A point of care test for interleukin-6 in amniotic fluid in preterm prelabor rupture of membranes: a step toward the early treatment of acute intra-amniotic inflammation/infection

Objective: Preterm prelabor rupture of membranes (preterm PROM) accounts for 30–40% of spontaneous preterm deliveries and thus is a major contributor to perinatal morbidity and mortality. An amniotic fluid (AF) interleukin-6 (IL-6) concentration is a key cytokine for the identification of intra-amniotic inflammation, patients at risk of impending preterm delivery and adverse pregnancy complications. The conventional method to determine IL-6 concentrations in AF is an enzyme-linked immunosorbent assay (ELISA). However, this technique is not available in clinical settings, and the results may take several days. A lateral flow-based immunoassay, or point of care (POC) test, has been developed to address this issue. The objective of this study was to compare the performance of AF IL-6 determined by the POC test to that determined by ELISA for the identification of intra-amniotic inflammation in patients with preterm PROM.

Materials and methods: This retrospective cohort study includes 56 women with singleton pregnancies who presented with preterm PROM. Amniocentesis was performed at the time of diagnosis, and AF was analyzed using cultivation techniques for aerobic and anaerobic bacteria as well as genital mycoplasmas. AF Gram stain and AF white blood cell counts were determined. AF IL-6 concentrations were measured using both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation defined as AF ELISA IL-6?≥?2600?pg/ml. A previously determined cut-off of 745?pg/ml was used to define a positive POC test.

Results: (1) The POC test for AF IL-6 concentrations had 97% sensitivity and 96% specificity for the identification of intra-amniotic inflammation, as defined using ELISA among patients with preterm PROM and (2) the diagnostic performance of the POC test for IL-6 was strongly correlated to that of an ELISA test for the identification of intra-amniotic inflammation and was equivalent for the identification of acute inflammatory placental lesions and microbial invasion of the amniotic cavity (MIAC).

Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in patients with preterm PROM. Results can be available within 20?min – this makes it possible to implement interventions designed to treat intra-amniotic inflammation and improve pregnancy outcomes.     

Amniotic fluid markers of oxidative stress in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To determine amniotic fluid total antioxidant capacity (TAC), ferric-reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substances (TBARS), markers of oxidative stress, in pregnancies complicated by preterm prelabor rupture of membranes (pPROM) and their correlation to microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA).

Methods: One-hundred thirty-eight women with singleton pregnancies complicated by pPROM were included in this study. Amniotic fluid was collected by transabdominal amniocentesis at the time of admission and amniotic fluid concentrations of TAC, FRAP and TBARS were measured.

Result: The presence of MIAC and/or HCA did not show any significant differences in the amniotic fluid TAC, FRAP and TBARS concentrations. Positive correlations between gestational age at sampling and amniotic fluid TAC and FRAP concentrations were found (TAC: rho?=?0.32; p?=?0.0002; FRAP: rho?=?0.36; p?<?0.0001). A negative correlation between gestation age at sampling and amniotic fluid TBARS concentrations was identified (rho?=?–0.25; p?=?0.004).

Conclusions: Oxidative stress is associated with pPROM as indicated by the presence of markers tested in the amniotic fluid; however, oxidative stress markers tested are not influenced by the presence of MIAC or HCA.     

Do the first,second and third trimester maternal serum hepcidin concentrations clarify obstetric complications?

Objective: To evaluate whether first, second, and third-trimester maternal serum hepcidin levels are different in pregnancies with and without adverse pregnancy outcomes (APO).

Methods: A 165 nullipar pregnant women were included in this prospective cohort study. Serum hepcidin, ferritin, IL-6, C-reactive protein (CRP) and Hb values were measured at 11–14, 24–28, and 30–34 weeks of gestation. The relation between these parameters and APO and neonatal outcomes were investigated. Preterm delivery, intrauterine growth restriction, pre-eclampsia, gestational hypertension and placental abruption were determined as adverse pregnancy outcomes.

