Endocrine Abstracts

Introduction
We have previously demonstrated profound effects of hormone replacement treatment (HRT) in post-menopausal women on the IGF-system. HRT is widely used to prevent osteoporosis. The IGF-system has been implicated in bone formation. IGFBP-4 and IGFBP-5 are known to be important in modulation of IGF activity in bone. In this larger study we have examined the effects of HRT on circulating IGFBP-4 levels.
Method
Oral conjugated equine estrogen (CEE) alone or in combination with Medroxyprogesterone acetate (MPA), Desogestrel (DG) or Norethisterone (NE) were given in a randomised triple crossover fashion to 35 healthy postmenopausal women and the effects on the IGF-system were determined.
Results
IGFBP-4 levels were significantly higher in subjects on oestrogen alone (723+/-50ng/ml) than at baseline (no HRT) (575+/-32ng/ml), p=0.001). IGFBP-4 levels remained higher than baseline with addition of progestogens (MPA 683+/-32 ng/ml, DG 691+/-40ng/ml, NE 704+/-34ng/ml) (p=0.002). There was no difference in IGFBP-4 between progestogens of differing androgenicity. Conversely baseline circulating IGF-I levels were significantly reduced by CEE (134+/-12 vs 83+/-11ng/ml, p=0.001). This effect was reversed by progestins according to their androgenicity (MPA 96+/-9ng/ml, DG 109+/-9ng/ml, NE 131+/-10ng/ml)(F=6.2, p=0.001). Plasma IGFBP-1 concentration increased significantly from baseline to CEE alone (29.6+/-3mcg/l vs 67+/-6 mcg/l, p<0.001). This rise was opposed by progestogens of increasing androgenicity (MPA 60+/-5mcg/l, DG 57+/-5mcg/l, NE 45+/-5 mcg/l)(F=4.1, p=0.02). IGF-II levels were unaffected by CEE or progestogens.
Conclusion
There are marked differences in the response of circulating IGF-I, IGF-II, IGFBP-1 and IGFBP-4 to particular HRT combinations. In the context of the known effects of IGFs and oestrogens on bone formation, our findings would strongly suggest that HRT preparations may have differing long term effects on bone formation according to their precise formulation. Prospective trials will be required to examine this further. This novel study suggests that the effects of hormone replacement (HRT) on circulating IGFBP-4 levels may be important in mediating longer term benefits of HRT on bone mineral density.