Does menarche mark a period of elevated resting metabolic rate?

Jennifer L. Spadano,1,3 Linda G. Bandini,1,2 Aviva Must,3,4,5 Gerard E. Dallal,3,4 and William H. Dietz6

1General Clinical Research Center, Massachusetts Institute of Technology, Cambridge 02139; 2Department of Health Sciences, Boston University, Boston, 02215; 3Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, 4Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, and 5Department of Family Medicine and Community Health, Tufts University School of Medicine, Boston, Massachusetts 02111; and 6Division of Nutrition and Physical Activity, Center for Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia 30341

Submitted 10 September 2003 ; accepted in final form 12 November 2003


    ABSTRACT
 TOP
 ABSTRACT
 PARTICIPANTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Resting metabolic rate (RMR) and body composition were measured in 44 initially nonoverweight girls at three time points relative to menarche: premenarche (Tanner stage 1 or 2), menarche (±6 mo), and 4 yr after menarche. Mean absolute RMR was 1,167, 1,418, and 1,347 kcal/day, respectively. Absolute RMR was statistically significantly higher at menarche than at 4 yr after menarche despite statistically significantly less fat-free mass (FFM) and fat mass (FM), suggesting an elevation in RMR around the time of menarche. The pattern of change in RMR, adjusted for FFM, log transformed FM, age, race, parental overweight, and two interactions (visit by parental overweight, parental overweight by FFM), was also considered. Adjusted RMR did not differ statistically between the visits for girls with two normal-weight parents. For girls with at least one overweight parent, adjusted RMR was statistically significantly lower 4 yr after menarche than at premenarche or menarche. Thus parental overweight may influence changes that occur in RMR during adolescence in girls.

parental overweight; puberty; adolescence; obesity; energy expenditure


ADOLESCENCE, THE PERIOD OF GROWTH from puberty to adulthood, has been proposed as a critical period in the development of obesity (13). Females in particular appear to be at greater risk for the onset of obesity during this time and are more likely than males to develop obesity that persists into adulthood (9). Because obesity results from positive energy balance, understanding the pattern of change in energy intake and energy expenditure that occurs during adolescence may provide insight into the etiology of incident obesity during this time period.

Approximately 60-80% of daily energy expenditure is accounted for by resting metabolic rate (RMR) (39). The single best predictor of metabolic rate is fat-free mass (FFM) (39), whose metabolically active components are organ mass and muscle mass. On average, organ mass has a metabolic rate 15-25 times greater than that of muscle mass (24). After the first year of life, muscle mass increases more rapidly than organ mass and therefore makes up an increasingly greater proportion of FFM (52). As the ratio of muscle mass to organ mass increases, RMR per kilogram of FFM decreases (26). The metabolic contribution of 1 kg of FFM to RMR has been shown cross-sectionally to decrease from infancy to adolescence to adulthood (52). Observations of an inverse relationship between age (30, 46) or pubertal maturation (32, 44) and RMR adjusted for FFM in children and adolescents have been attributed to a decline in the metabolic activity of FFM. Longitudinal data are needed to evaluate this proposed decline.

Fat mass (FM) (4, 18, 30, 46), sex (7, 18, 30, 46), and race/ethnicity (4, 12, 32, 44, 46, 48) also independently predict metabolic rate in children. In addition, an influence of parental weight status on metabolic rate has been explored, but the findings lack accord (4, 17, 20, 48, 58). Finally, because of known pubertal changes in growth velocity and hormone concentrations (28), an effect of puberty on metabolic rate has been hypothesized. Among the studies (4, 5, 7, 8, 10, 30, 32, 44, 46, 47) that have examined a relationship with pubertal maturation, the findings are inconsistent. Most of these studies have been cross-sectional and used Tanner staging (45) to gauge pubertal maturation, and many have presented combined results for boys and girls. The aim of the present study was to examine longitudinally the pattern of change in RMR relative to menarche, a well-defined event in the course of pubertal maturation for females. We measured RMR and body composition in 44 girls before menarche [Tanner stage 1 or 2 (45)], at menarche (±6 mo), and 4 yr after menarche.


    PARTICIPANTS AND METHODS
 TOP
 ABSTRACT
 PARTICIPANTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Participants. Between September 1990 and June 1993, 196 girls aged 8-12 yr were enrolled in the Massachusetts Institute of Technology (MIT) Growth and Development study, a prospective cohort study. Criteria for enrollment were premenarcheal status and a triceps skinfold thickness less than the 85th percentile for age and sex (33). Girls were recruited from the Cambridge and Somerville (Massachusetts) public school systems and the MIT summer day camp; other recruits were friends and siblings of enrollees. All participants were initially healthy, free of disease, and not taking any medications known to affect body composition or metabolic rate. The study was approved by both the Committee on the Use of Humans as Experimental Subjects at MIT (Cambridge, MA) and the Tufts-New England Medical Center Institutional Review Board (Boston, MA). As part of the cohort study design, RMR and body composition were measured at study entry and at the study exit visit, which was scheduled for the 4-yr anniversary of menarche (± 1 mo). Some of the girls had additional measure(s) of RMR and body composition during the course of the study as part of their participation in one of the two nested subcohorts (energy expenditure subcohort and menarcheal subcohort). Inclusion criteria for the present analyses were a valid measure of RMR and body composition (by total body water) at three specific time points: at study entry (hereafter referred to as the premenarche visit), within ±6 mo of menarche, and at the exit visit 4 yr after menarche. The analyses were further restricted to those girls who were classified as Tanner stage 1 or 2 (45) at their premenarche visit. Forty-four girls met the inclusion criteria.

