This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maison, P. Articles by Chanson, P. Search for Related Content PubMed PubMed Citation Articles by Maison, P. Articles by Chanson, P.

Impact of Growth Hormone (GH) Treatment on Cardiovascular Risk Factors in GH-Deficient Adults: A Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials

Clinical Pharmacology (P.M.), Clinical Research Unit, Assistance Pubique-Hôpitaux de Paris, Henri Mondor University Hospital, F-94010 Créteil, France; Institut National de la Santé et de la Recherche Médicale U258 (P.M., M.N.-B., N.H., B.B.), F-94807 Villejuif, France; Institute of Public Health (S.G.), CB2 2SR Cambridge, United Kingdom; and Endocrinology and Reproductive Diseases (P.C.), Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, and University Paris XI, F-94275 Le Kremlin-Bicêtre, France

Address all correspondence and requests for reprints to: P. Chanson, M.D., Endocrinology, Bicêtre University Hospital, 78 rue du Général Leclerc, F-94275 Le Kremlin-Bicêtre, France. E-mail: philippe.chanson{at}bct.ap-hop-paris.fr.

	Abstract

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
Patients with hypopituitarism have an increased risk of cardiovascular mortality. GH treatment could modify the cardiovascular risk in adults with GH deficiency, but most published clinical trials involved few patients and the results are variable.

We conducted a systematic review of blinded, randomized, placebo-controlled trials of GH treatment in adult patients with GH deficiency published up to August 2003. Thirty-seven trials were identified. We combined the results for effects on lean and fat body mass; body mass index; triglyceride and cholesterol [high-density lipoprotein, low-density lipoprotein (LDL), and total] levels; blood pressure; glycemia; and insulinemia. Overall effect size was used to evaluate significance, and weighted differences between GH and placebo were used to appreciate the size of the effect.

GH treatment significantly reduced LDL cholesterol [–0.5 (SD 0.3) mmol/liter], total cholesterol [–0.3 (0.3) mmol/liter], fat mass [–3.1 (3.3) kg], and diastolic blood pressure [–1.8 (3.8) mm Hg] and significantly increased lean body mass [+2.7 (2.6) kg], fasting plasma glucose [+0.2 (0.1) mmol/liter], and insulin [+8.7 (7.0) pmol/liter]. All effect sizes remained significant in trials with low doses and long-duration GH treatment.

Thus, GH treatment has beneficial effects on lean and fat body mass, total and LDL cholesterol levels, and diastolic blood pressure but reduces insulin sensitivity. The global cardiovascular benefit remains to be determined in large trials with appropriate clinical endpoints.

	Introduction

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
SINCE THE ADVENT of recombinant GH in 1985, GH therapy has been extended to adults with pituitary deficiency, in whom GH deficiency (GHD) has been hypothesized to be a cardiovascular risk factor (1, 2, 3, 4). An adult GHD syndrome was recently described (5), in which patients exhibit cardiovascular risk factors such as abdominal obesity, hypercholesterolemia, and hypertriglyceridemia. GH replacement therapy may reduce some of these cardiovascular risk factors (reviewed in Ref.6). Adverse effects include insulin resistance and increased volemia (7). Because hypertension and diabetes are common in patients with acromegaly and are also well-known cardiovascular risk factors, these effects are of particular interest. Most clinical trials of GH therapy in GH-deficient adults have involved small numbers of patients. Reported effects on cardiovascular risk factors varied according to the dose and duration of GH therapy, age at onset of GHD, and gender.

To obtain a more reliable picture of the effects of GH treatment on the main cardiovascular risk factors in GH-deficient adults (body mass, lipids, blood pressure, plasma glucose, and insulin), we conducted a systematic review of all blinded, randomized, placebo-controlled trials of GH in adults with GHD published up to August 2003.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
Identification of relevant trials

We searched the Medline (Ovid), Experta Medica (EMBASE), and Biosis electronic databases, from their year of inception to August 2003. The medical literature was searched for all reports containing the key words, growth hormone (or somatotropin), trial, and human. The search strategy was not limited by study design or language.

A manual search of the Journal of Clinical Endocrinology and Metabolism since 1985 was used to assess the sensitivity of our electronic search. Additional information was requested from GH manufacturers, references cited in published articles, and clinical trials investigators.

Inclusion criteria

We included all randomized, blinded, placebo-controlled trials involving patients aged over 17 yr with GHD corresponding to less than 5 µg/liter after stimulation, as recommended by the consensus guidelines for the diagnosis and treatment of adults with GHD (8).

Included trials had at least one of the following outcome measures: diastolic blood pressure, systolic blood pressure, fasting blood glucose, fasting insulinemia, triglyceridemia, cholesterolemia [high-density lipoprotein, low-density lipoprotein (LDL), or total], lean body mass, fat mass (when expressed in absolute terms), and body mass index (BMI). These outcomes are the main cardiovascular risk factors in this setting and are the most frequently reported in clinical trials. Lean body mass is not, strictly speaking, a direct cardiovascular risk factor, but, because of the relationship between BMI, fat mass, and lean body mass, the effects of GH on these three parameters are of interest. From more than 3000 published reports, one of the authors (P.M.) selected the abstracts of trials that potentially met the inclusion criteria. The corresponding articles were then checked for the inclusion criteria, independently by three authors (N.H., M.N.-B., and P.M.). Discrepancies were resolved through discussion with all the authors. To detect a possible publication bias, we asked GH manufacturers what proportion of randomized, placebo-controlled trials were finally published.

Data extraction and outcomes

Three metaanalysts (N.H., M.N.-B., and P.M.) extracted data from published reports to a standard form. Authors were contacted to verify the extracted data where necessary. Discrepancies were resolved by discussion among all the authors of the present paper. The following data were extracted: population characteristics (setting, age, sex, number, weight, BMI, and disease onset), treatment (dose, duration, and frequency), study quality (design, randomization method, blinding, placebo vials, and statistical methods), losses to follow-up (for each outcome measure), baseline and follow-up values and changes (means and SD or SEM), and methods used to measure outcomes. All data extracted were summary data.

Statistical methods

For primary analyses of continuous outcome measures, we first calculated standardized effect sizes for each trial and then the global effect size for each outcome (9). The effect size is a measure of the overlap in the distribution of outcome scores between two treatment groups. The effect size was calculated differently for parallel-group and cross-over studies, to reflect intergroup and intragroup comparisons (9). For parallel groups, the effect size was computed as the mean difference (GH minus placebo) in the changes (follow-up minus baseline) for each outcome divided by the estimated variance of changes in the two groups. For cross-over trials, the effect size was calculated as the mean difference in values at the end of each period divided by the variance in the placebo group at follow-up. In some instances, these values had to be estimated from graphs in the articles [four for lean body mass (10, 11, 12, 13, 14), two for insulin (10, 11), one for glucose (10), and three for blood pressure (15, 16, 17). To calculate the overall effect size, the effect size in each study was weighted by the reciprocal of the variance. We present these scores with their 95% confidence intervals. A positive effect size implies an increase in the frequency of the outcome with GH treatment, and a negative effect size implies a decrease.

Because the variances for changes were not directly reported in all articles, they were calculated from t statistics, probability values, or confidence intervals (variances) for the GH and placebo groups (parallel design) or the study period (cross-over design) (9). We used a Q test to explore heterogeneity between studies. The analyses were repeated using a random-effects model when the effect size was significant in a fixed model (18). Because the random-effects model incorporates statistical heterogeneity (results, methodology, and publication bias) and provides a more conservative estimate of the pooled effect size than a fixed model, we present all the results of effect-size according to a random model. Funnel plots were drawn and their asymmetry was assessed to determine the possible influence of publication and location biases (19). The intercept of the weighted and unweighted linear regression lines, when the effect size divided by the SE is regressed against the reciprocal of the SE, provides a measure of asymmetry. Because the effect size may be significant because of a single trial (e.g. large trials or trials with large effects), we also conducted a sensitivity analysis. When the effect was carried by one or two trials, these studies were dropped from the analysis to verify whether the same trend was observed with the remaining trials. To quantify the size of the effect, we present the weighted (by the variance) mean difference (and SD) between the GH and placebo groups for each outcome measure.

The effects of the GH dose, GH treatment duration, percentage of patients with adult onset, and study design on overall estimates were assessed by stratification or metaregression. Weighted least-squares regression analysis was used for metaregression, individual study effects being weighted by the reciprocal of the estimated variance. The ß-coefficient and its significance are presented, along with the adjusted R² value, to show the overall variability explained by the model. Analyses were conducted using the SPSS (SPSS Inc., Chicago, IL) for Windows package.

	Results

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
The combined search strategy identified 37 blinded, randomized, placebo-controlled trials of GH in GH-deficient adults that included at least one of the necessary outcome measures (Tables 1 and 2) (7, 10, 11, 12, 13, 14, 15, 16, 17, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54). Different publications describing the same trial may refer to different outcomes. Eight trials could not be included because the required summary data could not be obtained. One trial was single blinded (13, 14). The trials were generally of good quality. Median losses to follow-up were 10% of patients [95% confidence interval = (0, 57)], and data were rarely analyzed on an intention-to-treat basis: their low number did not allow pertinent specific analysis of this subgroup of trials. Most reported comparisons were pretreatment vs. posttreatment rather than GH vs. placebo. Whatever the outcome measure, no significant heterogeneity was observed (Table 3). However, to obtain more conservative estimates, we present effect sizes with random-effects models. Funnel plotting and linear regression suggested a selection bias for insulin only (intercept, 9.4; P = 0.03 with weighted regression, and intercept, 7.3; P = 0.02 with unweighted regression), but publication bias was unlikely when this outcome was reported because it rarely reached statistical significance in individual trials. Three of the five GH manufacturers informed us that all the randomized, placebo-controlled trials they sponsored were finally published; the other two manufacturers did not answer or were unable to provide us with this information.

	Body mass

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

The overall effect size was significantly negative for fat mass [–0.62 (–0.78; –0.48)], with a weighted mean dif-ference of –3.05 kg (3.29). No effect was found on BMI (Table 3).

	Lipids

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
Significant beneficial effects were observed only for LDL and total cholesterol (Table 3). Weighted mean differences were –0.53 (0.29) mmol/liter and –0.34 (0.31) mmol/liter, respectively. Effect sizes were –0.35 (–0.52; –0.17) and –0.24 (–0.39; –0.08), respectively. In the analysis of sensitivity for LDL cholesterol, excluding the two trials (27, 48) with the most marked effects on this outcome measure, the overall effect size was still significant [–0.26 (–0.47; –0.05)].

	Blood pressure

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
Ten trials involving a total of 401 patients were included in the metaanalysis (Table 3). Ambulatory blood pressure was measured in two trials (15, 41). In the other eight trials, blood pressure was measured manually, usually after the participants had been lying or sitting for at least five min. The effect size was not significant for systolic blood pressure. In contrast, the overall effect size was significantly negative for diastolic blood pressure [–0.25 (–0.43; –0.07)]. The weighted mean difference in diastolic blood pressure was –1.80 (3.77) mm Hg. The effect size was still significant after exclusion of one large trial (27).

