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Journal of Clinical Endocrinology & Metabolism Vol. 72, No. 2 374-381
doi:10.1210/jcem-72-2-374
Copyright © 1991 by the Endocrine Society.
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Contrasting Effects of Oral and Transdermal Routes of Estrogen Replacement Therapy on 24-Hour Growth Hormone (GH) Secretion, Insulin-Like Growth Factor I, and GH-Binding Protein in Postmenopausal Women*

ANDREW J. WEISSBERGER{dagger}, KEN K. Y. HO and LESLIE LAZARUS

Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, Australia

Address correspondence and requests for reprints to: Dr. K. Y. Ho, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales 2010, Australia.

Estrogen deficiency may account for lower circulating GH and insulin-like growth factor I (IGF-I) concentrations in the menopause. Since the liver is the major source of circulating IGF-I and oral estrogens have nonphysiological effects on hepatic function, we have compared GH secretion over 24 h from 20 min sampling and serum IGF-I levels in premeno-pausal women (n = 7, follicular phase) and postmenopausal women before and after 2 months of cyclical replacement therapy with either oral ethinyl estradiol (EE, 20 µg daily; n = 7) or transdermal 17µ-estradiol (E2, 100 µg patches applied twice weekly; n = 7). The extent of GH binding to its serum binding protein was also examined by measuring the percent specific binding of [125I] GH in serum.

Mean 24-h serum GH and serum IGF-I were significantly lower (P < 0.05) in postmenopausal than in premenopausal women. Oral and transdermal estrogen therapy resulted in a comparable degree of gonadotropin suppression. Oral EE treatment increased mean 24-h serum GH (2.0 ± 0.4 to 7.0 ± 0.6 mlU/L, P < 0.0005) and mean pulse amplitude (5.3 ± 1.2 to 11.2 ± 2.5 mlU/L, P < 0.01) but significantly reduced circulating IGF-I (0.70 ± 0.09 to 0.47 ± 0.04 U/mL, P < 0.02) levels. Oral EE increased the percent specific binding of [125I]GH (22.0 ± 1.6 to 32.0 ± 1.9%, P < 0.0005), however the derived mean 24-h free serum GH concentrations were significantly higher (P < 0.0005) after treatment. By contrast, transdermal E2 administration, which restored circulating E2 concentrations to the midfollicular range, increased circulating IGF-I (0.86 ± 0.15 to 1.10 ± 0.14 U/mL, P < 0.005) to hvels that were not significantly different from those of premencpausal women (1.41 ± 0.21 U/mL). This was not accompanied by changes in 24-h GH secretion or the percent specific binding of [125I]GH in serum.

The route of administration is a major determinant of the effects of exogenous estrogens on the GH/IGF-I axis. Oral estrogen administration inhibits hepatic IGF-I synthesis and increases GH secretion through reduced feedback inhibition. Reduced GH secretion in the menopause is not explained by estrogen deficiency since GH socretion is not restored by the attainment of physiological E2 (oncentrations using the trans-dermal route. The contrasting route dependent IGF-I responses have important implications for the long-term benefit of hormone replacement therapy in the menopause.

* This work was supported in part by a Centre grant from the National Health and Medical Research Council of Australia.

{dagger} Recipient of a Medical Postgraduate Research Scholarship from the National Health and Medical Research Council of Australia.

Received June 16, 1989.




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 Arterioscler. Thromb. Vasc. Bio.Home page
E. J. Giltay, L. J. G. Gooren, J. J. Emeis, T. Kooistra, and C. D. A. Stehouwer
Oral, but Not Transdermal, Administration of Estrogens Lowers Tissue-Type Plasminogen Activator Levels in Humans Without Affecting Endothelial Synthesis
Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1396 - 1403.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
Y. J. H. Janssen, F. Helmerhorst, M. Frölich, and F. Roelfsema
A Switch from Oral (2 mg/Day) to Transdermal (50 {micro}g/Day) 17{beta}-Estradiol Therapy Increases Serum Insulin-Like Growth Factor-I Levels in Recombinant Human Growth Hormone (GH)-Substituted Women with GH Deficiency
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 464 - 467.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
D. M. Cook, W. H. Ludlam, and M. B. Cook
Route of Estrogen Administration Helps to Determine Growth Hormone (GH) Replacement Dose in GH-Deficient Adults
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3956 - 3960.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
P. Garnero, Y. Tsouderos, I. Marton, C. Pelissier, C. Varin, and P. D. Delmas
Effects of Intranasal 17{beta}-Estradiol on Bone Turnover and Serum Insulin-Like Growth Factor I in Postmenopausal Women
J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2390 - 2397.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
A. G. Johansson, B. E. Engström, S. Ljunghall, F. A. Karlsson, and P. Burman
Gender Differences in the Effects of Long Term Growth Hormone (GH) Treatment on Bone in Adults with GH Deficiency
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2002 - 2007.
[Abstract] [Full Text]

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 Am. J. Physiol. Endocrinol. Metab.Home page
E. Ghigo, G. Aimaretti, M. Maccario, G. Fanciulli, E. Arvat, F. Minuto, G. Giordano, G. Delitala, and F. Camanni
Dose-response study of GH effects on circulating IGF-I and IGFBP-3 levels in healthy young men and women
Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1009 - E1013.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
N. Shah, W. S. Evans, and J. D. Veldhuis
Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1999; 276(5): R1351 - R1358.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. K. Støving, A. Flyvbjerg, J. Frystyk, S. Fisker, J. Hangaard, M. Hansen-Nord, and C. Hagen
Low Serum Levels of Free and Total Insulin-Like Growth Factor I (IGF-I) in Patients with Anorexia Nervosa Are Not Associated with Increased IGF-Binding Protein-3 Proteolysis
J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1346 - 1350.
[Abstract] [Full Text]

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 Endocr. Rev.Home page
A. Giustina and J. D. Veldhuis
Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human
Endocr. Rev., December 1, 1998; 19(6): 717 - 797.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
T. M. Fiad, T. P. Smith, S. K. Cunningham, and T. J. McKenna
Decline in Insulin-Like Growth Factor I Levels after Clomiphene Citrate Does Not Correct Hyperandrogenemia in Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2394 - 2398.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
N. Mauras, S. Welch, A. Rini, and M. W. Haymond
Ovarian Hyperandrogenism Is Associated with Insulin Resistance to Both Peripheral Carbohydrate and Whole-Body Protein Metabolism in Postpubertal Young Females: A Metabolic Study
J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1900 - 1905.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
M. E. Wilson
Regulation of the Growth Hormone-Insulin-Like Growth Factor I Axis in Developing and Adult Monkeys Is Affected by Estradiol Replacement and Supplementation with Insulin-Like Growth Factor I
J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2018 - 2028.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
P. Ovesen, N. Vahl, S. Fisker, J. D. Veldhuis, J. S. Christiansen, and J. O. L. Jørgensen
Increased Pulsatile, But Not Basal, Growth Hormone Secretion Rates and Plasma Insulin-Like Growth Factor I Levels during the Periovulatory Interval in Normal Women
J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1662 - 1667.
[Abstract] [Full Text]

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 Clin. Chem.Home page
M. Andersen, P. H. Petersen, O. Blaabjerg, J. Hangaard, and C. Hagen
Evaluation of growth hormone assays using ratio plots
Clin. Chem., May 1, 1998; 44(5): 1032 - 1038.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
R. R. Kraemer, L. G. Johnson, R. Haltom, G. R. Kraemer, H. Gaines, M. Drapcho, T. Gimple, and V. D. Castracane
Effects of hormone replacement on growth hormone and prolactin exercise responses in postmenopausal women
J Appl Physiol, February 1, 1998; 84(2): 703 - 708.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
M. Hettiarachchi, S. Chalkley, S. M. Furler, Y.-S. Choong, M. Heller, G. J. S. Cooper, and E. W. Kraegen
Rat amylin-(8---37) enhances insulin action and alters lipid metabolism in normal and insulin-resistant rats
Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E859 - E867.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
C. H. Gravholt, R. W. Naeraa, S. Fisker, and J. S. Christiansen
Body Composition and Physical Fitness Are Major Determinants of the Growth Hormone-Insulin-Like Growth Factor Axis Aberrations in Adult Turner's Syndrome, with Important Modulations by Treatment with 17{beta}-Estradiol
J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2570 - 2577.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
J. Escalada, F. Sanchez-Franco, B. Velasco, and L. Cacicedo
Regulation of Growth Hormone (GH) Gene Expression and Secretion During Pregnancy and Lactation in the Rat: Role of Insulin-Like Growth Factor-I, Somatostatin, and GH-Releasing Hormone
Endocrinology, August 1, 1997; 138(8): 3435 - 3443.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. Argente, N. Caballo, V. Barrios, M. T. Munoz, J. Pozo, J. A. Chowen, G. Morande, and M. Hernandez
Multiple Endocrine Abnormalities of the Growth Hormone and Insulin-Like Growth Factor Axis in Patients with Anorexia Nervosa: Effect of Short- and Long-Term Weight Recuperation
J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2084 - 2092.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
M. Hornum, D. M. Cooper, J. A. Brasel, A. Bueno, and K. E. Sietsema
Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women
J Appl Physiol, June 1, 1997; 82(6): 1946 - 1951.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Barnard, F.-y. Chan, and H. D. McIntyre
Growth Hormone-Binding Protein in Normal and Pathologic Gestation: Correlations with Maternal Diabetes and Fetal Growth
J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1879 - 1884.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. Burman, A. G. Johansson, A. Siegbahn, B. Vessby, and F. A. Karlsson
Growth Hormone (GH)-Deficient Men Are More Responsive to GH Replacement Therapy Than Women
J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 550 - 555.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
B. Andersson, L.-A. Mattsson, L. Hahn, L. Lapidus, G. Holm, B.-A. Bengtsson, and P. Bjorntorp
Estrogen Replacement Therapy Decreases Hyperandrogenicity and Improves Glucose Homeostasis and Plasma Lipids in Postmenopausal Women With Noninsulin-Dependent Diabetes Mellitus
J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 638 - 643.
[Abstract] [Full Text] [PDF]


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