Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer.
Tamoxifen, an estrogen antagonist, is usually employed in the treatment of breast cancer. Its mechanism of action is not well known because an antiproliferative effect of the drug has been shown also in estrogen receptor negative tumors, most likely mediated by the inhibition of local growth factors and particularly IGF-I. However, the action of tamoxifen on the GH-IGF-I axis is still open to investigation. We have investigated the influence of acute and chronic treatment with tamoxifen on GH response to GHRH and IGF-I serum levels in six postmenopausal women with metastatic breast cancer. A GHRH test (50 microg i.v. at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a) basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8 weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally and after chronic tamoxifen therapy. No significant modifications in GH response to GHRH were observed after acute or chronic treatment with tamoxifen vs the basal test. On the contrary, chronic tamoxifen treatment induced a significant decrease in serum IGF-I levels. Basal pretreatment levels of 123+/-18 microg/l were suppressed to 65+/-11 microg/l (mean suppression 47%, P < 0.001). These preliminary data confirm the inhibitory effect of tamoxifen on IGF-I production but seem to exclude the possibility that this effect may be due to an inhibition of GH secretion.
Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy.
S M
SM
Corsello
C A
CA
Rota
P
P
Putignano
S
S
Della Casa
A
A
Barnabei
M G
MG
Migneco
V
V
Vangeli
A
A
Barini
M
M
Mandalà
C
C
Barone
A
A
Barbarino
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D017698:Postmenopause; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone