Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels
Open accessAbstract
Context: Aging is associated with declining gonadal steroid production, low bone mineral density (BMD), and fragility fractures. The efficacy and safety of testosterone replacement in older men remains uncertain. Objective: The objective of the study was to assess the effects of aromatase inhibition on BMD in older men with low testosterone levels. Design and Setting: This was a 1-yr, double-blind, randomized, placebo-controlled trial that was conducted at a tertiary care academic center in Boston, MA. Participants: Participants included 69 men aged 60+ yr with borderline or low testosterone levels and hypogonadal symptoms. Intervention: Intervention included 1 mg anastrozole daily or placebo. Main Outcome Measures: Changes in gonadal steroid hormone levels, BMD, and bone turnover markers were measured. Results: Mean serum testosterone increased from 319 ± 93 ng/dl at baseline to 524±139 ng/dl at month 3 (P < 0.0001) and declined slightly to 474 ± 145 ng/dl by 1 yr. Estradiol levels decreased from 15 ± 4 pg/ml at baseline to 12 ± 4 pg/ml at month 3 and then remained stable (P < 0.0001). Posterior-anterior (PA) spine BMD decreased in the anastrozole group as compared with placebo (P = 0.0014). In the anastrozole group, PA spine BMD decreased from 1.121 ± 0.141 g/cm2 to 1.102 ± 0.138 g/cm2, whereas in the placebo group, PA spine BMD increased from 1.180 ± 0.145 g/cm2 to 1.189 ± 0.146 g/cm2. Qualitatively similar, but not statistically significant, changes occurred at the other sites. Bone turnover markers were not affected by anastrozole therapy. Conclusions: In older men, aromatase inhibition increases testosterone levels, decreases estradiol levels, and appears to decrease BMD. Aromatase inhibition does not improve skeletal health in aging men with low or low normal testosterone levels.
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Long-term AI use has been associated with decreases in bone mineral density due to suppression of E2, and the AUA recommends against use of AI for prolonged periods.
“As long-term AI use has been associated with decreases in bone mineral density due to suppression of E2, the AUA recommends against the use of AI for prolonged periods (1,72).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [72]
Tamoxifen was much more effective than anastrozole in the prevention of gynecomastia in bicalutamide-treated men.
“Tamoxifen was much more effective, however, in the prevention of gynecomastia in these men [69,70].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [69]
Anastrozole at a dose of 1 mg daily appeared to be mildly effective against the appearance of gynecomastia in prostate cancer patients treated with bicalutamide.
“A dose of 1 mg daily appeared to be mildly effective against the appearance of gynecomastia.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [69]
A 12-month trial of anastrozole found significant reductions in bone mineral density.
“while Burnett-Bowie’s group identified significant reductions in bone mineral density with therapy.”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [126]
In a 3-month trial of 68 men treated with anastrozole 1 mg/day, there was no change in markers of bone turnover despite greater mean reductions in estradiol.
“Results from the Leder trial reported no change in markers of bone turnover, despite greater mean reductions in estradiol”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [126]
A 3-month anastrozole study showed no significant change in markers of bone resorption, while a subsequent 12-month study showed direct radiologic evidence of bone mineral density loss despite unchanged markers of bone resorption.
“Although one publication of men undergoing anastrozole therapy over a 3-month period demonstrated no significant change in markers of bone resorption, a subsequent 12-month study demonstrated direct radiologic evidence of bone mineral density loss despite unchanged markers of bone resorption.125, 126”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [126]
Significant variation in bone mineral density among reported therapies evidences that outcomes from different testosterone forms should not be used interchangeably.
“This is evidenced by the significant variation on bone mineral density among the reported therapies.126, 127, 135”
From Challenges in Testosterone Measurement, Data Interpretation, and Methodological Appraisal of Interventional Trials (2016) · cites this paper as [126]
AIs reduce bone density.
“Moreover, as discussed below, AIs reduce bone density.”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [110]
BMD at the spine decreased significantly after 12 months of anastrozole, presumably because of the decrease in circulating oestradiol.
“Of concern, BMD at the spine decreased significantly after 12 months of anastrozole, presumably because of the decrease in circulating oestradiol.110”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [110]
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- Authors
- Burnett-Bowie, S.-A. M., McKay, E. A., Lee, H., & Leder, B. Z.
- Affiliations
- Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
- Massachusetts General Hospital (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-12-01
- Volume
- 94
- Issue
- 12
- Pages
- 4785-4792
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2795655
- OpenAlex
- W2062086785
- Cited by
- 146
- References
- 49
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 14 · 2019: 9 · 2018: 4 · 2017: 8 · 2016: 16 · 2015: 8 · 2014: 12 · 2013: 8 · 2012: 11
- FWCI
- 6.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- National Institute on Aging (R01AG025099, R01-AG-025099-03)
- National Center for Research Resources (K23-RR-161310, M01RR001066, M01-RR01066)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- aromatase inhibition, anastrozole, bone mineral density, bone turnover markers, androgen deficiency, hypogonadism, older men, aging, testosterone replacement therapy, estradiol, sex steroids, fragility fractures
- MeSH terms
- Anastrozole, Aged, Aging, Bone and Bones, Double-Blind Method, Enzyme-Linked Immunosorbent Assay, Hormones, Humans, Male, Middle Aged, Nitriles, Patient Compliance, Steroids, Testis, Testosterone, Triazoles, Biomarkers, Bone Density, Endpoint Determination, Aromatase Inhibitors
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