THE EFFECTS OF ENDOCRINE DISRUPTORS ON FEMALE GONADAL AXIS: AN UPDATE.

Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period.

The effect of metformin and myoinositol on metabolic outcomes in women with polycystic ovary syndrome: role of body mass and adiponectin in a randomized controlled trial.

PURPOSE: To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS: In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS: After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014). CONCLUSION: Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women. TRIAL REGISTRATION: ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered.

EFFECT OF ORAL CONTRACEPTIVES ON BONE MINERAL DENSITY.

Contraceptives are widely used in our times and a lot of research has been conducted to clarify their impact on Bone Mineral Density. Combined Oral Contraceptives (COCs) may be detrimental to the BMD of adolescents. However, low-dose are more protective than ultra-low-dose COCs. When it comes to premenopause and perimenopause, COCs have no impact on BMD in women with good ovarian function and no estrogen deficiency. In women with impaired ovarian function, it seems that COCs have a positive influence on BMD. Progestin only-pills may not affect BMD, but further research is needed. Depot medroxyprogesterone acetate injection (DMPA) has a negative impact, especially in adolescents, which is duration related but evidence shows that BMD recovers after discontinuation. Levonorgestrel-releasing intrauterine system (LNG-IUS) has no impact on BMD.

THE EFFECT OF MYOINOSITOL AND METFORMIN ON CARDIOVASCULAR RISK FACTORS IN WOMEN WITH POLYCYSTIC OVARY SYNDROME: A RANDOMIZED CONTROLLED TRIAL.

CONTEXT: Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? OBJECTIVE: To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). DESIGN: Open label, parallel randomized, single center study. SUBJECTS AND METHODS: Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. RESULTS: Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. CONCLUSIONS: Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.

Progestins and the Risk of Breast Cancer.

OBJECTIVES: The present paper aims to investigate the effects of both progesterone and progestin treatment mainly related to the occurrence of breast cancer in women. MATERIALS AND METHODS: Extensive systematic bibliographic review of Greek and International articles was conducted through the electronic databases Pubmed, Cinahl, Uptodate, and Google Scholar for the identification of articles related to progesterone, progestins and breast cancer treatment. RESULTS: Hormone therapy with the use of estrogen alone presents a small increased risk or does not present at all an increased risk of breast cancer. With ORs in some studies below 1.0 in current users for 3 plus years and safe option until 7 years, while in other studies the risk was increased with the ORs 1.29. However, the use of estrogen in combination with progestogens, depending on the type of progestogens, shows an increased risk of breast cancer, with the ORs to vary between 1.14- 2.38 from 3 to 5 years and is inversely proportional to the time of its use. This risk varies depending on the combination of the preparations. Other factors that are associated with breast cancer risk when receiving hormone therapy are the years that hormone therapy is taken, directly proportional to the risk. At higher risk are older women, women with low body mass index in menopause (BMI <25kg/m2) and women with increased mammographic breast density. Continued use of hormone therapy is associated with an increased risk for breast cancer compared to sequential. The risk became visible sooner to women who used in the past hormone therapy and were using it again. Starting hormone therapy in the immediate postmenopausal period also increased the risk for breast cancer. Hormone therapy was associated with tumors with positive estrogen and progesterone receptors, and also the lobular histological type was associated with its use. Tibolone use was associated with an increased risk.

Peptide hormone analysis in diagnosis and treatment of Differences of Sex Development: joint position paper of EU COST Action 'DSDnet' and European Reference Network on Rare Endocrine Conditions.

