Overweight Premenopausal Women Research Articles

Fenretinide in young women at genetic or familial risk of breast cancer: A placebo-controlled biomarker trial.

Fenretinide, a retinoid with a low toxicity profile that accumulates in the breast, has been shown to prevent second breast cancer in young women. Fenretinide exhibits apoptotic and anti-invasive properties and it improves insulin sensitivity in overweight premenopausal women with insulin resistance. The present study aimed to further characterize its role in cancer prevention by measuring circulating biomarkers related to insulin sensitivity and breast cancer risk. Sixty-two women, aged 20 to 46 years, healthy or who had already undergone breast cancer surgery, with a known BRCA1/2 mutation or a likelihood of mutation ≥ 20% according to the BRCAPRO model, were randomly assigned to receive fenretinide (200 mg/day) or placebo for 5 years (trial registration: EudraCT Number: 2009-010260-41). Fasting blood samples were drawn at baseline, 12 and 36 months, and the following biomarkers were analyzed: retinol, leptin, adiponectin, retinol-binding protein 4, total cholesterol, HDL and LDL cholesterol, triglycerides, glucose, insulin, IGF-I, IGFBP-3, SHBG, testosterone, and VEGF. After 12 months of treatment, we observed a favorable effect of fenretinide on glucose (decrease; P=0.005), insulin (decrease; P=0.03), HOMA index (decrease; P=0.004), HDL cholesterol (increase; P=0.002), even though these effects were less prominent after 36 months. Retinol and retinol-binding protein 4 markedly decreased (P<0.0001) throughout the study. None of the other measured biomarkers changed.

Nonalcoholic Fatty Liver Disease and Risk of Early-Onset Vasomotor Symptoms in Lean and Overweight Premenopausal Women.

The role of nonalcoholic fatty liver disease (NAFLD) in vasomotor symptom (VMS) risk in premenopausal women is unknown. We examined the prevalence of early-onset VMSs according to NAFLD status in lean and overweight premenopausal women. This cross-sectional study included 4242 premenopausal Korean women (mean age 45.4 years). VMSs (hot flashes and night sweats) were assessed using the Korean version of the Menopause-Specific Quality of Life questionnaire. Hepatic steatosis was determined using liver ultrasound; lean was defined as a body mass index of <23 kg/m2. Participants were categorized into four groups: NAFLD-free lean (reference), NAFLD-free overweight, lean NAFLD, and overweight NAFLD. Compared with the reference, the multivariable-adjusted prevalence ratios (PRs) (95% confidence intervals (CIs)) for VMSs in NAFLD-free overweight, lean NAFLD, and overweight NAFLD were 1.22 (1.06–1.41), 1.38 (1.06–1.79), and 1.49 (1.28–1.73), respectively. For moderate-to-severe VMSs, the multivariable-adjusted PRs (95% CIs) comparing NAFLD-free overweight, lean NAFLD, and overweight NAFLD to the reference were 1.38 (1.10–1.74), 1.73 (1.16–2.57), and 1.74 (1.37–2.21), respectively. NAFLD, even lean NAFLD, was significantly associated with an increased risk of prevalent early-onset VMSs and their severe forms among premenopausal women. Further studies are needed to determine the longitudinal association between NAFLD and VMS risk.

Implementation of Christian Orthodox fasting improves plasma adiponectin concentrations compared with time-restricted eating in overweight premenopausal women

The exact mechanisms mediating the metabolic effects of Orthodox fasting remain unclear. Plasma adiponectin, biochemical and anthropometrical data were evaluated in 55 Orthodox fasters (OF) and 42 time-restricted eating controls (all women, mean age 47.8 years) at three time points: baseline, end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). In the OF group, there was an increase in adiponectin values at 12 weeks compared with baseline (9815.99 vs 8983.52 mg/ml, p = 0.02) and a reduction in body fat mass between baseline and 12 weeks (35.44 vs 32.17%, p = 0.004) and between 7 and 12 weeks (35.33 vs 32.17%, p = 0.003). In the same group, an inverse correlation between adiponectin and waist circumference values was observed over the entire study period. Our results provide novel evidence that Orthodox fasting has favourable metabolic effects related to improved adiponectin concentrations.

