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Cited by 418Hormonal and reproductive studiesAdrenal Hormones and DisordersMenopause: Health Impacts and Treatments

The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.

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Morales, A. J., Haubrich, R. H, Hwang, J. Y., Asakura, H, Yen, S. S. C·1998·Clinical Endocrinology
DOI 10.1046/j.1365-2265.1998.00507.x
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Abstract

OBJECTIVE: The biological role of the adrenal sex steroid precursors ‐ DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age‐advanced men and women resulted in an elevation (10%) of serum levels of insulin‐like growth factor‐I (IGF‐I) accompanied by improvement of self‐reported physical and psychological well‐being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX). SUBJECTS AND DESIGN: Healthy non‐obese age‐advanced (50–65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double‐blind placebo‐controlled cross‐over trial. Sixteen subjects completed the one‐year study of six months of placebo and six months of 100 mg oral DHEA daily. MEASUREMENTS: Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF‐I, IGFBP‐1, IGFBP‐3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment. RESULTS: Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender‐specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P < 0.02) response in women (−40 ± 8%; P = 0.002) than in men (−5 ± 4%; P = 0.02). Relative to baseline, DHEA administration resulted in an elevation of serum IGF‐I levels in men (16 ±6%, P = 0.04) and in women (31 ±12%, P = 0.02). Serum levels of IGFBP‐1 and IGFBP‐3 were unaltered but GHBP levels declined in women (28 ±6%; P = 0.02) not in men. In men, but not in women, fat body mass decreased 1.0 ± 0.4 kg (6.1 ± 2.6%, P = 0.02) and knee muscle strength 15.0 ± 3.3% (P = 0.02) as well as lumbar back strength 13.9 ± 5.4% (p = 0.01) increased. In women, but not in men, an increase in total body mass of 1.4 ± 0.4 kg (2.1 ± 0.7%; P = 0.02) was noted. Neither gender had changes in basal metabolic rate, bone mineral density, urinary pyridinoline cross‐links, fasting insulin, glucose, cortisol levels or lipid profiles. No significant adverse effects were observed. CONCLUSIONS: A daily oral 100 mg dose of DHEA for 6 months resulted in elevation of circulating DHEA and DS concentrations and the DS/cortisol ratio. Biotransformation to potent androgens near and slightly above the range of their younger counterparts occurred in women with no detectable change in men. Given this hormonal milieu, an increase in serum IGF‐I levels was observed in both genders but dimorphic responses were evident in fat body mass and muscle strength in favour of men. These differences in response to DHEA administration may reflect a gender specific response to DHEA and/or the presence of confounding factor(s) in women such as oestrogen replacement therapy.

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  • The improvement in lean muscle mass mirrors that seen in previous studies with DHEA supplementation in aging or postmenopausal women.

    “The improvement in lean muscle mass mirrors that seen in previous studies with DHEA supplementation in aging or postmenopausal women (7,8).”

    From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [7]

    The Body composition, muscle strength and BMR section reports a trend toward increased lean body mass in women taking DHEA (0.7 ± 0.4 kg, P = 0.08), but not a statistically significant improvement; it reports no increase in men. Thus this study offers limited support for the comparison, but does not establish the claimed improvement in lean muscle mass in aging or postmenopausal women. A page number is not available for the indexed passage. (LLM, conf=0.88)

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  • Positive effects of DHEA replacement have been described on psychological well-being, body composition, and bone mineral density in older, normal adults.

    “positive effects of DHEA replacement have been described on psychological well-being (6), body composition (7,8), and bone mineral density (BMD) (9) in older, normal adults.”

    From Long-Term DHEA Replacement in Primary Adrenal Insufficiency: A Randomized, Controlled Trial (2008) · cites this paper as [7]

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Research works printed but not linked: 3

  1. [11]11. A. J. Morales et al. ᭧ 1998 Blackwell Science Ltd, Clinical Endocrinology, 49, 421-432 13652265, 1998, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.1998.00507.x by Mount Vernon Nazarene University, Wiley Online Library on [23/06/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Metabolic effects of 12-month percutaneous dehydroepidandroster- one replacement therapy in postmenopausal women. Journal of Endocrinology, 150, S43-S50.
  2. [21]21. Khorram, O.A., Vu, L. & Yen, S.S.C. (1977) Activation of immune function by dehydroepiandrosterone in age advanced men. Journal of Gerontology, 52A, M1-M7.
  3. [32]32. Morales, A.J., Nolan, J.J., Nelson, J.C. & Yen, S.S.C. (1994) Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. Journal of Clinical Endocrinology & Metabolism, 78, 1360-1367.

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Authors
Morales, A. J., Haubrich, R. H., Hwang, J. Y., Asakura, H., & Yen, S. S. C.
Affiliations
University of California San Diego (US)
Corresponding author
Yen, S. S. C
ORCID
Haubrich, R. H
Venue
Clinical Endocrinology
Publisher
Wiley
Published
1998-10
Volume
49
Issue
4
Pages
421-432
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1046/j.1365-2265.1998.00507.x
OpenAlex
W1965370016
Semantic Scholar
9195feb5880ef9d117ab8ef0277fe34effab93fe
Cited by
418
References
56
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 12 · 2017: 9 · 2016: 11 · 2015: 14 · 2014: 11 · 2013: 9 · 2012: 13
FWCI
13.90
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1191 d)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsches Krebsforschungszentrum
  • National Institutes of Health (5r01ag010979-03)
  • National Institute on Aging (5R01AG10979-3)
  • National Center for Research Resources (MO1 RR00827, M01RR000827)
  • NIH Clinical Center
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD012303, P50HD12303-19)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords
dehydroepiandrosterone, DHEA sulfate, sex steroids, aging, body composition, muscle strength, insulin-like growth factor I, sex hormone-binding globulin, androstenedione, testosterone, dihydrotestosterone, cortisol, growth hormone binding protein, estrogen replacement therapy, lipid profile, older adults
MeSH terms
Aged, Aging, Androstenedione, Body Composition, Dehydroepiandrosterone, Double-Blind Method, Drug Administration Schedule, Female, Humans, Hydrocortisone, Insulin-Like Growth Factor I, Male, Middle Aged, Muscle Contraction, Sex Factors, Sex Hormone-Binding Globulin, Gonadal Steroid Hormones, Dihydrotestosterone, Testosterone, Estrogen Replacement Therapy, Muscle, Skeletal, Dehydroepiandrosterone Sulfate

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