Differences of Sex Development (DSD) comprise a variety of congenital conditions characterized by atypical chromosomal, gonadal, or anatomical sex. Diagnosis and monitoring of treatment of patients suspected of DSD conditions include clinical examination, measurement of peptide and steroid hormones, and genetic analysis. This position paper on peptide hormone analyses in the diagnosis and control of patients with DSD was jointly prepared by specialists in the field of DSD and/or peptide hormone analysis from the European Cooperation in Science and Technology (COST) Action DSDnet (BM1303) and the European Reference Network on rare Endocrine Conditions (Endo-ERN). The goal of this position paper on peptide hormone analysis was to establish laboratory guidelines that may contribute to improve optimal diagnosis and treatment control of DSD. The essential peptide hormones used in the management of patients with DSD conditions are follicle-stimulating hormone, luteinising hormone, anti-Müllerian hormone, and Inhibin B. In this context, the following position statements have been proposed: serum and plasma are the preferred matrices; the peptide hormones can all be measured by immunoassay, while use of LC-MS/MS technology has yet to be implemented in a diagnostic setting; sex- and age-related reference values are mandatory in the evaluation of these hormones; and except for Inhibin B, external quality assurance programs are widely available.

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline

COSPONSORING ASSOCIATIONS: The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. OBJECTIVE: To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). PARTICIPANTS: The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. CONCLUSIONS: FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation

Effect of endocrine disruptors on male reproduction in humans: why the evidence is still lacking?

The so-called "endocrine disruption hypothesis" suggests that exposures to endocrine disruption (EDs) during fetal, neonatal and adult life may interfere with the development of reproductive organs and alter semen quality and reproductive hormone production. Even though animal studies provide substantial evidence of adverse effects of EDs on male reproductive system, epidemiological studies in humans arrive at conflicting results. The aim of the present study was to systematically review the literature to locate methodological characteristics of the studies that struggle the formation of an association between EDs and human male reproduction. Such characteristics include: (i) definition of the exposed and the non-exposed population, (ii) age, (iii) insufficient control for confounders, (iv) ED assay and threshold, (v) time parameters of ED exposure, and (vi) study outcomes. Additional issues are: (i) the late effect of an early exposure, (ii) the multiple exposure effect, and (iii) the fact the same ED may exhibit different modes of action. Unfortunately, the nature of the field precludes the conduction of randomized-controlled trials, which could result to etiological associations between EDs and human male reproduction. Consequently, there is a great need to conduct well-designed studies of case-control or cohort type to evaluate EDs effects on human male reproductive health, and apply possible measures that could limit dangerous exposures.

Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond.

Glucococorticoids play a critical role in the developmental programing and fetal growth. Key molecules mediating and regulating tissue-specific glucocorticoid actions are 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 isozymes, both of which are expressed in the placenta and the fetal membranes. 11beta-HSD1 is implicated in the pathogenesis of metabolic syndrome and its dysregulation has been observed in pregnancy-related complications (pre-eclampsia, intrauterine growth restriction). Interestingly, preliminary clinical data have associated certain 11beta-HSD1 gene polymorphisms with hypertensive disorders in pregnancy, suggesting, if confirmed by further targeted studies, it's potential as a putative prognostic marker. Animal studies and observations in humans have confirmed that 11beta-HSD2 insufficiency is related with pregnancy adversity (pre-eclampsia, intrauterine growth restriction, preterm birth). Importantly, down-regulation or deficiency of placental 11beta-HSD2 is associated with significant restriction in fetal growth and low-birth weight, and unfavorable cardio-metabolic profile in adulthood. The potential association of 11beta-HSD1 tissue-specific dysregulation with gestational diabetes, as well as the plausible utility of 11beta-HSD2, as a biomarker of pregnancy adversity and later life morbidity, are emerging areas of intense scientific interest and future investigation.

ANTIMÜLLERIAN HORMONE AS INDICATOR OF OVARIAN DYSFUNCTION.

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.

Efficiency of GnRH analogues in treating large functional ovarian cysts.

AIM: The aim of this study was to determine the potential therapeutic benefit of a single administration of a GnRH analogue in pre- menopausal 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: Anew 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.

New molecular targets in the pathophysiology of obesity and available treatment options under investigation.

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.

Uterobrush method in the detection of endometrial pathology.

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 Uterobrush 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 8/9 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.