Abstract C124: Breast density and metabolic risk factors: Cross-sectional analysis of the baseline data from a phase II breast cancer prevention trial

Abstract Breast density is an established breast cancer risk factor. Metabolic disturbances and high adiposity also increase breast cancer burden, but their relationships with breast density are not clearly defined, possibly due to the limitation of mammography density measurements in obese women. We are presently conducting a phase II double-blind, randomized, placebo-controlled clinical trial to study the effect of metformin on obesity-associated breast cancer risk in overweight and obese premenopausal women with metabolic disturbances. One hundred and fifty-one participants with a large waist (≥88 cm or ≥80 cm for Asian Americans and individuals with PCOS) and one other component of metabolic syndrome (elevated triglyceride, reduced HDL-C, elevated blood pressure, or elevated fasting glucose) were accrued and randomized (1:1) to receive metformin 850 mg BID or placebo for 12 months. The primary study endpoint is change in breast density. Secondary endpoints are changes in serum insulin, insulin-like growth factor axis, adipokines, waist circumference and body weight. Thirty-six percent of the accrued participants are Hispanics. The average body mass index, waist circumference and waist-to-hip ratio of the accrued participants are 37.8 ± 6.8 kg/m2, 110.8 ± 12.4 cm and 0.90 ± 0.07, respectively. We expect to complete our clinical trial in December 2018. We performed cross-sectional analyses of the baseline data to determine the associations between metabolic disturbances and breast density parameters acquired by fat-water MRI on noncompressed breasts. This is especially relevant in our study cohort because the compressed breast thickness is greater in obese women, which results in decreased image contrast on mammogram. Potential differences by ethnicity were explored. We showed that percent density and absolute density were not related to anthropometric measurements of adiposity for the overall cohort, with similar results by ethnicity. Having elevated fasting glucose in women with a large waist was related to a lower percent density and absolute density for the overall cohort, and the association was only observed in Hispanics. Our work is the first to compare breast density assessed by fat-water MRI by ethnicity. Further research is required to confirm our findings. Due to the rising rates of obesity in the United States, we strongly believe that this trial will have an important impact in public health, especially in minority population. Citation Format: Jesse Trujillo, Edgar Tapia, Diana Villa-Guillen, Pavani Chalasani, Cynthia Thomson, Maria Altbach, Jean-Phillipe Galons, Jessica Martinez, Denise Roe, Amit Algotar, H.H. Sherry Chow. Breast density and metabolic risk factors: Cross-sectional analysis of the baseline data from a phase II breast cancer prevention trial [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C124.

24‐hour Urinary Epinephrine and Interleukin‐6 are Independent Correlates of Endogenous Erythropoietin among Overweight Premenopausal Women

PurposeAfrican American (AA) women frequently exhibit lower hemoglobin (Hb) and are less responsive to erythropoietin stimulating agents (ESAs) compared to European American (EA) women. These differences have led to the practice of AA receiving higher doses of ESAs compared to EA to achieve a similar level of improvement in Hb for treatment of anemia. However, higher doses of ESAs are associated with a greater risk of mortality. To date, it remains unclear whether differences in ESA responsiveness are due to race‐related differences in endogenous erythropoietin (EPO) production or other contributing factors. The objectives of the present work were two‐fold: 1) compare EPO between a cohort of AA and EA women and 2) identify potential physiological correlates of EPO using variables linked with ESA hyporesponsiveness.MethodsSecondary analyses were performed on 36 (AA; n = 14) overweight (28.3 ± 1.4 kg/m2), premenopausal women. Measurements were conducted following a 4‐week period wherein participants were held in energy balance (i.e., weight stable &lt; 1% weekly fluctuation) via dietary control. Whole blood was collected after an overnight fast during the follicular phase of the menstrual cycle. Serum inflammatory biomarkers (interleukin‐6, tumor necrosis factor alpha) were measured in duplicate, while 24‐hour urinary fractionated catecholamines (epinephrine, norepinephrine, and dopamine) were measured with high‐performance liquid chromatography. Group allocation was based on self‐reported race. Non‐normally distributed data were log‐transformed. Between‐group comparisons were performed with independent t‐tests. Substantive differences were quantified using Hedges’ g. Following significant zero‐order correlations, a stepwise multiple linear regression was used to test the independent effects of variables on the variance in EPO.ResultsConsistent with previous work, AA had lower Hb (g·dL−1) (11.3 ± 0.7 vs. 12.6 ± 0.8 g·dL−1; p &lt; 0.001; g = 1.67) and higher EPO (mIU·mL−1) (13.3 ± 6.8 vs. 8.0 ± 2.4; p = 0.014; g = 1.12). Significant between‐group differences were also observed for dopamine (p = 0.001) and total urinary catecholamines (p = 0.003). Among AA, Hb, interleukin‐6, and urinary epinephrine were significant correlates of EPO (all p &lt; 0.05). Whereas only Hb correlated with EPO (p = 0.019) in EA. In the combined sample, regression modeling revealed Hb, interleukin‐6, and urinary epinephrine were significant correlates of EPO (R2 = 0.68; p &lt; 0.001) independent of race. Of note, interleukin‐6 and urinary epinephrine respectively accounted for 17% and 19% of the variance in EPO.ConclusionsCompared with EA, AA women had higher EPO concentrations, however; other factors including systemic adrenergic activity and inflammation may explain these differences.Support or Funding InformationThis investigation was supported by the following grants from the National Institutes of Health: R25CA47888, R01AG027084‐01, R01AG027084‐S, P30DK056336, P60DK079626, and UL1RR025777.