Results: The risk of APO was three times higher in women with high IL-6 levels in the second trimester. High hepcidin levels in the second trimester were associated with a 1.6 times increased risk of APO. Newborns of women with high IL-6 levels in the third trimester had a 1.6-fold increased risk of neonatal complications. High ferritin levels in the third trimester were associated with minimally increased risk of neonatal complications.

Conclusions: Mean serum hepcidin levels were similar in all pregnant women, however, elevated second trimester serum hepcidin and IL-6 levels were associated with a higher risk of APO and high third trimester hepcidin, ferritin and IL-6 levels were associated with higher risk of neonatal complications.     

Polycystic ovary syndrome and low-grade inflammation with special reference to YKL-40

Objective: To evaluate the plasma level of YKL-40 in a Danish polycystic ovary syndrome (PCOS) population and to investigate whether YKL-40 is associated with CVD risk factors such as waist circumference, body mass index (BMI), insulin resistance (IR), fasting glucose, fasting insulin, blood lipids and CRP.

Design: Cross-sectional study.

Setting: Gynecological clinics at three Danish University Hospitals.

Patients: One hundred seventy-one premenopausal women with PCOS recruited consecutively from April 2010 to February 2012. PCOS was diagnosed according to the Rotterdam criteria.

Main outcome measures: Plasma level of YKL-40 in four phenotypes of PCOS defined by BMI and IR.

Results: No statistically significant difference was observed in the plasma level of YKL-40 across the four BMI/IR-phenotypes. Positive associations were observed between YKL-40 and BMI, total and free testosterone, triglycerides, and CRP. Total and free testosterone were independent predictors of YKL-40.

Conclusion: YKL-40, the marker of low-grade inflammation is not increased in women with PCOS.     

Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis

Objective: Neonatal sepsis remains a major cause of morbidity and mortality in newborns. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in inflammatory states. However, it is unclear how chemokines respond to late-onset neonatal sepsis.

Methods: Patients were classified into the groups of septic and non-septic ones. Samples of venous blood were obtained from all septic and non-septic newborns at the beginning and within 48–72?h after initiation of treatment. Serum levels of CXCR4 and CXCL12 were measured.

Results: Concentrations of IL-6, CXCR4 and CXCL12 at the time of diagnosis were significantly higher in the septic neonates compared with the non-septic ones. Additionally, there were statistically significant differences in septic neonates between the first and the second levels of IL-6, CXCR4, CXCL12 and I/T ratio. ROC curve analyses revealed that IL-6, CXCR4, CXCL12 and I/T ratio resulted in significant AUC with respect to early identification of septic neonates. Univariate logistic regression analysis showed that increased IL-6, CXCR4 and CXCL12 were strong predictors of neonatal LOS.

Conclusions: Serum CXCR4 and CXCL12 levels increase in septic neonates and that both chemokines decrease within 48–72?h of treatment. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis.     

What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

Objective: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls.

Methods: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay.

Results: The mean age of RPL and control cases were 31.6?±?0.6 and 32.1?±?0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk.

Conclusion: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.     

A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes

Objective: Preterm birth is associated with 5–18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated AF IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow-based immunoassay for measurement of AF IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection and those destined to deliver spontaneously before term among women with preterm labor and intact membranes.

Methods: One-hundred thirty-six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6?≥?2600?pg/ml.

Results: (1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%) and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745?pg/ml; (2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta and patients at risk of impending spontaneous preterm delivery.

Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20?min – this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.     

The Janus face of maternal serum relaxin: a facilitator of birth,might it also induce preterm birth?

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.     

Diminished activity of circulating α1-antitrypsin is associated with pre-gestational isolated obesity

Objective: To examine possible correlation between α1-antitrypsin (AAT) levels and activity in patients with and without obesity, after excluding complications such as gestational diabetes mellitus (GDM), during pregnancy.

