Normal Weight Women Research Articles

Leiyomiyomu olan kadınlarda dolaşımdaki obestatin düzeyleri

Objective: Uterine leiomyomas are the most common benign tumors of reproductive age women with symptoms of bleeding, pain, pressure and consequences on reproduction. Obestatin is a recently discovered secreted peptide encoded by the preproghrelin gene. The role of obestatin in the regulation of metabolism is still under debate. In this article, we investigate the use of biomarker in patients with uterine leiomyoma. Our goal is to study the obestatin as a biomarker for the diagnosis and monitoring of uterine leiomyoma.
 Methods: This cross-sectional observational study was conducted between January 2015–June 2015 in outpatient gynecology clinic of Zekai Tahir Burak Women’s Health Education and Research Hospital, Ankara. A total of 82 women were recruited as 48 with uterine leiomyoma and 34 healthy controls.The obestatin levels were reviewed prospectively.
 Results: The obestatin levels of study group was lower than the control group (1.91±2.64 pg/mL vs. 3.58±4.81 pg/mL, p ꓿.009). The obestatin levels without normal distribution, Mann–Whitney U-test was performed for two independent groups.
 Conclusion: Increased obestatin characterized obesity in women, supporting the hypothesis that the imbalance of obestatin may have a role in the pathophysiology of leiomyoma due to obesity. On the other hand, some relevant differences between our data on circulating blood levels of obestatin in normal-weight women who had leiomyoma subjects and those reported in the few studies published so far imply that further extensive research in this new area is needed.

Changes of biochemical parameters in normal weight and overweight/obese women with polycystic ovary Syndrome

Objectives: Polycystic ovary syndrome (PCOS) is an endocrine disease in reproductiveage women, which interferes with fertility, menstruation, and body composition. Some biochemical parameters change in women with PCOS, a feature which can be a consequence of the disease itself or of the accompanying obesity. This study investigated the glucose and lipid profiles, sex hormones, and hsCRP in normal weight and overweight/ obese Iranian women with and without PCOS.
 Methods: 314 women with PCOS and 138 healthy and fertile women were recruited for the study. The patients and controls were divided according to body mass index (BMI) into two groups as follows: BMI<25 Kg/m2 and BMI≥ 25 Kg/m2 . Blood samples were collected from all participants to assess fasting blood glucose, fasting insulin, lipid profile, FSH, LH, free testosterone, and hs-CRP levels. The homeostasis model of insulin resistance (HOMA-IR) was calculated for assessing insulin sensitivity.
 Results: BMI, fasting insulin, HOMA-IR, triglyceride, FT, LH, and hs-CRP levels were significantly higher in the PCOS group, while lower levels of FSH were observed in comparison to non-PCOS women. Among overweight PCOS women, hs-CRP levels were significantly elevated compared to normal-weight PCOS women. However, there was no significant difference in circulating hs-CRP levels between normal-weight and overweight participants in the control group.
 Conclusion: The study results suggest that both insulin resistance and an increase in hs-CRP may be relevant to PCOS. Moreover, the findings indicated that chronic inflammation in PCOS is not solely dependent on the pathogenesis of the disease but may be exacerbated by increased body weight.

Maternal overweight and obesity and its association with metabolic changes and fetal overgrowth in the absence of gestational diabetes mellitus: A prospective cohort study.