Elevated GTP Cyclohydrolase I Pathway in Endothelial Progenitor Cells of Overweight Premenopausal Women.

Background/Aims. Sexual differences exist in endothelial progenitor cells (EPCs), and various cardiovascular risk factors are associated with the preservation of endothelial function in premenopausal women. However, it is unclear whether differences in endothelial function and circulating EPCs exist between overweight premenopausal women and age-matched men. Methods. We compared EPC counting and functions in normal-weight and overweight premenopausal women and men, evaluated endothelial function in each group, and detected the expression of the guanosine triphosphate cyclohydrolase I (GTPCH I) pathway. Results. The number of EPCs was lower in the male group than in the female group, regardless of normal-weight or overweight status, and there was no significant difference between the different weight groups among females or males. Endothelial function and EPC migration and proliferation were preserved in overweight premenopausal women compared with overweight men as were nitric oxide (NO) levels in plasma and secreted by EPCs. Endothelial function, the circulating EPC population, and NO levels were not different between normal-weight and overweight premenopausal women. Flow-mediated dilatation was significantly correlated with EPC function, plasma NO levels, and EPC-secreted NO. Conclusions. This investigation provides the first evidence for sex-based differences in EPC activity and endothelial function in overweight middle-aged individuals; these differences are associated with alterations in NO production and may partly occur through downregulation of the GTPCH I pathway. The present results provide new insights into the mechanism underlying the preserved endothelial function in overweight premenopausal women and may uncover a potential therapeutic target for endothelial repair in overweight population.

Cardiovascular and metabolic health effects of team handball training in overweight women: Impact of prior experience.

We tested the hypothesis that participation in small-sided team handball training could provide beneficial effects on cardiovascular and metabolic parameters in overweight premenopausal women with special focus on the importance of prior team handball experience. A 16-week RCT training intervention was conducted in overweight premenopausal women randomized into three groups: a team handball training group without prior experience (UN;n=13), a team handball group with prior experience (EXP; n=10), and an inactive control group (CON;n=9). Both UN and EXP completed 1.6±0.3 training sessions per week with average heart rates of 84±5 and 85±9% of maximal heart rate, respectively. Cardiovascular and metabolic parameters were assessed before and after the intervention. Compared to CON, UN had significant increases in VO2max (7±4%) and intermittent endurance performance (26±14%) as well as reduced total fat mass (4±6%), total fat percentage (4±5%), and android fat mass (7±12%), respectively (all P<.05). Compared to UN and CON, EXP displayed increased left ventricular mass and left ventricular mass index (both P<.05) after the training period. There were no significant changes between any of the groups in muscle mass, blood lipids, resting heart rate, and blood pressure (all P>.05). Small-sided team handball training in overweight premenopausal women resulted in improvement of VO2max and body composition for participants with minimal team handball experience, indicating that prior team handball experience is not a prerequisite for improving physiological parameters of importance for health. Furthermore, EXP displayed cardiac adaptations, including increased left ventricular mass and left ventricular mass index.

Effects of Whole-Body Electromyostimulation on the Energy-Restriction-Induced Reduction of Muscle Mass During Intended Weight Loss.