Study design: A prospective case–control study was conducted. AAT levels were determined by standard human AAT ELISA according to the manufacturer's instructions. Elastase inhibition was determined by kinetic assay according to manufacturer recommendations. Assays were performed in duplicates and repeated twice for each sample in separate sessions. Patients with diabetes mellitus were excluded from the study. The Mann–Whitney U-test was performed in order to determine statistical differences between the groups, and AAT concentration and activity.

Results: During the study period, 43 patients were recruited: 21 with isolated obesity and 22 non-obese parturients (control group). According to ELISA, AAT concentrations were mildly lower in obese women compared with non-obese women (8.31?±?0.28?mg/ml versus 9.5?±?0.37?mg/ml, p?=?0.0155). However, the elastase inhibitory capacity was markedly lower in obese versus non-obese parturients (mean 27.33?±?2.08 % versus 43.73?±?3.1%, p?<?0.001).

Conclusions: Isolated obesity in pregnancy is associated with lower activity of AAT. These findings correlate with the reduced concentration and activity of AAT found in patients with GDM. Accordingly, it might suggest an inflammatory axis shared by obesity and the development of insulin resistance.     

Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.

Objective: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.

Methods: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex Pro^TM Human Cancer Biomarker Panels 1 and 2.

Results: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8–29.8 times in the study population.

Conclusion: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered.     

Little beneficial effect of maternal vitamin supplement on metabolic disturbances in the offspring from the obese mother mice

Objective: To examine whether vitamin supplement before and during pregnancy alters the detrimental effect of maternal obesity on the offspring.

Methods: Obese C57BL/6 female mice were randomly divided into four groups and fed with the control, vitamin D, folic acid or multivitamin supplement diet before and during pregnancy. Physiologic and biochemical variables were obtained.

Results: No significant differences were observed in glucose and lipid variables among offspring from each maternal obese group.

Conclusions: Overall, vitamin D, folic acid or multivitamin supplement cannot ameliorate the detrimental effect of maternal obesity on the metabolic disturbances in the offspring.     

An evaluation of homocysteine,C-reactive protein,lipid levels,neutrophils to lymphocyte ratio in postmenopausal osteopenic women

Objective: In the present study, the risk coefficients of serum homocysteine (hcy), lipid levels, C-reactive protein (CRP), neutrophils to lymphocyte ratio (NLR) in postmenopausal osteopenic women were determined.

Methods: We enrolled 269 patients with postmenopausal women from Hangzhou No.1 Hospital gynecological clinic, who aged 45 to 60 years old and never received menopause hormone therapy. According to the bone mineral density determination results, subjects were divided into normal group (n = 128), osteopenia group (n = 141). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). Serum hcy, CRP and lipid indexes were determined by enzyme chemiluminescence immunoassay.

Results: The odds ratios (OR) and 95% confidence intervals (CI) of those variables (menopausal age, duration of menopause, LDL, CRP, hcy and NLR) were found significant (p < 0.05). Menopausal age, duration of menopause, LDL, CRP, hcy and NLR variables were found statistically significant in the analysis of receiver operating characteristic (ROCs).

Conclusion: The present study shows that menopause age, duration of menopause, serum LDL, CRP, hcy and NLR levels are risk factors for postmenopausal osteopenic women, which may be used as the indicators of bone loss in postmenopausal women.     

Concentration of amoxicillin in maternal serum,cord blood,amniotic fluid and the placenta after vaginal administration

Objective: The aim of this study was to assess the amoxicillin concentration in maternal serum, cord blood, amniotic fluid and the placenta, 2?h following vaginal administration and the factors influencing the drug level.

Methods: Twenty-eight full-term pregnant women who qualified for elective cesarean delivery were included in the study. Vaginal suppositories containing 250?mg of amoxicillin were administered 2?h prior to the operation. Amoxicillin levels were determined using the diffusion microbial assay.

