Effects of conjugated equine estrogen vs. raloxifene on serum insulin-like growth factor-i and insulin-like growth factor binding protein-3: a 2-year, double-blind, placebo-controlled study.
OBJECTIVE
To assess and compare the effect of conjugated estrogen and of the selective estrogen receptor modulator raloxifene on serum levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) and on the IGF-I/IGFBP-3 ratio.


METHODS
A 2-year randomized, double-blind, placebo-controlled study.


METHODS
Endocrinology outpatient department.


METHODS
Fifty-six postmenopausal, hysterectomized women.


METHODS
Women received raloxifene hydrochloride in doses of 60 mg/day (n = 15) or 150 mg/day (n = 13), conjugated equine estrogen (CEE) in doses of 0.625 mg/day (n = 15), or a placebo (n = 13) over the course of 2 years.


METHODS
At baseline and after 6, 12, and 24 months of treatment, serum levels of IGF-I, IGFBP-3, and insulin were measured, and an IGF-I/IFGBP-3 ratio was calculated.


RESULTS
Both raloxifene and CEE decreased serum IGF-I concentration. In contrast to CEE, which had no effect, both raloxifene doses of 60 and 150 mg/day significantly increased serum IGFBP-3 during the 2 years. Compared with placebo, the decrease in IGF-I/IGFBP-3 ratio was -32.5% (95% CI: -20.1; -44.8%) for CEE; -16.4% (95% CI: -3.6; -29.2%) for raloxifene at 150 mg/day; and -15.4% (95% CI: -1.0; -29.8%) for raloxifene at 60 mg/day. No effect of CEE or raloxifene was found on insulin concentration at any time point.


CONCLUSIONS
Long-term use of both CEE and raloxifene decreases serum IGF-I and the IGF-I/IGFBP-3 ratio, but, unlike CEE, raloxifene produced a significant yet small increase in IGFBP-3.
Duschek
Erik J J
EJ
Department of Endocrinology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. e.duschek@vumc.nl
de Valk-de Roo
Gerdien W
GW
Gooren
Louis J
LJ
Netelenbos
Coen
C
D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D013997:Time Factors
D004965:Estrogen Antagonists; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I