Body composition. At all three time points, participants were admitted to the General Clinical Research Center at MIT for an overnight stay. A study physician obtained a medical history and performed a brief examination to assess the participant's health. Body composition was estimated from total body water (TBW) measured by 18O dilution space. A baseline urine sample was collected, and an overnight fast was initiated approximately an hour before the administration of H218O. Between 7:00 and 8:00 PM, a dose of either 0.25 or 0.07 g of H218O/kg estimated TBW was administered to the study participant. The larger dose was provided when 18O was used to estimate total energy expenditure as well as TBW. Urine was then collected until 6:00 AM the next morning to determine urinary losses of isotope. The second urine void of the morning was used to measure 18O enrichment above the baseline value. The 18O enrichment of the urine samples was measured on a Hydra Gas Isotope Ratio Mass Spectrometer (PDZ Europa) at the mass spectrometry laboratory of the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University (Boston, MA). The 18O dilution space was calculated according to the method of Halliday and Miller (22) and assumed to be 1% higher than TBW. FFM was estimated from TBW assuming a hydration constant of 0.73. FM was calculated as the difference between body weight and FFM, and percent body fat was calculated by dividing FM by body weight (x100%).

RMR. RMR was measured in the morning, as described previously (3), by use of an open-circuit indirect calorimeter that was fitted with a ventilated hood. Each participant fasted overnight for >=12 h and engaged in minimal activity before the determination of her metabolic rate. After body temperature was measured to confirm the absence of a fever, the participant lay down to rest for 30 min. A 5-min equilibration period preceded the 30-min measurement period. RMR was calculated from measures of oxygen consumption and carbon dioxide production according to the modified Weir's equation (53). On the morning of each measurement, the linearity of the gas analyzers was confirmed by calibrating them against two standard gases and checking the concentration of a third standard gas. In addition, the calibration of the entire system was checked before each scheduled visit by pushing known amounts of a standard gas through the hood at a constant rate with a 3-L calibrated syringe (Warren E. Collins, Braintree, MA). At the premenarche visit, RMR was measured on two separate occasions, {approx}2 wk apart, with the average of the two values used in all analyses. The intraclass correlation of these two measures for the overall cohort was 0.96 (4). Because there was no evidence of a training effect and the reproducibility of the two measures was so high, only a single measure of RMR was made at subsequent visits.

Pubertal status. Tanner staging (45) of breast development was assessed by either the study physician or a female coinvestigator. The girls were instructed to call the study when they had their first period. For some participants, the date of menarche was based on self-report during one of their annual follow-up visits. At these abbreviated visits, girls were asked whether they had started their period during the preceding year; if the answer was yes, the girl was asked to recall the date.

Other variables. At each visit, weight was measured in the morning with participants in a fasted state, by means of a digital scale (Seca, Hamburg, Germany) accurate to 0.1 kg. Height (without shoes) was also measured at this time with a wall-mounted stadiometer. Percentiles of body mass index (BMI, kg/m2) for age, using the 2000 Centers for Disease Control growth charts (11), were calculated for each girl on the basis of her measured height and weight at each visit. Race/ethnicity (white, black, Hispanic, Asian, and "other") was based on self-report on a questionnaire completed at study entry.

Early in the study, data on the height and weight of each participant's biological parents were collected from either direct measurements at MIT (in normal clothing, without shoes) or from self-report. Parental overweight was defined as a BMI >=25 (54). Girls were classified as having two normal-weight biological parents (NWP group) or at least one overweight biological parent (OWP group). Four sister pairs were among the 44 participants; for analyses considering parental overweight, we randomly selected one sister from each pair. In addition, four girls were missing data on parental weight status; consequently, only 36 of the 44 participants are included in the analyses involving parental overweight. Parental weight status for 33 of the 36 girls was based on measured values.

Statistical analysis. All statistical analyses were performed using SAS version 8.01 (SAS Institute, Cary, NC). Mean (±SD) age, height, weight, BMI percentile, FFM, FM, and percent body fat were calculated for each visit and for each parental weight group at each visit. A log transformation was applied to FM (lnFM) before formal analyses, because its distribution was skewed to the right. The relationship between RMR and FFM at each visit was assessed cross-sectionally using simple linear regression. A mixed-model repeated-measures analysis (using Proc Mixed in SAS) was then performed to test statistically whether the univariate relationship between RMR and FFM changed with pubertal maturation by evaluating the interaction term "FFM by visit." A three-way interaction term (FFM by visit by parental overweight) was tested to determine whether parental overweight (assessed around the time of the premenarcheal visit) influenced any changes that occurred in the relationship between RMR and FFM across the three visits.