Results: The amoxicillin level in amniotic fluid was significantly higher in comparison to that of maternal serum, cord blood or the placenta. Maternal age positively and gestational weight gain negatively correlated with the amoxicillin concentration in maternal serum. The maternal serum hemoglobin level and red blood cell count were positively correlated with amoxicillin concentration in the amniotic fluid. Neonatal birth weight was positively correlated with maternal serum and cord blood amoxicillin levels. Hypertensive women had significantly higher amoxicillin concentrations in amniotic fluid, and women with thrombocytopenia presented significantly higher cord blood amoxicillin concentrations.

Conclusions: Amoxicillin presented poor concentration in maternal–fetal compartments after vaginal administration, but the factors influencing the drug level in different compartments require further investigation.     

Dose-dependent sickness behavior,abortion and inflammation induced by systemic LPS injection in pregnant mice

Objective: Clinical and experimental evidences indicate that intrauterine inflammation during pregnancy is associated to brain damage. The objective of this study is to determine the effects of lipopolysaccharide in temperature, cytokine production and sickness behavior of pregnant dams.

Methods: A single i.p. injection of lipopolysaccharide (LPS) (50, 150 or 300?µg/kg) was administered on E18. Controls received isotonic saline. Body temperature was controlled before and 3?h after injections. Animals’ behavior was assessed by the OF test 3?h following treatment. Animals were sacrificed for leukocyte, IL-1β and TNF-α determination. Placental tissue and abortion were also examined.

Results: LPS administration elicited hypothermia. Abortion was observed in LPS 150 and 300?µg/kg. Leukocyte levels were significantly lower with LPS 300?µg/kg than in controls. LPS induced dose-dependent impairment in animals’ locomotion. IL-1β serum and amniotic fluid were higher than the saline, and TNF-α serum and amniotic fluid increased when compared to controls. Placental histopathologic abnormality was not found.

Conclusion: LPS induces dose-dependent sickness behavior and hypothermia in pregnant mice. Our findings suggest that the presence of inflammation may be a causative factor for premature labor and that Escherichia coli antigens modify the concentration of pro-inflammatory agents in circulatory system and intra-uterine environment.     

Pentraxin 3 concentrations of the mothers with preterm premature rupture of membranes and their neonates,and early neonatal outcome

Background: Pentraxin 3 (PTX3) is an acute phase reactant which has been used to detect intra-amniotic infections (IAI) in pregnancy, but the prognostic value of PTX3 concentrations on neonates has not been studied. We aimed to investigate the relationship between maternal PTX3–neonatal PTX3 concentrations and early neonatal outcome.

Methods: The mothers diagnosed with preterm prelabor rupture of membranes (PPROM) (n?=?28) and their preterm infants (n?=?28) were included in the study. PTX3 concentrations were studied in plasma in the maternal peripheral blood and umbilical/peripheral vein in the neonates. The relationship between the mPTX3–nPTX3 concentrations and neonatal outcome were investigated using non-parametric tests and binary logistic regression analysis.

Results: The mean mPTX3 concentration was 10.35?±?7.82?μg/L. Ten (35.7%) of all mothers were within the normal range and 18 (64.3%) in high percentile (≥97.5 percentile). There was no relation between mPTX3 concentrations and clinical or histologic chorioamnionitis, latency of PPROM, and early neonatal outcome. Mean nPTX3 concentrations was 9.18?±?7.83?μg/L and high nPTX3 concentrations were detected in five (17.8%) neonates. nPTX3 concentrations were inversely correlated with gestational age and correlated with rate of intraventricular hemorrhage (IVH) and mortality. Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay.

Conclusion: High PTX3 concentrations of the newborns are associated with some worsened early neonatal outcome including lower gestational age at delivery, increased rate of IVH and mortality. Maternal PTX3 concentrations are not an adequate marker in defining clinical or histologic chorioamnionitis and early neonatal outcome.     

