Circulating insulin-like growth factor system changes in women with acute estrogen deficiency induced by GnRH agonist

S Poiraudeau, C Roux, F De Ceuninck, L Tsagris, D Borderie, B Cherruau, M F Dumontier, M Corvol
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 1997 · doi:10.1007/s001980050034 · PMID:9425505
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GnRH agonist treatment for endometriosis increased circulating IGF-I and IGF-II concentrations, with distinct correlations between IGF-II and bone mineral density changes.

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This prospective longitudinal study examined short-term (6-month) effects of acute estrogen withdrawal on the circulating insulin-like growth factor (IGF) system in 40 women with endometriosis, using pre- and post-treatment plasma sampling during GnRH agonist therapy with calcium, with or without nasal salmon calcitonin. After treatment-induced hypoestrogenism, plasma IGF-I and IGF-II concentrations increased (24% and 40%, respectively), and ligand blot/immunoblot analyses showed a significant increase in IGF-II binding to a 29–31 kDa region associated with IGFBP-3 or IGFBP-1. Changes in IGF-I correlated with urinary deoxypyridinoline, C-telopeptide, and total alkaline phosphatases, whereas changes in IGF-II correlated with lumbar bone mineral density (L-BMD); IGF-I changes did not correlate with L-BMD. The paper reports no significant differences between the treatment groups, but it does not establish how these IGF changes relate to long-term clinical outcomes beyond bone remodeling markers. This paper is centrally about endometriosis — it studies IGF system changes in women with endometriosis during GnRH-agonist–induced estrogen deficiency.

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Abstract

This prospective longitudinal study was undertaken to examine the short-term effects (6 months) of estrogen withdrawal on the circulating IGF system. A series of 40 patients suffering from endometriosis was studied before and after a 6-month treatment period with gonadotrophin releasing hormone (GnRH) agonist and calcium, with or without nasal salmon calcitonin. The plasma concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) were measured by radioimmunoassay and radioreceptor assay respectively. Plasma IGF binding proteins (IGFBPs) were quantified and characterized by ligand blot and immunoblot. In all patients, a secondary hypoestrogenism was observed, including a 4% decrease in lumbar bone mineral density (L-BMD). The plasma IGF-I and IGF-II concentrations increased after treatment (24%, p < 0.0005 and 40%, p < 0.004 respectively), with no significant difference between the treatment groups. There was a positive correlation between plasma IGF-I (but not IGF-II) changes and changes in urinary deoxypyridinoline (r = 0.32, p < 0.05), urinary C telopeptide of type 1 collagen (r = 0.33, p < 0.04) and total plasma alkaline phosphatases (r = 0.33, p < 0.04). No correlation was found between IGF-I and L-BMD changes, while there was a positive correlation between the changes in plasma IGF-II and L-BMD (r = 0.32, p < 0.05). Ligand blot analysis revealed a significant increase in IGF-II binding to a 29-31 kilodalton region where positive staining with specific antibodies to IGFBP-3 or IGFBP-1 was observed. In conclusion, IGF-I and IGF-II plasma concentrations are both increased following a short period of treatment with a GnRH agonist. The changes in individual IGF peptides are differently correlated with changes in markers of bone remodelling and L-BMD.
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Abstract: This prospective longitudinal study was undertaken to examine the short-term effects (6 months) of estrogen withdrawal on the circulating IGF system. A series of 40 patients suffering from endometriosis was studied before and after a 6-month treatment period with gonadotrophin releasing hormone (GnRH) agonist and calcium, with or without nasal salmon calcitonin. The plasma concentrations of insulin-like growth factor I (IGF-I9 and insulin-like growth factor II (IGF-II) were measured by radioimmunoassay and radioreceptor assay respectively. Plasma IGF binding proteins (IGFBPs) were quantified and characterized by ligand blot and immunoblot. In all patients, a secondary hypoestrogenism was observed, including a 4% decrease in lumbar bone mineral density (L-BMD). The plasma IGF-I and IGF-II concentrations increased after treatment (24%, p < 0.0005 and 40%, p < 0.004 respectively), with no significant difference between the treatment groups. There was a positive correlation between plasma IGF-I (but not IGF-II) changes and changes in urinary deoxypyridinoline (r = 0.32, p < 0.05), urinary C telopeptide of type I collagen (r = 0.33, p < 0.04) and total plasma alkaline phosphatases (r = 0.33, p < 0.04). No correlation was found between IGF-I and L-BMD changes, while there was a positive correlation between the changes in plasma IGF-II and L-BMD (r = 0.32, p < 0.05). Ligand blot analysis revealed a significant increase in IGF-II binding to a 29–31 kilodalton region where positive staining with specific antibodies to IGFBP-3 or IGFBP-1 was observed. In conclusion, IGF-I and IGF-II plasma concentrations are both increased following a short period of treatment with a GnRH agonist. The changes in individual IGF peptides are differently correlated with changes in markers of bone remodelling and L-BMD. Similar content being viewed by others Author information Authors and Affiliations Additional information Rights and permissions About this article Cite this article Poiraudeau, S., Roux, C., De Ceuninck, F. et al. Circulating Insulin-Like Growth Factor System Changes in Women with Acute Estrogen Deficiency Induced by GnRH Agonist. Osteoporos Int 7, 463–470 (1997). https://doi.org/10.1007/s001980050034 Issue date: DOI: https://doi.org/10.1007/s001980050034

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Condition tags

endometriosis

MeSH descriptors

Gonadotropin-Releasing Hormone Insulin-Like Growth Factor I Insulin-Like Growth Factor II Luteolytic Agents Triptorelin Pamoate Acute Disease Adult Blotting, Western Bone and Bones Bone and Bones Bone Density Bone Density Electrophoresis, Polyacrylamide Gel Estrogens Estrogens Female Gonadotropin-Releasing Hormone Humans Insulin-Like Growth Factor Binding Proteins Insulin-Like Growth Factor Binding Proteins

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