untreated (ΔIL-6 = 0.96 ± 0.14) and treated (ΔIL-6 = 0.91 ± 0.47) patients and controls (ΔIL-6 = 0.96 ± 0.18); IL-1β was increased only in controls. Hence, the HPA axis of untreated sarcoidosis patients and controls responded similarly to treadmill exercise. In sarcoidosis patients, increased IL-6 was associated with HPA stimulation. Cortisol concentrations were similar between patients and controls, although IL-6 concentrations were higher in patients. Thus, in the face of chronically elevated IL-6 levels in sarcoidosis, there may be dysfunctional IL-6-induced HPA responses or HPA adaptation to high IL-6 concentrations. © Informa Healthcare USA, Inc.

Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their "add-on effect" on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metforminresistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of pioglitazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

OBJECTIVE: To investigate the association between Gestational Diabetes Mellitus (GDM) and the variants rs10830963 and rs1387153 in the MTNR1B locus in a sample of the Greek population. DESIGN: One hundred seventy-five unrelated pregnant Greek women (77 with GDM and 98 non-diabetic control subjects) were enrolled and the SNaPshot method was employed in order to investigate the association between GDM and the variants rs10830963 and rs1387153 in the MTNR1B locus. Pregnant women were screened for GDM at the 26th week with the 75 g glucose oral glucose tolerance test according to the American Diabetes Association criteria. RESULTS: The GG genotype and the G-allele of the rs10830963 (C/G) variant was found to be positively associated with a significantly increased risk for GDM (p = 0.047 and p = 0.012, respectively). No differences in fasting glucose and insulin levels were found between GDM patients with and without the studied variants. The MTNR1B locus (rs10830963 C/G) seems to predispose for GDM in Greek pregnant women. CONCLUSIONS: Our study confirms the association of GDM with the rs10830963 (C/G) variant in a sample of the Greek population. Population based whole genome screening studies and larger studies with detailed phenotypic data in patients with GDM are needed to address the clinical significance of this finding.

We report a longstanding selective memory deficit in a euthyroid 45-year-old woman who was being treated with levothyroxine for Hashimoto thyroiditis. The patient had complained of memory problems and deterioration of her concentration skills for about 2 years. Her endocrinologist thought that she was depressed. The patient's physical examination was normal. She scored a full 30 points on the Mini-Mental State Examination, but neuropsychological evaluation showed a significant deficit in her verbal memory. Routine blood tests and cerebrospinal fluid analysis showed only antithyroid peroxidase antibodies. Brain magnetic resonance imaging was normal. Electroencephalogram showed scarce intermittent bilateral multifocal theta waves. We increased the patient's daily dose of levothyroxine and started her on dexamethasone therapy. Five months later, we repeated the entire evaluation and found both her cognitive function and her electroencephalogram to be normal. Autoimmune encephalopathy associated with Hashimoto thyroiditis is already known to present with either stroke-like episodes or diffuse progressive deterioration. Our patient shows that the encephalopathy can present as a chronic selective memory deficit that can spare executive functions and short-term memory. This presentation can be missed or mistaken for depression, but can be diagnosed with a detailed neuropsychological evaluation. Copyright © 2012 by Lippincott Williams & Wilkins.

Pancreatic adenocarcinoma is the 5th leading cause of cancer-related death in Western countries and insulinomas are rare endocrine neoplasms of the pancreas. The concurrent appearance of pancreatic adenocarcinoma and insulinoma is very rare and to the best of our knowledge has never been reported again. Herein, we present such an occurrence in a 74-year-old man. Resection of a mass in the uncinate process of the pancreas revealed pancreatic adenocarcinoma with severe desmoplastic reaction. Two years later, due to symptomatology persistence the patient was re-examined and a new 2cm mass in the uncinate process was found leading to surgery, which demonstrated a 2cm endocrine islet-cell tumor. Establishing a diagnosis in patients with insulinoma is difficult and the imaging studies still have low sensitivity and specificity except for intra-operative ultrasonography, which is the most accurate method detecting 90% of these lesions. © 2011 Athanasopoulos et al; licensee BioMed Central Ltd.

