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The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women.
Open accessAbstract
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.”
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]
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“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]
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Metadata
- 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
- Published
- 1998-09-01
- Volume
- 102
- Issue
- 5
- Pages
- 1035-1040
- ISSN
- 0021-9738 (ISSN-L)
- 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
- bronze
- doi.org
- 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 › Endocrinology › 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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