Maturitas
Volume 55, Issue 4 , Pages 325-333 , 20 November 2006

Association between androgen receptor gene polymorphism and bone density in older women using hormone replacement therapy

  • Fréderique Retornaz

      Affiliations

    • Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France
    • Department of Hormonology, University Hospital, Montpellier, France
  • ,
  • Françoise Paris

      Affiliations

    • Department of Hormonology, University Hospital, Montpellier, France
  • ,
  • Serge Lumbroso

      Affiliations

    • Department of Hormonology, University Hospital, Montpellier, France
  • ,
  • Françoise Audran

      Affiliations

    • Department of Hormonology, University Hospital, Montpellier, France
  • ,
  • Fabien Tigoulet

      Affiliations

    • Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France
  • ,
  • Cécile Michelon

      Affiliations

    • Department of Medical Information, University Hospital, Montpellier, France
  • ,
  • Claude Jeandel

      Affiliations

    • Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France
  • ,
  • Charles Sultan

      Affiliations

    • Department of Hormonology, University Hospital, Montpellier, France
  • ,
  • Hubert Blain

      Affiliations

    • Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France
    • Corresponding Author InformationCorresponding author. Tel.: +33 467336778; fax: +33 467336887.

Received 21 November 2005 ,Revised 25 April 2006 ,Accepted 28 April 2006.