Purpose: Overweight and obesity are an increasing problem worldwide. However, most studies that focus on weight reduction by energy restriction and/or aerobic exercise reported considerable loss of muscle mass as well. Increased protein intake and/or resistance exercise might inhibit this detrimental effect during a negative energy balance. Whole-body electromyostimulation (WB-EMS), a time effective, joint-friendly, and highly customizable training technology, showed similar hypertrophic effects compared with high-intensity resistance training. The aim of this study is to evaluate the effect of WB-EMS on body composition during negative energy balance with maintained/increased protein intake in overweight premenopausal women.Patients and Methods: Ninety premenopausal, 25–50-year-old, overweight women were randomly assigned to three groups (n = 30 each). (1) Negative energy balance (−500 kcal/day) by energy restriction with compensatory protein intake (CG). (2) Negative energy balance (−500 kcal/day) by energy restriction (−250 kcal/day) and increased physical activity (−250 kcal/day) with increased protein intake (PA). (3) Negative energy balance (−500 kcal/day) due to energy restriction and increased physical activity with increased protein intake plus WB-EMS. The duration of the intervention was 16 weeks. Participants underwent restrictions in kcal per days and supplementation of protein (CG: 1.2 or PA/WB-EMS: 1.7 g/kg body mass/day) where needed. Bipolar WB-EMS was applied 1.5× week for 20 min (85 Hz; 350 μs; intermittent 6 s impulse, 4 s rest; rectangular). The primary study endpoint “lean body mass” (LBM) and secondary endpoint body fat mass (BFM) were assessed by bio-impedance analysis (BIA).Results: LBM decreased in the CG and PA group (CG: −113 ± 1,872 g; PA: −391 ± 1,832 g) but increased in the WB-EMS group (387 ± 1,769 g). However, changes were not significant (p > 0.05). Comparing the groups by ANOVA, no significant differences were observed (p = 0.070). However, pairwise adjusted comparisons determined significant differences between WB-EMS and PA (p = 0.049). BFM decreased significantly (p < 0.001) in all groups (CG: −2,174 ± 4,331 g; PA: −3,743 ± 4,237 g; WB-EMS: −3,278 ± 4,023 g) without any significant difference between the groups (ANOVA: p = 0.131).Conclusion: WB-EMS is an efficient, joint-friendly, and highly customizable training technology for maintaining muscle mass during energy restriction and can thus be considered as an alternative to more demanding resistance exercise protocols.

Effect of eight weeks' selected resistance training on serum levels of estradiol, sex hormone-binding globulin (SHBG) and body composition in obese and overweight premenopausal women

هدف: از بین هورمون های مهم جنسی که تغییرات در غلظت آنها با پاتوژنز بیماری های مختلف مرتبط است، می توان بهگلوبولین متصل شونده به هورمون جنسی ) SHBG ( و استرادیول اشاره کرد. هدف این پژوهش، بررسی تاثیر هشت هفتهتمرین مقاومتی منتخب بر سطوح سرمی استرادیول، SHBG و ترکیب بدن در زنان پیش یائسه دارای اضافه وزن بود.روشها: بیست زن پیش یائسه دارای اضافه وزن، به دو گروه تجربی )میانگین سنی 11 / 2± 3/ 44 سال( و کنترل )میانگینسنی 37 / 3± 5/ 42 سال( تقسیم شدند. گروه تجربی به مدت هشت هفته، هر هفته سه جلسه، تمرینات ورزشی مقاومتی باتراباند را انجام دادند. تمرینات مقاومتی شامل 16 حرکت برای بالاتنه، تنه و پایین تنه بود. هر حرکت با 10 تکرار، 3 نوبتو 2 دقیقه استراحت بین نوبت ها و یک دقیقه استراحت بین حرکات اجرا شد. 48 ساعت پس از آخرین جلسه تمرین،نمونههای خونی جمع آوری و سطوح متغیرهای مورد نظر ) SHBG و استرادیول( به روش الایزا اندازه گیری شد. داده ها باآزمون آنالیز کوواریانس تجزیه و تحلیل شد.نتایج: نتایج پژوهش نشان دهنده آن است که افزایش SHBG و کاهش درصد چربی بدن در گروه تمرین معنادار، ولیتغییرات سطوح سرمی استرادیول گروه ها از نظر آماری فاقد معنا است.نتیجه گیری: با توجه به یافتهها به نظر می رسد که انواع مختلف تمرینات ورزشی، نقش مهمی در تعدیل سطوحهورمون های جنسی ایفا می کنند. بر مبنای نتایج این پژوهش، احتمالاً تمرینات مقاومتی با تراباند اثرات مثبتی بر تعدیلسطوح هورمون-های جنسی زنان دارای اضافه وزن دارد.

Testosterone imbalance may link depression and increased body weight in premenopausal women

Accumulating evidence supports a link between depression and being overweight in women. Given previously reported sex differences in fat accumulation and depression prevalence, as well as the likely role of sex hormones in both overweight and mood disorders, we hypothesised that the depression-overweight association may be mediated by sex hormones. To this end, we investigated the association of being overweight with depression, and then considered the role of sex hormones in relation to being overweight and depression in a large population-based cohort. We included a total of 3124 women, 970 premenopausal and 2154 postmenopausal from the LIFE-Adult cohort study in our analyses. We evaluated associations between being overweight (BMI >25 kg/m2), sex hormone levels, and depressive symptomatology according to Centre for Epidemiologic Studies Depression (CES-D) scores, and explored mediation of depression in a mediation model. Being overweight was significantly associated with depressive symptoms in premenopausal but not postmenopausal women. Both premenopausal and postmenopausal overweight women had higher free testosterone levels compared with normal weight women. Premenopausal women with depressive symptomatology had higher free testosterone levels compared to women without. We found a significant mediation effect of depressive symptomatology in overweight premenopausal women through free testosterone level. These findings highlight the association between being overweight and depressed, and suggest that high free testosterone levels may play a significant role in depression of overweight premenopausal women. Based on this, pharmacological approaches targeting androgen levels in overweight depressed females, in particular when standard anti-depressive treatments fail, could be of specific clinical relevance.

