| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital (R.D., J.O.L.J., J.S.C.), DK-8000 Aarhus, Denmark; Department of Clinical Medicine and Cardiovascular Sciences, University Federico II (S.L., A.C., L.S., R.N.), 80131 Naples, Italy; Research Center for Endocrinology and Metabolism, Sahlgrenska Hospital (C.E., T.R., B.A.B.), S-41345 Gothenburg, Sweden; Metabolic Research Unit, Department of Medicine, and Department of Social and Preventive Medicine, University of Queensland, Princess Alexandra Hospital (R.C.C.), 4102 Brisbane, Queensland, Australia; Department of Endocrinology, St. Thomas’s Hospital (N.K., M.A.B., P.H.S.), London, United Kingdom SE1 7EH; Institute of Mathematics and Statistics, University of Kent (E.E.B.), Canterbury, Kent, United Kingdom CT 7NF; and Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital (R.C.B.), St. Leonards 2065, New South Wales, Australia
Address all correspondence and requests for reprints to: Rolf Dall, M.D., Aarhus Kommunehospital, Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital, DK-8000 Aarhus, Denmark. E-mail: rd{at}dadlnet.dk
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In the circulation most IGF-I circulates as a 150-kDa ternary complex consisting of IGF-I plus a specific binding protein (IGFBP-3) and a nonbinding component, termed acid labile subunit (ALS) (6, 7). Both IGFBP-3 and ALS are partly regulated by GH, as reflected by low and elevated levels in GH deficiency and active acromegaly, respectively (7).
In contrast to patients with GH disorders, less is known about the regulation of serum IGF-I in healthy adults. Serum IGF-I levels decline gradually with age, which is weakly correlated with the concomitant decline in GH secretion (8), but it has recently been shown that endogenous GH status is a surprisingly weak predictor of serum IGF-I (9). Possible residual determinants of IGF-I in normal adults include gender and sex steroids, body composition, and physical fitness. Even less is known about the impact of exogenous GH exposure on IGF-I and related variables in healthy adults. Such information would seem to be of general interest when considering the use of GH for nonlicensed indications such as catabolic states, sarcopenia, and rejuvenation of age-associated changes in body composition. Moreover, there is increasing evidence to suspect widespread illicit use of GH as a performance-enhancing agent among athletes (10).
The aim of the present study was to assess the effects of GH administration in supraphysiological doses on serum concentrations of IGF-I and pertinent related variables and subsequently to evaluate the usefulness of such variables to predict exposure to exogenous GH. To this end a large cohort of healthy, fit, young adults of both sexes were studied before, during, and after GH administration with two doses in a randomized, placebo-controlled, parallel trial.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Ninety-nine subjects (50 men and 49 women) were recruited among
healthy volunteers in 4 different countries: Denmark (n = 31),
Italy (n = 27), Sweden (n = 30), and the United Kingdom
(n = 11). The inclusion criteria were age between 18–40 yr,
unremarkable medical history, no intake of medications, and regular
participation in at least 2 exercise sessions/week for at least 1 yr.
None of the subjects was an elite athlete, and participation in
organized sport competitions was not allowed during the study period.
All women documented a negative pregnancy test before study entry and
were confirmed to be using safe contraception; 9 women used oral
contraceptives (1 in the placebo group, 3 in the 0.1 IU/kg·day GH
group, and 5 in the 0.2 IU/kg·day group), and the remaining females
used barrier methods. Treatment with GH/placebo started randomly with
respect to the menstrual cycle. In each country the protocol was
approved by the ethical committee system and the national health
authorities. Oral and written consents were obtained from each subject
in accordance with the principles stated in the Declaration of
Helsinki. The baseline characteristics of the subjects are presented in
Tables 1
and 2.
|
|
The study was performed in a randomized, double blind, placebo-controlled, parallel design involving three arms: I) 0.1 IU/kg·day GH (GH 0.1; maximum dose, 9.5 IU/day; n = 30; 15 women and 15 men), II) 0.2 IU/kg·day GH (GH 0.2; maximum dose, 19 IU/day; n = 29; 15 women and 14 men), and III) placebo (PLA; n = 40; 19 women and 21 men). GH (Genotropin, Pharmacia & Upjohn, Inc., Stockholm, Sweden; or Norditropin, Novo Nordisk, Copenhagen, Denmark) and placebo were administered as daily sc self-injections in the evening. To minimize side effects, only 50% of the target dose was given during the first week. In case of side effects the dosage was reduced by 50%, and treatment was discontinued if the complaints persisted for more than 1 week. Compliance was monitored by collection of vials and reports about missing injections. At baseline the subjects attended the hospital for 1 day for blood sampling, interview, and physical examination. Blood samples were subsequently collected at the end of each week during the treatment phase (days 7, 14, 21, and 28) and on days 30, 33, 42, and 84 in the wash-out period.
Assays
All serum samples were stored at -80 C, and all samples from one subject were analyzed in the same run. Serum IGF-I was measured by RIA using a monoclonal antibody after acid-ethanol extraction (Nichols Institute Diagnostics, San Juan Capistrano, CA).
IGFBP-2 (11), IGFBP-3 (6), and ALS
(7) were assayed using in-house RIAs and polyclonal
antibodies (Robert Baxter, Sydney, Australia). The intraassay
coefficients of variations (CVs) are given in Table 4.
|
Unpaired two-tailed t test was used to test for gender differences at baseline. The variance in the PLA group was tested by ANOVA for repeated measures approached by general linear modeling (GLM repeated measures). The CVs for the variables in the PLA group were calculated as the mean ± SEM of the SD/mean for each subject. Temporal changes in serum levels of each variable were tested by GLM repeated measures with each time point as a with-in subject factor, and randomization and gender as between-factors. If GLM repeated measures revealed significant changes, post-hoc analysis was made by gender-stratified one-way ANOVA, and multiple comparisons were made using the Bonferroni correction. The area under the curve (AUC) during the treatment period (days 1–28) of each variable was estimated according to the trapezoidal rule. Differences in AUC among the three groups were analyzed by one-way ANOVA. Where appropriate, post-hoc analysis was performed by multiple comparisons with the Bonferroni correction. Pearson correlation analyses (r) as well as multiple linear regression analyses were used to relate variables. P < 0.05 was considered significant. Results are expressed as the mean ± SE.
Side effects
During the study, 8 subjects (3 women and 5 men) of the 30 enrolled in the GH 0.1 group experienced side effects; among these, 1 subject reduced the dose (1 men). In the GH 0.2 group, 20 subjects (7 women and 12 men) experienced side effects; among these, 5 reduced the dose (2 women and 3 men). In the PLA group, 12 subjects (7 women and 5 men) had side effects, of whom 1 subject reduced the dose and 1 subject stopped the treatment on day 14 due to headache and tachycardia. The most frequently reported side effects were attributable to transient fluid retention. In addition, increased sweating and arthralgia were reported.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
and 2). Baseline levels of
IGF-related variables were similar in each group, apart from slightly
higher serum IGFBP-3 concentrations among females in the PLA group
(Tables 1 and 2). Levels of IGF-I, IGFBP-2, and IGFBP-3 and the
IGF-I/IGFBP-3 ratio showed no gender differences at baseline, whereas
ALS levels were significantly higher in women (P <
0.0005; Table 3).
|
Gender-stratified multiple linear regression models with IGF-I, IGFBP-2, IGFBP-3, and ALS as dependent variables and age and BMI as independent variables were performed at baseline. IGF-I correlated negatively with age in men [age: ß = -0.5; P < 0.0005; body mass index (BMI): ß = 0.07; P < 0.6; overall: P < 0.001; r2 = 0.23], but not in women (P < 0.22). For both genders IGFBP-2 levels correlated positively with age and negatively with BMI (women: age: ß = 0.4; P < 0.005; BMI: ß = -0.04; P < 0.03; overall: P < 0.008; r2 = 0.16; males: age: ß = 0.3; P < 0.04; BMI: ß = -0.4; P < 0.005; overall: P < 0.01; r2 = 0.16). ALS levels in females did not correlate significantly with age and BMI (P < 0.4), but in males there was a negative correlation with age (age: ß = -0.4; P < 0.02; BMI: ß = 0.1; P < 0.4; overall: P < 0.049; r2 = 0.08).