The expression of corticotropin-releasing hormone (CRH) receptor 1 messenger RNA in stages of follicle growth was examined by reverse transcriptase-polymerase chain reaction in long-term cultures of early preantral mouse follicles with and without CRH addition. Corticotropin-releasing hormone receptor 1 is present in stages of mouse follicle growth, whereas 10 -9, 10-7, and 10-6 mol/L CRH inhibits oocyte maturation in vitro, an effect reversed by antalarmin addition. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

Background: Endometrial brush cytology is a widely accepted method for the detection of endometrial lesions. The aim of this study was to evaluate the role of cytological sampling using Uterobrush in the screening of endometrial pathology. Patients and Methods: This is a prospective double-blind study evaluating the efficacy of the Utero brush method (Cooper Surgical, Trumbull, USA) in the detection of endometrial abnormalities. Endometrial cytology was performed during the period January 2009 to April 2010 in all symptomatic patients that underwent dilatation and curettage. The collected samples were firstly smeared directly onto a glassslide and consequently into Thin-Prep buffer. Cytologic features were evaluated according to the criteria of Tao. The main objective was to evaluate the efficacy of Uterobrush method comparing the results of cytologic and histopathologic examination. Results: The sample of the study consisted of 100 women aged 55.8 years (range 38-78 years) with recorded data regarding Uterobrush test and classic histologic examination. Fifty-five patients were postmenopausal. A total of 92% of the samplings were performed by trainees. Endometrial carcinoma was cytologically diagnosed in 819 patients, whereas endometrial polyps were diagnosed in 5/34 patients (14.7%). All the patients with simple hyperplasia were correctly diagnosed with the Uterobrush method, whereas the diagnosis of complex hyperplasia with or without atypia was correct in 85.7% and 100% of patients, respectively. Regarding endometrial carcinoma, the sensitivity, specificity, positive and negative predictive values were 88.9%, 100%, 100% and 98.9%, respectively. On the other hand, regarding endometrial polyps, the sensitivity, specificity, positive and negative predictive values were 14.7%, 100%, 100% and 69.5%, respectively. Conclusion: Uterobrush is a reliable direct intrauterine sampling for detecting endometrial abnormalities especially endometrial carcinoma and hyperplasia, but not endometrial polyps. It is a well-tolerated, easy to use method, which provides generous endometrial sampling without contamination from the endocervix or the vagina. Anticancer Res

Objective.Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. The present study was undertaken to determine whether IRS-1 Gly972Arg and IRS-2 Gly1057Asp influence hormonal and metabolic characteristics in Greek patients with polycystic ovary syndrome (PCOS) and controls. Material and methods.One hundred and eighty-three women with PCOS and 88 healthy volunteers were enrolled. Venous blood samples were obtained for genetic study and hormonal profile, glucose, and insulin assays, on days 3 to 7 from cycling patients. DNA was extracted by whole blood samples for genotyping and detection of IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms. Results.Fifty-six women with PCOS (30.60), whereas 12 women in the control group (13.64) carried the IRS-1 polymorphism (p0.0026). No statistically significant differences in genotypes or allele frequencies for IRS-2 polymorphism were observed between controls and PCOS women. No significant differences in any clinical or hormonal measures between subjects on the basis of genotype were observed, except the increased levels of fasting glucose that exhibit the carriers of the Asp allele of the IRS-2 polymorphism. Conclusions.Only the IRS-1 polymorphism is associated with increased susceptibility to PCOS in a Greek population. These loci should not be considered as major contributors to the hormonal and metabolic phenotype of PCOS. © 2010 Informa UK Ltd.

The aim of the study was to examine the frequency and relationship of peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-δ gene polymorphisms to polycystic ovary syndrome (PCOS) characteristics. We conducted a case-control study protocol, which included 183 PCOS women and 148 healthy volunteers. Genetic, clinical, hormonal, and metabolic characteristics of PCOS patients and controls were estimated and compared. Genotype and allele frequencies did not differ significantly. The Pro12Ala polymorphism in exon 2 of the PPAR-γ gene was found in low frequency. Regarding the polymorphism in exon 6, the T-allele carrier PCOS women had significantly lower total testosterone levels. Regarding the +294TC polymorphism in the exon 4 of the PPAR-δ gene, the C-allele carrier PCOS women had significantly higher fasting glucose levels. In conclusion, the PPAR-γ gene polymorphisms do not appear to affect the risk for PCOS, except for the reduced testosterone levels. The +294TC polymorphism in the exon 4 of the PPAR-δ gene seems to cause an increase in fasting glucose levels. © 2010 New York Academy of Sciences.