	Glucose/insulin

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
With 13 trials involving 511 patients, a significant overall effect of GH treatment on fasting glucose was observed [+0.43 (0.26; 0.60)] (Table 3). The mean weighted difference in blood glucose between the groups was +0.22 (0.14) mmol/liter, but weighted mean fasting glucose values were within the normal range on both GH treatment [5.1 mmol/liter (0.5)] and placebo [4.8 mmol/liter (0.4)]. In the analysis of sensitivity, the effect size was still significant after excluding three large trials (7, 14).

With 11 trials involving 378 patients, a significant overall effect of GH treatment on fasting insulin was observed [+0.42 (0.23; 0.61)] (Table 3). The mean weighted difference in plasma insulin was 8.7 (7.0) pmol/liter between GH and placebo. This difference remained significant after exclusion of one large trial (7).

	Effects of the GH dose and treatment duration, gender, age, age at GHD onset, and trial designs

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
Effect of the GH dose (Table 4).

No significant relationship was observed between the GH dose and the effect size in meta-regression analysis. This result could be explained by a narrow dose distribution. A subgroup analysis was then done with trials using target doses of no more than 0.35 U/kg·wk and a target dose of 0.5 U/kg·wk. All effect sizes remained significant in the analysis of low-dose trials (Table 4). A smaller number of trials used high doses, and the effect size in this subgroup was significant only for fat mass, glucose, and insulin. A dose-dependent effect of GH was found on fat mass, with a lower effect size with low-dose GH [–0.2 (–0.4; –0.0)] than with high-dose GH [–0.6 (–1.0; –0.1)].

View this table: [in this window] [in a new window]   TABLE 4. Effect size (95% confidence interval) in subgroup analysis with trials using target doses of no more than 0.35 U/kg·wk, and with trials with a target dose of 0.5 U/kg·wk and with trials of short duration (<6 months) and with trials of longer duration (6 months)

Effect of the treatment duration (Table 4).

No significant relationship was observed between the treatment duration and the effect sizes in metaregression analysis. Thus, Table 4 shows only the results of subgroup analyses. All effect sizes remained significant in the analysis of trials with long-duration treatment. There were few short-term trials, explaining the smaller number of significant parameters. Overall, the results pointed to a greater effect of prolonged treatment on lean mass and diastolic blood pressure.

Effect of gender.

When comparing effects according to gender, a significant negative relationship was found only between proportion of women and the effect size for blood glucose (ß = –0.59, P = 0.03, adjusted R² = 0.30), suggesting a lesser effect in women than in men.

Effect of age.

A significant relationship was observed between mean age and the effect size for LDL cholesterol (ß = –0.60, P = 0.03, R² = 0.36) and total cholesterol (ß = –0.64, P < 0.04, R² = 0.41): the younger the patient, the stronger the effect.

Effect of age at GHD onset.

The relationship between the proportion of patients with adult-onset (vs. childhood-onset) GHD and the effect of GH treatment was significant for diastolic blood pressure (ß = –0.88, P = 0.02, R² = 0.71) and plasma insulin (ß = –0.76, P = 0.03, R² = 0.50), suggesting a greater beneficial effect on blood pressure and a lesser negative impact on insulin in patients with adult-onset GHD.

Effect of the trial design.

The overall effect size in subgroup analyses of parallel-group studies remained similar for all outcomes. There were few cross-over studies (one for cholesterol and lean body mass, two for insulin and glucose, and four for blood pressure), and the global effect sizes were not significant.

	Discussion

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 
This systematic review of 37 blinded, randomized, placebo-controlled trials shows a small but statistically significant beneficial effect of GH treatment on lean and fat body mass, LDL and total cholesterol, and diastolic blood pressure in GH-deficient adults. In contrast, GH therapy significantly increased plasma glucose and insulin levels.

A major potential source of bias in systematic reviews is that trials with positive results are more likely to be published than trials with neutral or negative results. In our metaanalysis, this bias seems unlikely with regard to blood pressure and total and LDL cholesterol (rare significant results) and blood glucose and insulin (negative results). Furthermore, information provided to us by GH manufacturers suggests that most GH trials in this setting are published. Another limitation of metaanalyses is the variable quality of the selected trials. To minimize this problem, we selected only studies with protocols meeting strict methodological quality criteria. This, of course, does not rule out quality problems arising during the trials’ progress.

Lean body mass increased and fat mass decreased after GH treatment, whereas total body weight remained constant. These results support a beneficial effect of GH on the cardiovascular risk and were observed, whatever the method used to measure lean mass.

Effects on LDL cholesterol and total cholesterol were variable. Half the trials showed no significant difference between placebo and GH. However, the overall effect size suggests a beneficial effect of GH on these cardiovascular risk factors. In contrast, no effect on high-density lipoprotein cholesterol or triglyceride levels was observed.

In most studies, mild fluid retention was observed and led to a reduction in the GH dose or withdrawal of patients from the trial. In one trial, GH treatment was associated with hypertension (10). On the contrary, another trial (23) showed a significant beneficial effect of GH on diastolic blood pressure. The overall effect size supports this result, with a decrease in diastolic blood pressure and no change in systolic blood pressure on GH. The relationship between blood pressure and GH therapy may be due to stimulation of the renin-aldosterone system (55), an increase in nitric oxide formation (15), or a decrease in intima-media thickness (56). However, this effect was observed during long-term treatment (at a time when fluid homeostasis had normalized) rather than during shorter treatment, suggesting that an effect of GH on blood vessels is more likely (57). It is noteworthy that GH effects on blood pressure were mentioned in only eight trial reports, even though blood pressure is probably monitored in all trials, suggesting that no significant effect was noted in most studies.

