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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“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]
Citations
Cites
Writing Group for the Women's Health Initiative Investigators (2002) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.288.3.321 · Cited by 15,889
Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410203311604 · Cited by 2,471
Shumaker, S. A., Legault, C., Rapp, S. R., Thal, L., Wallace, R. B., Ockene, J. K., Hendrix, S. L., Jones III, B. N., Assaf, A. R., Jackson, R. D., et al. (2003) · JAMA · doi:10.1001/jama.289.20.2651 · Cited by 2,178
Bone Quality — The Material and Structural Basis of Bone Strength and Fragility
Seeman, E., & Delmas, P. D. (2006) · New England Journal of Medicine · doi:10.1056/nejmra053077 · Cited by 2,157
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
Finkelstein, J. S., Hayes, A.-M., Hunzelman, J. L., Wyland, J. J., Lee, H., & Neer, R. M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035725 · Cited by 823
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
Validation of a screening questionnaire for androgen deficiency in aging males
Morley, J. E., Charlton, E., Patrick, P., Kaiser, F. E., Cadeau, P., McCready, D., & Perry, H. M. (2000) · Metabolism · doi:10.1053/meta.2000.8625 · Cited by 662
Wang, C., Cunningham, G., Dobs, A., Iranmanesh, A., Matsumoto, A. M., Snyder, P. J., Weber, T., Berman, N., Hull, L., & Swerdloff, R. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-032006 · Cited by 656
Bone Loss and Bone Size after Menopause
Ahlborg, H. G., Johnell, O., Turner, C. H., Rannevik, G., & Karlsson, M. K. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022464 · Cited by 647
van den Beld, A. W., de Jong, F. H., Grobbee, D. E., Pols, H. A. P., & Lamberts, S. W. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.9.6825 · Cited by 618
DHEA in elderly women and DHEA or testosterone in elderly men.
Nair, K. S., Rizza, R. A., O'Brien, P., Dhatariya, K., Short, K. R., Nehra, A., Vittone, J. L., Klee, G. G., Basu, A., Basu, R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054629 · Cited by 566
Long-term effect of testosterone therapy on bone mineral density in hypogonadal men
Behre, H. M., Kliesch, S., Leifke, E., Link, T. M., & Nieschlag, E. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.8.4163 · Cited by 559
Endogenous Sex Steroids and Bone Mineral Density in Older Women and Men: The Rancho Bernardo Study
Greendale, G. A., Edelstein, S. L., & Barrett-Connor, E. L. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.11.1833 · Cited by 550
Amory, J. K., Watts, N. B., Easley, K. A., Sutton, P. R., Anawalt, B. D., Matsumoto, A. M., Bremner, W. J., & Tenover, J. L. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031110 · Cited by 475
Effect of Testosterone Treatment on Bone Mineral Density in Men Over 65 Years of Age
Snyder, P. J. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.6.1966 · Cited by 460
Kenny, A. M., Prestwood, K. M., Gruman, C. A., Marcello, K. M., & Raisz, L. G. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.5.m266 · Cited by 456
Slemenda, C. W., Longcope, C., Zhou, L., Hui, S. L., Peacock, M., & Johnston, C. C. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119701 · Cited by 455
Khosla, S. (1998) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.7.2266 · Cited by 447
Osteoporosis in Men with Idiopathic Hypogonadotropic Hypogonadism
Finkelstein, J. S., KLIBANSKI, A., NEER, R. M., GREENSPAN, S. L., ROSENTHAL, D. I., & CROWLEY, W. F. (1987) · Annals of Internal Medicine · doi:10.7326/0003-4819-106-3- · Cited by 407
Mellström, D., Johnell, O., Ljunggren, Ö., Eriksson, A.-L., Lorentzon, M., Mallmin, H., Holmberg, A., Redlund-Johnell, I., Orwoll, E., & Ohlsson, C. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060110 · Cited by 337
Eastell, R., Hannon, R. A., Cuzick, J. M., Dowsett, M., Clack, G., & Adams, J. E. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060508 · Cited by 332
Differential Effects of Androgens and Estrogens on Bone Turnover in Normal Men
Leder, B. Z., LeBlanc, K. M., Schoenfeld, D. A., Eastell, R., & Finkelstein, J. S. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021036 · Cited by 283
Self-citationDuan, Y., Beck, T., Wang, X., & Seeman, E. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.10.1766 · Cited by 252
Hormonal and Biochemical Parameters in the Determination of Osteoporosis in Elderly Men*
Center, J. R., Nguyen, T. V., Sambrook, P. N., & Eisman, J. A. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6051 · Cited by 189
Sex hormones and bone mineral density in elderly men
Murphy, S., Khaw, K.-T., Cassidy, A., & Compston, J. E. (1993) · Bone and Mineral · doi:10.1016/s0169-6009(08)80022-0 · Cited by 187
Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels
Leder, B. Z., Rohrer, J. L., Rubin, S. D., Gallo, J., & Longcope, C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031467 · Cited by 149
Self-citationOestrogens and prostate cancer.
Risbridger, G. P., Bianco, J. J., Ellem, S. J., & McPherson, S. J. (2003) · Endocrine Related Cancer · doi:10.1677/erc.0.0100187 · Cited by 139
Rudman, D. R., Drinka, P. J., Wilsont, C. R., Mattson, D. E., Scherman, F., Cuisinier, M. C., & Schultz, S. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb03018.x · Cited by 133
Boonen, S., Vanderschueren, D., Cheng, X. G., Verbeke, G. N., Dequeker, J., Geusens, P., Broos, P. L. O., & Bouillon, R. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.12.2119 · Cited by 125
Arnold, J. T., Le, H., McFann, K. K., & Blackman, M. R. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00454.2004 · Cited by 122
Taxel, P., Kennedy, D., FALL, P. M., Willard, A. K., Clive, J. M., & Raisz, L. G. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.6.7541 · Cited by 117
Altered Bone Mineral Density in Patients with Complete Androgen Insensitivity Syndrome
Bertelloni, S., Baroncelli, G. I., Federico, G., Cappa, M., Lala, R., & Saggese, G. (1998) · Hormone Research in Paediatrics · doi:10.1159/000023296 · Cited by 92
Estradiol modulates the pulsatile secretion of biologically active luteinizing hormone in man.
Veldhuis, J. D., & Dufau, M. L. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113115 · Cited by 81
Burnett‐Bowie, S. M., Roupenian, K. C., Dere, M. E., Lee, H., & Leder, B. Z. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03327.x · Cited by 73
Self-citationQuantitative Computed Tomography for Spinal Density Measurement Factors Affecting Precision
Rosenthal, D. I., Ganott, M. A., Wyshak, G., Slovik, D. M., Doppelt, S. H., & Neer, R. M. (1985) · Investigative Radiology · doi:10.1097/00004424-198505000-00014 · Cited by 67
Taxel, P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.6.2869 · Cited by 53
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 · Cited by 45
Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men
Leder, B. Z., & Finkelstein, J. S. (2005) · Osteoporosis International · doi:10.1007/s00198-005-1890-8 · Cited by 44
Self-citationTravison, T. G., de Araújo, A. B., Beck, T., Williams, R. E., Clark, R. V., Leder, B. Z., & McKinlay, J. B. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0668 · Cited by 33
Self-citationLee, H., Finkelstein, J. S., Miller, M. E., Comeaux, S. J., Cohen, R., & Leder, B. Z. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2495 · Cited by 31
Self-citationTestosterone and Health Outcomes
Liverman, C. T., & Blazer, D. G. (2004) · Cited by 3
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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
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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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