Previous studies indicated an association between fetal overgrowth and maternal obesity independent of gestational diabetes mellitus (GDM). However, the underlying mechanisms beyond this possible association are not completely understood. This study investigates metabolic changes and their association with fetal and neonatal biometry in overweight and obese mothers who remained normal glucose-tolerant during gestation. In this prospective cohort study 893 women who did not develop GDM were categorized according to their pregestational body mass index (BMI): 570 were normal weight, 220 overweight and 103 obese. Study participants received a broad metabolic evaluation before 16 weeks and were followed up until delivery to assess glucose levels during the oral glucose tolerance test (OGTT) at mid-gestation as well as fetal biometry in ultrasound and pregnancy outcome data. Increased maternal BMI was associated with an adverse metabolic profile at the beginning of pregnancy, including a lower degree of insulin sensitivity (as assessed by the quantitative insulin sensitivity check index) in overweight (mean difference: -2.4, 95% CI -2.9 to -1.9, p < 0.001) and obese (mean difference: -4.3, 95% CI -5.0 to -3.7, p < 0.001) vs normal weight women. Despite not fulfilling diagnosis criteria for GDM, overweight and obese mothers showed higher glucose levels at fasting and during the OGTT. Finally, we observed increased measures of fetal subcutaneous tissue thickness in ultrasound as well as higher proportions of large-for-gestational-age infants in overweight (18.9%, odds ratio [OR] 1.74, 95% CI 1.08-2.78, p = 0.021) and obese mothers (21.0%, OR 1.99, 95% CI 1.06-3.59, p = 0.027) vs normal weight controls (11.8%). The risk for large for gestational age was further determined by OGTT glucose (60 min: OR 1.11, 95% CI 1.02-1.21, p = 0.013; 120 min: OR 1.13, 95% CI 1.02-1.27, P = 0.025, for the increase of 10 mg/dL) and maternal triglyceride concentrations (OR 1.11, 95% CI 1.01-1.22, p = 0.036, for the increase of 20 mg/dL). Mothers affected by overweight or obesity but not GDM had a higher risk for fetal overgrowth. An impaired metabolic milieu related to increased maternal BMI as well as higher glucose levels at mid-gestation may impact fetal overgrowth in women still in the range of normal glucose tolerance.

Rates of subjective and objective cure, satisfaction, and pain 10-20 years after tension-free vaginal tape (TVT) surgery: A retrospective cohort study.

To evaluate rates of subjective and objective cure, treatment satisfaction, pain, and the correlation between cure and body mass index (BMI), at 10 and 20 years after tension-free vaginal tape (TVT) surgery. Retrospective cohort study. Multicentre study including 19 units in Norway. Women undergoing TVT surgery for stress urinary incontinence (SUI) during 2001-2006 (20-year cohort) and 2011-2012 (10-year cohort). The Norwegian Female Incontinence Registry was used to identify women eligible for the study, who answered validated questionnaires about urinary incontinence, pain and satisfaction. Subjective cure of SUI (with stress index of <3, range 0-12), objective cure (<3 g on stress test) and persisting pain and satisfaction after TVT (scored on a five-point Likert scale). In total, 1210 of 1903 (64%) patients responded. The subjective cure rate was 68% after 10 years, versus 59% after 20 years, and did not significantly differ after adjusting for age, BMI, parity and preoperative stress index (adjusted OR 1.27, 95% CI 0.82-1.94). The objective cure rate was 100% versus 93% (P < 0.001), with 89% versus 76% reporting subjective satisfaction (P < 0.001), and with 4.7% versus 2.7% reporting persisting pain (P < 0.001), after 10 versus 20 years, respectively. Women in obesity classes I and II, compared with women of normal weight, had an increased risk of not being subjectively cured (crude OR 2.02, 95% CI 1.42-2.90; OR 2.95, 95% CI 1.60-5.46, respectively). Tension-free vaginal tape (TVT) provided high rates of subjective and objective cure at 10 and 20 years after surgery, with no significant difference between the two cohorts. Although 3%-5% of women experienced persisting pain, most women were satisfied with TVT surgery. Obesity was associated with a lower cure rate.

Associations between HT, BMI, and allergic rhinitis in perimenopausal women

BackgroundIncreasing evidence suggests that hormone therapy (HT) and obesity exert an influence on allergic rhinitis (AR). It is important to investigate the association and interactions between HT, BMI, and AR in perimenopausal women.MethodsFrom May 2020 to March 2021, a cross-sectional survey was completed by patients who visited the Allergy Department and Gynecology Department of Shijitan Hospital. The patients completed a questionnaire and stratified analyses by BMI in tertiles were performed. Logistic analyses were performed to evaluate the relationships between HT, BMI, and AR.ResultsA total of 950 patients completed the study, among which, 393 patients were receiving HT. HT was found to be associated with increased risks for AR (OR = 1.51 [95% CI: 1.151–1.985]), asthma (OR = 3.61 [95% CI: 2.21–5.89]), and their accompanying symptoms (OR = 3.54 [95% CI: 2.146–5.831]). In lean women, the use of HT was significantly associated with a higher risks for AR (OR = 2.26 [95% CI: 1.31–3.91]), the time course of AR (OR = 2.54 [95% CI: 1.37–4.74]), hay fever (OR = 2.54 [95% CI: 1.37–4.74]), and accompanying symptoms (including canker sores, diarrhea, and stomachache) (OR = 2.26 [95% CI: 1.309–3.907]) when compared to normal or heavier weight women (course of AR: pinteraction = 0.032; hay fever; pinteraction = 0.006; accompanying symptoms: pinteraction = 0.009).ConclusionsHT can reduce the risk for AR in perimenopausal women. Lean women who used HT were at a higher risk for AR when compared to overweight women who used AR. There exists an interaction between HT and BMI that influences AR. Furthermore, HT and obesity increase the risk for AR by some common pathways, more follow-up work is needed to explore common pathways.

A high-fat eucaloric diet induces reprometabolic syndrome of obesity in normal weight women.

We examined the effects of 1 month of a eucaloric, high-fat (48% of calories) diet (HFD) on gonadotropin secretion in normal-weight women to interrogate the role of free fatty acids and insulin in mediating the relative hypogonadotropic hypogonadism of obesity. Eighteen eumenorrheic women (body mass index [BMI] 18-25 kg/m2) were studied in the early follicular phase of the menstrual cycle before and after exposure to an HFD with frequent blood sampling for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), followed by an assessment of pituitary sensitivity to gonadotropin-releasing hormone (GnRH). Mass spectrometry-based plasma metabolomic analysis was also performed. Paired testing and time-series analysis were performed as appropriate. Mean endogenous LH (unstimulated) was significantly decreased after the HFD (4.3 ± 1.0 vs. 3.8 ± 1.0, P < 0.01); mean unstimulated FSH was not changed. Both LH (10.1 ± 1.0 vs. 7.2 ± 1.0, P < 0.01) and FSH (9.5 ± 1.0 vs. 8.8 ± 1.0, P < 0.01) responses to 75 ng/kg of GnRH were reduced after the HFD. Mean LH pulse amplitude and LH interpulse interval were unaffected by the dietary exposure. Eucaloric HFD exposure did not cause weight change. Plasma metabolomics confirmed adherence with elevation of fasting free fatty acids (especially long-chain mono-, poly-, and highly unsaturated fatty acids) by the last day of the HFD. One-month exposure to an HFD successfully induced key reproductive and metabolic features of reprometabolic syndrome in normal-weight women. These data suggest that dietary factors may underlie the gonadotrope compromise seen in obesity-related subfertility and therapeutic dietary interventions, independent of weight loss, may be possible.

AGER-1 Long Non-Coding RNA Levels Correlate with the Expression of the Advanced Glycosylation End-Product Receptor, a Regulator of the Inflammatory Response in Visceral Adipose Tissue of Women with Obesity and Type 2 Diabetes Mellitus.

The advanced glycosylation end-product receptor (AGER) is involved in the development of metabolic inflammation and related complications in type 2 diabetes mellitus (T2DM). Tissue expression of the AGER gene (AGER) is regulated by epigenetic mediators, including a long non-coding RNA AGER-1 (lncAGER-1). This study aimed to investigate whether human obesity and T2DM are associated with an altered expression of AGER and lncAGER-1 in adipose tissue and, if so, whether these changes affect the local inflammatory milieu. The expression of genes encoding AGER, selected adipokines, and lncAGER-1 was assessed using real-time PCR in visceral (VAT) and subcutaneous (SAT) adipose tissue. VAT and SAT samples were obtained from 62 obese (BMI > 40 kg/m2; N = 24 diabetic) and 20 normal weight (BMI = 20-24.9 kg/m2) women, while a further 15 SAT samples were obtained from patients who were 18 to 24 months post-bariatric surgery. Tissue concentrations of adipokines were measured at the protein level using an ELISA-based method. Obesity was associated with increased AGER mRNA levels in SAT compared to normal weight status (p = 0.04) and surgical weight loss led to their significant decrease compared to pre-surgery levels (p = 0.01). Stratification by diabetic status revealed that AGER mRNA levels in VAT were higher in diabetic compared to non-diabetic women (p = 0.018). Elevated AGER mRNA levels in VAT of obese diabetic patients correlated with lncAGER-1 (p = 0.04, rs = 0.487) and with interleukin 1β (p = 0.008, rs = 0.525) and resistin (p = 0.004, rs = 0.6) mRNA concentrations. In conclusion, obesity in women is associated with increased expression of AGER in SAT, while T2DM is associated with increased AGER mRNA levels and pro-inflammatory adipokines in VAT.