It has been suggested that GH treatment may impair glucose tolerance and even lead to diabetes (58). In one trial (14), two cases of incident diabetes were reported. However, the effect of GH on fasting insulin and glucose concentrations varied among the studies. The overall effect sizes in this review suggest significant increases in both insulin and glucose concentrations during GH treatment. The insulin-antagonistic effect of GH likely explains this finding (58). However, it must be emphasized that the mean glucose concentration remained in the normal range. Our results do not support previous suggestions that insulin resistance falls during low-dose and long-term GH therapy (31, 59). Men were more sensitive to the effect of GH on insulin sensitivity in our analysis. A similar gender difference in the response to GH treatment has been described with regard to lean body mass and fat mass (60) and is in keeping with the higher GH dose requirements in women than in men. However, very few studies with a prolonged follow-up (12 months) were included in this metaanalysis, and it must be pointed out that in the only trial reporting the effect of GH on this outcome, deleterious effects on insulin were not maintained at 12 and 18 months (14). Thus, studies with direct measurement of insulin sensitivity in patients treated on long-term with GH are needed before drawing firm conclusions about the effect (or absence of effect) of GH on this parameter in patients with GHD, despite a clear reduction in visceral fat.

Lower target doses are required to prevent adverse effects such as fluid retention and glucose elevation. However, our results suggest that, even at low doses, GH treatment is associated with elevated glucose and insulin concentrations, which are considered as cardiovascular risk factors. On the contrary, significant beneficial GH effects on cardiovascular risk factors such as lipid parameters and fat mass persisted at lower doses, even though the effect on fat mass tended to be weaker. Thus, the overall cardiovascular benefit of low-dose GH remains uncertain. However, taking into account the risk of cancer with GH treatment (61), the currently recommended use of low doses seems fully justified. Another important issue in all the trials reporting the effects of GH is the fact that many patients reduced the GH doses (due to side effects or according to IGF-I measurement), the final doses they achieved being lower than the target doses in a substantial number of patients. The issue of physiologic or pharmacological response to treatment is important. In this setting, it would have been interesting to study the dose-effect relationship in terms of IGF-I Z score, which takes into account the variance of age. Unfortunately, in the majority of studies, IGF-I was given in absolute terms, without any reference to normal age-adjusted ranges, which could have permitted a calculation of a SD score.

Our results suggest that young patients may be more sensitive than older patients to GH treatment. This negative relationship with age emerged for total and LDL cholesterol and has previously been described for lean body mass (33, 34).

Beneficial effects on body mass, cholesterol, and blood pressure increased with the duration of treatment, whereas adverse effects (on insulin and glucose) remained at a similar level. However, the results of subgroup analyses must be interpreted with caution because they involved a lower number of trials. Furthermore, long-term treatment usually corresponded to trials that did not exceed 6 months in duration.

We observed a difference between patients with adult-onset and childhood-onset GHD with regard to insulin and blood pressure. In contrast to previous studies (7, 20), GH treatment seemed to be more beneficial in adults with adult-onset GHD than in adults with childhood-onset GHD. We found no difference in GH effects between patients with multiple hormone deficiency and those with isolated GHD. However, the very small number of patients with isolated GH deficiency in most trials rules out firm conclusions.

In conclusion, this metaanalysis of blinded, placebo-controlled clinical trials shows that GH treatment has beneficial effects on lean body mass, fat mass, total and LDL cholesterol, and diastolic blood pressure in GH-deficient adults. GH may also have beneficial effects on other cardiovascular risk factors, such as fibrinogen (33), inflammatory parameters (14), cardiac function (62, 63), and intima-media thickness (56). As expected, GH reduced insulin sensitivity, whatever the dose and duration of treatment. Overall, however, the global cardiovascular benefit of GH treatment in adults remains to be determined in large, long-term trials with appropriate clinical end points.

	Acknowledgments

 
The authors thank Professor P. Sonksen, and Drs. G. Johannsson, L. Thuesen, N. Vahl, H. Simpson, C. Florkowski, and J. Mesa for their kind response to requests for new information about their data.

	Footnotes

 
Abbreviations: BMI, Body mass index; GHD, GH deficiency; LDL, low-density lipoprotein.

Received May 14, 2003.

Accepted February 18, 2004.

	References

Top Abstract Introduction Subjects and Methods Results Body mass Lipids Blood pressure Glucose/insulin Effects of the GH... Discussion References

 