Mixed-model repeated-measures analyses (Proc Mixed in SAS) were used to examine the pattern of change in RMR from premenarche (Tanner stage 1 or 2) to menarche (±6 mo) to 4 yr after menarche. The changes in both absolute RMR and RMR adjusted for race (black/nonblack), parental overweight status, and changes in age, FFM, and lnFM were evaluated after first determining the most appropriate covariance structure for the data by use of the log likelihood ratio test and Akaike Information Criterion. The unrestricted covariance structure proved best for the absolute RMR analyses, whereas the compound symmetry covariance structure was the most appropriate for the adjusted RMR analyses. Time was modeled as a categorical variable with the assumption that the premenarcheal measures, after adjustment for body composition and age, could be treated similarly among the Tanner 1 and Tanner 2 girls. This assumption was supported by the results of cross-sectional analyses using baseline data from the full MIT Growth and Development cohort (4), which revealed no difference in RMR adjusted for age, FFM, and FM between the 121 Tanner 1 girls and the 69 Tanner 2-3 girls (1,216 and 1,217 kcal/day, respectively). Because RMR adjusted for body composition has been observed to be lower in black than in white girls (4, 32, 48), we evaluated a race by visit interaction term to assess whether there were any racial differences in the changes that occurred in adjusted RMR over the course of pubertal maturation. In addition, we tested a parental overweight by visit interaction term to assess whether the effect of parental overweight observed in the baseline cross-sectional analyses of our larger cohort (4) persists throughout maturation. The parental overweight by visit interaction term was statistically significant, while the race by visit interaction term was not. We also found a statistically significant interaction between parental overweight and FFM after testing a global interaction term of parental overweight with the other covariates in our model. Consequently, our final adjusted RMR model was as follows

where i = 1.. .36 indexes the subjects and j = 1,2,3 indicates the time points.

Adjusted means at each visit for each parental weight group were estimated, and Tukey's honestly significant differences test was used to evaluate the difference in adjusted RMR across time in both parental weight groups. Proc Mixed was also used to determine the significance of changes in absolute FFM and in absolute FM over time. Results were considered statistically significant if the observed significance level (P value) was <0.05.


    RESULTS
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 ABSTRACT
 PARTICIPANTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
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At the premenarcheal visit, 37 of the 44 girls were classified as Tanner stage 1 and seven as Tanner stage 2. Thirty-two reported their race/ethnicity as white, 6 as black, 4 as Hispanic, 1 as Asian, and 1 as "other." Mean age (±SD) of actual menarche was 13.1 ± 1.0 yr, and the mean duration between menarche and the menarcheal visit was 1.9 ± 1.8 mo. Statistically significant increases in both FFM and FM were observed across the three visits; FFM increased from 23.4 to 37.3 to 42.9 kg, and FM increased from 7.3 to 11.8 to 16.5 kg (P < 0.001 for each comparison between visits). (See Supplemental Material, available at the journal web site.)1

Among the 36 girls included in the analyses considering parental overweight, 10 had two normal-weight parents (NWP girls), whereas the remaining 26 had at least one overweight parent (OWP girls). Thirty of these 36 girls were Tanner stage 1 and six were Tanner stage 2. Twenty-eight described themselves as white; three as black; three as Hispanic; one as Asian; and one as "other." Mean characteristics of the parental weight groups at each visit are presented in Table 1. The OWP girls, on average, weighed more and had a greater percentage of body fat at each visit than the NWP girls. In addition, menarche was experienced at a younger age in the OWP girls (13.0 ± 0.8 yr) than in the NWP girls (13.9 ± 1.1 yr).


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Table 1. Characteristics of the 36 girls by parental weight status at 3 visits relative to menarche: premenarche (Tanner stage 1 or 2), menarche (±6 mo), and 4 yr after menarche

 

Individual line plots of absolute RMR across the three visits are provided in Fig. 1; mean values differed significantly between the visits. RMR measured around the time of menarche (1,418 kcal/day) was statistically significantly elevated above RMR measured at premenarche (1,167 kcal/day, P < 0.001) or 4 yr after menarche (1,347 kcal/day, P = 0.001). The pattern of change across the three visits did not differ statistically between the NWP girls and the OWP girls. Mean absolute RMR was 1,087, 1,339, and 1,308 kcal/day, respectively, in the NWP group, and 1,203, 1,443, and 1,365 kcal/day, respectively, in the OWP group.



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Fig. 1. Individual line plots of absolute resting metabolic rate (RMR) measured in 44 girls at 3 visits relative to menarche: premenarche (Tanner stage 1 or 2), menarche (±6 mo), and 4 yr after menarche.

 

FFM was a statistically significant predictor of RMR cross-sectionally at premenarche, menarche, and 4 yr after menarche, explaining 58, 59, and 63% of the variance in RMR, respectively. The slope of the regression of RMR on FFM decreased from 30.3 to 25.3 to 23.6 kcal·kg-1·day-1. This apparent decline in the metabolic contribution of 1 kg of FFM to RMR when tested longitudinally was not statistically significant however (P = 0.62). On the other hand, the three-way interaction between FFM, visit, and parental overweight was found to be significant (P < 0.0001), indicating that the relationship between FFM and RMR across the three visits differed between the NWP and OWP girls. For the NWP girls, the slope of the regression of RMR on FFM was 38.7, 14.9, and 15.5 kcal·kg-1·day-1 (Fig. 2A), with FFM explaining 71, 25, and 74% of the variance in RMR at premenarche, menarche, and 4 yr after menarche, respectively. By comparison, the slopes for the OWP girls were 28.7, 30.8, and 27.8 kcal·kg-1·day-1 (Fig. 2B), with FFM explaining 56, 81, and 72% of the variance in RMR, respectively. Adding lnFM to the models did not remove the apparent differences in the slopes between the NWP and OWP girls.