Age and leptinemia association with anxiety and depression symptoms in overweight middle-aged women.

The aim of the study was to investigate the effect of menopause and of postmenopausal stages on depression and anxiety symptoms, and whether these symptoms associate with anthropometric, metabolic, and hormonal parameters in midlife women. Postmenopausal women (age 50-65), either at early (EPM, n=33) or late (LPM, n = 23) postmenopause, and 23 premenopausal controls (PreM, age 40-50), matched for BMI with the PM groups, were studied. Blood biochemical and hormonal determinations, bioimpedance anthropometry, and depression and anxiety symptoms (Beck's depression [BDI] and anxiety [BAI] inventories) were conducted. The BAI score was higher in both PM groups than in the PreM group. In contrast, only the LPM group showed a significantly elevated BDI score. All groups presented overweight and abdominal obesity, having similar BMI and waist/hip ratio values. Both PM groups showed insulin resistance, whereas only the LPM group presented decreased skeletal muscle mass and basal metabolic rate. Correlation analysis, including all 79 middle-aged women, showed age, percentage body fat, waist/hip ratio, and leptinemia to correlate positively with the anxiety and depression scores. Multivariate regression showed leptin and age to associate positively with depressive- and anxious-like symptoms. Postmenopausal women presented impaired body composition, energy expenditure, insulin sensitivity, and mental symptoms, in comparison to similarly overweight premenopausal women. Among all the overweight midlife women, these symptoms were more strongly associated with age and leptin levels than with reproductive aging itself. The data indicate that, among overweight middle-aged women with abdominal obesity, the aging process and the development of leptin resistance are associated with impairment of mental health.

Exercise training and/or diet on reduction of intra-abdominal adipose tissue and risk factors for cardiovascular disease.

To test the effects of weight loss with and without exercise training (aerobic or resistance) on intra-abdominal adipose tissue (IAAT) and risk factors for cardiovascular disease (CVD). Additionally, CVD risk factors was evaluated before and after weight loss using previously established IAAT cut-points. One hundred twenty-two overweight premenopausal women were randomly assigned to one of three groups: (1) diet only (Diet); (2) diet and aerobic training (Diet + AT); or (3) diet and resistance training (Diet + RT); until a BMI of < 25 kg/m2 was reached. Computerized tomography was used to measure IAAT and blood lipids were measured by assay. Evaluations were made before and after weight loss. Though no group-by-time effects were found after weight loss, we observed significant time effects for: IAAT (-38.0%, P < 0.001), total cholesterol (TC) (-2.2%, P = 0.008), low-density lipoprotein cholesterol (LDL-C) (-4.8%, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (+20.2%, P < 0.001), triglycerides (-18.7%, P < 0.001), TC/HDL-C (-16.3%, P < 0.001), and LDL-C/HDL-C (-18.0%, P < 0.001). Following weight loss, 40.2% of all participants reduced IAAT to < 40 cm2 (IAAT associated with low CVD risk). Furthermore, only 2.5% of participants had an IAAT > 110 cm2 (IAAT associated with high CVD risk) after weight loss. We also observed that decreases of IAAT were associated with decreased CVD risk factors after weight loss independent of race, changes in %fat mass and changes in maximal oxygen uptake. Caloric restriction leading to significant weight loss with or without exercise training appears to be equally effective for reducing IAAT and CVD risk factors.

Impact of Estrogen on the Relationship Between Obesity and Renal Cell Carcinoma Risk in Women.

The relationship between obesity and renal cell carcinoma (RCC) has been widely investigated. However, the effect of estrogen on this relationship in female RCC patients has not been evaluated. We conducted a case-control study to investigate the role of estrogen as a potential modifier of the association between obesity and RCC risk in Chinese women.A total of 497 consecutive female patients with pathologically confirmed RCC, including 364 clear cell RCC (ccRCC), were enrolled. Age-matched controls were selected from cancer-free females seeking physical examination in our institution. Estrogen receptor-β (ER-β) and insulin-like growth factor (IGF)-1 receptor (IGF-1R) expression levels were detected in RCC tissues. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression models.We observed a positive association between overweight and RCC risk in pre-menopausal but not post-menopausal women. Similar association was also observed between overweight and ccRCC risk. Overweight pre-menopausal women had an increased risk of RCC (OR: 1.67, 95%CI: 1.01–2.76), as well as an increased risk of ccRCC (OR: 1.73, 95%CI: 1.02–2.99), after adjusting for potential confounders. IGF-1R expression levels were higher in pre-menopausal compared with post-menopausal cases (P = 0.015).These results suggest that estrogen plays an important role in RCC etiology and may modify the association between obesity and RCC risk in women. We hypothesize that estrogen may up-regulate IGF-1R and potentiate the deleterious effects of obesity-related elevations of insulin and IGFs.