1. Rosen T, Bengtsson BA 1990 Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285–288[CrossRef][Medline]
2. Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, Sheppard MC, Stewart PM 2001 Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 357:425–431[CrossRef][Medline]
3. Bates AS, Van’t Hoff W, Jones PJ, Clayton RN 1996 The effects of hypopituitarism on life expectancy. J Clin Endocrinol Metab 81:1169–1172[Abstract]
4. Bates AS, Bullivant B, Sheppard MC, Stewart PM 1999 Life expectancy following surgery for pituitary tumours. Clin Endocrinol (Oxf) 50:315–319[CrossRef][Medline]
5. Cuneo RC, Salomon F, McGauley GA, Sonksen PH 1992 The growth hormone deficiency syndrome in adults. Clin Endocrinol (Oxf) 37:387–397[Medline]
6. Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sonksen PH, Tanaka T, Thorne M 1998 Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 83:382–395[Abstract/Free Full Text]
7. Chipman JJ, Attanasio AF, Birkett MA, Bates PC, Webb S, Lamberts SWJ 1997 The safety profile of GH replacement therapy in adults. Clin Endocrinol (Oxf) 46:473–481[CrossRef][Medline]
8. 1998 Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab 83:379–381
9. Follmann D, Elliott P, Suh I, Cutler J 1992 Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 45:769–773[CrossRef][Medline]
10. Salomon F, Cuneo RC, Hesp R, Sonksen PH 1989 The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 321:1797–1803[Abstract]
11. Beshyah SA, Freemantle C, Shahi M, Anyaoku V, Merson S, Lynch S, Skinner E, Sharp P, Foale R, Johnston DG 1995 Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults. Clin Endocrinol (Oxf) 42:73–84[Medline]
12. Beshyah SA, Henderson A, Niththyananthan R, Skinner E, Anyaoku V, Richmond W, Sharp P, Johnston DG 1995 The effects of short and long-term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance. J Clin Endocrinol Metab 80:356–363[Abstract]
13. Baum HB, Biller BM, Finkelstein JS, Cannistraro KB, Oppenhein DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A 1996 Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult-onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med 125:883–890[Abstract/Free Full Text]
14. Sesmilo G, Biller BM, Llevadot J, Hayden D, Hanson G, Rifai N, Klibanski A 2000 Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial. Ann Intern Med 133:111–122[Abstract/Free Full Text]
15. Boger RH, Skamira C, Bode-Boger SM, Brabant G, von zur Muhlen A, Frolich JC 1996 Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest 98:2706–2713[Medline]
16. Hoffman DM, Crampton L, Sernia C, Nguyen TV, Ho KK 1996 Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure. J Clin Endocrinol Metab 81:1123–1128[Abstract]
17. Johannsson G, Sverrisdottir YB, Ellegard L, Lundberg PA, Herlitz H 2002 GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis. J Clin Endocrinol Metab 87:1743–1749[Abstract/Free Full Text]
18. Hedges LV 1983 A random effects model for effect sizes. Psychol Bull 93:388–395[CrossRef]
19. Egger M, Davey Smith G, Schneider M, Minder C 1997 Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634[Abstract/Free Full Text]
20. Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, Hilsted J, Bengtsson BA, Strasburger CJ 1997 Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group. J Clin Endocrinol Metab 82:82–88[Abstract/Free Full Text]
21. Bell W, Davies JS, Evans WD, Scanlon MF 1998 Effect of growth hormone on total body potassium, fat-free mass and strength in growth hormone-deficient males. J Sports Sci 16:36–37
22. Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L 2003 Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle. J Clin Endocrinol Metab 88:1455–1463[Abstract/Free Full Text]
23. Caidahl K, Eden S, Bengtsson BA 1994 Cardiovascular and renal effects of growth hormone. Clin Endocrinol (Oxf) 40:393–400[Medline]
24. Christ ER, Cummings MH, Westwood NB, Sawyer BM, Pearson TC, Soenksen PH, Russell Jones DL 1997 The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency. J Clin Endocrinal Metab 82:2985–2990[Abstract/Free Full Text]
25. Christ ER, Cummings MH, Albany E, Umpleby AM, Lumb PJ, Wierzbicki AS, Naoumova RP, Boroujerdi MA, Sonksen PH, Russell-Jones DL 1999 Effects of growth hormone (GH) replacement therapy on very low density lipoprotein apolipoprotein B100 kinetics in patients with adult GH deficiency: a stable isotope study. J Clin Endocrinol Metab 84:307–316[Abstract/Free Full Text]
26. Christ ER, Cummings MH, Lumb PJ, Crook MA, Sonksen PH, Russell-Jones DL 1999 Growth hormone (GH) replacement therapy reduces serum sialic acid concentrations in adults with GH-deficiency: a double-blind placebo-controlled study. Clin Endocrinol (Oxf) 51:173–179[CrossRef][Medline]
27. Cuneo RC, Judd S, Wallace JD, Perry-Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung NW, Hurley D 1998 The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults. J Clin Endocrinol Metab 83:107–116[Abstract/Free Full Text]
28. Ezzat S, Fear S, Gaillard RC, Gayle C, Landy H, Marcovitz S, Mattioni T, Nussey S, Rees A, Svanberg E 2002 Gender-specific responses of lean body composition and nongender-specific cardiac function improvement after GH replacement in GH-deficient adults. J Clin Endocrinol Metab 87:2725–2733[Abstract/Free Full Text]
29. Fernholm R, Bramnert M, Hagg E, Hilding A, Baylink DJ, Mohan S, Thoren M 2000 Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab 85:4104–4112[Abstract/Free Full Text]
30. Florkowski CM, Collier GR, Zimmet PZ, Livesey JH, Espiner EA, Donald RA 1996 Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol (Oxf) 45:769–773[CrossRef][Medline]
31. Fowelin J, Attvall S, Lager I, Bengtsson BA 1993 Effects of treatment with recombinant human growth hormone on insulin sensitivity and glucose metabolism in adults with growth hormone deficiency. Metabolism 42:1443–1447[CrossRef][Medline]
32. Hwu CM, Kwok CF, Lai TY, Shih KC, Lee TS, Hsiao LC, Lee SH, Fang VS, Ho LT 1997 Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience. J Clin Endocrinol Metab 82:3285–3292[Abstract/Free Full Text]
33. Johannsson G, Bengtsson BA, Andersson B, Isgaard J, Caidahl K 1996 Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients. Clin Endocrinol (Oxf) 45:305–314[CrossRef][Medline]
