Prunes preserve cortical density and estimated strength of the tibia in a 12-month randomized controlled trial in postmenopausal women: The Prune Study.

Non-pharmacological therapies, such as whole-food interventions, are gaining interest as potential approaches to prevent and/or treat low bone mineral density (BMD) in postmenopausal women. Previously, prune consumption preserved two-dimensional BMD at the total hip. Here we demonstrate that prune consumption preserved three-dimensional BMD and estimated strength at the tibia. PURPOSE: Dietary consumption of prunes has favorable impacts on areal bone mineral density (aBMD); however, more research is necessary to understand the influence on volumetric BMD (vBMD), bone geometry, and estimated bone strength. METHODS: This investigation was a single center, parallel arm 12-month randomized controlled trial (RCT; NCT02822378) to evaluate the effects of 50 g and 100 g of prunes vs. a Control group on vBMD, bone geometry, and estimated strength of the radius and tibia via peripheral quantitative computed tomography (pQCT) in postmenopausal women. Women (age 62.1 ± 5.0yrs) were randomized into Control (n = 78), 50 g Prune (n = 79), or 100 g Prune (n = 78) groups. General linear mixed effects (LME) modeling was used to assess changes over time and percent change from baseline was compared between groups. RESULTS: The most notable effects were observed at the 14% diaphyseal tibia in the Pooled (50 g + 100 g) Prune group, in which group × time interactions were observed for cortical vBMD (p = 0.012) and estimated bone strength (SSI; p = 0.024); all of which decreased in the Control vs. no change in the Pooled Prune group from baseline to 12 months/post. CONCLUSION: Prune consumption for 12 months preserved cortical bone structure and estimated bone strength at the weight-bearing tibia in postmenopausal women.

Effects of Prune (Dried Plum) Supplementation on Cardiometabolic Health in Postmenopausal Women: An Ancillary Analysis of a 12-Month Randomized Controlled Trial, The Prune Study.

BACKGROUND: Estrogen withdrawal during menopause is associated with an unfavorable cardiometabolic profile. Prunes (dried plums) represent an emerging functional food and have been previously demonstrated to improve bone health. However, our understanding of the effects of daily prune intake on cardiometabolic risk factors in postmenopausal women is limited. OBJECTIVES: We conducted an ancillary investigation of a randomized controlled trial (RCT), The Prune Study, to evaluate the effect of 12-mo prune supplementation on cardiometabolic health markers in postmenopausal women. METHODS: The Prune Study was a single-center, parallel-design, 12-mo RCT in which postmenopausal women were allocated to no-prune control, 50 g/d prune, or 100 g/d prune groups. Blood was collected at baseline, 6 mo, and 12 mo/post to measure markers of glycemic control and blood lipids. Body composition was assessed at baseline, 6 mo, and 12 mo/post using dual-energy X-ray absorptiometry. Linear mixed-effects models were used to evaluate the effect of time, treatment, and their interaction on cardiometabolic health markers, all quantified as exploratory outcomes. RESULTS: A total of 183 postmenopausal women (mean age, 62.1 ± 4.9 y) completed the entire 12-mo RCT: control (n = 70), 50 g/d prune (n = 67), and 100 g/d prune (n = 46). Prune supplementation at 50 g/d or 100 g/d did not alter markers of glycemic control and blood lipids after 12 mo compared with the control group (all P > 0.05). Furthermore, gynoid percent fat and visceral adipose tissue (VAT) indices did not significantly differ in women consuming 50 g/d or 100 g/d prunes compared with the control group after 12 mo of intervention. However, android total mass increased by 3.19% ± 5.5% from baseline in the control group, whereas the 100 g/d prune group experienced 0.02% ± 5.6% decrease in android total mass from baseline (P < 0.01). CONCLUSIONS: Prune supplementation at 50 g/d or 100 g/d for 12 mo does not improve glycemic control and may prevent adverse changes in central adiposity in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02822378.

Prune Consumption Attenuates Proinflammatory Cytokine Secretion and Alters Monocyte Activation in Postmenopausal Women: Secondary Outcome Analysis of a 12-Mo Randomized Controlled Trial: The Prune Study.

