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STUDY: Tamoxifene vs Raloxifene in regards to GH, IFG-1, and Gonadal Axes
The Journal of Clinical Endocrinology & Metabolism Vol. 95, No. 12 5443-5448
Copyright © 2010 by The Endocrine Society
Neuroendocrine Regulation of Growth Hormone and Androgen Axes by Selective Estrogen Receptor Modulators in Healthy Men
Vita Birzniece, Akira Sata, Surya Sutanto and Ken K. Y. Ho
Garvan Institute of Medical Research and Department of Endocrinology (V.B., A.S., S.S., K.K.Y.H.), St. Vincent’s Hospital, Sydney, New South Wales 2010, Australia; and The University of New South Wales (V.B., K.K.Y.H.), Sydney, New South Wales 2052, Australia
Address all correspondence and requests for reprints to: Prof. Ken K. Y. Ho, Pituitary Research Unit, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Context: 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.
Design: We conducted a randomized, open-label crossover study.
Patients and Intervention: 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.
Main Outcome Measures: 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.
STUDY: Tamoxifene vs Raloxifene in regards to GH, IFG-1, and Gonadal Axes
The Journal of Clinical Endocrinology & Metabolism Vol. 95, No. 12 5443-5448
Copyright © 2010 by The Endocrine Society
Neuroendocrine Regulation of Growth Hormone and Androgen Axes by Selective Estrogen Receptor Modulators in Healthy Men
Vita Birzniece, Akira Sata, Surya Sutanto and Ken K. Y. Ho
Garvan Institute of Medical Research and Department of Endocrinology (V.B., A.S., S.S., K.K.Y.H.), St. Vincent’s Hospital, Sydney, New South Wales 2010, Australia; and The University of New South Wales (V.B., K.K.Y.H.), Sydney, New South Wales 2052, Australia
Address all correspondence and requests for reprints to: Prof. Ken K. Y. Ho, Pituitary Research Unit, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Context: 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.
Design: We conducted a randomized, open-label crossover study.
Patients and Intervention: 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.
Main Outcome Measures: 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.
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