Gonadal steroid–dependent effects on bone turnover and bone mineral density in men
Open accessAbstract
BACKGROUND: Severe gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain. METHODS: One hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men. RESULTS: As testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men. CONCLUSIONS: Estrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00114114. FUNDING: AbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.
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Oestradiol may be important for sexual function, prevention of abdominal adiposity, and insulin sensitivity.
“In addition to bone health, 119 oestradiol may be important for of sexual function, prevention of abdominal adiposity 68 and insulin sensitivity.69,120”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [119]
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- Authors
- Finkelstein, J. S., Lee, H., Leder, B. Z., Burnett-Bowie, S.-A. M., Goldstein, D. W., Hahn, C. W., Hirsch, S. C., Linker, A., Perros, N., Servais, A. B., Taylor, A. P., Webb, M. L., Youngner, J. M., & Yu, E. W.
- Affiliations
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2016-02-22
- Volume
- 126
- Issue
- 3
- Pages
- 1114-1125
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC4767351
- OpenAlex
- W2276919011
- Cited by
- 198
- References
- 47
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 16 · 2023: 20 · 2022: 24 · 2021: 14 · 2020: 24 · 2019: 25 · 2018: 20 · 2017: 19 · 2016: 5
- FWCI
- 28.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health
- National Institute on Aging (R01AG030545)
- National Center for Research Resources (UL1RR025758, M01RR001066, P41RR002305)
- 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 › Genetics › Estrogen and related hormone effects
- Keywords
- hypogonadism, testosterone, estradiol, bone mineral density, bone turnover, bone resorption, androgen deficiency, estrogen deficiency, aromatase inhibition, anastrozole, goserelin, bone microarchitecture, men
- MeSH terms
- Adult, Estradiol, Eunuchism, Humans, Male, Middle Aged, Osteoporosis, Testosterone, Bone Density, Bone Remodeling, Treatment Outcome, Young Adult
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