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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 3 1013-1019
Copyright © 2001 by The Endocrine Society

From the Clinical Research Centers

Increased Pulsatility, Process Irregularity, and Nocturnal Trough Concentrations of Growth Hormone in Amenorrheic Compared to Eumenorrheic Athletes1

Debra L. Waters, Clifford R. Qualls, Richard Dorin, Johannes D. Veldhuis and Richard N. Baumgartner

Department of Internal Medicine, University of New Mexico School of Medicine (D.L.W., R.N.B.); General Clinical Research Center, University of New Mexico (C.R.Q.); and Department of Internal Medicine, New Mexico Veterans Affairs Health Care System (R.D.), Albuquerque, New Mexico 87131; and Center for Biomathematical Technology, General Clinical Research Center, and Department of Internal Medicine, University of Virginia (J.D.V.), Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Debra L. Waters, Ph.D., University of New Mexico School of Medicine, 2701 Frontier Plaza NE, Surge Building, Room 215, Albuquerque, New Mexico 87131. E-mail: dwaters{at}salud.unm.edu


   Abstract
Top
 Abstract
Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 
Amenorrheic athletes exhibit a spectrum of neuroendocrine disturbances, including alterations in the GH-insulin-like growth factor I (IGF-I) axis. Whether these changes are due to exercise or amenorrhea is incompletely characterized. The present study investigates spontaneous (overnight) and exercise-stimulated GH secretion and associated IGF-binding proteins (IGFBPs) in amenorrheic (AA; n = 5), and eumenorrheic athletes ( n = 5) matched for age, percent body fat (dual energy x-ray absorptiometry), training history, and maximal oxygen consumption. Each volunteer participated in two hospital admissions consisting of a 50-min submaximal exercise bout (70% maximal oxygen consumption) and an 8-h nocturnal sampling period. Deconvolution analysis of serum GH concentration time series revealed increases in the half-life of GH (60%) and the number of secretory bursts (85%) as well as a decrease in their half-duration (50%) and the mass of GH secreted per pulse (300%) in the AA cohort. Time occupancy at elevated trough GH concentrations was significantly increased, and GH pulsatility (approximate entropy) was more irregular in the AA group. During exercise, AA exhibited a reversal of the normal relationship between IGF-I and GH, and a 4- to 5-fold blunting of stimulated peak and integrated GH secretion. Fasting levels of plasma IGF-I, IGFBP-3, and IGFBP-1 appeared to be unaffected by menstrual status. In ensemble, this phenotype of GH release in amenorrheic athletes suggests disrupted neuroregulation of episodic GH secretion, possibly reflecting decreased somatostinergic inhibition basally, and reduced GHRH output in response to exercise compared with eumenorrheic athletes. Accordingly, we postulate that the amenorrheic state, beyond the exercise experience per se, alters the neuroendocrine control of GH output in amenorrheic athletes.


   Introduction
Top
 Abstract
 Introduction
Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 
ATHLETIC AMENORRHEA occurs commonly in the female athletic community. However, the pathophysiological interpretation of endocrine alterations in strenuously exercising women has been confounded by variable weight changes and/or concomitant eating disorders (1, 2, 3, 4, 5). Metabolic alterations such as hypercholesterolemia, hypotension, decreased T3, and increased rT3 concentrations typically coexist with psychological impairment in classical anorexia nervosa, but are more often absent in otherwise healthy, lean athletes with amenorrhea (6). However, the precise endocrine phenotype of nonanorectic women with athletic amenorrhea is not well established.

The secretion of GH and other pituitary hormones is subject to complex feedback- and feedforward-dependent neuroregulation (7). There are also evident gender distinctions in GH neuroregulation, inferentially due to differences in the balance between respective stimulatory and inhibitory input by GHRH and somatostatin (8). In anorexia nervosa, increased GH pulse frequency and elevated integrated serum GH concentrations have been recognized, putatively reflecting a reduction of hypothalamic somatostatin tone and/or increased GHRH discharges (9, 10, 11). Whether these characteristics underlie the presumptively disrupted neuroregulation of GH secretion in women with nonanorectic amenorrhea is unknown (6, 12, 13).

The purpose of this study was to evaluate nocturnal GH secretion and the GH response to an exercise stimulus along with insulin-like growth factor (IGF)-binding protein (IGFBP) concentrations in amenorrheic and eumenorrheic athletes (EA) without eating disorders. To this end, we compared two cohorts of matched, strenuously training women who differed principally in menstrual cyclicity.


   Experimental Subjects
Top
 Abstract
 Introduction
 Experimental Subjects
Materials and Methods
 Results
 Discussion
 References
 
This study was approved by the University of New Mexico Health Sciences Center human research review committee. Ten female volunteers [amenorrheic (AA; n = 5) or eumenorrheic (EA; n = 5)] between the ages of 19–30 yr were recruited and gave informed consent. Each was in good health with no underlying endocrine disease, and none used birth control pills, intrauterine devices, or other medications. The groups were matched for age, training activity, maximal oxygen consumption (VO2max), and body composition (below).


   Materials and Methods
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
Results
 Discussion
 References
 
Each subject underwent a physical examination, baseline screening blood tests (Sequential Multichannel Analyzer Chemistries), and thyroid function panel [TSH, total T4, and T3 uptake (T3U)]. Serum progesterone measurements and a daily, prerising, 30-day basal body temperature record were used to document ovulatory status. The Eating Attitudes Test (EAT-26) was performed to rule out overt eating disorders. Basal hormonal determinations in EA volunteers were obtained during the early follicular phase for GH and during the midluteal phase of the menstrual cycle for progesterone; in AA volunteers these measurements were made during the hospital admission. Athletic amenorrhea was defined as the absence of menstruation for no less than 3 consecutive months before testing, menstrual disruption related to exercise training for greater than 2 yr, basal progesterone concentrations of less than 13 nmol/L, and a lack of biphasic elevation in basal body temperature over a period of 30 days.

Dietary records were collected for 30 days before the in-patient admission. Nutritional intake was determined by 24-h recall from data returned weekly to the dietician. Dietary intakes were analyzed by Nutritionist III software for kilocalories and grams of protein, fat, and carbohydrate consumed (N2 Computing, Salem, OR). Percent body fat and lean body mass were determined by dual energy x-ray absorptiometry (QDR-1000/W, Hologic, Inc., Waltham, MA) using Lunar Corp. (Madison, WI) Scanning Analysis (version 3.6, 1992).

Postexercise/nocturnal blood sampling

Subjects were admitted to the General Clinical Research Center (GCRC) for 2 nights and were provided meals. EA volunteers were admitted during the early follicular phase of the menstrual cycle. AA were admitted on alternate days during 1 month. The first night was used for acclimation to the GCRC. The second night was the nocturnal GH study. After the first night of admission and to mimic typical energy expenditure during a 24-h period, all athletes performed a 50-min submaximal exercise bout (70% VO2max) using their customary exercise modality (i.e. cycling or running). Blood samples were drawn every 10 min during the exercise test and every 5 min during 20 min of recovery. Immediately after the submaximal exercise, the subjects were provided breakfast, given a take-home lunch, and discharged until 1800 h. At 1800 h, the subjects returned to the GCRC and were fed a caffeine-free, balanced meal. At 2100 h, the subjects were allowed only water, and the iv heparin lock was converted to long tubing, which was run into an adjoining room. Lights were put out at 2200 h, and 2-mL blood samples were drawn every 20 min from 2300–0700 h. A one-way mirror in the room was used to monitor sleep.

Hormonal measurements

Blood samples for GH, IGF-I, IGFBP-1, IGFBP-3, and estradiol determinations were centrifuged to separate serum, which was frozen for subsequent analysis. GH and estradiol concentrations were analyzed using a double antibody method (Diagnostic Products, Los Angeles, CA). Intra- and interassay variabilities for GH were 2.8% and 5.3%, respectively, with 0.2 µg/L sensitivity. Intra- and interassay variabilities for estradiol were 7.0% and 8.1%, respectively, with 29 pmol/L sensitivity. IGF-I was analyzed using the RIA acid-ethanol extraction method (Nichols Institute Diagnostics, San Juan Capistrano, CA). Sensitivity was 60 µg/L. Intra- and interassay variabilities for IGF-I were 2.4% and 5.2%, respectively. IGFBP-3 was analyzed using RIA (Nichols Institute Diagnostics). Sensitivity was 0.0625 µg/mL, with intra- and interassay variabilities of 3.8% and 6.3%, respectively. IGFBP-1 was analyzed by immunoradiometric assay (Diagnostics Systems Laboratories, Inc., Webster, TX). Sensitivity was 33 µg/L, with intra- and interassay variabilities of 6.0% and 4.6%, respectively. Solid phase RIA was used to determine plasma progesterone. Interassay variability for progesterone was 6.1%, and sensitivity was 0.28 nmol/L serum. Solid phase RIA was used to determine total T4 (TT4; Nichols Institute Diagnostics), immunoradiometric assay was used to assess TSH (Nichols Institute Diagnostics), and the radioactive T3 resin saturation technique was used to determine T3U (Organon Technica, Durham, NC).