Downregulated GTCPH I/BH4 Pathway and Decreased Function of Circulating Endothelial Progenitor Cells and Their Relationship with Endothelial Dysfunction in Overweight Postmenopausal Women.

Endothelial progenitor cells (EPCs) have endogenous endothelium-reparative potential, but obesity impairs EPCs. Overweight premenopausal women have a normal number of circulating EPCs with functional activity, but whether EPCs in overweight postmenopausal women can repair obesity-related endothelial damage requires further investigation. For this purpose, we examined the function and number of circulating EPCs, evaluated vascular endothelial function, and explored the underlying mechanism. Compared with normal weight or overweight age-matched men, postmenopausal women (overweight or normal weight) had a diminished number of circulating EPCs and impaired vascular endothelial function, as detected by flow-mediated dilatation. Moreover, GTCPH I expression and the nitric oxide level in overweight postmenopausal women and men were significantly decreased. Together, our findings demonstrate that the number or function of circulating EPCs and endothelial function, which is partially regulated by the GTCPH I/BH4 signaling pathway, is not preserved in overweight postmenopausal women. The GTCPH I/BH4 pathway in circulating EPCs may be a potential therapeutic target for endothelial injury in overweight postmenopausal women.

Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS.

Background/aimsPolycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo.MethodsForty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n = 21) or placebo (n = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire.ResultsIncluded women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P < 0.05 vs changes during placebo. Escitalopram had no significant effect on measures of insulin sensitivity, insulin secretion, fasting lipids, mental health or HRQoL.ConclusionWaist circumference and cortisol levels increased during treatment with escitalopram in women with PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged.

Intermittent energy restriction induces changes in breast gene expression and systemic metabolism.

BackgroundObservational studies suggest weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight to the same extent as, or more than equivalent continuous energy restriction (CER) but the effects of IER on normal breast tissue and systemic metabolism as indicators of breast cancer risk are unknown.MethodsWe assessed the effect of IER (two days of 65 % energy restriction per week) for one menstrual cycle on breast tissue gene expression using Affymetrix GeneChips, adipocyte size by morphometry, and systemic metabolism (insulin resistance, lipids, serum and urine metabolites, lymphocyte gene expression) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised and supervised analyses of matched pre and post IER biopsies in 20 subjects were performed, whilst liquid and gas chromatography mass spectrometry assessed corresponding changes in serum and urine metabolites in all subjects after the two restricted and five unrestricted days of the IER.ResultsWomen lost 4.8 % (±2.0 %) of body weight and 8.0 % (±5.0 %) of total body fat. Insulin resistance (homeostatic model assessment (HOMA)) reduced by 29.8 % (±17.8 %) on the restricted days and by 11 % (±34 %) on the unrestricted days of the IER. Five hundred and twenty-seven metabolites significantly increased or decreased during the two restricted days of IER. Ninety-one percent of these returned to baseline after 5 days of normal eating. Eleven subjects (55 %) displayed reductions in energy restriction-associated metabolic gene pathways including lipid synthesis, gluconeogenesis and glycogen synthesis. Some of these women also had increases in genes associated with breast epithelial cell differentiation (secretoglobulins, milk proteins and mucins) and decreased collagen synthesis (TNMD, PCOLCE2, TIMP4). There was no appreciable effect of IER on breast gene expression in the other nine subjects. These groups did not differ in the degree of changes in weight, total body fat, fat cell size or serum or urine metabolomic markers. Corresponding gene changes were not seen in peripheral blood lymphocytes.ConclusionThe transcriptional response to IER is variable in breast tissue, which was not reflected in the systemic response, which occurred in all subjects. The mechanisms of breast responsiveness/non-responsiveness require further investigation.Trial registrationISRCTN77916487 31/07/2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0714-4) contains supplementary material, which is available to authorized users.

