Changes in Energy Balance and Body Composition at Menopause: A Controlled Longitudinal Study

THIS ARTICLE HAS BEEN RETRACTED Menopause heralds the onset of physiologic changes that increase the risk for cardiovascular disease [1-3]. Although many women report increased body weight during menopause, no longitudinal studies have examined energy intake and energy expenditure and their association with changes in body composition and fat distribution. Several cross-sectional studies have suggested that decreases in resting metabolic rate and physical activity may be accelerated in the postmenopausal years [4-6]. The decrease in energy expenditure during rest and physical activity may be related to the decreased fat-free mass that has been seen in postmenopausal women [7-9]. More-over, the decrease in energy expenditure may result in increased fat mass if daily energy intake is not reduced accordingly. Other researchers, however, have not found that menopause independently affects body weight gain [10, 11]. These studies [4-11] have provided incomplete information on menopause-related changes in energy expenditure and body composition. Cross-sectional designs do not allow a robust examination of the effects of menopause on metabolic and cardiovascular risk factors, and no longitudinal studies have included measures of resting metabolic rate and body composition. To this end, we compared longitudinal changes in resting metabolic rate, body composition, and physical activity in a cohort of healthy premenopausal women who experienced menopause with changes in these variables in a cohort of women who remained premenopausal. Methods THIS ARTICLE HAS BEEN RETRACTED Patients Thirty-eight healthy, nonsmoking, premenopausal white women (age range, 44 to 48 years) were tested for baseline metabolic characteristics. Women were recruited from the surrounding communities through advertisements in the local newspaper and radio and were then screened by a telephone interview. None had coronary heart disease (for example, ST-segment depression greater than 1 mm at rest or during a modified Balke exercise test), cardiomyopathy, or hypertension (resting blood pressure greater than 140/90 mm Hg); were receiving medications that could affect cardiovascular function or metabolic rate; or had a medical history of diabetes. All premenopausal women were tested between days 5 and 12 of the follicular phase of their menstrual cycle. Menopause status was determined by interview. Six years later, patients participated in an identical series of metabolic tests, for which identical testing equipment was used. The reproducibility of the metabolic tests over this time period has previously been reported [5]. After follow-up, 18 women had spontaneously stopped menstruating for at least 12 months (2 1 years after menopause began), and 17 reported normal menstrual function. We excluded three perimenopausal women from the analyses. None of the women had received hormone replacement therapy. The Committee on Human Research for the Medical Sciences approved the study, and each volunteer provided written informed consent before the study began. Timing and Description of Metabolic Tests The study methods have been previously described [4]. Briefly, resting metabolic rate was measured for 45 minutes on the morning (0730 hours) after a 12-hour overnight fast. Each volunteer was placed in a supine position, and a clear plastic hood was placed over her head. Room air was continuously drawn through the hood, and the flow rate was measured by a pneumotachograph. Oxygen consumption (Vo 2) and CO2 production were continuously measured and analyzed during this period and were converted to a caloric equivalent (kcal/d) [12]. Peak Vo 2 was assessed by a progressive, symptom-limited treadmill exercise test. Body fat was estimated from body density by underwater weighing [13], and fat-free mass was calculated as total body mass minus fat mass. Waists were measured at the minimal circumference between the xiphoid process and the superior anterior iliac crest, and hips were measured at the maximal protrusion of the buttocks. The physical activity level during leisure time was measured using a structured interview [14]. Plasma glucose levels were determined using a YSI glucose analyzer (Yellow Springs Instruments, Yellow Springs, Ohio). Plasma immunoreactive insulin levels were determined by radioimmunoassay. Food intake was measured from 3-day food intake diaries (2 weekdays and 1 weekend day). We used a Student t-test to compare changes in the outcome measures between baseline and the end of follow-up within each subgroup. Values are expressed as the mean SD. Results THIS ARTICLE HAS BEEN RETRACTED Baseline physical characteristics of the cohort of premenopausal women are shown in Table 1. No differences were seen between the baseline characteristics of women who experienced natural menopause and those of women who remained premenopausal (Table 1). When women were retested after 6 years of follow-up, 18 were