BACKGROUND: Proinflammatory cytokines are implicated in the pathophysiology of postmenopausal bone loss. Clinical studies demonstrate that prunes prevent bone mineral density loss; however, the mechanism underlying this effect is unknown. OBJECTIVE: We investigated the effect of prune supplementation on immune, inflammatory, and oxidative stress markers. METHODS: A secondary analysis was conducted in the Prune Study, a single-center, parallel-arm, 12-mo randomized controlled trial of postmenopausal women (55-75 y old; n = 235 recruited; n = 183 completed) who were assigned to 1 of 3 groups: "no-prune" control, 50 g prune/d and 100 g prune/d groups. At baseline and after 12 mo of intervention, blood samples were collected to measure serum high-sensitivity C-reactive protein (hs-CRP), serum total antioxidant capacity (TAC), plasma 8-isoprostane, proinflammatory cytokines [interleukin (IL)-1ß, IL-6, IL-8, monocyte chemoattractant protein-1, and tumor necrosis factor (TNF)-α] concentrations in plasma and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) culture supernatants, and the percentage and activation of circulating monocytes, as secondary outcomes. RESULTS: Prune supplementation did not alter hs-CRP, TAC, 8-isoprostane, and plasma cytokine concentrations. However, percent change from baseline in circulating activated monocytes was lower in the 100 g prune/d group compared with the control group (mean ± SD, -1.8% ± 4.0% in 100 g prune/d compared with 0.1% ± 2.9% in control; P < 0.01). Furthermore, in LPS-stimulated PBMC supernatants, the percent change from baseline in TNF-α secretion was lower in the 50 g prune/d group compared with the control group (-4.4% ± 43.0% in 50 g prune/d compared with 24.3% ± 70.7% in control; P < 0.01), and the percent change from baseline in IL-1ß, IL-6, and IL-8 secretion was lower in the 100 g prune/d group compared with the control group (-8.9% ± 61.6%, -4.3% ± 75.3%, -14.3% ± 60.8% in 100 g prune/d compared with 46.9% ± 107.4%, 16.9% ± 70.6%, 39.8% ± 90.8% in control for IL-1ß, IL-6, and IL-8, respectively; all P < 0.05). CONCLUSIONS: Dietary supplementation with 50-100 g prunes for 12 mo reduced proinflammatory cytokine secretion from PBMCs and suppressed the circulating levels of activated monocytes in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT02822378.

Randomised controlled trial of the effects of increased energy intake on menstrual recovery in exercising women with menstrual disturbances: the 'REFUEL' study.

STUDY QUESTION: Does increased daily energy intake lead to menstrual recovery in exercising women with oligomenorrhoea (Oligo) or amenorrhoea (Amen)? SUMMARY ANSWER: A modest increase in daily energy intake (330 ± 65 kcal/day; 18 ± 4%) is sufficient to induce menstrual recovery in exercising women with Oligo/Amen. WHAT IS KNOWN ALREADY: Optimal energy availability is critical for normal reproductive function, but the magnitude of increased energy intake necessary for menstrual recovery in exercising women, along with the associated metabolic changes, is not known. STUDY DESIGN, SIZE, DURATION: The REFUEL study (trial # NCT00392873) is the first randomised controlled trial to assess the effectiveness of 12 months of increased energy intake on menstrual function in 76 exercising women with menstrual disturbances. Participants were randomised (block method) to increase energy intake 20-40% above baseline energy needs (Oligo/Amen + Cal, n = 40) or maintain energy intake (Oligo/Amen Control, n = 36). The study was performed from 2006 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were Amen and Oligo exercising women (age = 21.0 ± 0.3 years, BMI = 20.8 ± 0.2 kg/m2, body fat = 24.7 ± 0.6%) recruited from two universities. Detailed assessment of menstrual function was performed using logs and measures of daily urinary ovarian steroids. Body composition and metabolic outcomes were assessed every 3 months. MAIN RESULTS AND THE ROLE OF CHANCE: Using an intent-to-treat analysis, the Oligo/Amen + Cal group was more likely to experience menses during the intervention than the Oligo/Amen Control group (P = 0.002; hazard ratio [CI] = 1.91 [1.27, 2.89]). In the intent-to-treat analysis, the Oligo/Amen + Cal group demonstrated a greater increase in energy intake, body weight, percent body fat and total triiodothyronine (TT3) compared to the Oligo/Amen Control group (P < 0.05). In a subgroup analysis where n = 22 participants were excluded (ambiguous baseline menstrual cycle, insufficient time in intervention for menstrual recovery classification), 64% of the Oligo/Amen + Cal group exhibited improved menstrual function compared with 19% in the Oligo/Amen Control group (χ2, P = 0.001). LIMITATIONS, REASONS FOR CAUTION: While we had a greater than expected dropout rate for the 12-month intervention, it was comparable to other shorter interventions of 3-6 months in duration. Menstrual recovery defined herein does not account for quality of recovery. WIDER IMPLICATIONS OF THE FINDINGS: Expanding upon findings in shorter, non-randomised studies, a modest increase in daily energy intake (330 ± 65 kcal/day; 18 ± 4%) is sufficient to induce menstrual recovery in exercising women with Oligo/Amen. Improved metabolism, as demonstrated by a modest increase in body weight (4.9%), percent body fat (13%) and TT3 (16%), was associated with menstrual recovery. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the U.S. Department of Defense: U.S. Army Medical Research and Material Command (Grant PR054531). Additional research assistance provided by the Penn State Clinical Research Center was supported by the National Center for Advancing Translation Sciences, National Institutes of Health, through Grant UL1 TR002014. M.P.O. was supported in part by the Loretta Anne Rogers Chair in Eating Disorders at University of Toronto and University Health Network. All authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT00392873. TRIAL REGISTRATION DATE: October 2006. DATE OF FIRST PATIENT'S ENROLMENT: September 2006.