34. Johannsson G, Bjarnason R, Bramnert M, Carlsson LM, Degerblad M, Manhem P, Rosen T, Thoren M, Bengtsson BA 1996 The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender. J Clin Endocrinol Metab 81:1575–1581[Abstract]
35. Johansson JO, Landin K, Johannsson G, Tengborn L, Bengtsson BA 1996 Long-term treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults. Thromb Haemost 76:422–428[Medline]
36. Jorgensen JO, Pedersen SA, Thuesen L, Jorgensen J, Ingemann-Hansen T, Skakkebaek NE, Christiansen JS 1989 Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet 1:1221–1225[Medline]
37. Jorgensen JOL, Pedersen SA, Ingerslev J, Moller J, Skakkebaek NE, Christiansen JS 1990 Growth hormone (GH) therapy in GH-deficient patients. The plasma factor vii von Willebrand factor complex and capillary fragility: a double-blind, placebo-controlled, crossover study. Scand J Clin Lab Invest 50:417–420[Medline]
38. Kousta E, Chrisoulidou A, Lawrence NJ, al-Shoumer KA, Parker KH, McCarthy MI, Johnston DG 1998 The circadian rhythm of leptin is preserved in growth hormone deficient hypopituitary adults. Clin Endocrinol (Oxf) 48:685–690[CrossRef][Medline]
39. Leese GP, Wallymahmed M, Van Heyningen C, Tames F, Wieringa G, MacFarlane IA 1998 HDL-cholesterol reductions associated with adult growth hormone replacement. Clin Endocrinol (Oxf) 49:673–677[CrossRef][Medline]
40. Mesa J, Gomez JM, Hernandez C, Pico A, Ulied A 2003 Growth hormone deficiency in adults: effects of replacement therapy on body composition and health-related quality of life. Med Clin (Barc) 120:41–46[CrossRef][Medline]
41. Moller J, Fisker S, Rosenfalck AM, Frandsen E, Jorgensen JO, Hilsted J, Christiansen JS 1999 Long-term effects of growth hormone (GH) on body fluid distribution in GH deficient adults: a four months double blind placebo controlled trial. Eur J Endocrinol 140:11–16[Abstract]
42. Nass R, Huber RM, Klauss V, Muller OA, Schopohl J, Strasburger CJ 1995 Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab 80:552–557[Abstract]
43. Nolte W, Radisch C, Armstrong VW, Hufner M, von zur Muhlen A 1997 The effect of recombinant human GH replacement therapy on lipoprotein(a) and other lipid parameters in adults with acquired GH deficiency: results of a double-blind and placebo-controlled trial. Eur J Endocrinol 137:459–466[Abstract]
44. Rosenfalck AM, Fisker S, Hilsted J, Dinesen B, Volund A, Jorgensen JOL, Christiansen JS, Madsbad S 1999 The effect of the deterioration of insulin sensitivity on ß-cell function in growth-hormone-deficient adults following 4-month growth hormone replacement therapy. Growth Horm IGF Res 9:96–105[CrossRef][Medline]
45. Russell-Jones DL, Weissberger AJ, Bowes SB, Kelly JM, Thomason M, Umpleby AM, Jones RH, Sonksen PH 1993 The effects of growth hormone on protein metabolism in adult growth hormone deficient patients. Clin Endocrinol (Oxf) 38:427–431[Medline]
46. Russell-Jones DL, Watts GF, Weissberger A, Naoumova R, Myers J, Thompson GR, Sonksen PH 1994 The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients. Clin Endocrinol (Oxf) 41:345–350[Medline]
47. Russell-Jones DL, Bowes SB, Rees SE, Jackson NC, Weissberger AJ, Hovorka R, Sonksen PH, Umpleby AM 1998 Effect of growth hormone treatment on postprandial protein metabolism in growth hormone-deficient adults. Am J Physiol 274:E1050–E1056
48. Cuneo RC, Salomon F, Watts GF, Hesp R, Sonksen PH 1993 Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 42:1519–1523[CrossRef][Medline]
49. Smith JC, Evans LM, Wilkinson I, Goodfellow J, Cockcroft JR, Scanlon MF, Davies JS 2002 Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study. Clin Endocrinol (Oxf) 56:493–501[CrossRef][Medline]
50. Snel YE, Brummer RJ, Doerga ME, Zelissen PM, Koppeschaar HP 1995 Energy and macronutrient intake in growth hormone-deficient adults: the effect of growth hormone replacement. Eur J Clin Nutr 49:492–500[Medline]
51. Vahl N, Jorgensen JO, Hansen TB, Klausen IB, Jurik AG, Hagen C, Christiansen JS 1998 The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study. Int J Obes Relat Metab Disord 22:529–536[CrossRef][Medline]
52. Valcavi R, Gaddi O, Zini M, Iavicoli M, Mellino U, Portioli I 1995 Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment. J Clin Endocrinol Metab 80:659–666[Abstract]
53. Webster JM, Stewart M, al-Maskari M, Osman I, Kendall-Taylor P, Mitcheson J, Laker MF 1997 The effect of growth hormone replacement therapy for up to 12 months on lipoprotein composition and lipoprotein(a) in growth hormone-deficient adults. Atherosclerosis 133:115–121[CrossRef][Medline]
54. Whitehead HM, Boreham C, McIlrath EM, Sheridan B, Kennedy L, Atkinson AB, Hadden DR 1992 Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study. Clin Endocrinol (Oxf) 36:45–52[Medline]
55. Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sonksen PH 1991 Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system. Clin Sci (Colch) 81:587–592[Medline]
56. Borson-Chazot F, Serusclat A, Kalfallah Y, Ducottet X, Sassolas G, Bernard S, Labrousse F, Pastene J, Sassolas A, Roux Y, Berthezene F 1999 Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J Clin Endocrinol Metab 84:1329–1333[Abstract/Free Full Text]
57. Ho KY, Kelly JJ 1991 Role of growth hormone in fluid homeostasis. Horm Res 36(Suppl 1):44–48
58. Cutfield WS, Wilton P, Bennmarker H, Albertsson-Wikland K, Chatelain P, Ranke MB, Price DA 2000 Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet 355:610–613[CrossRef][Medline]
59. O’Neal DN, Kalfas A, Dunning PL, Christopher MJ, Sawyer SD, Ward GM, Alford FP 1994 The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis. J Clin Endocrinol Metab 79:975–983[Abstract]
60. Hayes FJ, Fiad TM, McKenna TJ 1999 Gender difference in the response of growth hormone (GH)-deficient adults to GH therapy. Metabolism 48:308–313[CrossRef][Medline]
61. Swerdlow AJ, Higgins CD, Adlard P, Preece MA 2002 Risk of cancer in patients treated with human pituitary growth hormone in the United Kingdom, 1959–85: a cohort study. Lancet 360:273–277[CrossRef][Medline]
62. Volterrani M, Manelli F, Cicoira M, Lorusso R, Giustina A 2000 Role of growth hormone in chronic heart failure. Therapeutic implications. Drugs 60:711–719[CrossRef][Medline]
63. Maison P, Chanson P 2003 Cardiac effects of growth hormone (GH) in adults with GH-deficiency. A meta-analysis. Circulation 108:2648–2652[Abstract/Free Full Text]

