Our analysis of data collected from a cohort of girls who were followed from before menarche until 4 years after menarche offers a visualization of the interrelationships between changes in body composition and changes in leptin, estradiol, FSH and insulin, during the pubertal transition. Several studies have examined the relationship between leptin and body composition over the pubertal period (4
), and two have investigated the relationship between sex hormones and body composition during puberty (1
). Only a few have examined both leptin and sex hormones in relation to body composition at this time (5
). Adding to that knowledge, we have presented hormone levels and body composition in relation to menarche, and thus have standardized them to a biological time point. Hormonal and body composition changes during the pubertal period are best studied in relation to age at menarche
rather than chronological age
because of the large variability in maturational development among girls who are the same chronological age (18
Our observations are consistent with those of others. As would be expected insulin, FSH and estradiol rose well before menarche (16
). Our findings of an increase in FSH and estradiol 2 years before menarche are in agreement with those of Legro et al. (2
). We observed a decrease in FSH levels around the time of menarche and a leveling off of estradiol 2 years after menarche. Body composition and serum leptin levels at menarche were similar to those reported by Matkovic (8
As has been found in other studies (4
), we observed a very close association between relative body fatness and serum leptin levels as girls matured. Until about 3–6 months before menarche, mean percentage body fat in these girls was unchanged. Likewise until shortly before menarche, serum leptin levels were stable or only slightly increasing. The increase in slope of percentage body fat that occurred in the 6 month period before menarche coincided with an increase in slope of serum leptin levels, and when percentage body fat began to plateau a year or so after menarche, serum leptin levels also stabilized. Our data provide further evidence that changes in leptin levels reflect changes in body fatness across puberty in girls. We acknowledge, however, that we used an indirect measure of body composition, bioelectrical impedance, to estimate body fatness. We were able to use a cohort-specific equation developed from multiple measures of total body water at different time points. In order to calculate body fat from this measure, an assumption is made that the hydration of FFM is constant. Individual variability in the hydration constant could introduce some error in the measurement of FFM and percent body fat.
Our ability to draw conclusions about the dynamics of leptin changes more than 2 years before menarche is limited by having fewer observations from this maturational period. This is to be expected because premenarcheal girls between ages 8 and 12 years (mean 10.1 years) were enrolled in the study and at enrollment their age at menarche was unknown. In addition blood collection did not begin until 1993. Therefore when our observations are arrayed relative to age at menarche, as in the figures and GAM analyses that generated them, fewer observations are available from the early pubertal period.
Frisch suggested years ago that menarche required sufficient body fat stores to support reproduction (19
). Despite considerable research, this hypothesis remains controversial, in part, because of the lack of a molecular mechanism to signal that fat stores are adequate for reproduction. The discovery of leptin (3
) led to speculation that it might represent that molecular signal. Matkovic et al. (8
) studied pubertal girls for 4 years and investigated associations between leptin levels and age at menarche in relation to body composition. They concluded that for menarche to occur, leptin levels must reach a critical level. Although it is possible that a sufficient level of leptin is required to initiate menarche, our data do not support the notion that leptin rises sharply prior to menarche. Because changes in leptin parallel changes in body fatness, it remains uncertain whether leptin is the signal. The observation that leptin more closely tracks percentage body fat than fat mass beyond 2 years after menarche suggests that relative fatness may be more important than absolute body fat in body weight regulation and reproduction.
The strengths of our study include the prospective assessment of menarche, repeated measurements over the pubertal period, and concurrent measures of body composition and hormone levels. However, our study, like several others (7
), is limited by the number and timing of samples. In theory, patterns of change in hormone levels and body composition relative to menarche in girls could be studied in cross-sectional or prospective study designs, with different strengths and limitations of each approach.
Advantages of cross-sectional studies, such as reported by Horlick (5
), Ellis (17
) and Arslanian (4
) include ensuring consistency of methodology across measurements, speed and logistics. Disadvantages to this approach are that measurements cannot be ordered relative to age at menarche, because the time to menarche for premenarcheal girls is unknown, and for girls who are postmenarcheal their recalled age at menarche must be used and reliance on memory would be expected to introduce some misclassification error (20
). In addition, an important assumption underlying interpretation of hormone levels and body composition patterns relative to pubertal development in a study with a single measurement occasion is that the main difference between subjects is in sexual development. However, race/ethnicity, body type, or athleticism might also be associated with hormone levels and body composition. Thus, it is difficult to know whether differences in hormone levels or body composition across maturational stage observed in a cross-sectional study are due to maturation or to who
Optimally, a prospective study design would include closely spaced measurements of hormone levels and body composition in a large group of young girls followed for many years. This design would provide individual trajectories of change in hormone levels and body composition for each girl, and one could average these trajectories to estimate the pattern of change in hormone levels and body composition relative to age at menarche. The advantage of this type of study design would be direct measurement of change within individuals; however the difficulties in conducting such a study would be great in terms of time, cost, subject burden and logistics. Ahmed et al. (6
) and Matkovic et al. (8
) studied girls measured repeatedly during puberty; however, their analytic approach resulted in linear models of association. For non-linear trajectories to be estimated, individual observations would need to be closely spaced in time.
The analyses presented in our report, and those by Demerath (7
) represent a combination of cross-sectional and prospective designs. The participants in our study were followed over time, and age at menarche was determined prospectively, but participants varied in their number and spacing of measurements. The visualization of the interrelationships of hormone levels and body composition relative to age at menarche that we provide in the figures, using a GAM approach, allows for inclusion of all available measurements. Forty-five percent of subjects were measured on four or more occasions, 63% were measured on three or more occasions and 6% were measured on seven or more occasions. However, 14% of subjects were measured on only one occasion. With this number and variability in measurements, one can only fit a straight line. However, it is evident that much information is lost with this approach. For reasons of practicality, it was difficult to obtain repeated measures of sex hormone levels on the entire sample because the measurements need to be done during a small window of time relative to the menstrual cycle. Although only approximately half of the girls in the cohort elected to participate, reasons for non-participation are unlikely to bias our results.
In conclusion, this visual presentation of the hormonal and body composition changes occurring throughout the pubertal period in girls may be useful in generating new hypotheses related to the timing of menarche.