The Male Athlete Triad-A Consensus Statement From the Female and Male Athlete Triad Coalition Part 1: Definition and Scientific Basis.

ABSTRACT: The Male Athlete Triad is a syndrome of 3 interrelated conditions most common in adolescent and young adult male endurance and weight-class athletes and includes the clinically relevant outcomes of (1) energy deficiency/low energy availability (EA) with or without disordered eating/eating disorders, (2) functional hypothalamic hypogonadism, and (3) osteoporosis or low bone mineral density with or without bone stress injury (BSI). The causal role of low EA in the modulation of reproductive function and skeletal health in the male athlete reinforces the notion that skeletal health and reproductive outcomes are the primary clinical concerns. At present, the specific intermediate subclinical outcomes are less clearly defined in male athletes than those in female athletes and are represented as subtle alterations in the hypothalamic-pituitary-gonadal axis and increased risk for BSI. The degree of energy deficiency/low EA associated with such alterations remains unclear. However, available data suggest a more severe energy deficiency/low EA state is needed to affect reproductive and skeletal health in the Male Athlete Triad than in the Female Athlete Triad. Additional research is needed to further clarify and quantify this association. The Female and Male Athlete Triad Coalition Consensus Statements include evidence statements developed after a roundtable of experts held in conjunction with the American College of Sports Medicine 64th Annual Meeting in Denver, Colorado, in 2017 and are in 2 parts-Part I: Definition and Scientific Basis and Part 2: The Male Athlete Triad: Diagnosis, Treatment, and Return-to-Play. In this first article, we discuss the scientific evidence to support the Male Athlete Triad model.

The Male Athlete Triad-A Consensus Statement From the Female and Male Athlete Triad Coalition Part II: Diagnosis, Treatment, and Return-To-Play.

ABSTRACT: The Male Athlete Triad is a medical syndrome most common in adolescent and young adult male athletes in sports that emphasize a lean physique, especially endurance and weight-class athletes. The 3 interrelated conditions of the Male Athlete Triad occur on spectrums of energy deficiency/low energy availability (EA), suppression of the hypothalamic-pituitary-gonadal axis, and impaired bone health, ranging from optimal health to clinically relevant outcomes of energy deficiency/low EA with or without disordered eating or eating disorder, functional hypogonadotropic hypogonadism, and osteoporosis or low bone mineral density with or without bone stress injury (BSI). Because of the importance of bone mass acquisition and health concerns in adolescence, screening is recommended during this time period in the at-risk male athlete. Diagnosis of the Male Athlete Triad is best accomplished by a multidisciplinary medical team. Clearance and return-to-play guidelines are recommended to optimize prevention and treatment. Evidence-based risk assessment protocols for the male athlete at risk for the Male Athlete Triad have been shown to be predictive for BSI and impaired bone health and should be encouraged. Improving energetic status through optimal fueling is the mainstay of treatment. A Roundtable on the Male Athlete Triad was convened by the Female and Male Athlete Triad Coalition in conjunction with the 64th Annual Meeting of the American College of Sports Medicine in Denver, Colorado, in May of 2017. In this second article, the latest clinical research to support current models of screening, diagnosis, and management for at-risk male athlete is reviewed with evidence-based recommendations.