#139 : Outcomes of IVF-ET in Overweight/Obese and Normal-Weight Women with PCOS

Background and Aims: Overweight/obese women with polycystic ovary syndrome (PCOS) have poorer pregnancy outcomes, compared to normal-weight women. Body mass index (BMI) is a risk factor of in vitro fertilization-embryo transfer (IVF-ET). This study is to compare the outcomes of IVF-ET between the overweight/obese and normal-weight women with PCOS. Method: We performed a retrospective cohort study in a large reproductive center of a university hospital. The participants were the women with PCOS who underwent IVF-ET. We compared live birth, miscarriage and other clinical outcomes between the women with BMI ≥25 (overweight/obese group) and 18≤BMI&lt;25 (normal-weight group). Results: We included 3733 women with PCOS who underwent the first IVF-ET cycle from Jan 2016 to Dec 2020. 1693 of them were overweight/obese and had longer stimulation days and more doses of gonadotropins, while less numbers of oocytes retrieved and good quality embryos. Live birth rates were significantly lower in overweight/obese women, compared with normal-weight women (29.8% vs. 36.2%, OR 0.8 (0.7, 0.9)). Clinical pregnancy rates were significantly lower (38.5% vs. 43.0%, OR 0.8 (0.7, 0.9)). Miscarriage rates were significantly higher in overweight/obese women, compared with normal-weight women (21.5% vs. 14.6%, OR 1.6 (1.2, 2.1)). Multivariate logistic regression analysis showed BMI was an independent risk factor. Conclusion: Overweight/obese women with PCOS had poorer outcomes of IVF-ET, compared to normal-weight women with PCOS.

Gestational weight gain of multiparas and risk of primary preeclampsia: a retrospective cohort study in Shanghai

BackgroundIn all studies conducted so far, there was no report about the correlation between excessive gestational weight gain (GWG) and the risk of preeclampsia (PE) in multiparas, especially considering that multiparity is a protective factor for both excessive GWG and PE. Thus, the aim of this retrospective cohort study was to determine whether GWG of multiparas is associated with the increased risk of PE.MethodsThis was a study with 15,541 multiparous women who delivered in a maternity hospital in Shanghai from 2017 to 2021, stratified by early-pregnancy body mass index (BMI) category. Early-pregnancy body weight, height, week-specific and total gestational weight gain as well as records of antenatal care were extracted using electronic medical records, and antenatal weight gain measurements were standardized into gestational age-specific z scores.ResultsAmong these 15,541 multiparous women, 534 (3.44%) developed preeclampsia. The odds of preeclampsia increased by 26% with every 1 z score increase in pregnancy weight gain among normal weight women and by 41% among overweight or obese women. For normal weight women, pregnant women with preeclampsia gained more weight than pregnant women without preeclampsia beginning at 25 weeks of gestation, while accelerated weight gain was more obvious in overweight or obese women after 25 weeks of gestation.ConclusionsIn conclusion, excessive GWG in normal weight and overweight or obese multiparas was strongly associated with the increased risk of preeclampsia. In parallel, the appropriate management and control of weight gain, especially in the second and third trimesters, may lower the risk of developing preeclampsia.Graphical

Impact of maternal obesity on resting muscle sympathetic nerve activity during uncomplicated pregnancy: a longitudinal assessment.