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Fig. 2. Regression of RMR (kcal/day) on fat-free mass (FFM, kg) in girls with 2 normal-weight parents (NWP; A) and in girls with >=1 overweight parent (OWP; B) at 3 visits relative to menarche: premenarche ({bullet}), menarche ({blacksquare}) and 4 yr after menarche ({blacktriangleup}). The regression equations for the NWP girls at the 3 visits, respectively, are RMR = 226 + 38.7FFM, RMR = 794 + 14.9FFM, and RMR = 671 + 15.5FFM. The regression equations for the OWP girls are RMR = 516 + 28.7FFM, RMR = 286 + 30.8FFM, and RMR = 155 +27.8, respectively. By use of a repeated-measures mixed model, the slopes between the 3 visits were not statistically different in either the NWP girls (P = 0.26) or the OWP girls (P = 0.68).

 

In the longitudinal adjusted RMR analyses, age (P = 0.001), FFM (P < 0.0001), lnFM (P < 0.001), and race (P = 0.03) were overall significant predictors of RMR. In addition, we found a significant interaction between parental overweight and visit (P < 0.001), indicating that the pattern of change over time in adjusted RMR differed by parental overweight status. In the OWP girls, adjusted RMR 4 yr after menarche (1,156 kcal/day) was statistically significantly lower than adjusted RMR premenarche (1,370 kcal/day) and at menarche (1,308 kcal/day; Fig. 3). For NWP girls, no statistically significant differences in adjusted RMR between the three visits were observed. Adjusted RMR was 1,183, 1,305, and 1,297 kcal/day at premenarche, menarche, and 4 yr after menarche, respectively. The estimates for the NWP group were sensitive to the covariance structure of the mixed models, most likely because of the small sample size of this group (n = 10).



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Fig. 3. Mean adjusted RMR measured in 26 girls with >=1 overweight parent at 3 visits relative to menarche: premenarche (Tanner stage 1 or 2), menarche (±6 mo), and 4 yr after menarche. Mean values were generated from the least square means of a parental overweight by visit interaction term in a mixed-model repeated-measures analysis of RMR adjusted for changes in FFM, log transformed fat mass, and age as well as race (black/nonblack), parental overweight (2 normal-weight parents/>=1 overweight parent), and an interaction between parental overweight and FFM. Error bars represent the 95% confidence interval. Means with the same superscript do not differ statistically, P > 0.05.

 


    DISCUSSION
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 ABSTRACT
 PARTICIPANTS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Our study is among the first to publish longitudinal data on concomitant measures of RMR and body composition over the course of adolescence. Based on the comparison of absolute RMR, FFM, and FM between menarche and 4 yr after menarche, our data suggest an elevation in RMR around the time of menarche. In addition, our adjusted RMR analyses suggest that parental overweight may influence the changes that occur in RMR during pubertal maturation and adolescence in girls.

The physiological and morphological changes that characterize puberty are extensive. Sex differences in pubertal changes become manifest not only with respect to secondary sexual characteristics and sex steroid concentrations but also with respect to factors that may affect metabolic rate, such as changes in body composition (21), timing of the pubertal growth spurt [both chronologically and with respect to pubertal development (49)], and changes in growth hormone (GH) concentrations [in both magnitude and timing (1, 42)]. Most studies that have explored a possible effect of puberty on RMR have used Tanner staging to classify pubertal maturation and have presented combined results for boys and girls adjusted for sex. Such an approach may mask changes in metabolic rate associated with menarche or that occur around the time of menarche, because some girls become menarcheal at Tanner stage 3 and others at stage 4 or 5 (28). Furthermore, statistical adjustment for gender will not reveal the true relationship between pubertal maturation and RMR for either sex if sexual dimorphism in the relationship exists.

Our observation that mean absolute RMR was statistically significantly greater at menarche than 4 yr after menarche is surprising in light of the fact that FFM, the major determinant of RMR (39), and FM, an independent contributor to RMR (4, 18, 30, 46), increased significantly over this period. Our findings are consistent, however, with a 1932 longitudinal study that measured basal metabolic rate (BMR) at intervals of 6 mo to 1 yr for 1-4 yr in 28 girls and 10 boys aged 10 to 16 yr (47). In girls, an increase in absolute BMR above what was predicted was observed 1-8 mo before menarche and was maintained until 1-6 mo after menarche, with individual differences noted in the degree, duration, and timing of the increase in BMR. These results, coupled with our own, suggest that metabolic rate is elevated in girls around menarche. Whether the elevation is specific to menarche or begins earlier in the pubertal process and is maintained through menarche cannot be addressed with these data.

Changes in GH during puberty in girls provide one plausible mechanism for the observed elevation in metabolic rate. GH administration appears to elevate metabolic rate by ~7-8% in both normal adults (29, 56, 57) and GH-deficient children (19), independent of changes in lean body mass. In addition, in normal, healthy girls, BMR adjusted for FFM is associated with the area under the GH-time curve for endogenous overnight GH release [P = 0.054 (41)]. During Tanner stages 3 and 4 in girls, the secretion rate and nighttime concentration of GH are elevated (1, 42), with baseline GH concentrations elevated by Tanner stage 4. The secretion rate, nighttime level, and baseline concentration of GH all return to approximately prepubertal levels at Tanner stage 5. With most girls experiencing menarche while at Tanner stage 3 (<=25%) or 4 [~65% (28)], the transient increases in GH during puberty may explain the observed elevation in metabolic rate around the time of menarche. Any elevation in metabolic rate attributed to GH may be reduced or absent in obese children, because obese children (27), as well as obese adults (55), have a blunted GH response to GH-releasing hormone. The absence or blunting of a rise in metabolic rate around the time of menarche in obese girls may lead to either a continuation or a new period of positive energy balance that perpetuates their obesity into adolescence and adulthood.