Characterizing the resting metabolic rate ratio in ovulatory exercising women over 12 months.

PURPOSE: A reduced resting metabolic rate (RMR) ratio and suppressed total triiodothyronine (TT3 ) have been demonstrated to reflect metabolic compensation to chronic energy deficiency. However, it is unknown whether the relationship between RMR ratio and TT3 remains constant over time. OBJECTIVE: To examine the relationship between RMR ratio and TT3 in free-living exercising, ovulatory, weight-stable women (n = 14) for a 12-month observational period. METHODS: Dual-energy X-ray absorptiometry (DXA) and indirect calorimetry provided data on anthropometrics and energy expenditure. Harris-Benedict, DXA, and Cunningham (1980 and 1991) equations estimated RMR and RMR ratio (measured RMR/predicted RMR). Repeated measures analysis assessed changes over time (ANOVA and Friedman). Generalized linear modeling tested whether RMR ratio threshold predicted TT3  > 73.2 ng/dL or TT3  > 80 ng/dL over 12-months. RESULTS: Women were 25.9 ± 5.4 years, weighed 59.6 ± 5.2 kg with BMI 22.3 ± 1.4 kg/m2 at baseline, which remained constant throughout the study (weight: P = .523; BMI: P = .511). There was no significant effect of time for RMR (P = .886), TT3 (P = .890), energy availability (P = .212), and RMR ratio (Harris-Benedict: P = .852; DXA: P = .607; Cunningham1980 : P = .754; Cunningham1991 : P = .739). When TT3  > 73.2 ng/dL, each RMR ratio threshold (Harris-Benedict: P = .021; DXA: P = .019; Cunningham1980 : P = .019; Cunningham1991 : P = .016) significantly predicted participants as energy replete; however, when using a more lenient clinical TT3 threshold of >80 ng/dL, only the DXA ratio threshold yielded a significant prediction of TT3 (P < .001). CONCLUSIONS: The relationship between RMR ratio and TT3 remains significant and consistent over time in free-living exercising women, validating the use of RMR ratio for the longitudinal characterization of energetic status in this population (ie, prospective serial monitoring).

Eating behaviours related to psychological stress are associated with functional hypothalamic amenorrhoea in exercising women.

Functional hypothalamic amenorrhoea (FHA) can occur due to the independent or combined effects of psychogenic and energetic stressors. In exercising women, research has primarily focused on energy deficiency as the cause of FHA while psychological stressors have been ignored. To assess both psychological and metabolic factors associated with FHA in exercising women, we performed across-sectional comparison of 61 exercising women (≥2 hours/week, age 18-35 years, BMI 16-25kg/m2), who were eumenorrheic or amenorrhoeic confirmed by daily urine samples assayed for reproductive hormone metabolites. Psychological factors and eating behaviours were assessed by self-report questionnaires. Exercising women with FHA had lower resting metabolic rate (p=0.023), T3 (p<0.001), T4 (p=0.013), leptin (p=0.002), higher peptide YY (p<0.001), greater drive for thinness (p=0.017), greater dietary cognitive restraint (p<0.001), and displayed dysfunctional attitudes, i.e., need for social approval (p=0.047) compared to eumenorrheic women. Amenorrhoeic women displayed asignificant positive correlation between the need for social approval and drive for thinness with indicators of stress, depression, and mood, which was not apparent in eumenorrheic women. In exercising women with FHA, eating behaviours are positively related to indicators of psychological stress and depression.

Indices of Resting Metabolic Rate Accurately Reflect Energy Deficiency in Exercising Women.

