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Cited by 514Growth Hormone and Insulin-like Growth FactorsMenopause: Health Impacts and TreatmentsEstrogen and related hormone effects

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

WEISSBERGER, ANDREW J., HO, KEN K. Y., LAZARUS, LESLIE·1991·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem-72-2-374
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Abstract

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 premenopausal women (n = 7, follicular phase) and postmenopausal women before and after 2 months of cyclical replacement therapy with either oral ethinyl estradiol (EE, 20 micrograms daily; n = 7) or transdermal 17 beta-estradiol (E2, 100 micrograms 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 less than 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 mIU/L, P less than 0.0005) and mean pulse amplitude (5.3 +/- 1.2 to 11.2 +/- 2.5 mIU/L, P less than 0.01) but significantly reduced circulating IGF-I (0.70 +/- 0.09 to 0.47 +/- 0.04 U/mL, P less than 0.02) levels. Oral EE increased the percent specific binding of [125I]GH (22.0 +/- 1.6 to 32.0 +/- 1.9%, P less than 0.0005), however the derived mean 24-h free serum GH concentrations were significantly higher (P less than 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 less than 0.005) to levels that were not significantly different from those of premenopausal 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 secretion is not restored by the attainment of physiological E2 concentrations using the transdermal route. The contrasting route dependent IGF-I responses have important implications for the long-term benefit of hormone replacement therapy in the menopause.

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Authors
WEISSBERGER, A. J., HO, K. K. Y., & LAZARUS, L.
Affiliations
Garvan Institute of Medical Research (AU)
ORCID
HO, KEN K. Y.
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1991-02
Volume
72
Issue
2
Pages
374-381
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem-72-2-374
OpenAlex
W2050386090
Cited by
514
References
41
Citations by year
2026: 6 · 2025: 3 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 9 · 2020: 5 · 2019: 17 · 2018: 9 · 2017: 9 · 2016: 10 · 2015: 9 · 2014: 14 · 2013: 14 · 2012: 11
FWCI
10.18
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
estrogen replacement therapy, growth hormone secretion, insulin-like growth factor I, GH-binding protein, transdermal estradiol, ethinyl estradiol, postmenopausal women, menopause, gonadotropin suppression, estradiol patch, pulsatile GH secretion, liver function
MeSH terms
Administration, Cutaneous, Administration, Oral, Aged, Carrier Proteins, Estradiol, Ethinyl Estradiol, Female, Humans, Insulin-Like Growth Factor I, Menopause, Middle Aged, Growth Hormone, Estrogen Replacement Therapy

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