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. 2017 Dec 28;2(2):154-165.
doi: 10.1210/js.2017-00457. eCollection 2018 Feb 1.

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  1 , Rebecca J Yang  2 , Paul Y Takahashi  3 , Dana Erickson  4 , Cyril Y Bowers  5 , Johannes D Veldhuis  2
Affiliations

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 et al. J Endocr Soc. .

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 2 hours after combined GH-releasing hormone-ghrelin injection.

Main outcome measures: Pulsatile GH and stimulated GH secretion, and fasting levels of IGF-I, IGF-binding 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.

Keywords: SERM; breast cancer; elderly; growth hormone; men; toremifene.

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Figures

Figure 1.
Figure 1.
Measured GH time series in men and women (N = 40 total). Blood samples were drawn at 10-minute intervals, starting at 2200 hours until 0800 hours (upper two panels). At 0800 hours, the subjects received a bolus injection of 0.3 µg/kg of both GHRH and ghrelin and sampling was continued for another 2 hours. GH secretion under placebo and toremifene did differ significantly. Note differences in y-axis scales.
Figure 2.
Figure 2.
Serum IGF-I concentrations (vertical axis) plotted vs mean serum overnight GH concentration (mean of 60 samples) and age (horizontal and oblique axes) during placebo and toremifene treatment (upper two panels). The lower two panels show the regression between serum IGFBP1 concentration (vertical axis) and visceral fat and fasting insulin (horizontal and oblique axes) during placebo and toremifene treatment. Note differences in vertical axes scales.
See this image and copyright information in PMC

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