Energy deficiency in exercising women can lead to physiological consequences. No gold standard exists to accurately estimate energy deficiency, but measured-to-predicted resting metabolic rate (RMR) ratio has been used to categorize women as energy deficient. The purpose of the study was to (a) evaluate the accuracy of RMR prediction methods, (b) determine the relationships with physiological consequences of energy deficiency, and (c) evaluate ratio thresholds in a cross-sectional comparison of ovulatory, amenorrheic, or subclinical menstrual disturbances in exercising women (n = 217). Dual-energy X-ray absorptiometry (DXA) and indirect calorimetry provided data on anthropometrics and energy expenditure. Harris-Benedict, DXA, and Cunningham (1980 and 1991) equations were used to estimate RMR and RMR ratio. Group differences were assessed (analysis of variance and Kruskal-Wallis tests); logistic regression and Spearman correlations related ratios with consequences of energy deficiency (i.e., low total triiodothyronine; TT3). Sensitivity and specificity calculations evaluated ratio thresholds. Amenorrheic women had lower RMR (p < .05), DXA ratio (p < .01), Cunningham1980 (p < .05) and Cunningham1991 (p < .05) ratio, and TT3 (p < .01) compared with the ovulatory group. Each prediction equation overestimated measured RMR (p < .001), but predicted (p < .001) and positively correlated with TT3 (r = .329-.453). A 0.90 ratio threshold yielded highest sensitivity for Cunningham1980 (0.90) and Harris-Benedict (0.87) methods, but a higher ratio threshold was best for DXA (0.94) and Cunningham1991 (0.92) methods to yield a sensitivity of 0.80. In conclusion, each ratio predicted and correlated with TT3, supporting the use of RMR ratio as an alternative assessment of energetic status in exercising women. However, a 0.90 ratio cutoff is not universal across RMR estimation methods.

Female Athlete Triad and Relative Energy Deficiency in Sport: A Focus on Scientific Rigor.

We examine the scientific evidence supporting The Female Athlete Triad and Relative Energy Deficiency in Sport (RED-S) syndromes. More research is necessary to advance the understanding of both syndromes; however, it is premature to consider RED-S as an evidence-based syndrome. Future research should specifically define RED-S components, determine its clinical relevance, and establish the causality of relative energy deficiency on RED-S outcomes.

Comparison of Female Athlete Triad Coalition and RED-S risk assessment tools.

The Female Athlete Triad Coalition (Triad Coalition) and Relative Energy Deficiency in Sport (RED-S) consensus statements each include risk assessment tools to guide athlete eligibility decisions. This study examined how these tools categorized the same set of individuals to an overall risk factor score and qualitatively compared athlete eligibility decisions resulting from each tool. Exercising women (n = 166) with complete screening/baseline datasets from multiple previously conducted studies were assessed. Data used for risk assessment included: anthropometric measurements, dual-energy x-ray absorptiometry scans, exercise and health status surveys, and two disordered eating questionnaires (Three Factor Eating Questionnaire and Eating Disorder Inventory). Individuals were scored on each tool and subsequently categorized as either fully cleared, provisionally cleared, or restricted from play. Based on the Triad Coalition tool, 25.3% of subjects were classified as fully cleared, 62.0% as provisionally cleared, and 12.7% as restricted from play. Based on the RED-S tool, 71.7% of subjects were classified as fully cleared, 18.7% as provisionally cleared, and 9.6% as restricted from play. The Triad Coalition and RED-S tools resulted in different clearance decisions (p < 0.001), with the Triad Coalition tool recommending increased surveillance of a greater number of athletes.

Impact of hormonal contraception and weight loss on high-density lipoprotein cholesterol efflux and lipoprotein particles in women with polycystic ovary syndrome.

OBJECTIVE: To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women. DESIGN: Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks. PATIENTS: Eighty-seven overweight/obese women with PCOS at two academic centres. MEASUREMENTS: Change in HDL-C efflux capacity and lipoprotein particles. RESULTS: High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (rs = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (rs = -0·31, P = 0·009) and insulin sensitivity index (ISI; rs = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles. CONCLUSIONS: Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes.

Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments.

Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 ± 31 vs. 1,327 ± 18 kcal/day, P < 0.001) but not in OV (1,284 ± 24 vs. 1,252 ± 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 ± 2%) vs. OV (103 ± 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (ρ = 0.38, P < 0.001) and leptin (ρ = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation.

Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction.

