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Effects of Progestin-Opposed Transdermal Estrogen Administration on Growth Hormone and Insulin-Like Growth Factor-I in Postmenopausal Women of Different Ages^*

Endocrinology Section, Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health (M.F.B., S.M.H., M.R.B.) Baltimore, Maryland 21224
The Divisions of Geriatric Medicine and Gerontology (M.F.B.), Endocrinology and Metabolism (S.M.H., M.R.B.), and Gynecology (D.E.C.), Francis Scott Key Medical Center and Johns Hopkins University School of Medicine Baltimore, Maryland 21224

Address all correspondence and requests for reprints to: Michele F. Bellantoni, M.D., Gerontology Research Center, Room 2B19, 4940 Eastern Avenue, Baltimore, Maryland 21224.

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 17β-estradiol (Estraderm; 0, 50, 100, or 150 µg/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 µg/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 < 0.02) and basal IGF-I levels (r = –0.37; P < 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 > 0.2) andbody mass index (P > 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 < 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.

^* This work was supported in part by Ciba-Geigy Pharmaceutical Co. Grant MCS-220 (to M.R.B.), Bissendorf Peptides GmBH, and General Clinical Research Center Grant M01-RR-02719 from the Division of Research Resources, NIH.

Received May 7, 1990.

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