Statistical analyses

Demographics. A two-tailed t test was used to compare differences between the AA and EA groups in age, body composition (percent fat), years of training, VO2max, progesterone values, eating attitude test scores (EAT-26), and thyroid function (T4, T3U, and TSH).

Distributional analysis. A modification of the time occupancy analysis, as described by Matthews et al. (14, 15, 16, 17), was used to analyze nocturnal GH secretory patterns. Time occupancies are the percentage of time spent by data in the series at given concentrations. Modification of the time occupancy analysis allowed us to use a 2-bin histogram instead of a complete time occupancy distribution. We applied Fisher’s exact test directly to the resultant distribution instead of t tests on the percentiles of the distributions. This modification also made logarithmic transformation of GH concentrations unnecessary.

Monte Carlo simulation. In a Monte Carlo simulation, statistical power was estimated based on 1000 simulated samples, each consisting of 5 time series representing EA and 5 representing AA. The type I error was estimated by 1000 samples consisting of 2 groups of 5 time series, both representing EA.

Measures of power: receiver operator characteristics (ROC) curve. We first optimized the selection of a cut-score for trough GH concentrations, as this is the only adjustable parameter in time occupancy analysis. Optimization was based on an ROC-like analysis, which plots sensitivity (1 - {alpha} in the hypothesis setting) vs. 1 - specificity (ß) as parameterized by the cut-score. The cut-score is the threshold below which the values are in a trough. We estimated sensitivity and specificity in two separate simulations. Each threshold was applied to the resultant data to obtain the ROC-like curve, which was not necessarily monotonically increasing. The ROC-like tables contain rows representing either (AA, EA) or (EA, EA) and columns representing trough/nadir values.

Deconvolution analysis. A pulsatile model of hormone secretion and clearance was assumed, in which the plasma concentration of GH at any given instant is related to four simultaneous secretory and kinetic features of interest: 1) location of secretory bursts, 2), mass of secretory bursts, 3) duration of secretory bursts, and 4) endogenous hormone half-life. The basal rate of GH secretion was calculated simultaneously to reflect the lowest 5% sample GH concentrations in any given profile. A distinct secretory burst was approximated algebraically as a random (Gaussian) distribution of instantaneous secretory rates. Fitted burst mass values were distinguishable from zero based on 95% statistical confidence intervals. A convolution integral was used to relate the serum GH concentrations to the foregoing specific measure of pulsatile GH secretion and removal. Parameters were quantified by iterative nonlinear least squares parameter estimation. The disappearance function for GH was modeled as a one-component exponential decay function for each subject, assuming that the half-life and distribution volume of GH were approximately constant in each individual throughout the nocturnal period (10).

The above deconvolution analysis estimated 1) pulsatile production rate product of mass per burst and number of bursts, 2) secretory burst half-duration, 3) mass secreted per burst, 4) number of bursts, and 5) t1/2 of GH disappearance. Analyses were carried out blinded to the subject group assignment (10).

Approximate entropy (ApEn). ApEn, as described by Pincus (8), was used to analyze the orderliness/disorderliness of GH profiles. Normalized ApEn is a scale- and model-independent statistic for assessing the regularity of time-series data. ApEn is a distributional method that allows consideration of the joint distribution of adjacent points (m > 1) instead of marginal time occupancy distribution. A single nonnegative number is thereby assigned to a time series to quantify the serial orderliness or regularity of the data. ApEn specifically measures the logarithmic likelihood that patterns of data length (m) that are similar remain similar within a tolerance (r) on the next incremental (m + 1) comparison (8). Smaller ApEn values indicate a greater likelihood of successive comparisons remaining close and imply greater regularity, and vice versa. ApEn is stable to repeated small change in noise characteristics or infrequent large data artifacts (18).