We assessed the impact of energy deficiency on menstrual function using controlled feeding and supervised exercise over four menstrual cycles (1 baseline and 3 intervention cycles) in untrained, eumenorrheic women aged 18-30 yr. Subjects were randomized to either an exercising control (EXCON) or one of three exercising energy deficit (ED) groups, i.e., mild (ED1; -8 ± 2%), moderate (ED2; -22 ± 3%), or severe (ED3; -42 ± 3%). Menstrual cycle length and changes in urinary concentrations of estrone-1-glucuronide, pregnanediol glucuronide, and midcycle luteinizing hormone were assessed. Thirty-four subjects completed the study. Weight loss occurred in ED1 (-3.8 ± 0.2 kg), ED2 (-2.8 ± 0.6 kg), and ED3 (-2.6 ± 1.1 kg) but was minimal in EXCON (-0.9 ± 0.7 kg). The overall sum of disturbances (luteal phase defects, anovulation, and oligomenorrhea) was greater in ED2 compared with EXCON and greater in ED3 compared with EXCON AND ED1. The average percent energy deficit was the main predictor of the frequency of menstrual disturbances (f = 10.1, ß = -0.48, r(2) = 0.23, P = 0.003) even when weight loss was included in the model. The estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from -22 (ED2) to -42% (ED3), reflecting an energy deficit of -470 to -810 kcal/day, respectively. This is the first study to demonstrate a dose-response relationship between the magnitude of energy deficiency and the frequency of exercise-related menstrual disturbances; however, the severity of menstrual disturbances was not dependent on the magnitude of energy deficiency.

Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial.

UNLABELLED: Medical and surgical interventions for elevated breast cancer risk (e.g., BRCA1/2 mutation, family history) focus on reducing estrogen exposure. Women at elevated risk may be interested in less aggressive approaches to risk reduction. For example, exercise might reduce estrogen, yet has fewer serious side effects and less negative impact than surgery or hormonal medications. Randomized controlled trial. Increased risk defined by risk prediction models or BRCA mutation status. Eligibility: Age 18-50, eumenorrheic, non-smokers, and body mass index (BMI) between 21 and 50 kg/m(2). 139 were randomized. Treadmill exercise: 150 or 300 min/week, five menstrual cycles. Control group maintained exercise <75 min/week. PRIMARY OUTCOME: Area under curve (AUC) for urinary estrogen. Secondary measures: urinary progesterone, quantitative digitized breast dynamic contrast-enhanced magnetic resonance imaging background parenchymal enhancement. Mean age 34 years, mean BMI 26.8 kg/m(2). A linear dose-response relationship was observed such that every 100 min of exercise is associated with 3.6 % lower follicular phase estrogen AUC (linear trend test, p = 0.03). No changes in luteal phase estrogen or progesterone levels. There was also a dose-response effect noted: for every 100 min of exercise, there was a 9.7 % decrease in background parenchymal enhancement as measured by imaging (linear trend test, p = 0.009). Linear dose-response effect observed to reduce follicular phase estrogen exposure measured via urine and hormone sensitive breast tissue as measured by imaging. Future research should explore maintenance of effects and extent to which findings are repeatable in lower risk women. Given the high benefit to risk ratio, clinicians can inform young women at increased risk that exercise may blunt estrogen exposure while considering whether to try other preventive therapies.

Reductions in urinary collection frequency for assessment of reproductive hormones provide physiologically representative exposure and mean concentrations when compared with daily collection.

OBJECTIVE: To determine if reducing the frequency of urinary sample collection from daily to 5, 3, or 2 days per week during a menstrual cycle or 28-day amenorrheic monitoring period provide accurate representations of the reproductive hormone metabolites estrone-1-glucuronide (E1G) and pregnanediol glucuronide (PdG) exposure and mean concentrations. METHODS: Exercising women presenting with eumenorrhea or exercise-associated menstrual disturbances collected daily urine samples for the assessment of E1G and PdG concentrations. After enzyme immunoassay analysis of the daily samples, E1G and PdG data were systematically removed from each menstrual cycle or amenorrheic monitoring period to mimic three reduced collection frequencies, representing 5, 3, and 2 days per week. Exposure and mean concentration were calculated for both hormones and all four urinary collection frequencies. RESULTS: E1G and PdG exposure and mean cycle concentrations derived from reduced collection frequencies were not different from daily collection (P > 0.05), independent of whether menstrual cycles and monitoring periods were analyzed together or separately. Bland-Altman analysis indicated acceptable agreement between each reduced collection frequency and daily collection. CONCLUSIONS: Compared with daily urinary collection, a reduced collection frequency of 5, 3, or 2 days each week provides accurate E1G and PdG profiles of collection periods of various lengths and types of menstrual function. Reduction of urinary sample collection frequency may enable researchers to reduce participant burden and costs, increase compliance, and study a wider range of study populations.