All variables in the PLA group remained stable during the entire study
period, as ANOVA revealed no significant time effect in the PLA group
during the study period (Table 4 and
Figs. 1 and 3–6). IGFBP-2 levels showed
the highest intraindividual CV during the study period (20–25%),
whereas the CVs for IGF-I, IGFBP-3, and ALS were between 10–16%
(Table 4). The biological CVs, estimated as the intraindividual CVs
minus the intraassay CVs, were 6–9% for IGF-I, IGFBP-3, and ALS and
approximately 20% for IGFBP-2 (Table 4).
|
|
). Post-hoc analysis in
the female group revealed significantly higher IGF-I levels through day
30 in the GH 0.2 group compared with the PLA group (P
< 0.0005), whereas IGF-I levels in the GH 0.1 group were only
different from the PLA group on day 21 (P < 0.04).
Among females IGF-I levels were significantly higher in the GH 0.2
group compared with the GH 0.1 group through day 30 (day 30;
P < 0.04; Fig. 1, top panel). The
AUC of IGF-I (AUCIGF-I) in females during the
treatment period (days 1–28) was significantly increased in the GH 0.2
group, whereas no significant difference was detected between PLA and
the GH 0.1 group [mean ± SE;
AUCIGF-I, 9,670 ± 638 (Pla) vs.
11,762 ± 1,011 (GH 0.1) vs. 15,634 ± 812 (GH
0.2) µg/L·28 days; P < 0.0005].
In men IGF-I levels increased dose independently in the two GH groups
and had not returned completely to baseline levels on day 42
(P < 0.005; Fig. 1, bottom panel).
AUCIGF-I during active treatment in males
increased dose independently in the two GH groups compared with that in
the PLA group [mean ± SE;
AUCIGF-I, 7,681 ± 400 (Pla) vs.
17,532 ± 1,062 (GH 0.1) vs. 18,576 ± 993 (GH
0.2) µg/L·28 days; P < 0.0005].
Individual IGF-I values are presented as scatterplots for females and
males in Fig. 2. The upper 4
SD level of IGF-I measurements at baseline was chosen as an
arbitrary cut-off to separate normal from abnormal IGF-I values. Fifty
percent of IGF-I measurements among women in the GH 0.2 group were
above the cut-off on day 21 compared with 33% on day 28. The
corresponding values for women in the GH 0.1 group were 7% (day 21)
and 23% (day 28), respectively. By contrast, in men 86% and 64% of
IGF-I levels in the GH 0.2 group were above the cut-off on days 21 and
28, respectively. The corresponding values for males in the GH 0.1
group were 73% (day 21) and 60% (day 28), respectively. The ability
to discriminate between basal and GH-stimulated IGF-I values was much
poorer with IGFBP-3 and ALS than with IGF-I (data not shown).
|
). Post-hoc
analysis, however, was unable to demonstrate significant differences at
any specific time point, indicating that the GH-induced suppression of
IGFBP-2 depicted by ANOVA was small. Likewise,
AUCIGFBP-2 during active treatment (days 1–28)
did not differ between the groups.
The changes in serum IGFBP-3 concentrations exhibited a marked gender
difference, with a distinct, albeit dose-independent, increase in
GH-treated males compared with minimal fluctuations with time in women
(Fig. 4). This was reflected by ANOVA,
which revealed a significant interaction between time x
treatment x gender (P < 0.04). In men, IGFBP-3
levels remained significantly elevated through day 30 with either GH
dose (PLA vs. GH 0.1, P < 0.03; PLA
vs. GH 0.2, P < 0.01).
AUCIGFBP-3 during active treatment (days 1–28)
in women were similar in each group, whereas GH treatment among males
induced an increase [mean ± SE;
AUCIGFBP-3, 109 ± 5 (PLA) vs.
131 ± 8 (GH 0.1) vs.143 ± 10 (GH 0.2) mg/L·28
days; P < 0.006].
|
).
