Growth Hormone Withdrawal in Obese Premenopausal Women
Growth Hormone Withdrawal in Obese Premenopausal Women
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, 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.
Abdominal adiposity is associated with impaired growth hormone (GH) secretion and unfavourable cardiovascular risk marker and body composition profiles, including elevated high-sensitivity C-reactive protein (hsCRP), increased fat mass and decreased lean mass. Several studies have demonstrated that GH treatment in individuals with adult-onset GH deficiency due to pituitary disease improves cardiovascular risk makers and body composition, but can also cause abnormalities in glucose homeostasis. We recently reported results from a 6-month randomized, double-blind, placebo-controlled study, which demonstrated that GH treatment in abdominally obese premenopausal women improved body composition and cardiovascular risk markers, accompanied by a mild increase in both fasting and 2-h glucose after oral tolerance test (OGTT). These results are consistent with other studies in other obese populations, including obese men and postmenopausal women.
Important questions regarding GH treatment include: whether the beneficial effects of GH persist following GH withdrawal, whether GH-related effects reverse and whether withdrawal of GH results in a rebound effect in which body composition overshoots pretreatment levels. In adults with adult-onset GH deficiency (GHD) due to pituitary disease, studies have shown that the effects of GH administration on cardiovascular risk markers and function do not persist following cessation of GH treatment; however, results with regard to effects on body composition are conflicting. Both persistence and reversal of body fat reduction and increases in lean mass after GH withdrawal have been demonstrated. In adults with HIV lipodystrophy treated with GH at treatment doses, and in healthy men with abdominal adiposity treated with supraphysiologic doses of GH, the beneficial effects of decreased visceral adiposity reversed after GH withdrawal, and in the HIV study visceral adiposity rebounded to higher levels than had been observed pretreatment. In addition, in one study, GH-induced insulin resistance rapidly reversed after GH withdrawal in adults with GHD.
We hypothesized that 6 months after withdrawal of GH therapy, the cardiovascular and body composition benefits and altered glucose homeostasis would reverse to pre-treatment levels with no rebound effect.
Abstract and Introduction
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, 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.
Introduction
Abdominal adiposity is associated with impaired growth hormone (GH) secretion and unfavourable cardiovascular risk marker and body composition profiles, including elevated high-sensitivity C-reactive protein (hsCRP), increased fat mass and decreased lean mass. Several studies have demonstrated that GH treatment in individuals with adult-onset GH deficiency due to pituitary disease improves cardiovascular risk makers and body composition, but can also cause abnormalities in glucose homeostasis. We recently reported results from a 6-month randomized, double-blind, placebo-controlled study, which demonstrated that GH treatment in abdominally obese premenopausal women improved body composition and cardiovascular risk markers, accompanied by a mild increase in both fasting and 2-h glucose after oral tolerance test (OGTT). These results are consistent with other studies in other obese populations, including obese men and postmenopausal women.
Important questions regarding GH treatment include: whether the beneficial effects of GH persist following GH withdrawal, whether GH-related effects reverse and whether withdrawal of GH results in a rebound effect in which body composition overshoots pretreatment levels. In adults with adult-onset GH deficiency (GHD) due to pituitary disease, studies have shown that the effects of GH administration on cardiovascular risk markers and function do not persist following cessation of GH treatment; however, results with regard to effects on body composition are conflicting. Both persistence and reversal of body fat reduction and increases in lean mass after GH withdrawal have been demonstrated. In adults with HIV lipodystrophy treated with GH at treatment doses, and in healthy men with abdominal adiposity treated with supraphysiologic doses of GH, the beneficial effects of decreased visceral adiposity reversed after GH withdrawal, and in the HIV study visceral adiposity rebounded to higher levels than had been observed pretreatment. In addition, in one study, GH-induced insulin resistance rapidly reversed after GH withdrawal in adults with GHD.
We hypothesized that 6 months after withdrawal of GH therapy, the cardiovascular and body composition benefits and altered glucose homeostasis would reverse to pre-treatment levels with no rebound effect.