Effects of toremifene, a selective estrogen receptor modulator, on spontaneous and stimulated GH secretion, IGF-I, and IGF-binding proteins in healthy elderly subjects

Ferdinand Roelfsema, Rebecca J. Yang, Paul Y. Takahashi, Dana Erickson, Cyril Y. Bowers, Johannes D. Veldhuis

Research output: Contribution to journalArticle

Abstract

Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene. Objective: To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone-ghrelin stimulation. Additionally, effects on IGF-I, its binding proteins, and sex hormone-binding globulin (SHBG) were quantified. Participants and Design: Twenty men and 20 women, within an allowable age range of 50 to 80 years, volunteered for this double-blind, placebo-controlled prospective crossover study. Ten-minute blood sampling was done for 10 hours overnight and then for 2hours after combinedGH-releasing hormone-ghrelin injection. Main Outcome Measures: PulsatileGHand stimulatedGHsecretion, and fasting levels of IGF-I, IGFbinding protein (IGFBP)1, IGFBP3, and SHBG. Results: Toremifene did not enhance pulsatile or stimulated GH secretion, but decreased IGF-I by 20% in men and women. IGFBP3 was unchanged, whereas while IGFBP1 and SHBG increased in both sexes to a similar extent. Conclusions: The expected rise in spontaneous and stimulated GH secretion under the diminished negative feedback restraint of powered IGF-I favors a central inhibitory antiestrogenic effect of toremifene. Estrogenic effects of toremifene on the liver were present, as evidenced by increased IGFBP1 and SHBG levels. Men and women responded to this SERM comparably.

Original languageEnglish (US)
Pages (from-to)154-165
Number of pages12
JournalJournal of the Endocrine Society
Volume2
Issue number2
DOIs
StatePublished - Jan 1 2018

Fingerprint

Toremifene
Selective Estrogen Receptor Modulators
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor I
Growth Hormone
Healthy Volunteers
Sex Hormone-Binding Globulin
Ghrelin
Tamoxifen
Estrogens
Growth Hormone-Releasing Hormone
Cross-Over Studies
Fasting
Prostatic Neoplasms
Carrier Proteins
Placebos
Outcome Assessment (Health Care)
Hormones
Prospective Studies
Breast Neoplasms

Keywords

  • Breast cancer
  • Elderly
  • Growth hormone
  • Men
  • SERM
  • Toremifene

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Effects of toremifene, a selective estrogen receptor modulator, on spontaneous and stimulated GH secretion, IGF-I, and IGF-binding proteins in healthy elderly subjects. / Roelfsema, Ferdinand; Yang, Rebecca J.; Takahashi, Paul Y.; Erickson, Dana; Bowers, Cyril Y.; Veldhuis, Johannes D.

In: Journal of the Endocrine Society, Vol. 2, No. 2, 01.01.2018, p. 154-165.

Research output: Contribution to journalArticle

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abstract = "Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene. Objective: To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone-ghrelin stimulation. Additionally, effects on IGF-I, its binding proteins, and sex hormone-binding globulin (SHBG) were quantified. Participants and Design: Twenty men and 20 women, within an allowable age range of 50 to 80 years, volunteered for this double-blind, placebo-controlled prospective crossover study. Ten-minute blood sampling was done for 10 hours overnight and then for 2hours after combinedGH-releasing hormone-ghrelin injection. Main Outcome Measures: PulsatileGHand stimulatedGHsecretion, and fasting levels of IGF-I, IGFbinding protein (IGFBP)1, IGFBP3, and SHBG. Results: Toremifene did not enhance pulsatile or stimulated GH secretion, but decreased IGF-I by 20{\%} in men and women. IGFBP3 was unchanged, whereas while IGFBP1 and SHBG increased in both sexes to a similar extent. Conclusions: The expected rise in spontaneous and stimulated GH secretion under the diminished negative feedback restraint of powered IGF-I favors a central inhibitory antiestrogenic effect of toremifene. Estrogenic effects of toremifene on the liver were present, as evidenced by increased IGFBP1 and SHBG levels. Men and women responded to this SERM comparably.",
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AU - Yang, Rebecca J.

AU - Takahashi, Paul Y.

AU - Erickson, Dana

AU - Bowers, Cyril Y.

AU - Veldhuis, Johannes D.

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AB - Context: Estrogens amplify spontaneous and stimulated growth hormone (GH) secretion, whereas they diminish GH-dependent insulin-like growth factor (IGF)-I in a dose-dependent manner. Selective estrogen receptor modulators (SERMs), including tamoxifen and toremifene, are widely adjunctively used in breast and prostate cancer. Although some endocrine effects of tamoxifen are known, few data are available for toremifene. Objective: To explore sex-dependent effects of toremifene on spontaneous 10-hour overnight GH secretion, followed by GH-releasing hormone-ghrelin stimulation. Additionally, effects on IGF-I, its binding proteins, and sex hormone-binding globulin (SHBG) were quantified. Participants and Design: Twenty men and 20 women, within an allowable age range of 50 to 80 years, volunteered for this double-blind, placebo-controlled prospective crossover study. Ten-minute blood sampling was done for 10 hours overnight and then for 2hours after combinedGH-releasing hormone-ghrelin injection. Main Outcome Measures: PulsatileGHand stimulatedGHsecretion, and fasting levels of IGF-I, IGFbinding protein (IGFBP)1, IGFBP3, and SHBG. Results: Toremifene did not enhance pulsatile or stimulated GH secretion, but decreased IGF-I by 20% in men and women. IGFBP3 was unchanged, whereas while IGFBP1 and SHBG increased in both sexes to a similar extent. Conclusions: The expected rise in spontaneous and stimulated GH secretion under the diminished negative feedback restraint of powered IGF-I favors a central inhibitory antiestrogenic effect of toremifene. Estrogenic effects of toremifene on the liver were present, as evidenced by increased IGFBP1 and SHBG levels. Men and women responded to this SERM comparably.

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