classified as postmenopausal and 17 remained premenopausal. Although total body weight did not differ between groups after follow-up, the composition of body weight showed distinct differences. Postmenopausal women lost more fat-free mass and gained more fat mass than women who remained premenopausal (Table 1). Women who experienced natural menopause had a greater decrease in resting metabolic rate and physical activity during leisure time. Fasting insulin levels and the waist-to-hip ratio were also increased more in women who became postmenopausal. Menopause did not affect body weight, fasting glucose levels, energy intake, or peak Vo 2. Table 1. Longitudinal Changes in Women Who Experienced Menopause (n = 18) and in Women Who Remained Premenopausal (n = 17)* Discussion THIS ARTICLE HAS BEEN RETRACTED Women in the United States now live an average of 75 to 80 years [15]. Those who experience menopause can expect to live approximately 30 years beyond this natural event, a time period that is approximately equivalent to their reproductive life span. The onset of menopause may be a risk factor for cardiovascular disease in women [1-3]. We used a longitudinal design to compare cardiovascular and metabolic changes in women who spontaneously stopped menstruating with changes in age-matched women who remained premenopausal. Women who stopped menstruating had distinct changes in energy expenditure during rest and physical activity, body composition, and fat distribution that could increase the risk for cardiovascular and metabolic disorders. Although our study could not establish cause and effect, our results suggest that natural menopause is associated with a worsening cardiovascular and metabolic risk profile. Resting metabolic rate, the largest component of daily energy expenditure, regulates body weight, body composition, and daily energy needs [16]. Resting metabolic rate decreases with age in women, a process that is associated with the loss of fat-free mass [4]; however, the degree to which normal menopause accelerates this decrease is unclear. Cross-sectional data suggest that the decrease in resting metabolic rate and fat-free mass may be accelerated in postmenopausal women not receiving hormone replacement therapy [4, 17]. However, few previous longitudinal studies have been done on the effect of menopause on metabolic rate and body composition. In our study, fat-free mass decreased by 3 kg and resting metabolic rate declined by approximately 100 kcal/d in postmenopausal women; no marked changes were noted in women who remained premenopausal. Thus, it is likely that resting energy requirements are lower in postmenopausal women because of the associated loss of metabolically active tissue. We used a peak Vo 2 test to evaluate cardiovascular fitness and used an activity questionnaire to assess physical activity during leisure time. Postmenopausal women reported lower levels of leisure time physical activity than did premenopausal women, despite a similar decrease in peak Vo 2 in both groups. The decline in physical activity during leisure time may have been related to the increase in body fat and decline in fat-free mass seen in postmenopausal women. Although Wing and colleagues [11] did not measure body composition, they found greater weight gain in women who reported the largest decline in exercise-related behaviors over 3 years. Taken together, the decline in energy expenditure during rest and leisure (approximately 230 kcal/d), without a proportional reduction in energy intake, supports a period of positive energy imbalance that may be related to the increased fat mass seen in women who became postmenopausal. Cross-sectional studies have reported discrepant results on the independent effects of menopause on body fat and fat distribution. Some investigators found an accelerated accumulation of fat in the intra-abdominal region [8, 9], whereas others found no independent menopause-related effect [17]. Our results support an increase in total body fat, which, as evidenced by the increase in the waist-to-hip ratio, is probably stored in central regions of the body. An increase in central body fat increases the risk for many chronic disorders, including atherosclerosis, hypertension, hypercholesterolemia, and insulin resistance [18]. Fasting insulin levels increased in women who experienced menopause, a finding consistent with those of previous longitudinal investigations [3]. This increased insulin level could be predicted because increased levels of total and intra-abdominal body fat are associated with higher levels of fasting insulin [17]. Our findings cannot establish cause and effect and cannot be extrapolated to other racial and ethnic groups. Larger sample sizes consisting of women receiving and not receiving hormone replacement therapy are needed to confirm and extend our preliminary observations regarding the energy imbalance of menopause and the possible therapeutic benefits of hormone replacement. Nevertheless, our longitudinal findings sugge