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Showing papers by "Barbara A. Gower published in 2010"


Journal ArticleDOI
TL;DR: A scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint to arrive at major conclusions.
Abstract: Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. Participants in Development of Scientific Statement: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: Each expert conducted extensive literature searches of case control, cohort, and randomized controlled tria...

605 citations


Journal ArticleDOI
01 Apr 2010-Obesity
TL;DR: As little as 80 min/week aerobic or resistance training had modest positive effects on preventing weight regain following a diet‐induced weight loss and more importantly, both aerobic and resistance training prevented regain of potentially harmful visceral fat.
Abstract: The purpose of this study was to determine what effect aerobic and resistance exercise training has on gain of visceral fat during the year following weight loss. After being randomly assigned to aerobic training, resistance training, or no exercise training, 45 European-American (EA) and 52 African-American (AA) women lost 12.3 +/- 2.5 kg on a 800 kcal/day diet. Computed tomography was used to measure abdominal subcutaneous and visceral adipose tissue, whereas total fat and regional fat (leg, arm, and trunk) were measured by dual energy X-ray absorptiometry after weight loss and 1 year following the weight loss. Because not all the subjects adhered to the 2 time/week 40 min/day exercise training during the 1-year follow-up, subjects were divided into five groups for analysis: aerobic adherers, aerobic nonadherers, resistance adherers, resistance nonadherers, and no exercise. No significant differences were observed between the aerobic training and resistance training adherers for any variable. However, the aerobic (3.1 kg) and resistance (3.9 kg) exercise adherers gained less weight than any of the other three groups (all >6.2 kg). In addition, the two exercise adherence groups did not significantly increase visceral fat (<0.8%) as compared with the 38% increase for the two nonadhering exercise groups and the 25% for the nonexercise group. In conclusion, as little as 80 min/week aerobic or resistance training had modest positive effects on preventing weight regain following a diet-induced weight loss. More importantly, both aerobic and resistance training prevented regain of potentially harmful visceral fat.

127 citations


01 Sep 2010
TL;DR: Data is presented to show that a combination of weight gain, loss of muscle, and a shift from peripheral to central fat patterning contributes to this increase, and identify hormones that may be responsible for the shift.
Abstract: Fat distribution, especially increased visceral fat, may be as important as overall obesity in increasing risk of heart disease, type 2 diabetes and certain cancers. Risk of disease, as well as visceral fat, increases dramatically with age. Cross-sectional data suggests that increased risk of disease may be largely prevented if the age related increase in visceral fat does not occur. The objective of this short review is to present data that shows visceral fat increasing over 200% in men and 400% in women between the 3rd and 7th decades, show that a combination of weight gain, loss of muscle, and a shift from peripheral to central fat patterning contributes to this increase, and identify hormones that may be responsible for the shift. Finally, the review will show how participation in exercise can slow the age related shift in visceral fat.

113 citations


Journal ArticleDOI
TL;DR: It appears that greater levels of central rather than total adiposity may be deleterious for developing bone, and prepubertal overweight children with prediabetes may be at risk for poor skeletal development.
Abstract: Childhood studies of the fat-bone relationship are conflicting, possibly reflecting the influence of metabolic abnormalities in some but not all obese children. Bone mass was compared between prepubertal overweight children with (n = 41) and without (n = 99) prediabetes. Associations of bone mass with measures of total and central adiposity, glucose intolerance, insulin sensitivity, lipid profile, systemic inflammation, and osteocalcin also were determined. In 140 overweight children aged 7 to 11 years, an oral glucose tolerance test was used to identify those with prediabetes and for determination of glucose, 2-hour glucose, glucose area under the curve (AUC), insulin, 2-hour insulin, and insulin AUC. Blood samples also were assessed for lipids, C-reactive protein, and osteocalcin. Total-body bone mineral content (BMC), fat-free soft tissue mass (FFST), and fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA). Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) were assessed using MRI. Total-body BMC was 4% lower in overweight children with prediabetes than in those without prediabetes after controlling for sex, race, height, and weight (p = .03). In the total sample, FM was positively related with BMC (β = 0.16, p = .01) after adjusting for sex, race, height, and FFST. However, VAT (β = −0.13, p = .03) and SAAT (β = −0.34, p = .02) were inversely associated with BMC after controlling for sex, race, height, FFST, FM, and SAAT or VAT. No significant associations were found between BMC and the biochemical measurements. Prepubertal overweight children with prediabetes may be at risk for poor skeletal development. In addition, it appears that greater levels of central rather than total adiposity may be deleterious for developing bone. © 2010 American Society for Bone and Mineral Research.