We aimed to investigate possible alterations in circulating levels of the perinatal stress markers high sensitivity (hs)-CRP, PAI-1, and S100Bprobably reflecting brain and adipose tissue inflammationin intrauterine growth-restricted-(IUGR) and appropriate-for-gestational-age-(AGA) pregnancies, given that these groups differ in fat mass and metabolic mechanisms involving aseptic inflammation. Serum hs-CRP, PAI-1, and S100B levels were measured in 40 mothers, and their 20 AGA and 20 IUGR full-term fetuses and neonates on postnatal days 1 and 4. hs-CRP, PAI-1, and S100B levels did not differ at all time points between AGA and IUGR groups. We conclude that the lack of difference in hs-CRP, PAI-1 and S100B levels, between IUGR and AGA fetuses/neonatesdespite the lower birth weight, reflecting reduced fat mass in the formermight indicate more intense adipose tissue and nervous system inflammation in IUGRs. However, implication of other inflammation-related mechanisms, common in the IUGR state (e.g. preeclampsia), cannot be excluded. Copyright © 2010 Theodora Boutsikou et al.

Life exists by establishing a balanced equilibrium, called homeostasis, constantly challenged by adverse stimuli, called stressors. In response to these stimuli, a complex neurohormonal reaction exerted by the activation of the so-called stress system is initiated. The latter is activated in a coordinated fashion, leading to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chance for survival. The stress system suppressive effects on female reproduction involve suppression of the hypothalamic-pituitary-ovarian axis at the hypothalamic, pituitary, ovarian, and uterine levels. Experimental and human data suggest that adverse prenatal stimuli, of either maternal or fetal origin, acting in the developing embryo in utero, can lead to the development of short- and long-term health disorders. These include preterm birth of the offspring, low birth weight, and the development of adult diseases ranging from the metabolic syndrome to several neurodevelopmental disorders. Ann N Y Acad Sci

Life exists by establishing a balanced equilibrium, called homeostasis, constantly challenged by adverse stimuli, called stressors. In response to these stimuli, a complex neurohormonal reaction exerted by the activation of the so-called stress system is initiated. The latter is activated in a coordinated fashion, leading to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chance for survival. The stress system suppressive effects on female reproduction involve suppression of the hypothalamic-pituitary-ovarian axis at the hypothalamic, pituitary, ovarian, and uterine levels. Experimental and human data suggest that adverse prenatal stimuli, of either maternal or fetal origin, acting in the developing embryo in utero, can lead to the development of short- and long-term health disorders. These include preterm birth of the offspring, low birth weight, and the development of adult diseases ranging from the metabolic syndrome to several neurodevelopmental disorders. © 2010 New York Academy of Sciences.

During pregnancy, important changes take place in maternal metabolism because of the growing fetus and placental formation. The increase in insulin resistance during pregnancy is paralleled by the progressive increase of maternal adipose tissue deposition. This review examines the topography of fat mass deposition during pregnancy in relation to factors such as parity and maternal age that might affect this deposition. We also examine adipose tissue markers, such as pregravid weight and weight gain during pregnancy, and their effect on fetal growth and pregnancy outcomes. In addition, this review studies the possible effects of cytokines that are produced by adipose tissue and the placenta on maternal metabolism and its complications. Finally, we also consider the possible role of maternal adipocytokines and fetal adipocytokines on fetal growth.

Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide synthesized by neurons of the parvocellular and paraventricular hypothalamic nuclei. Central CRH is the principal regulator of the stress system influencing several systems in the brain and influenced by them. It activates the secretion of glucocorticoids and indirectly regulates the immune system and the immune response. Peripheral CRH is secreted by postganglionic sympathetic and unmyelinated sensory afferent neurons and has been identified in several peripheral tissues and organs, including those of the reproductive system (ovary, endometrium, placenta, and testis). In the human ovary, receptors are detected in thecal and stromal cells and in follicular fluid. Ovarian CRH regulates ovarian steroidogenesis and is involved in follicular maturation, ovulation, and luteolysis. In this concise review we briefly discuss the role of ovarian CRH in reproduction, emphasizing its role in oocyte maturation. © 2010 New York Academy of Sciences.