Elevations in GH during puberty may also be responsible for pubertal insulin resistance (2, 31), which in turn may contribute to the elevation in metabolic rate around the time of menarche. Insulin sensitivity is significantly decreased during puberty (2), reaching its lowest level at Tanner stage 3 and returning by Tanner stage 5 to levels that that are slightly yet statistically lower than prepubertal levels (31). In obese adults with insulin resistance (those with type 2 diabetes or impaired glucose tolerance), RMR per kilogram of FFM is significantly greater than in obese and normal-weight adults with normal glucose tolerance (34). A high rate of gluconeogenesis (34, 40) and/or a high rate of protein turnover may be responsible for the elevated energy expenditure.

As much as two-thirds of metabolic activity (24) is accounted for by the heart, brain, liver, and kidney. The metabolic rate of an organ is believed to be constant from infancy to maturity, with an organ's metabolic activity proportional to its size (24, 25). Differences in organ size account for as much as 5% of the variance in metabolic rate between individuals (16, 26). Around the time of peak height velocity, a growth spurt of the transverse diameter of the heart (28, 49), the length and breadth of the head, and the abdominal viscera, including the liver and kidneys, has been demonstrated or hypothesized (28). Because peak height velocity almost always precedes menarche and usually occurs in girls around Tanner stage 3 (28), an increase in the growth velocity of the more metabolically active organs may contribute to an elevation in RMR around the time of menarche.

Many studies have examined a possible influence of parental weight status on RMR in children. Since the initial study by Griffiths and Payne (20), suggesting a lower adjusted resting energy expenditure in children with at least one overweight parent, most studies have observed either no association between parental weight status and metabolic rate in children (17, 48) or a higher adjusted metabolic rate in children with at least one overweight parent (4, 58). The conflicting findings may be due, in part, to differences in the classification of parental weight status, the weight status of the children themselves (normal-weight or overweight), sample size, or measurement techniques. In the present study, parental overweight among the 36 girls was not a statistically significant predictor of RMR cross-sectionally at any time point in a model adjusting for FFM, lnFM, age, and race. However, a statistically significant interaction between parental overweight and visit was observed in the longitudinal analyses, suggesting that the pattern of change in RMR from premenarche to late adolescence may differ between girls with two normal-weight parents and girls with at least one overweight parent.

In the OWP girls, adjusted RMR 4 yr after menarche was statistically significantly lower than at premenarche or menarche, whereas in the NWP girls no statistically significant differences were noted in adjusted RMR between any of the visits. The values for the NWP girls should be interpreted with caution, because the estimates were extremely sensitive to the covariance structure, most likely because of the small sample size of this subgroup. A study with a larger sample is needed to confirm these findings. We did, however, rerun the analyses after reclassifying parental overweight by using the older BMI cutoffs (35) of 27.3 for women and 27.8 for men, which resulted in a larger sample size for the NWP group (n = 19) and greater balance between the parental weight groups. The observed pattern of change in adjusted RMR for both groups (unpublished observations) was similar to our original findings. An influence of parental weight status was not considered in the few cross-sectional studies (30, 32) that have compared RMR between premenarcheal and postmenarcheal girls and the one longitudinal study (44) that assessed changes in adjusted RMR across pubertal maturation (as defined by Tanner staging). The inverse relationship between Tanner stage and adjusted RMR observed in the longitudinal study by Sun et al. (44) and the lower adjusted RMR in the postmenarcheal girls in the cross-sectional study by Morrison et al. (32) were both attributed to the changing composition of FFM during growth.

Supporting the notion that the metabolic contribution of 1 kg of FFM declines during growth, Weinsier et al. (52), using pooled data from various cross-sectional studies, found that the slope of RMR on FFM declined significantly from 79 kcal·kg-1·day-1 in infants and preschool age children (n = 58) to 28.3 kcal·kg-1·day-1 in adolescents (n = 70) to 21.0 kcal·kg-1·day-1 in adults (n = 534). Our data allowed us to examine in a similar fashion changes over time in the metabolic contribution of 1 kg of FFM to RMR, this time focusing on the period of pubertal maturation in girls and using repeated-measures data on the same 44 persons. We observed a decrease in the slope of the regression of RMR on FFM from 30.3 to 25.3 to 23.6 kcal·kg-1·day-1 from premenarche to menarche to 4 yr after menarche, respectively. Although suggestive and potentially biologically important, this apparent decline in slopes was not statistically significant, perhaps because of the small sample size of our study. The three-way interaction between FFM, visit, and parental overweight, however, was statistically significant, suggesting that changes in the relationship between FFM and RMR across the three visits depended on parental overweight status.