Maturation time of new granule cells in the dentate gyrus of adult macaque monkeys exceeds six months.

We studied two groups of adult macaque monkeys to determine the time course of adult neurogenesis in the dentate gyrus of the hippocampus. In the first group, six adult monkeys (Macaca mulatta) received a single injection of the thymidine analog BrdU (75 mg/kg), which is incorporated into replicating DNA and serves as a marker for new cell birth. Brain tissue was collected 48 h, 2 wk, and 6 wk after BrdU injection to examine the initial stages of neurogenesis. Because mature neurons were not evident at 6 wk, we examined tissue collected over a longer time course in a second study. In this study, eight monkeys (Macaca fascicularis) who were subjects in a separate exercise study received 10 weekly injections of BrdU (75 mg/kg), and brain tissue was collected at 16 and 28 wk from the first injection. Based on the timing of expression of neuronal cell markers (ßIII-tubulin, doublecortin, NeuN), the extent of dendritic arborization, and acquisition of mature cell body morphology, we show that granule cell maturation in the dentate gyrus of a nonhuman primate is protracted over a minimum of a 6-mo time period, more than 6 times longer than in rodents. The lengthened time course for new cell maturation in nonhuman primates may be appropriate for preservation of neural plasticity over their longer life span and is relevant to our understanding of antidepressant and other therapies that have been linked to neurogenesis in humans.

2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad: 1st International Conference held in San Francisco, California, May 2012 and 2nd International Conference held in Indianapolis, Indiana, May 2013.

The Female Athlete Triad is a medical condition often observed in physically active girls and women, and involves three components: (1) low energy availability with or without disordered eating, (2) menstrual dysfunction and (3) low bone mineral density. Female athletes often present with one or more of the three Triad components, and an early intervention is essential to prevent its progression to serious endpoints that include clinical eating disorders, amenorrhoea and osteoporosis. This consensus statement represents a set of recommendations developed following the 1st (San Francisco, California, USA) and 2nd (Indianapolis, Indiana, USA) International Symposia on the Female Athlete Triad. It is intended to provide clinical guidelines for physicians, athletic trainers and other healthcare providers for the screening, diagnosis and treatment of the Female Athlete Triad and to provide clear recommendations for return to play. The 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad expert panel has proposed a risk stratification point system that takes into account magnitude of risk to assist the physician in decision-making regarding sport participation, clearance and return to play. Guidelines are offered for clearance categories, management by a multidisciplinary team and implementation of treatment contracts. This consensus paper has been endorsed by the Female Athlete Triad Coalition, an International Consortium of leading Triad researchers, physicians and other healthcare professionals, the American College of Sports Medicine and the American Medical Society for Sports Medicine.

2014 Female Athlete Triad Coalition consensus statement on treatment and return to play of the female athlete triad: 1st International Conference held in San Francisco, CA, May 2012, and 2nd International Conference held in Indianapolis, IN, May 2013.

The Female Athlete Triad is a medical condition often observed in physically active girls and women, and involves 3 components: (1) low energy availability with or without disordered eating, (2) menstrual dysfunction, and (3) low bone mineral density. Female athletes often present with 1 or more of the 3 Triad components, and an early intervention is essential to prevent its progression to serious endpoints that include clinical eating disorders, amenorrhea, and osteoporosis. This consensus statement represents a set of recommendations developed following the first (San Francisco, California) and second (Indianapolis, Indianna) International Symposia on the Female Athlete Triad. It is intended to provide clinical guidelines for physicians, athletic trainers, and other health care providers for the screening, diagnosis, and treatment of the Female Athlete Triad and to provide clear recommendations for return to play. The 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad Expert Panel has proposed a risk stratification point system that takes into account magnitude of risk to assist the physician in decision-making regarding sport participation, clearance, and return to play. Guidelines are offered for clearance categories, management by a multidisciplinary team, and implementation of treatment contracts. This consensus paper has been endorsed by The Female Athlete Triad Coalition, an International Consortium of leading Triad researchers, physicians, and other health care professionals, the American College of Sports Medicine, and the American Medical Society for Sports Medicine.