This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leder, B. Z. Articles by Finkelstein, J. S. Search for Related Content PubMed PubMed Citation Articles by Leder, B. Z. Articles by Finkelstein, J. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB TESTOSTERONE

Differential Effects of Androgens and Estrogens on Bone Turnover in Normal Men

Endocrine Unit (B.Z.L., K.M.L., J.S.F.) and Biostatistics Center (D.A.S.), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114; and Division of Clinical Sciences (R.E.), Northern General Hospital, Sheffield, United Kingdom

Address all correspondence and requests for reprints to: Benjamin Z. Leder, M.D., Endocrine Unit, Massachusetts General Hospital, Bulfinch 327, Fruit Street, Boston, Massachusetts 02114. E-mail: bzleder{at}partners.org.

The physiologic role of androgens and estrogens in the maintenance of normal bone turnover in men is a fundamental issue in bone biology. To address this question, we randomized 70 men between the ages of 20 and 44 yr to receive one of three treatment regimens. Group 1 (n = 25) received a GnRH analog (goserelin acetate 3.6 mg by sc injection every 4 wk) alone for 12 wk to suppress endogenous gonadal steroids to prepubertal levels. Group 2 (n = 22) received goserelin plus transdermal testosterone (Androderm 5 mg topically daily) to normalize circulating testosterone and estradiol levels. Group 3 (n = 23) received goserelin plus testosterone plus an aromatase inhibitor (anastrozole 1 mg orally daily) to induce selective estrogen deficiency. The selective effects of androgens and estrogens on skeletal homeostasis were then assessed by measuring changes in biochemical markers of bone turnover and analyzing the between-group differences. Bone resorption markers increased in both the hypogonadal group (group 1) and in the group with selective estrogen deficiency (group 3). Urinary deoxypyridinoline excretion increased more in group 1 than in group 3 (P = 0.023), suggesting a significant effect of androgens on bone resorption, whereas serum N-telopeptide levels increased more in group 3 than in group 2 (P = 0.037), suggesting a significant effect of estrogen on bone resorption. Bone formation markers initially declined in all groups and then increased in groups 1 and 3. The between-group comparisons were consistent for all formation markers. Bone formation markers increased more in group 1 than in group 2 (P = 0.001, 0.037, 0.005 for osteocalcin, carboxy-terminal propeptide of type I procollagen, and amino-terminal propeptide of type I procollagen, respectively). Bone formation markers also increased more in group 1 than in group 3 but these differences were not statistically significant (P = 0.065 0.073, 0.099 for osteocalcin, carboxy-terminal propeptide of type I procollagen, and amino-terminal propeptide of type I procollagen, respectively). Taken together, these data suggest that both androgens and estrogens play independent and fundamental roles in regulating bone resorption in men. These data also suggest that androgens may play an important role in the regulation of bone formation in men.

This work was supported by NIH Grants F32-AR08574 (to B.Z.L.), K23-RR16310 (to B.Z.L.), and K24-DK02759 (to J.S.F.); Massachusetts General Hospital Clinical Research Center Grant RR-1066; and an Endocrine Fellows Foundation grant (to B.Z.L.).

Abbreviations: BMD, Bone mineral density; DPD, deoxypyridinoline; NTX, N-telopeptide; OC, osteocalcin; PICP, carboxy-terminal propeptide of type I procollagen; PINP, amino-terminal propeptide of type I procollagen.

This article has been cited by other articles:

				S. Khosla, S. Amin, and E. Orwoll Osteoporosis in Men Endocr. Rev., June 1, 2008; 29(4): 441 - 464. [Abstract] [Full Text] [PDF]

				A. B. Araujo, T. G. Travison, B. Z. Leder, and J. B. McKinlay Correlations between Serum Testosterone, Estradiol, and Sex Hormone-Binding Globulin and Bone Mineral Density in a Diverse Sample of Men J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2135 - 2141. [Abstract] [Full Text] [PDF]

				A. M. Brufsky Cancer Treatment-Induced Bone Loss: Pathophysiology and Clinical Perspectives Oncologist, February 1, 2008; 13(2): 187 - 195. [Abstract] [Full Text] [PDF]

				M. R. Smith Treatment-related osteoporosis in men with prostate cancer. Clin. Cancer Res., October 15, 2006; 12(20): 6315s - 6319s. [Abstract] [Full Text] [PDF]

				J. P. Bilezikian What's Good for the Goose's Skeleton is Good for the Gander's Skeleton. J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1223 - 1225. [Full Text] [PDF]

				L. B. Michaud and S. Goodin Cancer-treatment-induced bone loss, part 1 Am. J. Health Syst. Pharm., March 1, 2006; 63(5): 419 - 430. [Abstract] [Full Text] [PDF]

