Effects of oral versus transdermal estrogen on the growth hormone/insulin-like growth factor I axis in younger and older postmenopausal women: A Clinical Research Center study

To compare the effects of oral vs. transdermal estrogens on GH secretion and levels of circulating insulin-like growth factor I (IGF-I) and IGF- binding protein-3 (IGFBP-3) in younger vs. older postmenopausal women, we conducted a placebo-controlled, cross-over trial of 6 weeks of oral conjugated estrogen (1.25 mg daily) or transdermal estradiol (100 μg/day) administered in random order and separated by an 8-week, treatment-free interval. Sixteen healthy postmenopausal women, ages 49-75 yr, were studied on an NIH-funded General Clinical Research Center grant. Data were analyzed for the combined group as well as in the younger (≤62 yr, n = 8) and older women (>62 yr, n = 8). Spontaneous GH secretion, as assessed by 12-h overnight blood sampling at 20-min intervals; GH responsiveness to iv bolus injection of GHRH; and levels of serum IGF-I and IGFBP-3, before and after GHRH stimulation, were measured at enrollment and after 6 weeks of each estrogen treatment. Before estrogen treatment, spontaneous nocturnal GH secretion and morning IGF-I levels tended to be lower, IGFBP-3 levels did not differ, and GHRH-stimulated GH levels were signifcantly reduced in older vs. younger postmenopausal women. Oral estrogens increased spontaneous GH secretion, decreased serum IGF-I levels, and did not alter IGFBP-3 levels, whereas transdermal estrogens did not alter nocturnal GH secretion or morning IGF-I levels and decreased IGFBP-3 levels only in the older women. GHRH- stimulated GH levels were similar before and after oral or transdermal estrogen treatment. In contrast, after GHRH administration, IGF-I levels were decreased only with oral estrogens, whereas IGFBP-3 levels were decreased with both oral (younger women only) and transdermal (younger and older women) estrogens. We conclude that, in postmenopausal women, oral and transdermal estrogens exert differing effects on the GH/IGF-I axis, but neither form of estrogen completely reverses the known age-related reductions in spontaneous or GHRH-stimulated GH and IGF-I.