Correlation Between Energy Balance And Body Composition Changes After 12 Weeks Of Exercise In Overweight Premenopausal Women

The national recommendation for the amount of physical activity (PA) needed to achieve and maintain a healthy body weight is 13-26 kcal/kg/day. The wide range in exercise dose is due partly to exercise studies that inadequately assessed energy balance components that either complement or compensate for experimental increases in exercise energy expenditure (ExEE). PURPOSE:To determine the energy balance correlates of changes in body composition resulting from a 12-week endurance training intervention. METHODS:Twenty-four previously sedentary, overweight women were randomly assigned to a high (26 kcal/kg/day) or low dose (13 kcal/kg/day) of endurance exercise. Twelve-week changes in weight, body composition estimates from air displacement plethysmography, waist circumference from anthropometry, 19-hour post-exercise resting energy expenditure (REE) from indirect calorimetry, energy intake (EI) from 7-day food diaries, and spontaneous physical activity (SPA) from 7-days of wearing piezoelectric pedometers were assessed. RESULTS:There were no mean differences between high- and low-dose exercise groups in the 12-week changes in average body weight (p=0.79), fat mass (p=0.44), fat-free mass (p=0.52), waist circumference (p=0.24), EI (p=0.94), or SPA (p=0.29). When groups were combined, there were significant 12-week changes in waist circumference (-1.0 ± 1.9 cm, p=0.02) and fat-free mass (+0.6 ± 1.2 kg, p=0.03). In addition, average ExEE was inversely correlated with changes in fat mass (r=-0.50, p=0.01) and waist circumference (r=-0.56, p<0.01), and positively correlated with post-exercise REE (r=0.42, p=0.04). Moreover, post-exercise REE was inversely correlated with changes in fat mass (r-0. 47, p=0.02) and waist circumference (r=-0.60, p<0.01), and positively correlated with changes in fat-free mass (r=0.47, p=0.02) and SPA (r=0.44, p=0.03). CONCLUSIONS:Exercise-related reductions in fat mass and waist circumference are correlated with higher ExEE and post-exercise REE. Furthermore, higher post-exercise REE is also correlated with greater exercise-related increases in fat-free mass and SPA. Our findings suggest that national physical activity recommendations aimed at improving body composition focus on effective ways to sustain increases in ExEE.

APotato (Poly)phenols on Postprandial Insulinemia and Platelet Aggregation in Premenopausal Overweight Women: A Pilot Study

Potatoes are known for their carbohydrate, potassium, vitamin C and fiber content; however potatoes also contain chlorogenic acids (CGA). Colored potatoes may contain additional (poly)phenols, such as anthocyanins (ACN) in purple potatoes. Polyphenols exert various health promoting biological effects. Previous work suggests CGA and ACN have a role in glycemic control and platelet function. The present study examined two potato varieties: white potato (WP) containing CGA and purple potato (PP) containing CGA and ACN in a 6 h postprandial study in women (n=12, crossover design) on postprandial metabolic and epinephrine (EPI)‐ and ADP‐ induced platelet aggregation responses. Potatoes (200 g cooked) were included in a high carbohydrate, high fat breakfast (~690 kcal). A demographically match control group (CON, n=8) consumed a rice substituted breakfast without CGA or ACN and were used for metabolic comparisons only. PP and WP significantly reduced postprandial insulin responses compared to CON (p&lt;0.05). Glucose responses were not different among groups. PP significantly inhibited EPI‐induced‐ (p=0.015) and ADP‐induced‐ (P=0.009) platelet aggregation compared to WP. Potatoes compared to a common starch replacement reduced the insulin demand to achieve post‐meal glucose homeostasis. PP with CGA and ACN prolonged platelet aggregation time compared to WP, suggesting a potential role for certain potato varieties containing (poly)phenols in cardiovascular disease risk reduction. The work supports future research to explore potatoes and cardio‐metabolic health.Supported by various donor funds.

The oestrogen-leptin paradox.