				H. Lee, J. S. Finkelstein, M. Miller, S. J. Comeaux, R. I. Cohen, and B. Z. Leder Effects of Selective Testosterone and Estradiol Withdrawal on Skeletal Sensitivity to Parathyroid Hormone in Men J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1069 - 1075. [Abstract] [Full Text] [PDF]

				S. Khosla, B. L. Riggs, R. A. Robb, J. J. Camp, S. J. Achenbach, A. L. Oberg, P. A. Rouleau, and L. J. Melton III Relationship of Volumetric Bone Density and Structural Parameters at Different Skeletal Sites to Sex Steroid Levels in Women J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5096 - 5103. [Abstract] [Full Text] [PDF]

				S. E. Borst, J. H. Lee, and C. F. Conover Inhibition of 5{alpha}-reductase blocks prostate effects of testosterone without blocking anabolic effects Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E222 - E227. [Abstract] [Full Text] [PDF]

				L. Gennari, R. Nuti, and J. P. Bilezikian Aromatase Activity and Bone Homeostasis in Men J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5898 - 5907. [Abstract] [Full Text] [PDF]

				E. Nieschlag, H.M. Behre, P. Bouchard, J.J. Corrales, T.H. Jones, G.K. Stalla, S.M. Webb, and F.C.W. Wu Testosterone replacement therapy: current trends and future directions Hum. Reprod. Update, September 1, 2004; 10(5): 409 - 419. [Abstract] [Full Text] [PDF]

				M. R. Smith, M. A. Fallon, H. Lee, and J. S. Finkelstein Raloxifene to Prevent Gonadotropin-Releasing Hormone Agonist-Induced Bone Loss in Men with Prostate Cancer: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3841 - 3846. [Abstract] [Full Text] [PDF]

				M. R. Smith, M. Goode, A. L. Zietman, F. J. McGovern, H. Lee, and J. S. Finkelstein Bicalutamide Monotherapy Versus Leuprolide Monotherapy for Prostate Cancer: Effects on Bone Mineral Density and Body Composition J. Clin. Oncol., July 1, 2004; 22(13): 2546 - 2553. [Abstract] [Full Text] [PDF]

				K. M. Wiren, X.-W. Zhang, A. R. Toombs, V. Kasparcova, M. A. Gentile, S.-I. Harada, and K. J. Jepsen Targeted Overexpression of Androgen Receptor in Osteoblasts: Unexpected Complex Bone Phenotype in Growing Animals Endocrinology, July 1, 2004; 145(7): 3507 - 3522. [Abstract] [Full Text] [PDF]

				D. Vanderschueren, L. Vandenput, S. Boonen, M. K. Lindberg, R. Bouillon, and C. Ohlsson Androgens and Bone Endocr. Rev., June 1, 2004; 25(3): 389 - 425. [Abstract] [Full Text] [PDF]

				C. Meier, P. Y. Liu, L. P. Ly, J. de Winter-Modzelewski, M. Jimenez, D. J. Handelsman, and M. J. Seibel Recombinant Human Chorionic Gonadotropin But Not Dihydrotestosterone Alone Stimulates Osteoblastic Collagen Synthesis in Older Men with Partial Age-Related Androgen Deficiency J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 3033 - 3041. [Abstract] [Full Text] [PDF]

				S. Khosla, B. L. Riggs, E. J. Atkinson, A. L. Oberg, C. Mavilia, F. Del Monte, L. J. Melton III, and M. L. Brandi Relationship of Estrogen Receptor Genotypes to Bone Mineral Density and to Rates of Bone Loss in Men J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1808 - 1816. [Abstract] [Full Text] [PDF]

				B. Z. Leder, J. L. Rohrer, S. D. Rubin, J. Gallo, and C. Longcope Effects of Aromatase Inhibition in Elderly Men with Low or Borderline-Low Serum Testosterone Levels J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1174 - 1180. [Abstract] [Full Text] [PDF]

				J. K. Amory, N. B. Watts, K. A. Easley, P. R. Sutton, B. D. Anawalt, A. M. Matsumoto, W. J. Bremner, and J. L. Tenover Exogenous Testosterone or Testosterone with Finasteride Increases Bone Mineral Density in Older Men with Low Serum Testosterone J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 503 - 510. [Abstract] [Full Text] [PDF]

				L. Gennari, D. Merlotti, G. Martini, S. Gonnelli, B. Franci, S. Campagna, B. Lucani, N. Dal Canto, R. Valenti, C. Gennari, et al. Longitudinal Association between Sex Hormone Levels, Bone Loss, and Bone Turnover in Elderly Men J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5327 - 5333. [Abstract] [Full Text] [PDF]

				S. Khosla and B. L. Riggs Androgens, Estrogens, and Bone Turnover in Men J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2352 - 2352. [Full Text] [PDF]

				B. Z. Leder and J. S. Finkelstein Authors' Response: Androgens, Estrogens, and Bone Turnover in Men J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2352 - 2353. [Full Text] [PDF]