Again, a dose dependency was recorded in women, where only the GH 0.2
group was significantly different from the PLA group on day 28
(P < 0.04). In men, both the GH 0.1 and GH 0.2 groups
had elevated levels on day 28 (P < 0.0005), and ANOVA
also revealed a difference among the three groups on day 30
(P < 0.001). AUCALS (nanomoles
per L/28 days) in women did not change significantly (P
< 0.06), whereas in men there were highly significant changes between
the two GH groups and the PLA group [6226 ± 211 (PLA)
vs. 9447 ± 496 (GH 0.1) vs. 9208 ±
415 (GH 0.2); P < 0.0005].
|
).
In women post-hoc analyses revealed a dose dependency, with
the GH 0.2 group displaying higher values through day 30 compared with
the PLA group (P < 0.001) and through day 28 compared
with the GH 0.1 group (P < 0.001). In men a GH
dose-independent increase was detected through day 42 in the two GH
groups compared with the PLA group (P < 0.008).
|
Gender differences in GH responsiveness on day 21
The increments in IGF-I, IGFBP-3, and ALS levels from baseline to
day 21 in the combined GH-treated groups (GH 0.1 and GH 0.2) were
tested for gender differences by comparing 
values (mean ±
SE): change in (
) IGF-I, 321 ± 37 µg/L (women)
vs. 527 ± 29 µg/L (men), P <
0.0005; IGFBP-3, 0.9 ± 0.2 mg/L (women) vs.
1.7 ± 0.2 mg/L (men), P < 0.02; ALS, 104
± 15 nmol/L (women) vs. 155 ± 11 nmol/L (men),
P < 0.007.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The main findings include 1) IGF-I is the most sensitive marker of GH exposure; 2) the GH-induced increase in IGFBP-3 and ALS is markedly lower compared with that in IGF-I; 3) IGFBP-2 responds very little to GH; and 4) a marked gender difference exists, with men being more responsive to exogenous GH administration.
The large sample size and the randomized design, including two different doses, strengthens the validity of the observations, but the study population, on the other hand, covered a narrow age range of young, healthy, and physically fit individuals. Extrapolations to older people or patients should therefore be made with caution.
At baseline no gender differences were recorded, apart from higher ALS levels among women. Comparable levels of IGF-I, IGFBP-3, and IGFBP-2 between healthy adult males and females has previously been reported (6, 13), but gender differences in IGF-I levels have been observed in particular age groups (14). Females may exhibit slightly higher IGF-I levels than males at puberty and in early adulthood, whereas the opposite has been reported in middle-aged adults (9, 15). In adult hypopituitary patients with documented GH deficiency IGF-I levels are consistently higher in men than in women (9, 16). Our observation of higher ALS levels in women has been reported recently (17), but is in contrast with a previous report in which no gender differences were observed in any age group (7).
The pattern among males was characterized by high and almost identical increments in IGF-I after the two GH doses. In women, the IGF-I response was lower, but a distinct dose responsiveness was observed. Thus, the lower GH dose group apparently reached the top of the dose-response curve in males, but not in females. It is evident that the present study involved the high end of the dose-response curve, but there is evidence from the literature that a gender difference in GH sensitivity also exists with lower GH doses. The relative GH resistance in women has been described by Ghigo et al. (18), who reported that the minimum exogenous GH dose needed to elicit an IGF-I response in normal subjects is higher in women than in men. Both spontaneous and stimulated GH levels are elevated in women compared with men (16, 19, 20), which has been causally linked to differences in estradiol levels. It is, however, unresolved whether the stimulatory effect of estradiol on GH release involves a central stimulation or a negative feedback linkage to peripheral reduction of IGF-I production. In favor of the latter hypothesis, several studies have shown that administration of exogenous estradiol lowers serum IGF-I levels concomitantly with amplification of endogenous GH release (21). It has, on the other hand, recently been reported that both GH release and serum IGF-I levels increase during the periovulatory phase in normal young women, which coincides with elevated endogenous estradiol levels (22). Alternatively, it could be hypothesized that androgens play a permissive role for GH-stimulated IGF-I production. This could explain the suppression of IGF-I production in postmenopausal women during exogenous estradiol administration, which is likely to inhibit endogenous androgen secretion, and it may also account for the low IGF-I levels in hypopituitary females. This theory is supported by Erfurth et al. (23), who found a significant correlation between free testosterone and IGF-I levels. Recently, Span et al. (24) reported that estrogen replacement in GH-deficient women significantly increased GH requirements, and androgen substitution in GH-deficient men increased GH sensitivity. Regardless of the physiological mechanisms the present study demonstrates that women, relative to men, are resistant to GH in terms of IGF-I generation. A similar gender difference has recently been shown regarding the acute lipolytic response to a physiological GH bolus (25). These observations in healthy adults are in accordance with the idea that the GH dose requirements in hypopituitary adults are higher in female patients, as judged by serum IGF-I levels as well as changes in body composition (19). In both sexes GH discontinuation was followed by an abrupt decline in total IGF-I levels.