96 citations


Journal ArticleDOI
01 Dec 2010-Obesity
TL;DR: Low postprandial fat oxidation may uniquely predispose obesity‐prone individuals to accrual of adipose tissue, and high nonsleeping RQ predicted 2‐year change in FM independently of energy balance, circulating insulin, and insulin sensitivity.
Abstract: High respiratory quotient (RQ) has been associated with fat mass (FM) gain in some, but not all studies. Variability among results may reflect differences in the RQ variable measured (fasting vs. 24-h) or may be due to differences in control for factors that affect RQ, such as diet, energy balance, circulating insulin, and insulin sensitivity. The objective of this study was to determine whether different RQ values (fasting, sleeping, nonsleeping, and 24-h) would predict change in FM over 2 years in obesity-prone women, controlling for diet and adjusting for energy balance, circulating insulin, and insulin sensitivity. Participants were 33 previously overweight premenopausal women. Fasting, sleeping, nonsleeping, and 24-h RQ values were measured during controlled-diet conditions by respiratory chamber calorimetry. Intravenous glucose tolerance tests were also performed to adjust for fasting insulin, acute insulin response to glucose, and insulin sensitivity. Over the following 2 years, changes in FM were tracked annually by dual energy X-ray absorptiometry. High nonsleeping RQ (NSRQ) predicted 2-year change in FM independently of energy balance, circulating insulin, and insulin sensitivity. This observation suggests that low postprandial fat oxidation may uniquely predispose obesity-prone individuals to accrual of adipose tissue.

65 citations


Journal ArticleDOI
01 Feb 2010-Obesity
TL;DR: Investigation of independent relationships of intra‐abdominal adipose tissue (IAAT), leg fat, and aerobic fitness with blood lipids and insulin sensitivity in European‐American and African‐American premenopausal women found maintenance of favorable fat distribution and aerobic Fitness may be important strategies for healthy aging, at least in pre menopausal EA and AA women.
Abstract: The purpose of this study was to determine independent relationships of intra-abdominal adipose tissue (IAAT), leg fat, and aerobic fitness with blood lipids and insulin sensitivity (Si) in European-American (EA) and African-American (AA) premenopausal women. Ninety-three EA and ninety-four AA with BMI between 27 and 30 kg/m2 had IAAT by computed tomography, total fat and leg fat by dual-energy X-ray absorptiometry, aerobic fitness by a graded exercise test, African admixture (AFADM) by ancestry informative markers, blood lipids by the Ektachem DT system, and Si by glucose tolerance test. Independent of age, aerobic fitness, AFADM, and leg fat, IAAT was positively related to low-density lipoprotein–cholesterol (LDL-C), cholesterol-high-density lipoprotein (HDL) ratio, triglycerides (TGs), and fasting insulin (standardized β varying 0.16–0.34) and negatively related to HDL-cholesterol (HDL-C) and Si (standardized β −0.15 and −0.25, respectively). In contrast, independent of age, aerobic fitness, AFADM, and IAAT, leg fat was negatively related to total cholesterol, LDL-C, cholesterol-HDL ratio, TGs, and fasting insulin (standardized β varying −0.15 to −0.21) and positively related to HDL-C and Si (standardized β 0.16 and 0.23). Age was not independently related to worsening of any blood lipid but was related to increased Si (standardized β for Si 0.25, insulin −0.31). With the exception of total cholesterol and LDL-C, aerobic fitness was independently related to worsened blood lipid profile and increased Si (standardized β varying 0.17 to −0.21). Maintenance of favorable fat distribution and aerobic fitness may be important strategies for healthy aging, at least in premenopausal EA and AA women.

60 citations


Journal ArticleDOI
TL;DR: 25(OH)D and PTH concentrations were independently associated with whole-body insulin sensitivity in a cohort of healthy women, which suggested that these variables may influence insulin sensitivity through independent mechanisms.