This article has been cited by other articles:

				N. Moller and J. O. L. Jorgensen Effects of Growth Hormone on Glucose, Lipid, and Protein Metabolism in Human Subjects Endocr. Rev., April 1, 2009; 30(2): 152 - 177. [Abstract] [Full Text] [PDF]

				A. Colao, C. Di Somma, S. Spiezia, S. Savastano, F. Rota, M. C. Savanelli, and G. Lombardi Growth Hormone Treatment on Atherosclerosis: Results of a 5-Year Open, Prospective, Controlled Study in Male Patients with Severe Growth Hormone Deficiency J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3416 - 3424. [Abstract] [Full Text] [PDF]

				A. A van der Klaauw, A. M Pereira, T. J Rabelink, E. P M Corssmit, A.-J. Zonneveld, H. Pijl, H. C de Boer, J. W A Smit, J. A Romijn, and E. J P de Koning Recombinant human GH replacement increases CD34+ cells and improves endothelial function in adults with GH deficiency Eur. J. Endocrinol., August 1, 2008; 159(2): 105 - 111. [Abstract] [Full Text] [PDF]

				A. A. van der Klaauw, T. van der Straaten, R. Baak-Pablo, N. R. Biermasz, H.-J. Guchelaar, A. M. Pereira, J. W. A. Smit, and J. A. Romijn Influence of the d3-Growth Hormone (GH) Receptor Isoform on Short-Term and Long-Term Treatment Response to GH Replacement in GH-Deficient Adults J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2828 - 2834. [Abstract] [Full Text] [PDF]

				A. L. Utz, A. Yamamoto, L. Hemphill, and K. K. Miller Growth Hormone Deficiency by Growth Hormone Releasing Hormone-Arginine Testing Criteria Predicts Increased Cardiovascular Risk Markers in Normal Young Overweight and Obese Women J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2507 - 2514. [Abstract] [Full Text] [PDF]

				C. Beauregard, A. L. Utz, A. E. Schaub, L. Nachtigall, B. M. K. Biller, K. K. Miller, and A. Klibanski Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2063 - 2071. [Abstract] [Full Text] [PDF]

				J. L. M. Oliveira, M. H. Aguiar-Oliveira, A. D'Oliveira Jr, R. M. C. Pereira, C. R. P. Oliveira, C. T. Farias, J. A. Barreto-Filho, F. D. Anjos-Andrade, C. Marques-Santos, A. C. Nascimento-Junior, et al. Congenital Growth Hormone (GH) Deficiency and Atherosclerosis: Effects of GH Replacement in GH-Naive Adults J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4664 - 4670. [Abstract] [Full Text] [PDF]

				M. Slawik, B. Klawitter, E. Meiser, M. Schories, O. Zwermann, K. Borm, M. Peper, B. Lubrich, M. J. Hug, M. Nauck, et al. Thyroid Hormone Replacement for Central Hypothyroidism: A Randomized Controlled Trial Comparing Two Doses of Thyroxine (T4) with a Combination of T4 and Triiodothyronine J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4115 - 4122. [Abstract] [Full Text] [PDF]

				H. Holmer, J. Svensson, L. Rylander, G. Johannsson, T. Rosen, B.-A. Bengtsson, M. Thoren, C. Hoybye, M. Degerblad, M. Bramnert, et al. Nonfatal Stroke, Cardiac Disease, and Diabetes Mellitus in Hypopituitary Patients on Hormone Replacement Including Growth Hormone J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3560 - 3567. [Abstract] [Full Text] [PDF]

				A. A van der Klaauw, N. R Biermasz, E. J M Feskens, M. B Bos, J. W A Smit, F. Roelfsema, E. P M Corssmit, H. Pijl, J. A Romijn, and A. M Pereira The prevalence of the metabolic syndrome is increased in patients with GH deficiency, irrespective of long-term substitution with recombinant human GH Eur. J. Endocrinol., April 1, 2007; 156(4): 455 - 462. [Abstract] [Full Text] [PDF]

