Effects of growth hormone withdrawal in obese premenopausal women

Abstract

Objective: We previously reported improved body composition and cardiovascular risk markers plus a small decrease in glucose tolerance with GH administration vs placebo for 6 months to abdominally obese premenopausal women. The objective of this study was to determine whether the effects of GH treatment on cardiovascular risk markers, body composition and glucose tolerance in obese women persist 6 months after GH withdrawal.

Design and patients: Fifty abdominally obese premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty-nine women completed a subsequent 6-month withdrawal observation period.

Measurements: IGF-I, body composition by CT, (1) H-MRS and DXA, serum cardiovascular risk markers, oral glucose tolerance test (OGTT).

Results: IGF-I standard deviation scores (SDS) within the GH group were -1.7 ± 0.1 (pretreatment),-0.1 ± 0.3 (after 6 months of GH) and -1.7 ± 0.1 (6 months post-GH withdrawal). Six months after GH withdrawal, total abdominal and subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP, apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint (P ≤ 0.05). All body composition and cardiovascular risk markers that had improved with GH returned to baseline levels by 6 months after GH discontinuation, as did fasting and 2-h OGTT glucose levels.

Conclusion: The effects of GH administration to abdominally obese premenopausal women have a short time-course. The beneficial effects on body composition and cardiovascular risk markers, and the side effect of altered glucose tolerance returned to pretreatment levels after GH withdrawal. There was no suppression of endogenous IGF-I levels, which returned to baseline after GH withdrawal.

Trial registration: ClinicalTrials.gov NCT00131378.

Conflict of interest statement

Declaration of Interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

© 2012 John Wiley & Sons Ltd.

Figures

Figure 1

Overview of study design. Obese premenopausal women were randomized to GH vs placebo for 6 months followed by a 6-month withdrawal period. This study reports the data from the 6-month withdrawal period.

Figure 2

Mean IGF-I (panel A) and IGF-I SDS (panel B) levels (± SEM) in women randomized to growth hormone (solid diamonds) or placebo (open diamonds) for the first six months, followed by 6-month withdrawal of study medication. p by repeated measures ANOVA between the two groups.

Figure 3

Mean body mass index (panel A), thigh muscle cross-sectional area (panel B), total abdominal adipose tissue (panel C), and trunk fat (panel D) (± SEM) in women randomized to growth hormone (solid diamonds) or placebo (open diamonds) for the first six months, followed by 6-month withdrawal of study medication. p by repeated measures ANOVA between the two groups.

Figure 4

Mean high-sensitivity C-reactive protein (panel A) and apolipoprotein B (panel B) (± SEM) in women randomized to growth hormone (solid diamonds) or placebo (open diamonds) for the first six months, followed by 6-month withdrawal of study medication. p by repeated measures ANOVA between the two groups.

Figure 5

Mean fasting glucose (panel A) and 120-minute oral glucose tolerance test glucose (panel B) levels (± SEM) in women randomized to growth hormone (solid diamonds) or placebo (open diamonds) for the first six months, followed by 6-month withdrawal of study medication. p by repeated measures ANOVA between the two groups.