56 citations


Journal ArticleDOI
01 May 2010-Obesity
TL;DR: The association between RPE and weight regain suggests that perception of exercise difficulty is an important predictor of weight regain following a weight‐loss intervention.
Abstract: It has been previously reported that overweight and obese individuals perceive exercise as more difficult than their lean counterparts, and this difference may not be solely attributed to physiological differences. Therefore, we tested the hypothesis that individual differences in the perception of exercise difficulty during exercise, independent of concurrently measured physiological markers of exertion, are predictive of weight regain, after completion of a weight loss program. A total of 113 formerly overweight women who had previously completed a weight-loss program to achieve a normal body weight (BMI <25 kg/m2) underwent a submaximal aerobic exercise task while measures of physiological and perceived exertion (rating of perceived exertion (RPE)) were recorded. Weight gain was assessed following a subsequent 1-year free-living period. Average weight regain 1 year following the intervention was 5.46 ± 3.95 kg. In regression modeling, RPE (β = 0.21, P = 0.01), but not physiological exertion (β = 0.02, P = 0.81), during the submaximal exercise task was positively associated with 1-year weight regain following weight loss in premenopausal women, independent of measured confounding variables. The association between RPE and weight regain suggests that perception of exercise difficulty is an important predictor of weight regain following a weight-loss intervention.

39 citations


Journal ArticleDOI
01 Nov 2010-Obesity
TL;DR: The hypothesis that the association of adiposity with indexes of insulin sensitivity (SI) and β‐cell function would differ with ethnicity and age was tested and it was suggested that the impact of adipulence on insulin secretion and action differs with age and ethnicity.
Abstract: The prevalence of type 2 diabetes is higher among African Americans (AA) vs. European Americans (EA), is highest at middle age, and is related to obesity. This study was conducted to test the hypothesis that the association of adiposity (percent body fat (%fat)) with indexes of insulin sensitivity (SI) and β-cell function would differ with ethnicity and age. Subjects were 168 healthy, normoglycemic AA and EA girls and women aged 7–12 years, 18–32 years, and 40–70 years. An intravenous glucose tolerance test (IVGTT) was used to assess indexes of insulin secretion and action: SI, acute C-peptide secretion (X0); basal, first-phase, second-phase, and total β-cell responsivity to glucose (PhiB, Phi1, Phi2, and PhiTOT, respectively); and the disposition index (DI = SI × PhiTOT). %Fat was assessed with dual energy X-ray absorptiometrys. Adiposity was significantly associated with SI among EA (−0.57, P < 0.001) but not AA (−0.20, P = 0.09). Adiposity appeared stimulatory to β-cell function in the two groups of younger subjects and in EA, but inhibitory in postmenopausal women, particularly AA postmenopausal women. Among AA postmenopausal women, %fat was inversely associated with Phi1 (r = −0.57, P < 0.05) and PhiTOT (r = −0.68, P < 0.01). These results suggest that the impact of adiposity on insulin secretion and action differs with age and ethnicity.

34 citations


Journal ArticleDOI
TL;DR: Novel findings are provided that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA and promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.
Abstract: Background: The prevalence of type 2 diabetes is higher among African Americans (AA) vs European Americans (EA), independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. Methods: Subjects were 115 African American (AA) and 137 European American (EA) healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI) with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. Results: Vitamin D intake was positively associated with S I (standardized β = 0.18, P = 0.05) and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007) in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/ resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI and HOMA-IR, respectively). Similar to vitamin D, dietary calcium was associated with S I and HOMA-IR among AA but not EA. Conclusions: This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

30 citations


Journal ArticleDOI
01 Nov 2010-Obesity
TL;DR: Dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women, and further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution.
Abstract: Calcium intake is reported to enhance weight loss with a preferential loss in trunk fat. Discrepant findings exist as to the effects of calcium intake on longitudinal changes in total fat mass and central fat deposition. Therefore, the purpose of this study was to determine associations between dietary calcium intake and 1-year change in body composition and fat distribution, specifically intra-abdominal adipose tissue (IAAT). A total of 119 healthy, premenopausal women were evaluated at baseline and 1 year later. Average dietary calcium was determined via 4-day food records. Total fat was determined by dual-energy X-ray absorptiometry (DXA) and subcutaneous abdominal adipose tissue (SAAT) and IAAT by computed tomography. Over the study period, participants' reported daily calcium and energy intakes were 610.0 ± 229.9 mg and 1,623.1 ± 348.5 kcal, respectively. The mean change in weight, total fat, IAAT, and SAAT was 4.9 ± 4.4 kg, 5.3 ± 4.0 kg, 7.7 ± 19.5 cm2, and 49.3 ± 81.1 cm2, respectively. Average calcium intake was significantly, inversely associated with 1-year change in IAAT (standardized β: −0.23, P < 0.05) after adjusting for confounding variables. For every 100 mg/day of calcium consumed, gain in IAAT was reduced by 2.7 cm2. No significant associations were observed for average calcium intake with change in weight, total fat, or SAAT. In conclusion, dietary calcium intake was significantly associated with less gain in IAAT over 1 year in premenopausal women. Further investigation is needed to verify these findings and determine the calcium intake needed to exert beneficial effects on fat distribution.