Women have lower systolic and diastolic blood pressure than men, with hypertension being less prevalent in young and middle-aged women but not in women over 60 (August & Oparil, 1999). While the cause of the rise in blood pressure in postmenopausal women is not known, the lower levels of oestrogen have been often suggested as a factor. Indeed transdermal oestrogen lowers blood pressure and sympathetic activity in postmenopausal women (Vongpatanasin et al. 2001). The adipokine leptin, a product of the ob gene, is primarily synthesized and secreted from fat as is the pancreatic hormone insulin. Both signal metabolic information to the central nervous system (CNS) via specific receptors within the hypothalamus and also signal to increase sympathetic activity and blood pressure. Oestrogen has been shown to increase the production of leptin in women and also in animal studies (Shimizu et al. 1997). While sex differences in the effects of leptin on energy balance and on interactions between leptin and oestrogen signalling have been much studied, we do not yet know whether there are sex differences in the sympatho-excitatory effects of leptin. Thus the study by Shi and Brooks in this issue of The Journal of Physiology (Shi & Brooks, 2015) is a major step forward in our understanding of the importance of oestrogen in altering the central sympatho-excitatory effects of leptin. They found that centrally administered leptin increased lumbar and renal sympathetic nerve activity (SNA) in male rats and only in females rats with high levels of oestrogen (ovariectomized plus exogenous oestrogen or during pro-oestrus). Leptin had no effect in females rat with low levels of oestrogen (ovariectomized or during dioestrus). Not only were basal levels of renal and lumbar SNA increased, there was marked amplification of both sympathetic baroreflexes. These findings are paradoxical as males that have even lower levels of circulating oestrogen than female rats in dioestrous also show amplification of the leptin's sympatho-excitation. Thus too little or too much oestrogen may be problematic when it comes to leptin's actions. A major discovery by Shi and Brooks was that the sympatho-excitatory effects of leptin given centrally to rats in pro-oestrous were attenuated by ∼30% with a melanocortin receptor type 3/4 specific antagonist injected directly into the paraventricular nucleus. While it is not known exactly where the interaction between oestrogen and leptin occurs, it is likely to be at least partly mediated by pro-opiomelanocortin (POMC) neurons in the hypothalamus. Interestingly, oestrogen and leptin receptors co-exist on many neurons within the hypothalamus (Del Bianco-Borges et al. 2010). These results highlight the importance of understanding the interactions of oestrogen and leptin, particularly as there are marked hormonal changes at peri-menopause that may contribute to increased abdominal fat accumulation (Davis et al. 2012). Further, overweight premenopausal women with higher levels of oestrogen may be at greater risk through amplifying the sympatho-excitatory effects of leptin but whether these effects of oestrogen amplifying the sympatho-excitatory actions of leptin translate to obese subjects needs to be determined. In recent decades there has been an alarming increase in the proportion of the population that are overweight or obese in developed, as well as developing, regions. The impact on the health of the individual is profound as there is a spectrum of metabolic and cardiovascular dysfunction that is, and will continue to be, the major burden of disease in society. These include insulin resistance, dyslipidaemia, type 2 diabetes as well as hypertension and cardiovascular disease. Thus to unravel the links between obesity and these sequelae is clearly a major health priority. However, the cardiovascular risk in men and women is not the same. Clearly further studies are also required to determine the precise site of action and to determine why females in dioestrous with lower levels of oestrogen (but higher than males) are protected from the sympatho-excitatory effects of leptin.

A randomized, controlled, crossover trial to assess the acute appetitive and metabolic effects of sausage and egg-based convenience breakfast meals in overweight premenopausal women.

BackgroundDietary protein at breakfast has been shown to enhance satiety and reduce subsequent energy intake more so than carbohydrate or fat. However, relatively few studies have assessed substitution of protein for carbohydrate on indicators of appetite and glucose homeostasis simultaneously.MethodsThe acute appetitive and metabolic effects of commercially-prepared sausage and egg-based breakfast meals at two different protein levels (30 g and 39 g/serving), vs. a low-protein pancake breakfast (3 g protein) and no breakfast (water), were examined in premenopausal women (N = 35; age 32.5 ± 1.6 yr; BMI 24.8 ± 0.5 kg/m2). Test products provided ~280 kcal/serving and similar fat (12–14 g) and fiber contents (0–1 g). Visual Analog Scale ratings for appetite (hunger, fullness, prospective consumption, desire to eat) and repeated blood sampling for plasma glucose and insulin concentrations were assessed throughout each test day. Energy intake was recorded at an ad libitum lunch meal at 240 min.ResultsResults showed increased satiety ratings for both the 30 and 39 g protein meals vs. the low-protein and no breakfast conditions (p < 0.001 for all). Postprandial glucose and insulin excursions were lower following the 30 g and 39 g protein conditions vs. the low-protein condition, with smaller responses following the 39 g vs. 30 g protein condition (p < 0.05 for all). Energy intake at lunch was significantly less (p < 0.001) following the 39 g protein meal (692 kcal) vs. the low-protein and no breakfast conditions (789 and 810 kcal, respectively). Total energy intake from the test condition + lunch was higher (p < 0.01) for the 30 and 39 g meals (982 and 983 kcal, respectively) vs. no breakfast (810 kcal), and less than the low protein breakfast (1064 kcal; p < 0.01 vs. 39 g condition only).ConclusionsResults suggest that convenience meals providing 30 or 39 g protein/serving produce greater appetite control, lower postprandial glycemia and insulinemia, and reduced subsequent intake at lunch relative to a low-protein control, or no breakfast.Trial registrationNCT01713114