Maternal obesity increases the risk of adverse pregnancy outcomes. The mechanisms that contribute to this elevated risk are unclear but may be related to greater activity of the sympathetic nervous system, which is associated with hypertensive disorders of pregnancy. We hypothesized that resting muscle sympathetic nerve activity (MSNA) would be greater in women with obesity during pregnancy when compared with normal-weight women. Blood pressure, heart rate, and MSNA were recorded during 5 min of supine rest in 14 normal-weight women [body mass index (BMI) 22.1 ± 2.1 (SD) kg/m2] and 14 women with obesity (BMI 33.9 ± 3.5 kg/m2) during (early and late) pregnancy and postpartum. All women had uncomplicated pregnancies. Resting MSNA burst frequency was not different between groups during early (normal weight 17 ± 10 vs. obesity 22 ± 15 bursts/min, P = 0.35) but was significantly greater in the obesity group during late pregnancy (23 ± 13 vs. 35 ± 15 bursts/min, P = 0.031) and not different postpartum (10 ± 6 vs. 9 ± 7 bursts/min, P = 0.74). These findings were also apparent when comparing burst incidence and total activity. Although still within the normotensive range, systolic blood pressure was greater in the obesity group across all time points (P = 0.002). Diastolic blood pressure was lower during pregnancy compared with postpartum (P < 0.001) and not different between groups (P = 0.488). Heart rate increased throughout pregnancy in both groups (P < 0.001). Our findings suggest that maternal obesity is associated with greater increases in sympathetic activity even during uncomplicated pregnancy. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.NEW & NOTEWORTHY The impact of maternal obesity on resting muscle sympathetic nerve activity was examined during (early and late) and after uncomplicated pregnancy. Resting muscle sympathetic nerve activity is not different during early pregnancy or postpartum but is significantly elevated in women with obesity during late pregnancy when compared with normal-weight women. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.

Metabolically healthy/unhealthy obesity and breast cancer: A possible role of plasma-derived extracellular vesicles on the cancerous behavior of triple-negative breast cancer

PurposeObesity has known detrimental effects on breast cancer (BC) development and progression. However, it's essential to consider the obesity phenotype based on metabolic health. This study aims to evaluate the impact of circulating extracellular vesicles (EVs) from women with metabolically healthy or unhealthy normal weight, overweight, and obesity on MDA-MB-231 cell migration, invasion, and apoptosis. MethodsPlasma EVs were isolated from different obesity phenotypes in women. EVs were characterized and EVs uptake by MDA-MB-231 cells was assessed. MDA-MB-231 cell lines were treated with EVs obtained from various studied groups, and migration, invasion, MMP-2 and MMP-9 activity, Bax and Bcl-2 mRNA expression, p-53 and Thr55 p-p53 protein expression, and apoptosis were assessed. ResultsEVs from obese individuals, regardless of phenotype, increased invasion and MMP-2 activity compared to healthy normal-weight EVs. Normal-weight EVs led to higher invasion under unhealthy conditions. BC cell migration was enhanced by EVs from healthy obese individuals compared to healthy normal-weight EVs. EVs from unhealthy obese women exhibited significantly lower p53/p-p53 levels and reduced apoptosis compared to healthy obese groups. ConclusionIt appears that EVs from both normal-weight women with unhealthy conditions and those with obesity or overweight, irrespective of metabolic status, worsened the cancerous behavior of TNBC cells. Therefore, considering metabolic health, in addition to BMI, is crucial for understanding obesity-related disorders.

Maternal myocardial recovery twelve months post-partum in women with pregnancies complicated by gestational diabetes or preeclampsia - single center, longitudinal cohort study

