The DOI matches its Crossref record; 45 of the 49 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“Moreover, as discussed below, AIs reduce bone density.”
From Hypogonadism and male obesity: Focus on unresolved questions (2018) · cites this paper as [110]
In the citing paper
“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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Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
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Bone Quality — The Material and Structural Basis of Bone Strength and Fragility
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The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications
Kaufman, J. M., & Vermeulen, A. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0013 · Cited by 1,079
Bhasin, S., Cunningham, G. R., Hayes, F. J., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., & Montori, V. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2847 · Cited by 965
The Effects of Parathyroid Hormone, Alendronate, or Both in Men with Osteoporosis
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Self-citationEffects of testosterone supplementation in the aging male
Tenover, J. S. (1992) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.75.4.1092 · Cited by 768
Falahati-Nini, A., Riggs, B. L., Atkinson, E. J., O’Fallon, W. M., Eastell, R., & Khosla, S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10942 · Cited by 757
Effects of testosterone supplementation in the aging male.
Tenover, J. S. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.4.1400877 · Cited by 702
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Estrogens and androgens in skeletal physiology and pathophysiology
Almeida, M., Laurent, M. R., Dubois, V., Claessens, F., O'Brien, C. A., Bouillon, R., Vanderschueren, D., & Manolagas, S. C. (2017) · Physiological Reviews · doi:10.1152/physrev.00033.2015 · Cited by 860
Petersenn, S., Fleseriu, M., Casanueva, F. F., Giustina, A., Biermasz, N., Biller, B. M. K., Bronstein, M., Chanson, P., Fukuoka, H., Gadelha, M., et al. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00886-5 · Cited by 411
Sex Steroid Actions in Male Bone
Vanderschueren, D., Laurent, M. R., Claessens, F., Gielen, E., Lagerquist, M. K., Vandenput, L., Börjesson, A. E., & Ohlsson, C. (2014) · Endocrine Reviews · doi:10.1210/er.2014-1024 · Cited by 327
A concise review of testosterone and bone health
Mohamad, N.-V., Soelaiman, I. N., & Chin, K. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s115472 · Cited by 305
Lowered testosterone in male obesity: Mechanisms, morbidity and management
Grossmann, M., Tang Fui, M., & Dupuis, P. (2014) · Asian Journal of Andrology · doi:10.4103/1008-682x.122365 · Cited by 293
Metadata
- 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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