Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators.
BACKGROUND
In men, GH secretion is stimulated by estradiol derived locally from aromatization of testosterone. Recently, we showed that local estrogen also plays a major role in the central regulation of GH secretion in women. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs), drugs that block central estrogen action but exert estrogen-like effects in the liver, inhibiting hepatic IGF-I production. The relative impact of SERMs on the GH-IGF-I axis in men and women has not been investigated.


OBJECTIVE
The aim of the study was to determine whether there is a gender difference in the impact of SERMs on the GH-IGF-I axis.


METHODS
We conducted a comparative, randomized, open-label, crossover study of tamoxifen and raloxifene.


METHODS
Ten healthy postmenopausal women and 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 washout of 2 wk between treatments.


METHODS
The GH response to arginine, IGF-I, testosterone, and SHBG was measured.


RESULTS
In women, but not in men, tamoxifen significantly attenuated the GH response to arginine. The GH response was not significantly blunted by raloxifene in both sexes. Both SERMs significantly reduced mean IGF-I levels to a similar degree in men and women. In men, both SERMs significantly increased LH and testosterone levels.


CONCLUSIONS
In summary, GH secretion was blunted by tamoxifen in women in the face of reduced IGF-I feedback inhibition but not in men in whom the gonadal axis was stimulated. We conclude that potential blunting of GH secretion in men by SERMs was counteracted by concomitant central stimulation of GH secretion by testosterone. In therapeutic doses, tamoxifen may induce detrimental metabolic effects in women, but not men.
Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Vita
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Birzniece
Surya
S
Sutanto
Ken K Y
KK
Ho
D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009489:Neurosecretion / Q000187:drug effects*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012727:Sex Characteristics; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D013739:Testosterone / Q000097:blood
D020845:Selective Estrogen Receptor Modulators; D012738:Sex Hormone-Binding Globulin; D013629:Tamoxifen; D019382:Human Growth Hormone; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D001120:Arginine