Abstract Background Gestational diabetes mellitus (GDM) and preeclampsia (PE) are the leading obstetric complications of pregnancy. Both are associated with a substantial increase in the risk of long-term cardiovascular disease. However, pregnant women are underrepresented in clinical research and the mechanisms of long-term cardiovascular complications in women with obstetric complications remain to be elucidated. Objectives This longitudinal cohort study was designed to assess maternal cardiac alterations during the third trimester of pregnancy and their recovery twelve-months post-partum in women with GDM (n=30) or preeclampsia (n=24) compared to women with healthy pregnancies (HP)(n=38). Methods 31P-MRS and CMR were used to define PCr/ATP, tissue characteristics, left ventricular (LV) volumes, mass, EF, global longitudinal shortening (GLS), and mitral in-flow E/A ratio. Investigations were repeated 12-months postpartum. With obesity as a common risk factor for both GDM and PE, 10 overweight and 10 normal-weight nulliparous women served as non-pregnant controls. Results Participants were matched for age and ethnicity(Table-1). Both the GDM and PE groups had higher BMI compared to the HP. Compared to the HP group, women with GDM had higher LV mass (90[85,94] vs 103[96,112]g; p=0.001) and lower myocardial PCr/ATP (2.2[2.1,2.4] vs 1.9[1.7,2]; p&amp;lt;0.0001), LV end-diastolic volumes (EDV)(76[72,80] vs 67[63,71]ml, p=0.03) and GLS (20[18,21] vs 18[17,19]%; p=0.008). Compared to the HP group, at similar magnitudes to women with GDM, the women with PE exhibited higher LV mass (90[85,94] vs 118[111,125]g; p&amp;lt;0.0001) and lower myocardial PCr/ATP (2.2[2.1,2.4] vs 1.9[1.8,2.1]; p=0.0004) and GLS (20[18,21] vs 16[14,17]%; p=0.01). There were no significant differences in PCr/ATP, LV EDV, mass or GLS between the GDM and PE groups. Twelve-months postpartum there were no significant changes in any of the cardiac assessments in women in the HP, GDM or PE groups compared to their respective third-trimester pregnancy assessments (Figure-1). Compared to nulliparous normal-weight controls, HP was associated with no significant differences in myocardial PCR/ATP, LV volumes, mass, EF or GLS. The overweight nulliparous controls showed significantly higher LV mass and lower myocardial PCr/ATP and GLS than normal-weight controls. There were no significant differences in LV mass, PCr/ATP or GLS between the overweight nulliparous controls and GDM or PE groups during or after pregnancy. Conclusions Despite distinct aetiologies women with GDM and PE exhibit a similar myocardial phenotype during and after pregnancy with persistent subtle abnormalities in myocardial PCr/ATP ratio, LV mass and GLS compared to women with HP during pregnancy and twelve months’ postpartum assessments. Women with GDM and PE show similar myocardial alterations to nulliparous women with obesity, suggesting that the myocardial changes are predominantly driven by obesity-associated metabolic dysfunction.

Higher childhood weight gain, lower skeletal muscle mass, and higher cereal consumption in normal-weight Japanese women with high-percentage trunk fat: a subanalysis study.

Normal-weight but high-percentage trunk fat phenotype was characterized in a setting where adiposity is not associated with educational and socioeconomic status. Body size trajectory since birth, current body composition measured using whole-body dual-energy X-ray absorptiometry, cardiometabolic traits, serum adipokines, and dietary intake were measured cross-sectionally in 251 normal weight Japanese female university students whose fasting triglyceride and homeostasis model assessment-insulin resistance (HOMA-IR) averaged 56mg/dL and 1.2, respectively. They were grouped according to tertile of percentage trunk fat. Although HOMA-IR did not differ among three groups, high-percentage trunk fat was associated with higher triglyceride and apolipoprotein B, and lower HDL cholesterol and apolipoprotein A1. In multivariate logistic regression analyses, weight-adjusted skeletal muscle mass (OR: 0.13, 95% CI: 0.04-0.38, p < 0.001), weight gain from birth to age 12years (OR: 1.214、95% CI: 1.008-1.463、p = 0.04), and cereal consumption (OR:1.008, 95% CI: 1.000-1.016, p = 0.04) were associated with high-percentage trunk fat independent of birthweight, HOMA-IR, adipose tissue-insulin resistance index (the product of fasting insulin and free fatty acid), triglyceride, HDL cholesterol, apolipoprotein A1 and B, leptin, adiponectin, blood pressure, and high-sensitivity C-reactive protein. Early childhood growth, lower skeletal muscle mass, and higher cereal consumption may be associated with normal-weight but high-percentage trunk fat phenotype in Japanese female university students in this subanalysis study. Atherogenic profile of lipids and apolipoproteins may be directly related to abdominal fat accumulation.

Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system.

Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.