Menopause is characterized by the progressive reduction of estrogens resulting to cessation of menses. It is associated with an increase of cardiovascular risk factors such as hyperglycemia, hypertension, dyslipidemia and of abdominal and/or selective visceral fat mass deposition. Obesity, a modern day epidemic, is promoted by an obesogenic environment that interacts with the genetic background. The result is a positive energy balance materialized by the accumulation of the adipose tissue. This process is marked by great individual variation. Obesity is also associated with the presence of cardiovascular risk factors. In this review, the main pathophysiologic processes for the increase of obesity in menopause and the possible effects of pre-menopausal obesity regarding the cessation of ovarian function are described. The interactions among the hypothalamic-pituitary-gonadal and -adrenal (stress system) axes and the environment are explored. Furthermore, the therapeutic means that a clinician can employ to help menopausal women to overcome the menopause-associated increase of their weight are developed. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

The role of insulin-like growth factor 1 (IGF-1) and ghrelin in intrauterine growth restricted (IUGR) neonates in comparison to appropriate for gestational age (AGA) ones was investigated. Levels of IGF-1/insulin-like growth factor binding protein 3 (IGFBP3), ghrelin, insulin, and cortisol were determined in 20 singleton, full-term IUGR and 20 respective AGA neonates at birth (umbilical cord-UC), on days 1 (d1) and 4 (d4) postnatally. The ratio of IGF-1 to birth weight was higher in IUGR than in AGA in both UC (18.2 ± 1.2 vs14.4 ± 0.9, P =.05) and d1 (9.6 ± 0.5 vs 6.8 ± 0.3, P =.05). A significant positive correlation was found between IGF-1 and ghrelin levels and a negative one between IGFBP3 and ghrelin only in IUGR. In both groups, fetal IGF-1 levels negatively correlated with fetal cortisol levels. Intrauterine growth restricted neonates demonstrate a relative IGF-1 resistance in an attempt to drive energy toward survival on the expense of growth. The observed correlations between ghrelin and IGF-1/IGFBP3 postnatally indicate that ghrelin might play a role in the compensation of intrauterine undernutrition, promoting postnatal growth.

OBJECTIVE - To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS - Forty inactive men (65-82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period. RESULTS- Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P < 0.001). CONCLUSIONS - Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals. © 2009 by the American Diabetes Association.

Endometriosis is a common gynecological disorder of the reproductive age characterised by pelvic pain, dysmenorrhea and infertility. Classic theories have failed to propose a precise pathogenetic mechanism. Recent studies have investigated the role of the immune system and oxidative stress in the development of endometriosis as well as the identification of biomarkers for a non-invasive diagnosis of the disease. At endometriotic sites, inflammatory cells including eosinophils, neutrophils and macrophages generate reactive oxygen species that contribute to the development of oxidative stress in the peritoneal cavity. Oxidative stress further augments immune response in affected sites. The oxidants exacerbate the development of endometriosis by inducing chemoattractants and endometrial cell growth-promoting activity. The oxidative proinflammatory state of the peritoneal fluid is an important mediator of endometriosis. Many studies investigate the correlation of endometriosis and oxidative stress but the results are discrepant. Furthermore, oxidative stress has been implicated in unexplained infertility and has been associated with some of its causative factors. Oxidative stress influences womens reproductive capacity. The association between endometriosis and infertility is described in several studies and still remains debated.

Prolactin (PRL), along with other hormones, plays a role in oocyte maturation, fertilization, and early embryonic development in mammals. In order to investigate the role of PRL on in vitro oocyte maturation from early follicular growth stages, as well as on fertilization and early embryonic development, we cultured preantral mouse follicles with and without PRL, followed by fertilization of the in vitro matured oocytes. Prolactin significantly improved the rate of oocyte maturation, fertilization, and early embryo development. Four isoforms of PRL-Receptor (R) have been found in whole ovaries of mice: one long (PRL-RL) and three short (-RS1, -RS 2, and -RS3). We examined expression of the four PRL-R isoforms in preantral follicles, in cumulus-oocyte complexes (COCs) and in germinal vesicle GV stage oocytes by RT-PCR. Prolactin-RL, -RS2 and -RS3 mRNA, but not -RS1, were expressed in preantral follicles, COCs, and GV stage oocytes. Our results indicate the prolactin pathway is functional in early preantral follicles, in COCs and in GV stage oocytes, and promotes oocyte maturation, meiosis, fertilization, and early embryonic development. © Copyright 2009, Mary Ann Liebert, Inc.