The effects of isolated single umbilical artery on first and second trimester aneuploidy screening test parameters

Objective: Reliability of first and second trimester screening tests largely depends on accurate estimation of maternal serum marker values. Reduced reliability could lead redundant invasive tests or misdiagnosis. Adjustments of serum marker values for confounding factors like insulin-dependent diabetes, maternal weight or maternal rhesus status are essential. We aimed to investigate whether isolated single umbilical artery alters first and second trimester test parameters or not.

Methods: Routine detailed obstetric ultrasonographies performed were retrospectively screened for this study. Among spontaneously conceived singleton pregnancies, women who were found to have single umbilical artery without any additional structural anomalies or aneuploidies were selected.

First and second trimester screening test results were accessible for 98 and 102 of the cases with isolated single umbilical artery, respectively.

Results: Among first trimester screening test parameters, PAPP-A (pregnancy-associated plasma protein A) MoMs were found significantly higher in isolated single umbilical artery group. AFP MoMs were found significantly elevated in isolated single umbilical artery group in second trimester quadruple tests.

Conclusion: Existence of single umbilical artery could alter the estimation of MoM values of maternal serum markers. Reliability of prenatal screening tests could be improved by adjusting these parameters in accordance with isolated single umbilical artery.     

Increased mood symptoms in postmenopausal women related to the polymorphism rs743572 of the CYP17 A1 gene

Background: Menopausal and depressive symptoms are highly prevalent after the menopause; but may vary from one population to another and genetics play a key role.

Objective: To analyze the intensity of these symptoms in relation to the genetic variants of the rs743572 polymorphism of the CYP17 A1 gene in postmenopausal women.

Methods: DNA was extracted from the whole blood of 168 natural postmenopausal women (40–65 years) and tested for the rs743572 polymorphism of the CYP17 A1 gene. Intensity of menopausal (Menopause Rating Scale, MRS) and depressive symptoms (Hospital Anxiety and Depressive Scale, HADS) were correlated to polymorphism genotypes.

Results: Women with the GG genotype of the rs743572 polymorphism displayed significantly higher scores for the MRS (items 5 and 6 [irritability and anxiety] and the psychological subscale) and the HADS (total and subscales).

Conclusion: The intensity of menopausal symptoms related to mood was found higher among postmenopausal women presenting the GG genotype of the rs743572 polymorphism of the CYP17 A1 gene. There is a need for more research in this regard.     

Gonadal hormone levels and platelet tryptophan and serotonin concentrations in perimenopausal women with or without depressive symptoms

Introduction: The etiology of depressive symptoms associated with the transition to menopause is still unknown; hormonal changes, serotonergic system or insomnia, could be a trigger to depressive symptomatology. The aim of the present study was to evaluate gonadal hormonal levels, platelet serotonin concentrations and platelet tryptophan concentrations in a group of depressed perimenopausal women and their healthy counterparts.

Methods: A total of 63 perimenopausal women between 45 and 55 years old were evaluated; of these, 44 were depressed patients, and 19 were perimenopausal women without depression. The instruments that were applied included the Center for Epidemiologic Studies Depression Scale (CES-D), the Hamilton Depression Rating Scale (HDRS) and the Green Climacteric Scale (GCS); gonadal hormone levels and platelet tryptophan and serotonin concentrations were measured in all participants. Differences in hormonal levels and tryptophan and serotonin concentrations were evaluated with respect to specific symptoms, such as insomnia, hot flashes, nervousness, depressed mood and loss of interest.

Results: No differences between groups were observed with respect to hormonal levels and tryptophan and serotonin concentrations; mean sleep hours and insomnia were significantly correlated with platelet tryptophan concentrations.

Conclusions: In this sample, all symptoms of depression could not be explained by platelet tryptophan and serotonin concentrations and hormonal levels; differences were observed only when we evaluated insomnia and hot flashes.