Journal ArticleDOI
01 Feb 2010-Obesity
TL;DR: In this article, a stepwise multiple linear regression (MLR) analysis was conducted to identify associations of free fatty acid (FFA) concentrations with measures of insulin secretion and action before and during a glucose challenge test.
Abstract: Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin(0)), the acute insulin response to glucose (AIR(g)), the insulin sensitivity index (S(I)), basal and nadir FFA (FFA(0), FFA(nadir)), and nadir time (TIME(nadir)) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA(0), FFA(nadir), and TIME(nadir) with ethnicity, age group, insulin measures, indexes of body composition from dual-energy X-ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin(0) and AIR(g) were higher among AAs vs. EAs, whereas S(I) was lower, independent of age group. MLR analyses indicated that FFA(0) was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), S(I), and insulin(0). FFA(nadir) was best predicted by FFA(0), age group, and intra-abdominal adipose tissue (IAAT). TIME(nadir) was best predicted by leg fat mass, AIR(g), and S(I). In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA(0) among AAs was independent of insulin(0) and S(I). Whether lower FFA(0) is associated with substrate oxidation or risk for obesity remains to be determined.

Journal ArticleDOI
01 Aug 2010-Obesity
TL;DR: In this paper, the authors found that greater insulin sensitivity may predispose to adiposity among weight reduced women, an effect that may be ameliorated by a lower GL diet.
Abstract: Among obesity-prone individuals, metabolic state may interact with diet in determining body composition. We tested the hypotheses that, among 103 weight-reduced women over 1 year, (i) insulin sensitivity would be positively associated with change in %fat; (ii) this association would be modulated by dietary glycemic load (GL); and (iii) changes in fat distribution would be related to indexes of glucose metabolism. Insulin sensitivity, glucose effectiveness, fasting and postchallenge insulin and glucose, and glucose tolerance were assessed during intravenous glucose tolerance test (IVGTT). Changes in %fat and fat distribution were examined using dual-energy X-ray absorptiometry and computed tomography. Dietary GL was assessed on 67 women using food records. On average, women showed a +5.3 ± 3.0% change in %fat over 1 year, with the magnitude of this change being greater in relatively insulin sensitive women (+6.0 ± 0.4%, mean ± s.e.m.) than in relatively insulin resistant women (+4.4 ± 0.4 kg; P < 0.05). Women who were relatively insulin sensitive and who consumed a higher GL diet showed a +6.8 ± 0.7% change in %fat, which was greater than those who were less insulin sensitive, regardless of diet (P < 0.05), but did not differ from women who were relatively insulin sensitive and who consumed a lower GL diet (P = 0.105). Changes in intra-abdominal and deep subcutaneous abdominal fat were inversely associated with the postchallenge decline in serum glucose. In conclusion, greater insulin sensitivity may predispose to adiposity among weight reduced women, an effect that may be ameliorated by a lower GL diet. The potential association between indexes of glucose disposal and changes in fat distribution warrants further study.

Journal ArticleDOI
TL;DR: The results suggest that population differences in IRS likely have a genetic component, but that the influence of genetic background may be masked by obesity.

01 Jan 2010
TL;DR: In this paper, the authors used computed tomography to measure abdominal subcutaneous and visceral adipose tissue, whereas total fat and regional fat (leg, arm, and trunk) were measured by dual energy X-ray absorptiometry after weight loss and 1 year following the weight loss.
Abstract: The purpose of this study was to determine what effect aerobic and resistance exercise training has on gain of visceral fat during the year following weight loss. After being randomly assigned to aerobic training, resistance training, or no exercise training, 45 European-American (EA) and 52 African-American (AA) women lost 12.3 +/- 2.5 kg on a 800 kcal/day diet. Computed tomography was used to measure abdominal subcutaneous and visceral adipose tissue, whereas total fat and regional fat (leg, arm, and trunk) were measured by dual energy X-ray absorptiometry after weight loss and 1 year following the weight loss. Because not all the subjects adhered to the 2 time/week 40 min/day exercise training during the 1-year follow-up, subjects were divided into five groups for analysis: aerobic adherers, aerobic nonadherers, resistance adherers, resistance nonadherers, and no exercise. No significant differences were observed between the aerobic training and resistance training adherers for any variable. However, the aerobic (3.1 kg) and resistance (3.9 kg) exercise adherers gained less weight than any of the other three groups (all >6.2 kg). In addition, the two exercise adherence groups did not significantly increase visceral fat (<0.8%) as compared with the 38% increase for the two nonadhering exercise groups and the 25% for the nonexercise group. In conclusion, as little as 80 min/week aerobic or resistance training had modest positive effects on preventing weight regain following a diet-induced weight loss. More importantly, both aerobic and resistance training prevented regain of potentially harmful visceral fat.

Journal ArticleDOI
TL;DR: Results suggest that an association of muscle lipids with insulin sensitivity may be influenced by the oxidative capacity of the muscle group studied and may vary with ethnicity.
Abstract: Intramyocellular lipid (IMCL) has been inversely associated with insulin sensitivity in some, but not all, studies. This study utilized fast, high-resolution, magnetic resonance spectroscopic imaging (MRSI) to: investigate relationships between muscle lipids (IMCL and extramyocellular lipid (EMCL)) and insulin sensitivity in muscles of varying oxidative capacity, explore ethnic differences in these relationships, and determine whether a eucaloric, low-fat dietary intervention would reduce IMCL and increase insulin sensitivity. Subjects were 30 healthy, African-American (AA; n=14) and European-American (EA; n=16) males, BMI 26.49 (±5.57) kg/m(2), age 21.80 (±7.84) yrs. Soleus and tibialis anterior muscle lipids were quantified using MRSI. Insulin sensitivity was assessed via intravenous glucose tolerance test. A 2-week, eucaloric, low-fat diet intervention was conducted in a sub-group (n=12) subjects with assessments at baseline and post-intervention. Neither IMCL nor EMCL levels differed between ethnicities. In the total group, and within EA (but not AA), both tibialis anterior IMCL and EMCL were inversely associated with insulin sensitivity (P<0.05 for both); soleus muscle lipids were not associated with insulin sensitivity. Soleus, but not tibialis anterior, IMCL declined in both ethnic groups (average 25.3%; p<0.01) following dietary intervention; insulin sensitivity was unchanged. Results suggest that an association of muscle lipids with insulin sensitivity may be influenced by the oxidative capacity of the muscle group studied and may vary with ethnicity.

Journal ArticleDOI
TL;DR: Women with low vitality or poor mental health, and poor dietary control may overperceive exertion, which may be a barrier to engage in physical activity and thus increase susceptibility to weight gain.
Abstract: Objective. We investigated whether perceived exertion, in comparison to the physiological response to exercise, was associated with self-reported vitality, mental health, and physical function during daily activities, or weight control behaviors. Design. Weight-reduced, formerly overweight women (n = 126, aged 22–46 years), completed health and dietary control questionnaires, and underwent a treadmill-walking task while heart rate, ventilation, respiratory exchange ratio, and ratings of perceived exertion were recorded. Results. Overperception of exertion (perceived exertion physiological exertion) was inversely associated with vitality (r = −0.190, P < .05), mental health (r = −0.188, P < .05), and dietary control (r values range −0.231 to −0.317, P < .05). In linear regression modeling, vitality or mental health, and cognitive dietary restraint were independently associated with accuracy of perceived exertion, independent of age, ethnicity, and engagement in exercise during weight loss. Each model explained 7%-8% of the variance in accuracy of perceived exertion. Conclusion. Women with low vitality or poor mental health, and poor dietary control may overperceive exertion. Such overperception may be a barrier to engage in physical activity and thus increase susceptibility to weight gain.

Journal ArticleDOI
TL;DR: A scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint to derive major conclusions.
Abstract: Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. Participants in Development of Scientific Statement: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunctionwiththeTaskForce,leadauthors(n25)andpeerreviewers(n13)foreachspecifictopicwereselected.Alldiscussions regardingcontentandgradingofevidenceoccurredviateleconferenceorelectronicandwrittencorrespondence.Nofundingwas provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence. Consensus Process: A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations Assessment, Development,andEvaluation)systemincommonusebyTheEndocrineSocietyforpreparingclinicalguidelines.Thefinaliteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors. Conclusions: The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms ofurogenitalatrophyandpreventionoffracturesanddiabetes.Risksincludedvenothromboticepisodes,stroke,andcholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, nonstatistically significant trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup,estrogenplussomeprogestogensincreasedtheriskofbreastcancer,whereasestrogenalonedidnot.Beneficialeffects oncolorectalandendometrialcancerandharmfuleffectsonovariancanceroccurredbutaffectedonlyasmallnumberofwomen. Data from the various Women’s Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.