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Cited by 210Menopause: Health Impacts and TreatmentsGrowth Hormone and Insulin-like Growth FactorsEstrogen and related hormone effects

The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women.

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O'Sullivan, A J, Crampton, L J, Freund, J, Ho, K K·1998·Journal of Clinical Investigation
DOI 10.1172/jci2773PMC PMC508969
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Abstract

The route of estrogen replacement therapy has a major impact on the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. Estrogen administration by the oral, but not the transdermal route, reduces IGF-I and increases GH levels in postmenopausal women. To investigate whether these perturbations have metabolic consequences, we compared the effects of 24 wk each of oral (Premarin 1.25 mg) and transdermal (Estraderm 100TTS) estrogen on energy metabolism and body composition in 18 postmenopausal women in an open-label randomized crossover study. Energy expenditure, lipid oxidation (lipid(ox)), and carbohydrate oxidation (CHOox) were measured by indirect calorimetry in the fasted and fed state before and after 2 and 6 mon treatment. Lean body mass, fat mass, and total body bone mineral density were measured by dual X-ray absorptiometry before and after 6 mon treatment. Mean (+/-SE) Luteinizing hormone levels fell to comparable levels during oral and transdermal estrogen, and bone mineral density was significantly increased by both treatments. Mean IGF-I was significantly lower during oral estrogen (77+/-7 versus 97+/-7 microg/liter, P < 0.05) treatment. Lipid(ox) 30-60 min after a standardized meal was significantly lower (36+/-5 versus 54+/-5 mg/min, P < 0.01) and CHOox higher (147+/-13 versus 109+/-12 mg/min, P < 0.05) with oral compared with transdermal estrogen. Oral estrogen resulted in a 1.2+/-0.5 kg (P < 0.05) increase in fat mass and a 1.2+/-0.4 kg (P < 0.01) decrease in lean mass compared with transdermal estrogen. Lean body mass (0.4+/-0.2 kg) and fat mass (0. 1+/-0.4 kg) did not change significantly during transdermal estrogen. In summary, when compared with the transdermal route, oral estrogen reduces lipid(ox), increases fat mass, and reduces lean body mass. The route of estrogen therapy confers distinct and divergent effects on substrate oxidation and body composition. The suppression of lipidox during oral estrogen therapy may increase fat mass although the fall in IGF-I may lead to a loss of lean body mass. The route-dependent changes in body composition observed during estrogen replacement therapy may have important implications for postmenopausal health.

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  • There do not seem to be any acute effects of testosterone replacement on postprandial fat oxidation.

    “There do not seem to be any acute effects of testosterone replacement on postprandial fat oxidation.”

    From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [125]

    The Results report that oral estrogen, compared with transdermal estrogen, caused greater suppression of postprandial lipid oxidation in postmenopausal women. A search for testosterone replacement and androgen effects found no passage addressing whether testosterone replacement has an acute effect; the estrogen finding neither supports nor contradicts that claim. Page numbers are unavailable in our copy. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Suppression of testosterone for at least 7-10 days using a GnRH agonist improved the ability of insulin to suppress fat oxidation.

    “Suppression of testosterone for at least 7-10 days using a gonadotropin-releasing hormone (GnRH) agonist improved the ability of insulin (using the insulin clamp technique) to suppress fat oxidation (125).”

    From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [125]

    The Results and Study techniques sections describe oral versus transdermal estrogen therapy in postmenopausal women, with lipid oxidation measured around a mixed meal. Searches for GnRH agonist, testosterone suppression, 7–10 days, and an insulin clamp found no passage addressing the claimed intervention or outcome. (LLM, conf=0.76)

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Authors
O'Sullivan, A. J., Crampton, L. J., Freund, J., & Ho, K. K.
Affiliations
  • Garvan Institute of Medical Research (AU)
  • St Vincent's Hospital Sydney (AU)
Corresponding author
Ho, K K
ORCID
Ho, K K
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1998-09-01
Volume
102
Issue
5
Pages
1035-1040
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci2773
PMC
PMC508969
OpenAlex
W1974680721
Cited by
210
References
48
Citations by year
2026: 3 · 2025: 1 · 2023: 6 · 2022: 8 · 2021: 7 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 6 · 2012: 7
FWCI
6.93
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
estrogen replacement therapy, route of administration, oral estrogen, transdermal estrogen, substrate oxidation, lipid oxidation, carbohydrate oxidation, energy expenditure, body composition, fat mass, lean body mass, bone mineral density, insulin-like growth factor I, growth hormone, postmenopausal women, energy metabolism, luteinizing hormone, conjugated equine estrogens, transdermal patch
MeSH terms
Administration, Cutaneous, Administration, Oral, Body Composition, Body Weight, Calorimetry, Energy Metabolism, Estradiol, Estrogens, Conjugated (USP), Female, Humans, Insulin-Like Growth Factor I, Luteinizing Hormone, Growth Hormone, Bone Density, Estrogen Replacement Therapy, Postmenopause

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