Modulating Effects of Progesterone on Spontaneous Nocturnal and Ghrelin-Induced GH Secretion in Postmenopausal Women

Oral administration of estradiol (E2) generally increases GH secretion in postmenopausal women. Oral administration of E2 is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E2 may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied. We hypothesized that moderately increased serum E2 levels stimulate GH and that P4 modulates E2-stimulated GH secretion.

Four parallel groups of randomly assigned postmenopausal women (n = 40). Treatments were saline placebo and oral placebo, saline placebo and oral micronized P4 (3 × 200 mg/d IM), E2 (5 mg IM) and oral placebo, and E2 IM and oral micronized P4. Outcome measures were overnight GH secretion (10 hours), stimulated (ghrelin, 0.3 µg/kg IV bolus) GH secretion, and CT-estimated visceral fat.

Intramuscular E2 administration did not alter nocturnal and ghrelin-stimulated GH secretion. Nocturnal GH secretion was not changed by P4 administration. However, P4 diminished ghrelin-stimulated pulsatile GH release with or without E2 (average, 7.20 ± 2.14 and 9.58 ± 1.97 µg/L/2 h, respectively; P = 0.045). Respective outcomes for mean GH concentrations and GH peak amplitudes were 0.97 ± 0.31 and 1.52 μg/L ± 0.29 (P = 0.025) and 2.76 ± 1.04 and 3.95 μg/L ± 0.90 (P = 0.031). Ghrelin-stimulated GH secretion correlated negatively with P4 concentration with or without correction for visceral fat area in the regression equation (R = 0.49, P = 0.04, β = -0.040 ± 0.016).

Low-range physiological E2 concentrations do not affect spontaneous or ghrelin-stimulated pulsatile GH secretion. Conversely, P4 inhibits ghrelin-stimulated GH secretion in a concentration-dependent fashion. The mechanistic aspects and physiological significance of natural P4's regulation of ghrelin-evoked GH secretion require further study.