Several potential limitations of our study are noteworthy. First, our sample was predominantly white. We assumed that the pattern of change in RMR from premenarche to menarche to 4 yr after menarche does not differ between black and white girls despite the lower metabolic rate we and others (4, 32, 48) have observed in black girls than in white girls. Although a race-by-visit interaction term was not significant (P = 0.19) in our models, our small sample limited power. When we excluded the three black girls from the analyses considering parental overweight, the pattern of change in adjusted RMR for both parental weight groups remained consistent. In further support of our assumption, Sun et al. (44) found no ethnic differences in the pattern of change in RMR across Tanner stage in their longitudinal study of 156 children. Second, because the cyclical variation in metabolic rate over the full course of the menstrual cycle is not fully characterized (6, 23, 43, 50, 51) and its effect on metabolic rate may actually be smaller than daily fluctuations from other factors (50), we elected not to correct the RMR data from 4 yr after menarche for timing of the menstrual cycle. RMR at that visit was measured during the luteal phase of the menstrual cycle for roughly one-quarter of the 44 girls, with an approximately equal distribution between the NWP girls and the OWP girls. An effect of the menstrual phase would not be a potential factor for the menarcheal RMR, because ovulation does not occur until there have been several menstrual periods (28), and 50-80% of menstrual cycles are anovulatory during the first 2 yr of menses (36). A final potential limitation is the lack of control for use of oral contraceptives (OC). Because of the conflicting results in the few published studies comparing metabolic rate in OC users and nonusers (14, 15, 38), the limited data on the effect of OC use on RMR within the individual (37), and the large number of hormonal formulations of OCs commercially available, we decided not to adjust for OC use in the nine girls who were taking OCs 4 yr after menarche.

In conclusion, we observed that absolute RMR was higher at menarche than 4 yr after menarche, which is surprising given that mean FFM and FM were statistically significantly higher 4 yr after menarche than at menarche. We observed no statistically significant differences between adjusted RMR at premenarche and at menarche in both parental weight groups, and we found a statistically significant decline in adjusted RMR at 4 yr after menarche only in the OWP girls. When RMR is adjusted for FFM and the comparison is made between adjusted RMR at premenarche and menarche, the proposed elevation in RMR around the time of menarche may be masked or mitigated by the counteracting effect of the changing composition of FFM. The changing composition of FFM would be expected to play a role during the perimenarcheal period in particular because of the substantial gains in FFM that occur during this time. Additional longitudinal studies with larger samples are needed to test the hypotheses generated from our analyses and to confirm these findings.


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 PARTICIPANTS AND METHODS
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This research was supported by National Institutes of Health Grants DK-HD-50537, MO1 RR-00088, and 5 PD30 DK-46200.


    ACKNOWLEDGMENTS
 
We gratefully acknowledge the girls who participated in this study as well as the staff at the General Clinical Research Center at MIT for their assistance. In addition, we thank Gail Rogers for statistical input.


    FOOTNOTES
 

Address for reprint requests and other correspondence: J. L. Spadano, Epidemiology Dept., Jean Mayer USDA HNRCA at Tufts University, 711 Washington St., Boston, MA 02111 (E-mail: jennifer.spadano{at}tufts.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 The Supplemental Material for this article (a table) is available online at http://ajpendo.org/cgi/content/full/00410.2003/DC1 Back


    REFERENCES
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 PARTICIPANTS AND METHODS
 RESULTS
 DISCUSSION
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 REFERENCES
 

