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Effect of Sex Hormone Replacement on the Insulin-Like Growth Factor System and Bone Mineral: A Cross-Sectional and Longitudinal Study in 595 Perimenopausal Women Participating in the Danish Osteoporosis Prevention Study¹

Department of Endocrinology and Metabolism (P.V., A.P.H., L.M.) and the Institute of Experimental Clinical Research (H.Ø.), Aarhus University Hospital, DK-8000 Aarhus C, Denmark

Address all correspondence and requests for reprints to: Dr. Peter Vestergaard, Osteoporosis Clinic, Aarhus Amtssygehus, Tage Hansens Gade 2, DK-8000 Aarhus C, Denmark.

This study used a cross-sectional design to investigate relationships among serum insulin-like growth factor (IGF) parameters (total serum IGF-I, IGF-II, and IGF-binding protein-3), serum estradiol, and bone mineral density (BMD) stratified for potential confounders, and a longitudinal design to investigate the effects of hormonal replacement therapy (HRT) on IGFs and BMD.

Five hundred and ninety-five perimenopausal women (median age, 50.0 yr; range, 45–56 yr) participating in the Danish Osteoporosis Prevention Study were investigated in a cross-sectional study, and a randomly selected subgroup of 110 was followed after 5 yr in a longitudinal study for changes in serum IGFs and BMD of lumbar spine, femoral neck, and ultradistal forearm during (n = 46) or without HRT (n = 64). In the cross-sectional study, serum IGF-I correlated positively to distal forearm BMD and spine BMD, but not to femoral neck BMD, after stratification for age, body mass index, and other variables. In the follow-up study, HRT decreased IGF-I and IGF-II, but did not influence the age-related decline in IGF-binding protein-3 significantly. Serum alkaline phosphatase and urinary hydroxyproline/creatinine ratio both decreased during HRT, whereas BMD increased compared to control values. After adjustment for age, body mass index, treatment, and other factors, IGF-I correlated positively to changes in forearm and femoral neck BMD, but not to changes in spine BMD.

We conclude that serum IGF-I was positively associated to bone mineral density. Oral HRT decreases IGF-I and IGF-II.

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