The elevations in IGFBP-3 and ALS were far less pronounced than those in IGF-I, and again, the response was lower in women than in men. Ghigo et al. (18) reported that IGFBP-3 levels were less increased than IGF-I levels after GH exposure.
It has previously been shown that the circulating total IGF-I/IGFBP-3 ratio is elevated in active acromegaly (13) and after GH administration in both GH-deficient adults (26) and healthy controls (18). Accordingly, we also recorded a significantly increased IGF-I/IGFBP-3 ratio in the present study, which prevailed even 2 weeks after cessation of GH administration.
Serum IGFBP-2 concentrations did not consistently change during GH administration, which contrasts with at least one previous study in which GH administration suppressed circulating IGFBP-2 levels (27). Juul et al. reported decreased IGFBP-2 levels in acromegalic patients (13), and Jørgensen et al. (5) observed suppressed IGFBP-2 levels in active acromegaly, which became normalized after successful surgery, whereas Clemmons et al. (28) reported normal IGFBP-2 levels in active acromegaly and moderately elevated levels in hypopituitary adults.
Our study clearly demonstrated that IGF-I is superior to IGFBP-2, IGFBP-3, and ALS regarding the ability to identify exposure to supraphysiological doses of exogenous GH in healthy subjects. Using the upper 4 SD level of IGF-I in the GH-untreated state as an arbitrary cut-off limit, 86% of men were identified while receiving the high GH dose, and the IGF-I level was not completely returned to baseline 14 days after termination of GH administration. As previously mentioned, this percentage was significantly lower in women. As a mean to detect GH abuse in athletes, a single measurement of IGF-I in serum is probably not sufficiently robust, at least not in females. Whether measurements of other GH-dependent growth markers, alone or in combination with IGF-I, will prove more efficacious must await further analysis.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 These authors contributed equally to the study.
Received June 2, 2000.
Revised July 31, 2000.
Accepted August 3, 2000.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  A. E. Nelson, U. Meinhardt, J. L. Hansen, I. H. Walker, G. Stone, C. J. Howe, K.-c. Leung, M. J. Seibel, R. C. Baxter, D. J. Handelsman, et al. Pharmacodynamics of Growth Hormone Abuse Biomarkers and the Influence of Gender and Testosterone: A Randomized Double-Blind Placebo-Controlled Study in Young Recreational Athletes J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2213 - 2222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, D. M. Bravata, I. Olkin, A. Friedlander, V. Liu, B. Roberts, E. Bendavid, O. Saynina, S. R. Salpeter, A. M. Garber, et al. Systematic Review: The Effects of Growth Hormone on Athletic Performance Ann Intern Med, May 20, 2008; 148(10): 747 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gibney, M.-L. Healy, and P. H. Sonksen The Growth Hormone/Insulin-Like Growth Factor-I Axis in Exercise and Sport Endocr. Rev., October 1, 2007; 28(6): 603 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Raschke, M. H. Rasmussen, S. Govender, D. Segal, M. Suntum, and J. S. Christiansen Effects of growth hormone in patients with tibial fracture: a randomised, double-blind, placebo-controlled clinical trial Eur. J. Endocrinol., March 1, 2007; 156(3): 341 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T. Vestergaard, R. Dall, K. H. W. Lange, M. Kjaer, J. S. Christiansen, and J. O. L. Jorgensen The Ghrelin Response to Exercise before and after Growth Hormone Administration J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 297 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Nelson, C. J. Howe, T. V. Nguyen, K.