The effects of adipose tissue and adipocytokines in human pregnancy.

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.

Peroxisome proliferator-activated receptor-γ and -δ polymorphisms in women with polycystic ovary syndrome.

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 Pro(12) Ala 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 +294T/C 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 +294T/C polymorphism in the exon 4 of the PPAR-δ gene seems to cause an increase in fasting glucose levels.

Gender, age, puberty, and BMI related changes of TSH and thyroid hormones in schoolchildren living in a long-standing iodine replete area.

The aim of the work was to assess thyroid function in children and adolescents in an iodine replete area and to explore possible effects of age, gender, puberty, and adiposity. Thyrotropin (TSH), total triiodothyronine (T (3)), total thyroxine (T (4)), free thyroxine (FT (4)), and the T (4)/T (3) ratio were determined for 440 schoolchildren (200 boys and 240 girls), aged 5-18 years, living in an iodine replete region. Body Mass Index (BMI), BMI standard deviation score (BMI-SDS), and Body Surface Area (BSA) were calculated. In girls there was a negative correlation of TSH, T (3), and FT (4) values with age. In boys there was a negative correlation only of T (3) values with age. Girls had lower TSH, T (4), and T (3) values, whereas boys had only lower T (3) values at puberty compared to the prepubertal stage. Girls had lower TSH values than boys (p<0.03) only at puberty. BMI-SDS in boys and girls were 0.21 and 0.03, respectively. BMI-SDS was not related to TSH, T (4), or T (3) in either gender, whereas it was negatively related to T (4)/T (3) ratio in boys and to FT (4) in girls. We conclude that estrogens may exert a suppressive effect on the pituitary-thyroid axis after puberty. TSH values are not correlated with BMI-SDS, whereas T (4)/T (3) ratio in boys and FT (4) in girls are negatively correlated with BMI-SDS.

Management of obesity in menopause: diet, exercise, pharmacotherapy and bariatric surgery.

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.

Positive association of serum interleukin-1beta and CRH levels in women with pre-term labor.

OBJECTIVE: The aim of this study was to investigate the hypothesis that interleukin-1beta (IL-1beta) 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 pre-term 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-1beta 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; 1.18+/-1.83 ng/ml) compared to those of group B (0.48+/-0.67 ng/ml) (p<0.01). Similarly, serum IL-1beta levels were significantly higher in women of group A (0.45+/-0.12 pg/ml) compared to those of group B (0.31+/-0.08 pg/ml) (p<0.01). A positive correlation was found between serum IL-1beta and CRH (r=0.68, p=0.001) in women of group A (pre-term labor). CONCLUSIONS: Our findings suggest that the increased levels of IL-1beta and CRH found in pregnant women presented with pre-term labor might be involved in the pathophysiologic mechanism of the latter. Furthermore, a positive interaction might exist between IL-1beta and placental CRH which might lead to enhanced production of the second, facilitating, thus, the onset of labor.

No association between insulin resistance and preeclampsia.

OBJECTIVE: To investigate the possible link between insulin resistance and preeclampsia. METHODS: The study included 30 primigravidas between 28 and 34 weeks of gestation. The study subjects were divided into two groups: Group A consisted of 15 normotensive women of a mean gestational age of 31.6 weeks and group B consisted of 15 preeclamptic women of a mean gestational age of 29.9 weeks. Glucose and insulin levels were measured at 0, 1 and 2 h of an OGTT (after 75 g oral glucose administration). Insulin resistance and sensitivity were evaluated with the use of IR HOMA, QUICKI and IS OGTT. RESULTS: Glucose and insulin levels at 0, 1 and 2 h of the OGTT as well as IR HOMA, QUICKI and IS OGTT were comparable between preeclamptic and normotensive pregnant women. CONCLUSIONS: Our results indicate that preeclampsia is not associated with hyperinsulinaemia and/or insulin resistance, in either the fasting or the postprandial state.