   Results
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
Discussion
 References
 
Descriptive characteristics

The characteristics of the subjects are presented in Table 1Go. No differences were noted in age, years of training, current training frequency or duration, V02max, percent body fat, thyroid status, or age at menarche between the groups. Significant differences emerged for progesterone and unstimulated mean GH concentrations and eating attitude test scores (EAT-26). EAT-26 scores were within the normal range for both groups (<20), but were significantly higher in the AA. Values for TT4, T3U, and TSH were within normal ranges and not significantly different between amenorrheics and eumennorheics, respectively (TT4, 75.9 ± 12.87 vs. 79.9 ± 25.74 nmol/L; T3U, 0.63 ± 0.03 vs. 0.63 ± 0.04 nmol/L; TSH, 2.8 ± 2 vs. 2.9 ± 0.9 mU/L).


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  		Table 1. Demographics

 
Nocturnal GH concentration data

Distributional analysis. The modified time occupancy analysis of the trough GH concentration revealed that AA spent a significantly greater portion of time at a higher GH trough concentration than EA (P < 0.001). Time occupancy analysis of nocturnal GH concentration data via Monte Carlo simulations (see Materials and Methods) was performed to estimate the type I error and power in this approach. Figure 1Go is presented as an ROC-like curve parameterized by the threshold definition of troughs. For a type I error of 0.01, a threshold of 1.8 µg/L (equal to the 25th percentile of the time occupancy distribution for AA in the simulation data) had 79% power. Amenorrheic women had a 39% time occupancy at or below the 1.8 µg/L threshold, whereas eumenorrheic individuals had 65% time occupancy at 1.8 µg/L. Using a threshold of 1.0 µg/L for a type I error of 0.04, statistical power was 88%. There was a negative correlation between high percent time occupancy of low trough values and mean GH concentrations (r = -0.73; P = 0.02).



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  		Figure 1. ROC-like curve parameterized by a threshold that defines serum GH concentrations.

 
Deconvolution analysis. Figure 2Go illustrates pulsatile profiles of GH release in each volunteer. Table 2Go demonstrates the differences between the groups based on deconvolution analysis. GH secretory burst half-duration and mass of GH secreted per peak were significantly lower in AA (P = 0.04 and P = 0.04, respectively). The number of peaks and GH half-life were significantly greater in AA (P = 0.03 and P = 0.04, respectively). The dispersion of key measures of pulsatile GH secretion (mass or frequency) among the 10 volunteers studied is given in Fig. 3Go, A and B. There was a negative relationship between mass per burst and half-life (r = -66; P = 0.04). Basal secretion, total mass (pulsatile production rate), and mean and integrated GH concentrations were not significantly different between groups (Table 2Go).



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  		Figure 2. Profiles of pulsatile serum GH concentrations obtained by 20-min blood sampling overnight in five AA and five EA athletes.

 

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  		Table 2. Deconvolution analysis of GH secretion in amenorrheic and eumenorrheic athletes

 


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  		Figure 3. Mass of GH secreted per burst (A), GH pulse frequency (B), and GH ApEn values (C) for nocturnal GH secretion profiles (m = 1; r = 20% SD). A higher ApEn indicates a more disordered GH release process. Data are the mean ± SEM. *, P < 0.01, AA vs. EA.

 
ApEn. Mean ApEn was significantly higher in AA [0.695 ± 0.048 (±SEM) vs. 0.373 ± 0.060; P = 0.004; Fig. 3CGo], indicating more irregular GH release. A post-hoc correlation analysis between methods revealed that ApEn was positively related to the number of peaks (r = 0.81; P = 0.004) and was negatively correlated to a high percent time occupancy of low trough values (r = -0.74; P = 0.01).

Nocturnal serum IGF-I, IGFBP-3, and IGFBP-1 concentrations. There were no significant differences between the groups in baseline parameters or peak and integrated area under the curve (AUC) for IGF-I, IGFBP-1, and IGFBP3 concentrations. GH peak and AUC values did not differ, and baseline GH concentrations showed a trend toward significance (P = 0.06). For both groups, peak IGFBP-1 was significantly correlated to peak GH regardless of time (r = 0.58; P = 0.03). IGFBP-1 was significantly correlated to GH AUC (r = 0.39; P = 0.05).

Exercise data: deconvolution and classical parameter analysis of serum GH concentrations after exercise

Figure 4Go summarizes contrasts in the GH response to exercise. The baseline GH concentration at the start of exercise was significantly greater in AA than EA (7.9 ± 6.7 vs. 0.94 ± 0.7 µg/L; P = 0.04) and was significantly correlated to nocturnal GH concentrations (r2 = 0.65; P = 0.04). Adjusting for differences in baseline GH concentrations, GH AUC and GH peak values were significantly lower in AA [AUC, 1571 ± 910 vs. 406 ± 230 µg/L (P = 0.01); peak, 33 ± 15 vs. 12 ± 7 µg/L (P = 0.02)]. Deconvolution analysis revealed that GH mass per burst and total GH production rate were significantly less in AA [mass, 26 ± 7 vs. 120 ± 17 µg/L (P = 0.003); production rate, 30 ± 9 vs. 124 ± 41 µg/L·min (P = 0.04)]. Figure 5Go demonstrates a reversal in the normal relationship between GH AUC and peak IGF-I during exercise in AA compared with EA (P = 0.004).



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  		Figure 4. Serum GH concentration response to 50-min treadmill exercise performed at 70% VO2max. P < 0.01, AA vs. EA, for peak GH concentrations and AUC.

 


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  		Figure 5. Relationship between integrated (AUC) GH response and IGF-I peak during 50-min treadmill exercise at 70% VO2max. Overall P = 0.004, AA vs. EA.

 
IGFBP-1 increased significantly from the start of exercise to 70 min (P = 0.02), with a trend toward a significant difference between the groups (AA, 10.6 ± 17.6 µg/L; EA, 19.3 ± 15.9; P = 0.054).


   Discussion
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
References
 
The multiple analyses used in this investigation revealed several distinct aberrations in GH secretion in AA. After acute exercise, GH secretion was blunted by 4- to 5-fold, and the normal relationship between IGF-I and GH was inverted. In relation to the nocturnal GH secretory process, the AA cohort showed heightened irregularity, elevated pulse frequency, high trough concentrations, and an attenuated duration and mass of GH secretory bursts. Other investigators have reported variable disruption of nocturnal GH secretory patterns in AA and anorexia nervosa (1, 3, 4, 6), but, to our knowledge, this is the first report of the foregoing constellation of findings. Our results are dissimilar from data in anorexia nervosa, in which the GH half-life remains unchanged, the mass of GH secreted per burst is elevated, its half-duration is prolonged, and the basal GH secretion rate is higher (10). The similarities between AA and anorexia nervosa are higher ApEn and an increased frequency of pulsatile GH secretion. Thus, AA patients without eating disorders compared with EA controls manifest distinct alterations in GH neuroregulation that differ from those reported in anorexia nervosa.

The increased interpeak basal (trough) serum GH concentration in anorexia nervosa ensued from augmentation of the basal (nonpulsatile) GH secretory rate rather than from a prolongation of the GH half-life (10). In contrast, in AA we observed an apparent 60% increase in GH half-life, whereas calculated basal (nonpulsatile) GH secretion estimates were unchanged. Although GH half-life is correlated inversely with BMI or estradiol in some analyses (19), our cohorts were not distinguishable in their dual energy x-ray absorptiometry-determined percent body fat or their serum estradiol concentrations. Other studies show that the elimination properties of GH are controlled by the rate of hormone entry into the circulation (20). The prolonged half-life in AA individuals correlated negatively with GH secretory burst mass (i.e. smaller peaks were associated with delayed GH removal). This observation may be relevant, because kinetic analyses of the impact of GH-binding protein (GHBP) t on GH elimination rates (21) predict that GH peaks less than the circulating GHBP capacity and will show half-lives more closely related to the off-rate of GH’s dissociation from its plasma binding protein (~20 min) than to free GH (approximate half-life, 3–7 min). Regardless of the kinetic mechanism involved, the somewhat longer GH half-life in AA could contribute to the relative hypersomatotropism observed here.

A dual pathophysiological mechanism of augmented pulsatile GH secretion has been postulated in anorexia nervosa, in which weight loss elicits greater GH secretory burst mass, and hypoestrogenemia results in increased GH pulse frequency (6). This inference has not been tested directly. However, in postmenopausal women, estrogen administration stimulates GH pulse mass without altering burst frequency (22). In contrast, GH secretory burst mass was reduced by 300% in our women with AA. Pulse mass is believed to reflect joint somatostatinergic and GHRH inputs, whereas pulse frequency may be driven primarily by variations in somatostatin output (7). Frequent low mass bursts of GH, as observed in AA, may influence physiological responses to GH. For example, GH secretory patterns in the rat control body growth, GH receptor and GHBP levels, and liver and muscle gene expression (23). Inferentially, GH peaks seem to be critical to stimulate linear growth, whereas GH trough values may especially impact body composition and metabolic parameters (15). Indeed, sustained low levels of GH can exert powerful (lipolytic) effects on fuel metabolism, resulting in protein and glucose sparing (24). In addition, pulses of GH are coordinated with GH receptor turnover (25), which may be essential for other tissue responses (14, 16). If sustained (nonpulsatile) trough GH concentrations secondarily affect GH signaling (16, 26, 27), then the high trough GH concentrations in AA patients could account for their inversion of the normal (EA) reciprocal relationships between GH, IGF-I, and its binding proteins. Evidently, a sufficient GH stimulus is still maintained in AA to support normal mean fasting plasma concentrations of IGF-I, IGFBP-1, and IGFBP-3.