Left ventricular remodeling in perimenopausal women

Aim to reveal specific features of the left ventricle (LV) structural and functional state and the pro-inflammatory status indicators in women of perimenopausal age.&#x0D; Material and methods. The cross-sectional study included 80 women (age 45 to 55 years) who were divided into 2 groups: a menopausal transition group and an early postmenopausal group according to the STRAW + 10 classification. Anthropometric measurements were taken; blood tests for homocysteine C, interleukin-6 (IL6), C-reactive protein (CRP), and echocardiography were performed according to the standard technique.&#x0D; Results. The study findings were as follows: 1. women in early postmenopause had higher levels of CRP when compared with women in the menopausal transition (4.5 (1.5; 8.0) mg/l versus 2.5 (0.6; 7.4) mg/l), in obese women, the level of IL6 was higher than in normal-weight women regardless of menopausal status (1.8 (0.6; 2.8) pg/ml versus 0.6 (0.2; 1.3) pg/ml); 2. the distribution of participants according to the type of myocardial remodeling did not differ in the comparison groups; 3. the presence of arterial hypertension and menopause was associated with myocardial hypertrophy; 4. significant differences were found in the distribution of myocardial geometry in women with obesity and overweight when compared to women with a normal body mass index (BMI) regardless of menopausal status; 5. significant direct correlation was registered between the structural and volume parameters of the LV and age, blood pressure, BMI, waist to hips circumference ratio. A positive correlation was found between the level of pro-inflammatory biomarkers and structural parameters of LV.&#x0D; Conclusion. In women of perimenopausal age, a myocardial remodeling was revealed that could not be explained by traditional risk factors. The activation of the systemic inflammatory response in menopause and obesity was accompanied by the pathological LV remodeling and myocardial hypertrophy.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy

Background and aimsObesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. Methods and resultsThirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. ConclusionsOur study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

Prospective Association between Total and Trimester-Specific Gestational Weight Gain Rate and Physical Growth Status in Children within 24 Months after Birth.

In this study, our aim was to investigate the potential correlation between the mother's total gestational weight gain (GWG) rate and the trimester-specific GWG rate (GWGR) with the physical development status of the child within 24 months of age. We utilized linear regression models and linear mixed effects models to explore both time point and longitudinal relationships between GWGR and children's anthropometric outcome z-scores at 0, 1, 2, 4, 6, 9, 12, 18, and 24 months. To examine the critical exposure windows, we employed multiple informant models. We also conducted a stratified analysis considering pre-pregnancy BMI and the gender of the children. Our findings revealed notable positive associations between total GWGR and z-scores for body mass index for age (BMIZ), head circumference for age (HCZ), weight for age (WAZ), length for age (LAZ), and weight for length (WHZ) across different trimesters of pregnancy (pint < 0.05). The GWGR during the first two trimesters mainly influenced the relationship between total GWGR and BMIZ, WAZ, and LAZ, while the GWGR during the first trimester had a significant impact on the correlation with HCZ (0.206, 95% CI 0.090 to 0.322). Notably, the associations of GWGR and children's BMIZ were pronounced in male children and pre-pregnancy normal-weight women. In conclusion, our study findings indicated that a higher GWGR during each trimester was associated with greater physical growth during the first 24 months of life, especially GWGR in the first and second trimesters.

Factors Associated with Longitudinal Changes in Mammographic Density in a Multiethnic Breast Screening Cohort of Postmenopausal Women.

Breast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention. This study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression. 7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density. The associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.

Increased Demand of Obese Women for Protectins, Maresin, and Resolvin D1 in the Last Trimester of Pregnancy.

Pregnancy is a physiological state during which inflammation occurs. This complex biological response is necessary for the implantation process as well as delivery. In turn, its suppression during gestation favors the normal course of the pregnancy. Therefore, the presence of pro-resolving mediators, EPA and DHA derivatives, The aim of this study was to investigate the changes in the levels of anti-inflammatory resolvins and their precursors in different trimesters of pregnancy with consideration of the women's weight, including overweight and obese women before pregnancy. A total of 78 women participated in this study; the mean age and BMI before pregnancy were 32.3 ± 5.52 and 27.73 ± 6.13, respectively. The patients were divided into two groups, considering their BMI before pregnancy. The extraction of eicosanoids was performed by high-performance liquid chromatography. The results obtained were subjected to statistical analysis. The levels of all studied parameters showed statistically significant differences between the study group (SG) and the control group (CG) in the different trimesters of pregnancy. Over the course of pregnancy, the levels of protection (PDX), maresin, resolvins (RvD1, RvE1), and their precursors differed in relation to the trimester of pregnancy and the division into groups considering the correct body weight before pregnancy. Overweight or obese women had significantly lower levels of RvE1 in the third trimester and their precursors compared to normal-weight women. While the levels of PDX and RvD1 were significantly higher, this may be due to both a lower intake of products rich in omega-3 fatty acids by obese women and an increased need of obese women's bodies to quench chronic inflammatory processes associated with obesity. Both EPA and DHA derivatives are involved in calming down inflammation during pregnancy, which was observed.