OBJECTIVE - To investigate the effect of acute resistance exercise on adipose tissue tria- cylglycerol lipase activity (TGLA) in lean and obese men. RESEARCH DESIGN AND METHODS - Nine lean and eight obese men performed 30 min of circuit resistance exercise. Adipose tissue and blood were sampled during exercise for TGLA, metabolite, and hormone determinations. Respiratory exchange ratio (RER) was measured throughout exercise. RESULTS - Energy expenditure of exercise relative to body mass was higher in the lean and RER was higher in the obese men, suggesting lower fat oxidation. TGLA increased 18-fold at 5 min of exercise in the lean men and 16-fold at 10 min of exercise in the obese men. The delayed lipolytic activation in the obese men was reflected in erum nonesterified fatty acid and glycerol concentrations. Plasma insulin increased in the obese but did not change in the lean men. CONCLUSIONS - Resistance exercise upregulated adipose tissue lipolysis and enhanced energy expenditure in lean and obese men, with a delayed lipolytic activation in the obese men. © 2008 by the American Diabetes Association.

Diabetes mellitus type 2 (DM type 2) is associated with depressive symptomatology and intermittent hyperfunction of the hypothalamic-pituitary- adrenal (HPA) axis. DM type 2 is also accompanied by increased tissue levels of angiotensin II (Ang II), which stimulates the HPA axis through the Ang II type 1 receptors (AT1). We investigated the effect of candesartan, an angiotensin receptor blocker (ARB) that crosses the blood brain barrier, on the activity of the HPA axis and on the affect of 17 patients with DM type 2, aged 40-65 years, who were treated with 4 mg/day candesartan per os for at least 3 months. Before and after candesartan administration, a corticotropin-releasing hormone (CRH) stimulation test and psychological tests were performed. In response to hCRH, time-integrated secretion of ACTH was not altered by candesartan administration, however, the cortisol response was decreased significantly compared to baseline (mean ± SEM, 2327 ± 148.3 vs. 1943 ± 131.9 μg/dl, P = 0.005) suggesting reduced sensitivity of the adrenals to ACTH. In parallel, there was a significant improvement in interpersonal sensitivity (0.91 ± 0.16 vs. 0.70 ± 0.15, P = 0.027) and depression scores (0.96 ± 0.15 vs. 0.71 ± 0.10, P = 0.026). We suggest that candesartan resets the HPA axis of patients with DM type 2 and improves their affect. © 2008 Informa UK Ltd.

Iodine is essential for thyroid function. Thyroid disorders related to iodine deficiency decreased progressively with the continuous iodine prophylaxis and the increased iodine intake. An adverse effect resulting from iodine prophylaxis may be the induction of thyroid autoimmunity. Although experiments performed in animal models suggest that iodine could initiate or exacerbate thyroid autoimmunity, the role of iodine in humans remains controversial. Several observational studies in areas with adequate or high iodine intake suggest that there is an increase in the incidence of thyroid autoimmune disease. Moreover, intervention studies suggest that increased iodine intake may enhance thyroid autoimmunity too. However, not all studies generated the same findings, probably because of genetic, racial, and environmental differences. It seems that autoimmune exacerbation is a transient phenomenon. Studies have shown that in persons presenting thyroid antibodies, the levels of these antibodies progressively decrease when the majority of them react against a nonspecific pattern of thyroglobulin (Tg) epitopes. However, in a small number of these persons, the anti-Tg antibodies are similar to those in patients with patent thyroid autoimmune disease, reacting against specific immunodominant Tg epitopes, and their levels persist. One possible attractive explanation is that enhanced iodine intake increases the antigenicity of Tg through the incorporation of iodine into its molecule and the formation of iodinated Tg epitopes or even the generation of noniodinated pathogenetic Tg epitopes that are normally cryptic. © Mary Ann Liebert, Inc.

Objective: The aim of this study was to investigate the hypothesis that interleukin-1β (IL-1β) might be involved in the increase of the circulating levels of placental-derived CRH leading to the initiation of pre-term labor. Subjects and methods: Forty-eight primigravidae with a singleton viable pregnancy between 28 and 34 weeks of gestation were studied. The subjects were divided in two groups: group A consisted of 30 pregnant women (mean age±SD; 22±1.1 yr old) presented with preterm labor (mean gestational age±SD; 30.6±2.3 weeks) and group B consisted of 18 pregnant women (24±2.6 yr old) with normal pregnancies (29.8±3.1 weeks). CRH and IL-1β levels were measured in blood specimens collected from all the study subjects on admission. Results: Women of group A presented significantly higher serum CRH levels (mean±SE; 1.1 8±1.83 ng/ml) compared to those of group B (0.48±0.67 ng/ml) (p