Inhibitory action on GHRH-induced GH secretion of chronic tamoxifen treatment in breast cancer

De Marinis1, Mancini1, Izzi1

  • 1Institutes of, Endocrinology,Internal Medicine and Geriatrics, Clinical,Biochemistry,Clinical Surgery, Catholic University School of Medicine, Rome;,Eli-Lilly, Florence, Italy.

Clinical Endocrinology
|August 11, 2017
PubMed
Abstract

Insights

Tamoxifen (TAM) significantly reduces growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-1) levels in postmenopausal women. This tamoxifen effect may contribute to its antiproliferative action in breast cancer treatment.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Previous studies suggest tamoxifen (TAM) inhibits growth hormone (GH) secretion, but human data are conflicting.
  • TAM is a widely used treatment for breast cancer, particularly in postmenopausal women.

Purpose of the Study:

  • To evaluate the effect of chronic TAM treatment on GH secretory dynamics in postmenopausal women with breast cancer.
  • To assess changes in GH, insulin-like growth factor-1 (IGF-1), and related markers during TAM therapy.

Main Methods:

  • Ten postmenopausal breast cancer patients were studied before and during 6-12 months of chronic TAM treatment (20 mg/day).
  • Growth hormone-releasing hormone (GHRH) tests were performed to assess GH response (peak and area under the curve).
  • Circulating levels of IGF-1, IGF-binding protein-3 (IGF-BP3), SHBG, FSH, LH, estradiol, and prolactin were measured.

Main Results:

  • Chronic TAM treatment significantly reduced GH peak response (59.8%) and GH area under the curve (53.8%) following GHRH stimulation.
  • Plasma IGF-1 levels were significantly decreased by TAM treatment.
  • No significant changes were observed in IGF-BP3 levels or the IGF-1/IGF-BP3 ratio. An inverse correlation between SHBG and IGF-1 was noted.

Conclusions:

  • Long-term tamoxifen treatment effectively blocks GH response to GHRH and lowers IGF-1 levels in postmenopausal women.
  • These effects may be mediated by a central mechanism, potentially contributing to TAM's antiproliferative action in cancer.
  • Reduced IGF-1, a mitogen for cancer cells, may be a key factor in tamoxifen's therapeutic efficacy.

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