-C. Leung, G. J. Trout, M. J. Seibel, R. C. Baxter, D. J. Handelsman, R. Kazlauskas, and K. K. Ho Influence of Demographic Factors and Sport Type on Growth Hormone-Responsive Markers in Elite Athletes J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4424 - 4432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chung, D. Clifford, M. Buckley, and R. C. Baxter Novel Biomarkers of Human Growth Hormone Action from Serum Proteomic Profiling Using Protein Chip Mass Spectrometry J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 671 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Al-Zahrani, M. S. Sandhu, R. N. Luben, D. Thompson, C. Baynes, K. A. Pooley, C. Luccarini, H. Munday, B. Perkins, P. Smith, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer Hum. Mol. Genet., January 1, 2006; 15(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K Gleeson and S. M Shalet GH responsiveness varies during the menstrual cycle Eur. J. Endocrinol., December 1, 2005; 153(6): 775 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. McHugh, R. T. Park, P. H. Sonksen, and R. I.G. Holt Challenges in Detecting the Abuse of Growth Hormone in Sport Clin. Chem., September 1, 2005; 51(9): 1587 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Berggren, C. Ehrnborg, T. Rosen, L. Ellegard, B.-A. Bengtsson, and K. Caidahl Short-Term Administration of Supraphysiological Recombinant Human Growth Hormone (GH) Does Not Increase Maximum Endurance Exercise Capacity in Healthy, Active Young Men and Women with Normal GH-Insulin-Like Growth Factor I Axes J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3268 - 3273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Healy, R. Dall, J. Gibney, E. Bassett, C. Ehrnborg, C. Pentecost, T. Rosen, A. Cittadini, R. C. Baxter, and P. H. Sonksen Toward the Development of a Test for Growth Hormone (GH) Abuse: A Study of Extreme Physiological Ranges of GH-Dependent Markers in 813 Elite Athletes in the Postcompetition Setting J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 641 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Coutant, F. B. de Casson, S. Rouleau, O. Douay, E. Mathieu, F. Gatelais, N. Bouhours-Nouet, C. Voinot, M. Audran, and J. M. Limal Divergent Effect of Endogenous and Exogenous Sex Steroids on the Insulin-Like Growth Factor I Response to Growth Hormone in Short Normal Adolescents J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6185 - 6192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yuen, J. Frystyk, M. Umpleby, L. Fryklund, and D. Dunger Changes in Free Rather Than Total Insulin-Like Growth Factor-I Enhance Insulin Sensitivity and Suppress Endogenous Peak Growth Hormone (GH) Release following Short-Term Low-Dose GH Administration in Young Healthy Adults J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3956 - 3964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Lissett and S. M. Shalet The Impact of Dose and Route of Estrogen Administration on the Somatotropic Axis in Normal Women J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4668 - 4672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ehrnborg, K. H. W. Lange, R. Dall, J. S. Christiansen, P.-A. Lundberg, R. C. Baxter, M. A. Boroujerdi, B.-A. Bengtsson, M.-L. Healey, C. Pentecost, et al. The Growth Hormone/Insulin-Like Growth Factor-I Axis Hormones and Bone Markers in Elite Athletes in Response to a Maximum Exercise Test J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 394 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yuen, K. Ong, S. Husbands, P. Chatelain, L. Fryklund, P. Gluckman, M. Ranke, D. Cook, R. Rosenfeld, J. Wass, et al. The Effects of Short-Term Administration of Two Low Doses Versus the Standard GH Replacement Dose on Insulin Sensitivity and Fasting Glucose Levels in Young Healthy Adults J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 1989 - 1995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Buckway, J. Guevara-Aguirre, K. L. Pratt, C. P. Burren, and R. G. Rosenfeld The IGF-I Generation Test Revisited: A Marker of GH Sensitivity J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5176 - 5183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Parkinson, W. D. J. Ryder, and P. J. Trainer The Relationship between Serum GH and Serum IGF-I in Acromegaly Is Gender-Specific J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5240 - 5244. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||
, GH
0.2 group.
