Neuroendocrine regulation of growth hormone and androgen axes by selective estrogen receptor modulators in healthy men.
BACKGROUND
In men, the stimulation of GH and inhibition of LH secretion by testosterone requires aromatization to estradiol. Tamoxifen, a selective estrogen receptor modulator (SERM), possesses central estrogen antagonistic effect but peripheral hepatic agonist effect, lowering IGF-I. Thus, tamoxifen is likely to perturb the neuroendocrine regulation of GH and gonadal axes. Raloxifene, a SERM, is used for therapy of osteoporosis in both sexes. Its neuroendocrine effects in men are poorly understood.


OBJECTIVE
The aim was to compare the impact of raloxifene and tamoxifen on GH-IGF-I and gonadal axes in healthy men.


METHODS
We conducted a randomized, open-label crossover study.


METHODS
Ten healthy men were randomized to 2-wk sequential treatment with tamoxifen (10 and 20 mg/d) and raloxifene (60 and 120 mg/d), with a 2-wk intervening washout period.


METHODS
We measured the GH response to arginine and circulating levels of IGF-I, LH, FSH, testosterone, and SHBG.


RESULTS
Tamoxifen, but not raloxifene, significantly reduced IGF-I levels by 25±6% (P<0.01) and increased SHBG levels by 20±7% (P<0.05) at the higher therapeutic dose. There was a nonstatistically significant trend toward a reduction in the GH response to arginine with both SERMs. Both drugs significantly increased LH, FSH, and testosterone concentrations. The mean increase in testosterone (40 vs. 25%; P<0.05) and LH (70 vs. 30%; P<0.01) was significantly greater with tamoxifen than with raloxifene treatment.


CONCLUSIONS
Tamoxifen, but not raloxifene, reduces IGF-I levels. Both SERMs stimulate the gonadal axis, with tamoxifen imparting a greater effect. We conclude that in therapeutic doses, raloxifene perturbs the GH and gonadal axes to a lesser degree than tamoxifen.
Birzniece
Vita
V
Garvan Institute of Medical Research, Department of Endocrinology, St. Vincent's Hospital, and The University of New South Wales, Sydney, New South Wales 2010, Australia.
Sata
Akira
A
Sutanto
Surya
S
Ho
Ken K Y
KK
D000368:Aged; D000728:Androgens / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology; D018592:Cross-Over Studies; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D012016:Reference Values; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood
D000728:Androgens; D020845:Selective Estrogen Receptor Modulators; D012738:Sex Hormone-Binding Globulin; D013629:Tamoxifen; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone; D001120:Arginine