Endogenous Estrogen Regulates Somatostatin-Induced Rebound GH Secretion in Postmenopausal Women

Systemic concentrations of T, estradiol (E₂), GH, IGF-1, and IGF binding protein-3 decline in healthy aging individuals. Conversely, T and E₂ stimulate GH and IGF-1 production in hypogonadal patients.

Because E₂ stimulates GH secretion, putatively via the nuclear estrogen receptor-α and E₂ and GH fall with menopause, we postulated that diminished endogenous E₂ contributes to low GH output in older women.

The study was conducted at the Mayo Center for Clinical and Translational Science.

This was a randomized, double-blind, controlled study in 60 healthy postmenopausal women treated with the following: 1) double placebo; 2) anastrozole, a potent inhibitor of aromatase-enzyme activity, which mediates E₂ synthesis from T; and/or 3) fulvestrant, a selective estrogen receptor-α antagonist.

GH pulse generation was quantified by frequent GH sampling before and after short-term iv somatostatin infusion, thought to induce hypothalamic GHRH-mediated rebound-like GH secretion.

On anastrozole, E₂ fell from 3.1 ± 0.35 pg/mL to 0.36 ± 0.04 pg/mL, and estrone from 13 ± 1.4 pg/mL to 1.9 ± 0.01 pg/mL (P < .001) by mass spectrometry. Estrogen values were unchanged by fulvestrant. T concentrations did not change. One-hour peak GH rebound after somatostatin infusion declined markedly during both estrogen-deprivation schedules (P < .001). Mean (150 min) maximal GH rebound decreased comparably (P < .001). Measures of GH rebound correlated negatively with computed tomography-estimated abdominal visceral fat (all P < .05).

These data suggest a previously unrecognized dependence of hypothalamo-pituitary GH regulation on low levels of endogenous estrogen after menopause.