References 

  1. Cummings SR, Nevitt MC, Bowner WS, Stone K, Fox KM, Ensrud KE. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332:767–773
  2. Pocok NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S. Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 1987;80:706–710
  3. Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC. Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on gene heritability estimates. J Bone Miner Res. 1991;6:561–567
  4. Seeman E, Tsalamandris C, Formica C, Hopper JL, Mc Kay J. Reduced femoral neck bone density in the daughters of women with hip fractures: the role of low peak bone density in the pathogenesis of osteoporosis. J Bone Miner Res. 1994;9:739–743
  5. Labrie F, Luu-The V, Labrie C, et al. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev. 2003;24:152–182
  6. Miller K. Androgen deficiency in women. J Clin Endocrinol Metab. 2001;86:2395–2401
  7. Slemenda CW, Longcope C, Peacok M, Hui S, Johnston CC. Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri- and postmenopausal women. J Clin Invest. 1996;97:14–21
  8. Greendale GA, Edelstein S, Barrett-Connor E. Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernado Study. J Bone Miner Res. 1997;12:1833–1843
  9. Davis SR, McCLoud P, Strauss BJ, Burger H. Testosterone enhances estradiol's effect on postmenopausal bone density and sexuality. Maturitas. 1995;21:227–236
  10. Raisz LG, Wiita B, Artis A, et al. Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. J Clin Endocrinol Metab. 1996;81:37–43
  11. Barrett-Connor E, Young R, Notelovitz M, et al. A two-year double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles. J Reprod Med. 1999;44:1012–1020
  12. Notelovitz M. Androgen effects on bone and muscle. Ferti Steril. 2002;77(Suppl. 4):S34–S41
  13. Abu EO, Horner A, Kusec V, Trifitt JT, Compston JE. The localization of androgen receptors in human bone. J Clin Endocrinol Metab. 1997;82:3493–3497
  14. Wiren KM, Zhang X, Chan C, Keenan E, Orwoll ES. Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. Endocrinology. 1997;138:2291–2300
  15. Sultan C, Lumbroso S, Paris F, et al. Disorders of androgen action. Semin Reprod Med. 2002;20:217–228
  16. Bertenolli S, Baroncelli GI, Federico G, Cappa M, Lala R, Saggese G. Altered bone mineral density in patients with complete androgen insensitivity syndrome. Horm Res. 1998;50:309–314
  17. Marcus R, Leary D, Schneider DL, Shane E, Favus M, Quigley CA. The contribution of testosterone to skeletal development and maintenance: lesson from the androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000;85:1032–1037
  18. Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res. 1994;22:3181–3186
  19. Gobinet J, Poujol N, Sultan C. Molecular action of androgens. Mol Cel Endo. 2002;198:15–24
  20. Yu H, Bharaj B, Vassilikos EJ, Giai M, Diamandis EP. Shorter CAG repeat length in the androgen receptor gene is associated with more aggressive forms of breast cancer. Breast Cancer Res Treat. 2000;59:153–161
  21. Yaron M, Levy T, Chetrit A, et al. The polymorphic CAG repeat in the androgen receptor in Jewish Israeli women with endometrial carcinoma. Cancer. 2001;92:1190–1194
  22. Levine D, Boyd J. The androgen receptor and genetic susceptibility to ovarian cancer: results from a case series. Cancer Res. 2001;61:908–911
  23. Giguere Y, Dewailly E, Brisson J, et al. Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population. Cancer Res. 2001;61:5869–5874
  24. Hickey T, Chandy A, Norman RJ. The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:161–165
  25. Ibanez L, Ong KK, Mongan N, et al. Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism. J Clin Endocrinol Metab. 2003;88:3333–3338
  26. Buller RE, Sood AK, Lallas T, Skilling JS. Association between non-random X-chromosome inactivation and BRCA1 mutation in germline DNA of patients with ovarian cancer. J Natl Cancer Inst. 1999;91:339–346
  27. Busque L, Mio R, Mattioli J, et al. Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. Blood. 1996;88:59–65
  28. Sharp A, Robinson D, Jacobs P. Age-and tissue-specific variation of X chromosome inactivation ratios in normal women. Hum Genet. 2000;107:343–349
  29. Van Dijk JP, Heuver L, Stevens-Linders E, et al. Acquired skewing of Lyonisation remains stable for a prolonged period in healthy blood donors. Leukemia. 2002;16:326–327
  30. Vottero A, Stratakis CA, Ghizzoni L, Longui CA, Karl M, Chrousos GP. Androgen receptor-mediated hypersensitivity to androgens in women with nonhyperandrogenic hirsutism: skewing of X-chromosome inactivation. J Clin Endocrinol Metab. 1999;84:1091–1095
  31. Kristiansen M, langerød A, Knudsen GP, Weber BL, Børresen-dale AL, Ørstavik KH. High frequency of skewed X inactivation in young breast cancer patients. J Med Genet. 2002;39:30–33
  32. Sowers M, Willing M, Burns T, et al. Genetic markers, bone mineral density, and serum osteocalcin levels. J Bone Miner Res. 1999;14:1411–1419
  33. Salmen T, Heikkinen A, Mahonen A, et al. Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. J Bone Miner Res. 2003;18:319–324
  34. Langdahl BL, Stenkjaer L, Carstens M, Tofteng CL, Eriksen EF. A CAG repeat polymorphism in the androgen receptor gene is associated with reduced bone mass and increases risk of osteoporotic fractures. Calcif Tissue Int. 2003;73:237–238
  35. Chen HY, Chen WC, Wu MC, Tsai FJ, Tsai CH. Androgen receptor gene microsatellite polymorphism in postmenopausal women: correlation to bone mineral density and susceptibility to osteoporosis. Eur J Obstet Gynecol Reprod Biol. 2003;107:52–56
  36. Tofteng CL, Kindmark A, Brändström H, et al. Polymorphisms in the CYP19 and AR genes: relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy: The Danish Osteoporosis Prevention Study. Calcif Tissue Int. 2004;74:25–34
  37. Stiger F, Gerdhem P, Brändström H, et al. A microsatellite marker in the estrogen receptor α gene, but not a microsatellite marker in the androgen receptor gene, is associated with bone mineral density in 75-year old Swedish women. J Bone Miner Res. 2000;15(Suppl. 1):S362
  38. Yamada Y, Ando F, Noaakira N, Shimokata H. Association of polymorphisms of the androgen receptor and klotho genes with bone mineral density in Japanese women. J Mol Med. 2005;83:50–57
  39. Van Pottelbergh I, Lumbroso S, Goemaere S, Sultan C, Kaufman JM. Lack of influence of the androgen receptor gene CAG-repeat polymorphism on sex steroid status and bone metabolism in elderly men. Clin Endocrinol (Oxf). 2001;55:659–666
  40. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen receptor gene correlates with X chromosome inactivation. Am J Hum Genet. 1992;51:1229–1239
  41. Naumova AK, Plenge RM, Bird LM, et al. Heritability of X chromosome-inactivation phenotype in a large family. Am J Hum Genet. 1996;58:1111–1119
  42. Cummings SR, Block G, McHenry K, Baron RB. Evaluation of two food frequency methods of measuring dietary calcium intake. Am J Epidemiol. 1987;126:796–802
  43. Khosla S, Riggs BL, Robb RA, et al. Relationship of volumetric bone density and structural parameters at different skeletal sites to sex steroid levels in women. J Clin Endocrinol Metab. 2005;90:5096–5103
  44. Cohen O, Vinker S, Yaphe J, Kitai E. Hormone replacement therapy and WONCA/COOP functional status: a cross-sectional population-based study of women in Israel. Climacteric. 2005;8:171–176
  45. Genazzani AR, Nicolucci A, Campagnoli C, et al. Assessment of the QoL in Italian menopausal women: comparison between HRT users and non-users. Maturitas. 2002;42:267–280
  46. Ferrari S, Rizzoli R, Slosman D, Bonjour JP. Familial resemblance for bone mineral mass is expressed before puberty. J Clin Endocrinol Metab. 1998;83:358–361
  47. Danielson ME, Cauley JA, Baker CE, et al. Familial resemblance of bone mineral density (BMD) and calcaneal ultrasound attenuation: The BMD in mothers and daughters study. J Bone Miner Res. 1999;14:102–110
  48. Lyon M. The William Allan memorial award address: X-chromosome inactivation and the location and expression of X-linked genes. Am J Hum Genet. 1988;42:8–16
  49. Platz EA, Rimm EB, Willett WC, Kantoff PW, Giovannucci E. racial variation in prostate cancer incidence and in hormonal system markers among male health professionals. J Natl Cancer Inst. 2000;92:2009–2017
  50. Irvine RA, Yu MC, Ross RK, Coetzee GA. The CAG and GCG microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res. 1995;55:1937–1940

PII: S0378-5122(06)00162-9

doi: 10.1016/j.maturitas.2006.04.025

Maturitas
Volume 55, Issue 4 , Pages 325-333 , 20 November 2006