An unexpected finding in our study was the positive relationship between elevated trough GH concentrations and disordered pulsatility. This may indicate that elevated trough concentrations reflect mechanisms of GH production that are less effectual at orderly pulse generation. A plausible basis for both alterations is reduced somatostatin tone in AA, as high trough GH concentrations are believed to mirror somatostatin withdrawal. Sustained somatostatin withdrawal also impedes the generation of high amplitude GH pulses, which require recurring somatostatin exposure (28, 29). Interestingly, some exercise studies indicate that exercise stimulates GH secretion in part via somatostatin withdrawal (7, 30).

Exercise is a well known stimulus of GH secretion, and several mechanisms have been proposed to mediate the exercise-induced release of GH (2, 6, 18, 31). Regardless of the particular neurotransmitters involved, the final common pathway probably entails either an increase in GHRH and/or a decrease in somatostatin release or action (2). We observed that AA subjects had significantly lower (4- to 5-fold) peak and integrated GH responses to exercise. These deficits would be consistent with reduced GHRH secretion or excessive somatostatin inhibition. We favor the former possibility, as elevated nocturnal trough concentrations of GH are more consistent with reduced somatostatin release. Although daytime exercise may reduce nocturnal GH secretion (2), alternate day exercise does not (32). Thus, we suggest that elevated nocturnal trough GH concentrations and a reduced mass of GH release per burst both before and after exercise in our AA volunteers result from a combined reduction in somatostinergic and GHRH inputs.

IGFBP-1 is acutely regulated by exercise and is elevated during prolonged exercise. This binding protein is elevated in AA and anorexia nervosa and may serve as a marker of metabolic stress or insulinopenia (1, 33, 34, 35). In our AA patients, IGFBP-1 rose throughout exercise and peaked 20 min after recovery. Baseline IGFBP-1 concentrations were in the high normal range, but not significantly so. This trend could reflect insulin actions, as insulin (negatively) regulates IGFBP-1 production (36). Although the clinical role of this binding protein is not well understood, IGFBP-1 may modulate sex steroid hormone action and fuel homeostasis (6). For example, together with IGF-I, insulin, ovarian sex steroids, cytokines, and other factors, IGFBP-1 is involved in a complex system that impacts menstrual cyclicity, ovulation, decidualization, blastocyte implantation, and fetal growth (37).

In conclusion, we employed trough time occupancy, deconvolution analysis, and ApEn to evaluate the dynamic properties of GH secretion in amenorrheic and eumenorrheic athletes with similar percent body fat. Time occupancy analysis disclosed an increased time spent in elevated troughs. Deconvolution analysis revealed an increased number of GH peaks, a prolonged half-life, and brief GH secretory bursts of reduced mass in the AA. ApEn analysis disclosed more disorderly patterns of GH secretion, which paralleled elevated trough concentrations. Both disorderly and elevated trough GH release were correlated to a blunting of the GH secretory response to acute exercise. Concentrations of plasma IGF-I and its associated binding proteins remained normal. We conclude that in the absence of eating disorders and when controlled for their reduction in percent body fat, volunteers with AA, compared with EA subjects, display multiple alterations in GH secretory control. The precise neurochemical basis for disrupted neuroregulation in AA, the role of estrogen depletion in this context, and the degree and tempo of its reversibility are not yet known.


   Acknowledgments
 
Our appreciation to the University of New Mexico GCRC nurses, dietitians, and laboratory staff for their time and efforts with both the in-patient and out-patient procedures. Thanks to George Montoya and Janice Wilson for their work in the analysis of IGF-I binding proteins and thanks to Dr. Paul Motner for his contributions to the in-patient admissions in the GCRC.


   Footnotes
 
1 This work was supported by NIH National Center Research Resources General Clinical Research Center Grants 5MO1-RR-00997 and RO1-AG-14799. Back

Received August 23, 2000.

Revised December 1, 2000.

Accepted December 4, 2000.


   References
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 

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