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Differential Effects of Androgens and Estrogens on Bone Turnover in Normal Men
Abstract
The physiologic role of androgens and estrogens in the maintenance of normal bone turnover in men is a fundamental issue in bone biology. To address this question, we randomized 70 men between the ages of 20 and 44 yr to receive one of three treatment regimens. Group 1 (n = 25) received a GnRH analog (goserelin acetate 3.6 mg by sc injection every 4 wk) alone for 12 wk to suppress endogenous gonadal steroids to prepubertal levels. Group 2 (n = 22) received goserelin plus transdermal testosterone (Androderm 5 mg topically daily) to normalize circulating testosterone and estradiol levels. Group 3 (n = 23) received goserelin plus testosterone plus an aromatase inhibitor (anastrozole 1 mg orally daily) to induce selective estrogen deficiency. The selective effects of androgens and estrogens on skeletal homeostasis were then assessed by measuring changes in biochemical markers of bone turnover and analyzing the between-group differences. Bone resorption markers increased in both the hypogonadal group (group 1) and in the group with selective estrogen deficiency (group 3). Urinary deoxypyridinoline excretion increased more in group 1 than in group 3 (P = 0.023), suggesting a significant effect of androgens on bone resorption, whereas serum N-telopeptide levels increased more in group 3 than in group 2 (P = 0.037), suggesting a significant effect of estrogen on bone resorption. Bone formation markers initially declined in all groups and then increased in groups 1 and 3. The between-group comparisons were consistent for all formation markers. Bone formation markers increased more in group 1 than in group 2 (P = 0.001, 0.037, 0.005 for osteocalcin, carboxy-terminal propeptide of type I procollagen, and amino-terminal propeptide of type I procollagen, respectively). Bone formation markers also increased more in group 1 than in group 3 but these differences were not statistically significant (P = 0.065 0.073, 0.099 for osteocalcin, carboxy-terminal propeptide of type I procollagen, and amino-terminal propeptide of type I procollagen, respectively). Taken together, these data suggest that both androgens and estrogens play independent and fundamental roles in regulating bone resorption in men. These data also suggest that androgens may play an important role in the regulation of bone formation in men.
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“It is well known that aromatase inhibition results in a dramatic reduction of tumor estrogen concentrations [66].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [66]
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Self-citation
Metadata
- Authors
- Leder, B. Z., LeBlanc, K. M., Schoenfeld, D. A., Eastell, R., & Finkelstein, J. S.
- Affiliations
- Massachusetts General Hospital (US)
- Northern General Hospital (GB)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2003-01
- Volume
- 88
- Issue
- 1
- Pages
- 204-210
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2143514874
- Cited by
- 283
- References
- 41
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 11 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 17 · 2015: 6 · 2014: 15 · 2013: 16 · 2012: 17
- FWCI
- 17.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f32ar008574-02)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK02759, K24DK002759)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (F32-AR08574)
- National Center for Research Resources (K23 RR 16310, M01RR001066, K23RR016310, RR-1066)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- androgens, estrogen, bone turnover, bone resorption, bone formation, testosterone, estradiol, aromatase inhibition, goserelin, GnRH analogues, hypogonadism, men, bone turnover markers, deoxypyridinoline, N-telopeptide, osteocalcin, type I procollagen, skeletal homeostasis
- MeSH terms
- Anastrozole, Administration, Cutaneous, Adult, Androgens, Bone Resorption, Drug Synergism, Enzyme Inhibitors, Estrogens, Hormones, Humans, Injections, Subcutaneous, Gonadotropin-Releasing Hormone, Male, Nitriles, Osteogenesis, Testosterone, Triazoles, Biomarkers, Bone Remodeling, Goserelin, Aromatase Inhibitors
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