Association of Hypogonadism and Estradiol Levels with Bone Mineral Density in Elderly Men from the Framingham Study

  1. Shreyasee Amin, MD, FRCP(C), MPH;
  2. Yuqing Zhang, DSc;
  3. Clark T. Sawin, MD;
  4. Stephen R. Evans, MPH;
  5. Marian T. Hannan, DSc, MPH;
  6. Douglas P. Kiel, MD, MPH;
  7. Peter W.F. Wilson, MD; and
  8. David T. Felson, MD, MPH
  1. From Boston University Multipurpose Arthritis and Musculoskeletal Diseases Center, Boston University School of Medicine, Hebrew Rehabilitation Center for Aged, Research and Training Institute, and Harvard Medical School Division on Aging, Boston, Massachusetts; Veterans Administration Headquarters, Washington, D.C.; and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.

    Abstract

    Background: Both hypogonadism and low estrogen levels adversely affect bone health in young men. In elderly men, who are at greatest risk for osteoporotic fracture, the influence of hypogonadism on bone mineral density remains unclear, as does the relative effect of estrogen status compared to hypogonadism.

    Objective: To examine the relation of hypogonadism and estrogen status to bone mineral density in elderly men.

    Design: Community-based, prospective cohort study.

    Setting: Framingham, Massachusetts.

    Patients: Male participants of the Framingham Study.

    Measurements: Total testosterone, total estradiol, and luteinizing hormone were measured in participants at all four biennial examinations from 1981 to 1989. Values from at least three of four examinations were averaged. Hypogonadism was defined as a mean testosterone level less than 10.4 nmol/L (<3.0 ng/mL) or a mean luteinizing hormone level of 20 IU/L or greater. An alternate definition of hypogonadism based only on a mean testosterone level less than 10.4 nmol/L (<3.0 ng/mL) was also used. In 1988–1989, bone mineral density was measured at the proximal femur (femoral neck, Ward triangle, and trochanter) and lumbar spine by using dual-photon absorptiometry and at the radial shaft by using single-photon absorptiometry. The association of hypogonadism with bone mineral density was examined with adjustment for confounders, including estradiol levels. A similar model that adjusted for hypogonadism was used to examine the association of estradiol level (ranked as quartiles) with bone mineral density.

    Results: Of 448 men with bone mineral density measurements, 405 had evaluable hormone levels (mean age, 75.7 years [range, 68 to 96 years]); 71 (17.5%) of the 405 men were hypogonadal. Bone mineral density at any site did not significantly differ in hypogonadal men compared with eugonadal men (for example, bone mineral density at the femoral neck was 0.89 g/cm2 vs. 0.87 g/cm2, respectively; P > 0.2), even when alternate definitions of hypogonadism were used. In contrast, compared with the lowest estradiol quartile, men with higher estradiol levels had greater mean bone mineral density at all sites (for example, bone mineral density at the femoral neck was 0.84 g/cm2, 0.88 g/cm2, 0.86 g/cm2, and 0.91 g/cm2 from the lowest to the highest estradiol quartile; P for trend = 0.002). The difference in mean bone mineral density between men in the lowest and those in the highest estradiol quartile levels was similar to the effect of 10 years of aging on bone mineral density.

    Conclusions: In elderly men, hypogonadism related to aging has little influence on bone mineral density, but serum estradiol levels have a strong and positive association with bone mineral density.

    Article and Author Information

    • Acknowledgments: The authors thank the Framingham cohort and staff; Pamela Bacharach, who performed all sex hormone measurements; and Cherlyn Mercier and Mimi Brodsky, who performed bone mineral density measurements.

    • Grant Support: This work is from the National Heart, Lung, and Blood Institute's Framingham Heart Study, supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract N01-HC-38038. This work was also supported in part by grants AR20613 and AR/AG41398 from the National Institutes of Health and by the Veterans Administration Research Institute, Boston Veterans Affairs Medical Center. Dr. Amin was supported by a research fellowship awarded by the Arthritis Foundation and, in part, by Merck Frosst Canada, Inc.

    • Requests for Single Reprints: Shreyasee Amin, MD, FRCP(C), MPH, Division of Rheumatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

    • Current Author Addresses: Dr. Amin: Division of Rheumatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.

    • Drs. Zhang and Felson: Multipurpose Arthritis and Musculoskeletal Diseases Center, Boston University School of Medicine, 715 Albany Street, A203, Boston, MA 02118.

    • Dr. Sawin: Department of Veterans Affairs (Room 774y), Veterans Health Administration, Office Medical Inspector (1OMI), 810 Vermont Avenue NW, Washington, DC 20420.

    • Mr. Evans: Data Coordinating Center, Boston University School of Public Health, 715 Albany Street, T4E, Boston, MA 02118.

    • Drs. Hannan and Kiel: HRCA Research and Training Institute, Hebrew Rehabilitation Center for Aged, 1200 Centre Street, Boston, MA 02131-1097.

    • Dr. Wilson: Boston University School of Medicine, 715 Albany Street, A206, Boston, MA 02118.

    • Author Contributions: Conception and design: S. Amin, Y. Zhang, C.T. Sawin, M.T. Hannan, D.P. Kiel, D.T. Felson.

    • Analysis and interpretation of the data: S. Amin, Y. Zhang, C.T. Sawin, S.R. Evans, M.T. Hannan, D.P. Kiel, P.W.F. Wilson, D.T. Felson.

    • Drafting of the article: S. Amin, Y. Zhang, C.T. Sawin, D.T. Felson.

    • Critical revision of the article for important intellectual content: S. Amin, Y. Zhang, C.T. Sawin, S.R. Evans, M.T. Hannan, D.P. Kiel, P.W.F. Wilson, D.T. Felson.

    • Final approval of the article: S. Amin, Y. Zhang, C.T. Sawin, S.R. Evans, M.T. Hannan, D.P. Kiel, P.W.F. Wilson, D.T. Felson.

    • Provision of study materials or patients: C.T. Sawin, P.W.F. Wilson, D.T. Felson.

    • Statistical expertise: S. Amin, Y. Zhang, S.R. Evans, M.T. Hannan, D.T. Felson.

    • Obtaining of funding: P.W.F. Wilson, D.T. Felson.

    • Administrative, technical, or logistic support: C.T. Sawin, S.R. Evans, D.P. Kiel, P.W.F. Wilson.

    • Collection and assembly of data: S. Amin, C.T. Sawin, S.R. Evans, M.T. Hannan, D.T. Felson.

    Summary for Patients

    • Summaries for Patients:Levels of Testosterone and Estrogen and Bone Density in Elderly Men Ann Intern Med December 19, 2000 133:S62
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    1. Ann Intern Med December 19, 2000 vol. 133 no. 12 951-963
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