Neuroendocrine Regulation of Growth Hormone and Androgen Axes by Selective Estrogen Receptor Modulators in Healthy Men

Birzniece, Vita; Sata, Akira; Sutanto, Surya; Ho, Ken K. Y.

doi:10.1210/jc.2010-1477

Cited by 22Growth Hormone and Insulin-like Growth FactorsEstrogen and related hormone effectsHormonal and reproductive studies

Neuroendocrine Regulation of Growth Hormone and Androgen Axes by Selective Estrogen Receptor Modulators in Healthy Men

Birzniece, Vita, Sata, Akira, Sutanto, Surya, Ho, Ken K. Y.·2010·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2010-1477

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Abstract

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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SERMs via oestrogen-like actions in the liver may reduce insulin-like growth factor-1, potentially reducing anabolism.
“In contrast to testosterone treatment, SERMs via oestrogen-like actions in the liver may reduce insulin-like growth factor-1, potentially reducing anabolism, while the increase in SHBG may limit testosterone bioavailability.109”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [109]
The increase in SHBG with SERMs may limit testosterone bioavailability.
“In contrast to testosterone treatment, SERMs via oestrogen-like actions in the liver may reduce insulin-like growth factor-1, potentially reducing anabolism, while the increase in SHBG may limit testosterone bioavailability.109”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [109]

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Authors: Birzniece, V., Sata, A., Sutanto, S., & Ho, K. K. Y.
Affiliations: Garvan Institute of Medical Research (AU)
Corresponding author: Ho, Ken K. Y.
ORCID: Birzniece, Vita
Sutanto, Surya
Ho, Ken K. Y.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2010-12
Volume: 95
Issue: 12
Pages: 5443-5448
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2010-1477
OpenAlex: W2018968573
Cited by: 22
References: 30
Citations by year: 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 1
FWCI: 1.45
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council
National Health and Medical Research Council
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: tamoxifen, raloxifene, selective estrogen receptor modulators, growth hormone, insulin-like growth factor I, gonadal axis, luteinizing hormone, follicle-stimulating hormone, testosterone, sex hormone-binding globulin, arginine stimulation, aromatization, neuroendocrine regulation, healthy men
MeSH terms: Aged, Androgens, Arginine, Follicle Stimulating Hormone, Humans, Insulin-Like Growth Factor I, Luteinizing Hormone, Male, Middle Aged, Reference Values, Sex Hormone-Binding Globulin, Growth Hormone, Tamoxifen, Testosterone, Cross-Over Studies, Selective Estrogen Receptor Modulators, Raloxifene Hydrochloride

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Neuroendocrine Regulation of Growth Hormone and Androgen Axes by Selective Estrogen Receptor Modulators in Healthy Men

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