  1. Albertsson-Wikland K, Rosberg S, Karlberg J, and Groth T. Analysis of 24-hour growth hormone profiles in healthy boys and girls of normal stature: relation to puberty. J Clin Endocrinol Metab 78: 1195-1201, 1994.[Abstract]
  2. Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, and Tamborlane WV. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 315: 215-219, 1986.[Abstract]
  3. Bandini LG, Morelli JA, Must A, and Dietz WH. Accuracy of standardized equations for predicting metabolic rate in premenarcheal girls. Am J Clin Nutr 62: 711-714, 1995.[Abstract]
  4. Bandini LG, Must A, Spadano JL, and Dietz WH. Relationship of body composition, parental overweight, pubertal stage, and race-ethnicity to energy expenditure among premenarcheal girls. Am J Clin Nutr 76: 1040-1047, 2002.[Abstract/Free Full Text]
  5. Bandini LG, Schoeller DA, and Dietz WH. Energy expenditure in obese and nonobese adolescents. Pediatr Res 27: 198-203, 1990.[Abstract]
  6. Bisdee JT, James WP, and Shaw MA. Changes in energy expenditure during the menstrual cycle. Br J Nutr 61: 187-199, 1989.[ISI][Medline]
  7. Bitar A, Fellmann N, Vernet J, Coudert J, and Vermorel M. Variations and determinants of energy expenditure as measured by whole-body indirect calorimetry during puberty and adolescence. Am J Clin Nutr 69: 1209-1216, 1999.[Abstract/Free Full Text]
  8. Bitar A, Vernet J, Coudert J, and Vermorel M. Longitudinal changes in body composition, physical capacities and energy expenditure in boys and girls during the onset of puberty. Eur J Nutr 39: 157-163, 2000.[CrossRef][ISI][Medline]
  9. Braddon FE, Rodgers B, Wadsworth ME, and Davies JM. Onset of obesity in a 36 year birth cohort study. Br Med J 293: 299-303, 1986.[ISI][Medline]
  10. Brown D, Kelnar CJ, and Wu FC. Energy metabolism during male human puberty. I. Changes in energy expenditure during the onset of puberty in boys. Ann Hum Biol 23: 273-279, 1996.[ISI][Medline]
  11. Centers for Disease Control and Prevention. 2000 CDC Growth Charts: United States [online]. http://www.cdc.gov/growthcharts [21 May 2002].
  12. DeLany JP, Bray GA, Harsha DW, and Volaufova J. Energy expenditure in preadolescent African American and white boys and girls: the Baton Rouge Children's Study. Am J Clin Nutr 75: 705-713, 2002.[Abstract/Free Full Text]
  13. Dietz WH. Critical periods in childhood for the development of obesity. Am J Clin Nutr 59: 955-959, 1994.[Abstract]
  14. Diffey B, Piers LS, Soares MJ, and O'Dea K. The effect of oral contraceptive agents on the basal metabolic rate of young women. Br J Nutr 77: 853-862, 1997.[ISI][Medline]
  15. Eck LH, Bennett AG, Egan BM, Ray JW, Mitchell CO, Smith MA, and Klesges RC. Differences in macronutrient selections in users and nonusers of an oral contraceptive. Am J Clin Nutr 65: 419-424, 1997.[Abstract]
  16. Garby L and Lammert O. Between-subjects variation in energy expenditure: estimation of the effect of variation in organ size. Eur J Clin Nutr 48: 376-378, 1994.[ISI][Medline]
  17. Goran MI, Carpenter WH, McGloin A, Johnson R, Hardin JM, and Weinsier RL. Energy expenditure in children of lean and obese parents. Am J Physiol Endocrinol Metab 268: E917-E924, 1995.[Abstract/Free Full Text]
  18. Goran MI, Kaskoun M, and Johnson R. Determinants of resting energy expenditure in young children. J Pediatr 125: 362-367, 1994.[ISI][Medline]
  19. Gregory JW, Greene SA, Jung RT, Scrimgeour CM, and Rennie MJ. Changes in body composition and energy expenditure after six weeks' growth hormone treatment. Arch Dis Child 66: 598-602, 1991.[Abstract]
  20. Griffiths M and Payne PR. Energy expenditure in small children of obese and non-obese parents. Nature 260: 698-700, 1976.[ISI][Medline]
  21. Guo SS, Chumlea WC, Roche AF, and Siervogel RM. Age- and maturity-related changes in body composition during adolescence into adulthood: the Fels longitudinal study. Appl Radiat Isot 49: 581-585, 1998.[CrossRef][ISI][Medline]
  22. Halliday D and Miller AG. Precise measurement of total body water using trace quantities of deuterium oxide. Biomed Mass Spectrom 4: 82-87, 1977.[ISI][Medline]
  23. Hitchcock FA and Wardwell FR. Cyclic variations in the basal metabolic rate of women. J Nutr 2: 203-215, 1929.
  24. Holliday MA. Metabolic rate and organ size during growth from infancy to maturity and during late gestation and early infancy. Pediatrics 47, Suppl 2: 169-179, 1971.[Abstract]
  25. Holliday MA, Potter D, Jarrah A, and Bearg S. The relation of metabolic rate to body weight and organ size. Pediatr Res 1: 185-195, 1967.[ISI][Medline]
  26. Illner K, Brinkmann G, Heller M, Bosy-Westphal A, and Müller MJ. Metabolically active components of fat free mass and resting energy expenditure in nonobese adults. Am J Physiol Endocrinol Metab 278: E308-E315, 2000.[Abstract/Free Full Text]
  27. Loche S, Cappa M, Borrelli P, Faedda A, Crino A, Cella SG, Corda R, Muller EE, and Pintor C. Reduced growth hormone response to growth hormone-releasing hormone in children with simple obesity: evidence for somatomedin-C mediated inhibition. Clin Endocrinol (Oxf) 27: 145-153, 1987.[ISI][Medline]
  28. Marshall WA. Puberty. In: Human Growth, edited by Falkner F and Tanner JM. New York: Plenum, 1978, p. 141-180.
  29. Møller J, Jørgensen JO, Møller N, Christiansen JS, and Weeke J. Effects of growth hormone administration on fuel oxidation and thyroid function in normal man. Metabolism 41: 728-731, 1992.[ISI][Medline]
  30. Molnar D and Schutz Y. The effect of obesity, age, puberty, and gender on resting metabolic rate in children and adolescents. Eur J Pediatr 156: 376-381, 1997.[CrossRef][ISI][Medline]
  31. Moran A, Jacobs DR Jr, Steinberger J, Hong CP, Prineas R, Luepker R, and Sinaiko AR. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 48: 2039-2044, 1999.[Abstract]
  32. Morrison JA, Alfaro MP, Khoury P, Thornton BB, and Daniels SR. Determinants of resting energy expenditure in young black girls and young white girls. J Pediatr 129: 637-642, 1996.[ISI][Medline]
  33. Must A, Dallal GE, and Dietz WH. Reference data for obesity: 85th and 95th percentiles of body mass index (wt/ht2) and triceps skinfold thickness. Am J Clin Nutr 53: 839-846, 1991.[Abstract]
  34. Nair KS, Webster J, and Garrow JS. Effect of impaired glucose tolerance and type II diabetes on resting metabolic rate and thermic response to a glucose meal in obese women. Metabolism 35: 640-644, 1986.[ISI][Medline]
  35. National Institutes of Health. Health implications of obesity National Institutes of Health Consensus Development Conference, 11-13 February, 1985. Ann Intern Med 103: 977-1077, 1985.[Medline]
  36. O'Connell BJ. The pediatrician and the sexually active adolescent. Treatment of common menstrual disorders. Pediatr Clin North Am 44: 1391-1404, 1997.[ISI][Medline]
  37. Pelkman CL, Chow M, Heinbach RA, and Rolls BJ. Short-term effects of a progestational contraceptive drug on food intake, resting energy expenditure, and body weight in young women. Am J Clin Nutr 73: 19-26, 2001.[Abstract/Free Full Text]
  38. Piers LS, Diffey B, Soares MJ, Frandsen SL, McCormack LM, Lutschini MJ, and O'Dea K. The validity of predicting the basal metabolic rate of young Australian men and women. Eur J Clin Nutr 51: 333-337, 1997.[CrossRef][ISI][Medline]
  39. Ravussin E and Bogardus C. Relationship of genetics, age, and physical fitness to daily energy expenditure and fuel utilization. Am J Clin Nutr 49, Suppl 5: 968-975, 1989.[ISI][Medline]
  40. Ravussin E, Bogardus C, Schwartz RS, Robbins DC, Wolfe RR, Horton ES, Danforth E Jr, and Sims EA. Thermic effect of infused glucose and insulin in man. Decreased response with increased insulin resistance in obesity and noninsulin-dependent diabetes mellitus. J Clin Invest 72: 893-902, 1983.[ISI][Medline]
  41. Roemmich JN, Clark PA, Mai V, Berr SS, Weltman A, Veldhuis JD, and Rogol AD. Alterations in growth and body composition during puberty. III. Influence of maturation, gender, body composition, fat distribution, aerobic fitness, and energy expenditure on nocturnal growth hormone release. J Clin Endocrinol Metab 83: 1440-1447, 1998.[Abstract/Free Full Text]
  42. Rose SR, Municchi G, Barnes KM, Kamp GA, Uriarte MM, Ross JL, Cassorla F, and Cutler GB Jr. Spontaneous growth hormone secretion increases during puberty in normal girls and boys. J Clin Endocrinol Metab 73: 428-435, 1991.[Abstract]
  43. Solomon SJ, Kurzer MS, and Calloway DH. Menstrual cycle and basal metabolic rate in women. Am J Clin Nutr 36: 611-616, 1982.[Abstract]
  44. Sun M, Gower BA, Bartolucci AA, Hunter GR, Figueroa-Colon R, and Goran MI. A longitudinal study of resting energy expenditure relative to body composition during puberty in African American and white children. Am J Clin Nutr 73: 308-315, 2001.[Abstract/Free Full Text]
  45. Tanner JM. Growth and endocrinology of the adolescent. In: Endocrine and Genetic Diseases of Childhood and Adolescence, edited by Gardner LI. Philadelphia, PA: Saunders, 1975, p. 14-54.
  46. Tershakovec AM, Kuppler KM, Zemel B, and Stallings VA. Age, sex, ethnicity, body composition, and resting energy expenditure of obese African American and white children and adolescents. Am J Clin Nutr 75: 867-871, 2002.[Abstract/Free Full Text]
  47. Topper A and Mulier H. Basal metabolism of normal children. Arch Pediatr Adolesc Med (Am J Dis Child) 43: 327-336, 1932.
  48. Treuth MS, Butte NF, and Wong WW. Effects of familial predisposition to obesity on energy expenditure in multiethnic prepubertal girls. Am J Clin Nutr 71: 893-900, 2000.[Abstract/Free Full Text]
  49. Van Vliet G. Clinical aspects of normal pubertal development. Horm Res 36: 93-96, 1991.[ISI]
  50. Wakeham G. Basal metabolism and the menstrual cycle. J Biol Chem 56: 555-567, 1923.[Free Full Text]
  51. Webb P. 24-Hour energy expenditure and the menstrual cycle. Am J Clin Nutr 44: 614-619, 1986.[Abstract]
  52. Weinsier RL, Schutz Y, and Bracco D. Reexamination of the relationship of resting metabolic rate to fat-free mass and to the metabolically active components of fat-free mass in humans. Am J Clin Nutr 55: 790-794, 1992.[Abstract]
  53. Weir JBdV. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 109: 1-9, 1949.[ISI]
  54. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. In: WHO Technical Report Series, 2000, p. i-xii, 1-253.
  55. Williams T, Berelowitz M, Joffe SN, Thorner MO, Rivier J, Vale W, and Frohman LA. Impaired growth hormone responses to growth hormone-releasing factor in obesity. A pituitary defect reversed with weight reduction. N Engl J Med 311: 1403-1407, 1984.[Abstract]
  56. Wolthers T, Grøfte T, Møller N, Christiansen JS, Ørskov H, Weeke J, and Jørgensen JO. Calorigenic effects of growth hormone: the role of thyroid hormones. J Clin Endocrinol Metab 81: 1416-1419, 1996.[Abstract]
  57. Wolthers T, Grøfte T, Nørrelund H, Poulsen PL, Andreasen F, Christiansen JS, and Jørgensen JO. Differential effects of growth hormone and prednisolone on energy metabolism and leptin levels in humans. Metabolism 47: 83-88, 1998.[ISI][Medline]
  58. Wurmser H, Laessle R, Jacob K, Langhard S, Uhl H, Angst A, Muller A, and Pirke KM. Resting metabolic rate in preadolescent girls at high risk of obesity. Int J Obes Relat Metab Disord 22: 793-799, 1998.[CrossRef][Medline]