OR35-05 Interaction of Cortisol with Testosterone Predicts Abdominal Fat Mass in Normal-weight Polycystic Ovary Syndrome Women with Normal Serum 11-Oxygenated Androgens

Abstract Disclosure: D.A. Dumesic: Consulting Fee; Self; Ferring Pharmaceuticals, Precede Biosciences, Inc, Spruce Biosciences, Inc. Grant Recipient; Self; National Institutes of Health. A.F. Turcu: None. H. Liu: None. T.R. Grogan: None. D.H. Abbott: None. G. Lu: None. D. Dharanipragada: None. G.D. Chazenbalk: None. Adrenal and ovarian steroidogenesis are interwoven with endocrine-metabolic dysfunction into polycystic ovary syndrome (PCOS). Women with PCOS and normal weight have androgen excess along with preferential abdominal adipose deposition (1,2), which is partially reversed by androgen receptor blockade (3). The role of adrenal steroids in this relationship, however, remains unclear. The present study examines whether serum levels of 11-oxygenated adrenal androgens, cortisol and/or cortisone differ between normal-weight PCOS women and body mass index (BMI)/age-matched normo-androgenic ovulatory women (controls) and whether adrenal steroids associate with abdominal adipose deposition. Twenty normal-weight PCOS women and 20 age- and BMI-matched controls underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing and total-body dual-energy x-ray absorptiometry. Clinical characteristics and hormonal values were compared between PCOS and control subjects. An unpaired Student’s t-test and Pearson correlation coefficients, adjusting for serum cortisol, were used as appropriate. Serum total/free testosterone (T) and androstenedione (A4) levels, and android/gynoid fat mass ratio, were greater in PCOS women with low-normal insulin sensitivity than in controls (all androgens P&amp;lt;0.001; android/gynoid fat mass ratio, P=0.026). A positive correlation of serum androgens with android/gynoid fat mass ratio was observed in all women combined (total T: R=+0.41, P=0.013; free T: R=+0.49, P=0.003; A4: R=+0.45, P=0.006). Serum 11ß-hydroxyA4 (11OHA4), 11-ketoA4 (11KA4), 11ß-hydroxyT (11OHT) and 11-ketoT (11KT), cortisol and cortisone levels were comparable between PCOS women and controls, and were unrelated to body fat distribution. Serum 11-oxygenated adrenal androgens correlated negatively with % total body fat (11OHA4: R=-0.42, P=0.011; 11KA4: R=-0.34, P=0.046; 11OHT: R=-0.36, P=0.031; 11KT: R=-0.37, P=0.027), but were no longer significant when adjusting for a concomitant negative relationship of serum cortisol with % total body fat (R=-0.45, P=0.006). Serum cortisol levels also correlated negatively with android fat mass in all women combined (R=-0.38, P=0.021) and were accompanied by a trend (P=0.075) towards reduced serum cortisol to cortisone ratio, as a marker of reduced 11β-hydroxysteroid dehydrogenase type 1 (HSD11ß1) conversion of cortisone to cortisol, in PCOS women versus controls (P=0.075). Ratios of 11KT/11KA4 and 11KT/11OHT as markers of AKR1C3and HSD11ß2 activities, respectively, did not differ by female type (both enzyme markers, P=nonsignificant). Conclusion: Reduced cortisol action, mediated in part through decreased HSD11ß1, interacts with an elevated androgens pathway to determine abdominal fat mass in normal-weight PCOS women with normal serum 11-oxygenated androgens.