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 Study

J Clin Endocrinol Metab. 1999 Jul;84(7):2286-90. doi: 10.1210/jcem.84.7.5865.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density
  • Cross-Sectional Studies
  • Denmark
  • Estradiol / administration & dosage
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy
  • Female
  • Humans
  • Hysterectomy
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Longitudinal Studies
  • Menopause*
  • Middle Aged
  • Norethindrone / administration & dosage
  • Norethindrone / analogs & derivatives*
  • Norethindrone / therapeutic use
  • Norethindrone Acetate
  • Osteoporosis, Postmenopausal / prevention & control*


  • Insulin-Like Growth Factor Binding Protein 3
  • Estradiol
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Norethindrone Acetate
  • Norethindrone