				M. Rizzo, R. Trepp, K. Berneis, and E. R Christ Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy Eur. J. Endocrinol., March 1, 2007; 156(3): 361 - 367. [Abstract] [Full Text] [PDF]

				P. Le Corvoisier, L. Hittinger, P. Chanson, O. Montagne, I. Macquin-Mavier, and P. Maison Cardiac Effects of Growth Hormone Treatment in Chronic Heart Failure: A Meta-Analysis J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 180 - 185. [Abstract] [Full Text] [PDF]

				A A van der Klaauw, J A Romijn, N R Biermasz, J W A Smit, J van Doorn, O M Dekkers, F Roelfsema, and A M Pereira Sustained effects of recombinant GH replacement after 7 years of treatment in adults with GH deficiency. Eur. J. Endocrinol., November 1, 2006; 155(5): 701 - 708. [Abstract] [Full Text] [PDF]

				R. Abs, U. Feldt-Rasmussen, A. F Mattsson, J. P Monson, B.-A. Bengtsson, M. I Goth, P. Wilton, and M. Koltowska-Haggstrom Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a KIMS database analysis. Eur. J. Endocrinol., July 1, 2006; 155(1): 79 - 90. [Abstract] [Full Text] [PDF]

				J. L. Menezes Oliveira, C. Marques-Santos, J. A. Barreto-Filho, R. Ximenes Filho, A. V. de Oliveira Britto, A. H. Oliveira Souza, C. M. Prado, C. R. Pereira Oliveira, R. M. C. Pereira, T. de Almeida Ribeiro Vicente, et al. Lack of Evidence of Premature Atherosclerosis in Untreated Severe Isolated Growth Hormone (GH) Deficiency due to a GH-Releasing Hormone Receptor Mutation J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2093 - 2099. [Abstract] [Full Text] [PDF]

				Y. Wei, Z. Rhani, and C. G. Goodyer Characterization of Growth Hormone Receptor Messenger Ribonucleic Acid Variants in Human Adipocytes J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1901 - 1908. [Abstract] [Full Text] [PDF]

				M. E. Molitch, D. R. Clemmons, S. Malozowski, G. R. Merriam, S. M. Shalet, M. L. Vance, and for The Endocrine Society's Clinical Guidelines Su Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1621 - 1634. [Abstract] [Full Text] [PDF]

				A. Baessler, A. E. Kwitek, M. Fischer, M. Koehler, W. Reinhard, J. Erdmann, G. Riegger, A. Doering, H. Schunkert, and C. Hengstenberg Association of the Ghrelin Receptor Gene Region With Left Ventricular Hypertrophy in the General Population: Results of the MONICA/KORA Augsburg Echocardiographic Substudy Hypertension, May 1, 2006; 47(5): 920 - 927. [Abstract] [Full Text] [PDF]

				J. Bollerslev, T. Ueland, A. P Jorgensen, K. J Fougner, R. Wergeland, T. Schreiner, and P. Burman Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency. Eur. J. Endocrinol., April 1, 2006; 154(4): 537 - 543. [Abstract] [Full Text] [PDF]

				S. K. Paulsen, S. B. Pedersen, J. O. L. Jorgensen, S. Fisker, J. S. Christiansen, A. Flyvbjerg, and B. Richelsen Growth Hormone (GH) Substitution in GH-Deficient Patients Inhibits 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression in Adipose Tissue J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1093 - 1098. [Abstract] [Full Text] [PDF]

				A. R. Hoffman, B. M. K. Biller, D. Cook, J. Baptista, B. L. Silverman, L. Dao, K. M. Attie, P. Fielder, T. Maneatis, B. Lippe, et al. Efficacy of a Long-Acting Growth Hormone (GH) Preparation in Patients with Adult GH Deficiency J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6431 - 6440. [Abstract] [Full Text] [PDF]

				J. Bollerslev, J. Hallen, K. J Fougner, A. P. Jorgensen, C. Kristo, H. Fagertun, O. Gudmundsen, P. Burman, and T. Schreiner Low-dose GH improves exercise capacity in adults with GH deficiency: effects of a 22-month placebo-controlled, crossover trial Eur. J. Endocrinol., September 1, 2005; 153(3): 379 - 387. [Abstract] [Full Text] [PDF]

				A. Colao, C. Di Somma, A. Cuocolo, L. Spinelli, W. Acampa, S. Spiezia, F. Rota, M. C. Savanelli, and G. Lombardi Does a Gender-Related Effect of Growth Hormone (GH) Replacement Exist on Cardiovascular Risk Factors, Cardiac Morphology, and Performance and Atherosclerosis? Results of a Two-Year Open, Prospective Study in Young Adult Men and Women with Severe GH Deficiency J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5146 - 5155. [Abstract] [Full Text] [PDF]

				K. Chihara, E. Koledova, A. Shimatsu, Y. Kato, H. Kohno, T. Tanaka, A. Teramoto, P. C Bates, and A. F Attanasio An individualized GH dose regimen for long-term GH treatment in Japanese patients with adult GH deficiency Eur. J. Endocrinol., July 1, 2005; 153(1): 57 - 65. [Abstract] [Full Text] [PDF]

				M. Gola, S. Bonadonna, M. Doga, and A. Giustina Growth Hormone and Cardiovascular Risk Factors J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1864 - 1870. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maison, P. Articles by Chanson, P. Search for Related Content PubMed PubMed Citation Articles by Maison, P. Articles by Chanson, P.