title: Effects of progestin-opposed transdermal estrogen administration on growth hormone and insulin-like growth factor-I in postmenopausal women of different ages.
abstract: Prior studies in women have shown a positive correlation of endogenous estrogen levels with spontaneous and stimulated GH secretion and basal insulin-like growth factor-I (IGF-I) levels. In postmenopausal women, estrogen replacement therapy (ERT) by the oral route increases basal and GHRH-stimulated GH secretion but decreases basal IGF-I levels. To assess the corresponding effects of transdermal ERT (tERT) on this axis, we administered four 8-week regimens of transdermal 17 beta-estradiol (Estraderm; 0, 50, 100, or 150 micrograms/day) combined with oral medroxyprogesterone acetate (10 mg each day) during weeks 3-4 and 7-8 of each 8-week regimen (except placebo) to 28 healthy nonobese postmenopausal women, aged 45.3-71.8 yr. Basal levels of estradiol (E2), GH, and IGF-I as well as GH responsivity to bolus iv administration of GH-releasing hormone-(1-44) (1 micrograms/kg), were measured before tERT and at weeks 6 and 8 of each regimen; estrone (E1) levels were measured before tERT and at week 6 of each regimen. Before tERT, age was inversely correlated with both the peak GH response to GHRH (r = -0.43; P less than 0.02) and basal IGF-I levels (r = -0.37; P less than 0.05), but not with basal E2, E1, or GH levels. There were progressive increases in plasma E2 and E1 levels with increasing doses of tERT (P = 0.0001), independent of age (P greater than 0.2) and body mass index (P greater than 0.2). Mean basal GH and IGF-I levels were not altered significantly by tERT or medroxyprogesterone acetate. Peak and integrated GH secretory responses to exogenous GHRH decreased with increasing tERT dose (P less than 0.01) in both younger and older postmenopausal women. Our findings suggest that the known effects of tERT on bone and other tissues are not mediated via increases in circulating levels of immunoreactive GH or IGF-I, but do not preclude the possibility of tERT-induced increases in the biological activity or paracrine action of IGF-I.
authors.affiliation: Endocrinology Section, National Institute on Aging, National Institutes of Health, Francis Scott Key Medical Center, Baltimore, Maryland 21224.
authors.forename: M F
authors.initials: MF
authors.lastname: Bellantoni
authors.forename: S M
authors.initials: SM
authors.lastname: Harman
authors.forename: D E
authors.initials: DE
authors.lastname: Cho
authors.forename: M R
authors.initials: MR
authors.lastname: Blackman
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D015992:Body Mass Index; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D004970:Estrone / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate; D008593:Menopause / Q000502:physiology*; D008875:Middle Aged
chemical_list: D004970:Estrone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone