Abstract
Although it has been known for some time that estrogen deficiency is a major pathogenetic factor for osteoporosis related fractures among postmenopausal women, the capability of estrogen (with or without a progestin) to prevent fractures has often been questioned. The publication of the data from the two hormone clinical trials of the Women’s Health Initiative lays that discussion to rest. In both studies what have been considered a standard dose of conjugated estrogen with or without medroxyprogesterone acetate significantly reduced the risk of all fractures, including clinical vertebral fractures and hip fracture, in a population of postmenopausal women, average age 63 yr, not selected for osteoporosis by BMD. These results are particularly impressive given the difficulty of finding a fracture benefit in lower risk populations with other anti-resorptive agents. Surrogate data on lower doses of hormone therapy suggest a fracture benefit would be seen if studies were to be done. The other outcomes in WHI make it important to define appropriate clinical guidelines for use of hormone therapy for prevention of fractures in postmenopausal women.
Similar content being viewed by others
References
Albright, F., Bloomburg, E., and Smith, P. H. (1940). Trans. Assoc. Am. Phys. 55, 298–305.
Albright, F. (1947). Rec. Prog. Hormone Res. 1, 293–353.
Henneman, P. H. and Wallach, S. (1957). Arch. J. Med. 100, 715–723.
Aitken, J. M., Hart, D. M., and Lindsay, R. (1973). Br. Med. J. 3, 515–518.
Lindsay, R., Hart, D. M., Aitken, J. M., et al. (1976). Lancet 1, 1038–1041.
Lindsay, R., Hart, D. M., Forrest, C., and Baud, C. (1980). Lancet 2, 1151–1153.
Nachtigall, L. E., Nachtigall, R. H., Nachtigall, R. D., and Beckman, E. M. (1979). Obstet. Gynecol. 53, 277–281.
Lufkin, E. G., Wahner, H. W., O’Fallon, A.. W. M., et al. (1992). Ann. Intern. Med. 117, 1–9.
Al-Azzawi, F., Hart, D. M., and Lindsay, R. (1987). Br. Med. J. 294, 1261–1262.
Horsman, A., Gallagher, J. C., Simpson, J., and Nordin, B. E. C. (1977). Br. Med. J. 2, 789–792.
Recker, R. R., Saville, P. D., and Heaney, R. P. (1977). Ann. Intern. Med. 87, 649–655.
Christiansen, C., Christensen, S., McNair, P., Hagen, C., Stocklund, K. E., and Transbol, I. (1980). Eur. J. Clin. Invest. 10, 273–279.
Genant, H. K., Cann, C. E., Ettinger, B., and Gordan, G. S. (1982). Ann. Intern. Med. 97, 699–705.
Munk-Jensen, N., Nielsen, S. P., Obel, E. B., and Eriksen, P. B. (1988). Br. Med. J. 296, 1150–1152.
Gallagher, J. C., Kable, W. T., and Goldgar, D. (1991). Am. J. Med. 90, 171–178.
Christiansen, C. and Riis, B. J. (1990). J. Clin. Endocrinol. Metab. 71, 836–841.
Komulainen, M. H., Kroger, H., Tuppurainen, M. T., et al. (1998). Maturitas 31, 45–54.
Mosekilde, L., Beck-Nielsen, H., Sorensen, O. H., et al. (2000). Maturitas 36, 181–193.
Writing Group for the Women’s Health Initiative. (2002). JAMA 288, 321–333.
Cauley, J. A., Robbins, J., Chen, Z., et al. (2003). JAMA 290, 1729–1738.
The Women’s Health Initiative Steering Group. (2004). JAMA 291, 1701–1712.
Lindberg, J. S., Fears, W. B., and Hunt, M. M. (1984). Ann. Intern. Med. 101, 647–648.
Linnel, S. L. and Stager, M. M. (1989). Med. Sci. Sports Exerc. 16, 343–348.
Marcus, R., Cann, C., and Madvig, D. (1985). Ann. Intern. Med. 102, 158–163.
Sanborn, C. F., Martin, B. J., and Wagner, W. W. (1982). Am. J. Obstet. Gynecol. 143, 859–861.
Cann, C. E., Martin, M. C., and Genant, H. (1984). JAMA 252, 626–629.
Drinkwater, B. L., Nilson, K., Chestnut, C. H. I., et al. (1984). N. Engl. J. Med. 311, 277–281.
Gonzalez, E. R. (1982). JAMA 248, 513–514.
Warren, M. P., Brooks-Gunn, J., Hamilton, L. H., Warrant, L. J., and Hamilton, W. G. (1991). J. Clin. Endocrinol. Metab. 72, 847–853.
Klibanski, A., Neer, R. M., Beitins, I. Z., Ridgeay, C., Zervas, N. T., and MacArthur, J. (1980). N. Engl. J. Med. 303, 1511–1514.
Rigotti, N. A., Nussbaum, S. R., Herzog, D. B., et al. (1984). N. Engl. J. Med. 311, 1601–1606.
Putukian, M. (1994). Med. Clin. North. Am. 78, 345–356.
Albright, F., Smith, P. H., and Fraser, R. W. (1942). Am. J. Med. Sci. 204, 625–648.
Smith, M. A., Wilson, J., and Price, W. H. (1982). J. Med. Gen. 19, 100–103.
Barr, D. G. (1974). Arch. Dis. Child. 49, 821–22.
Shore, R. M., Chesney, R. W., Mazess, R. B., Rose, P. G., and Bargman, G. H. (1982). Calcif. Tissue Int. 34, 519–522.
Brown, D. M., Jowsey, J., Bradford, D. S., and Brincar, T. (1974). J. Pediatr. 84, 816–820.
Heaney, R. P., Recker, R. R., and Saville, P. D. (1990). J. Lab. Clin. Med. 92, 953–963.
Nordin, B. E. C. (1987). Calcif. Tissue Int. 41, 51–59.
Epstein, S., Bryce, G., Hinman, J. W. S., et al. (1986). Bone 7, 421–425.
Seibel, M., Cosman, F., Shen, V., et al. (1993). J. Bone Miner. Res. 8, 881–889.
Hesp, R., Hulme, P., Williams, D., and Reeve, J. (1981). Metab. Bone Dis. Relat. Res. 2, 331–334.
Alexandersen, D., Hassafe, C., and Riis, B. J. (1995). Scand. J. Clin. Lab. Invest. 55, 571–576.
Hassager, C., Colwell, A., Assiri, A. M. A., Eastell, R., Russell, R. G. G., and Christiansen, C. (1992). Clin. Endocrinol. 37, 45–50.
Hassager, C., Ristel, J., Ristel, I., and Christiansen, C. (1994). Osteoporosis Int. 4, 349–352.
Gerai, I., Tapuchi, Y., Chai, O., et al. (1997). Calcif. Tissue Int. 60, 317–3222.
Ebeling, P., Atley, L., Guthrie, J., et al. (1996). J. Clin. Endocrinol. Metab. 81, 3366–3371.
Perchl, P., Griesmachei, A., et al. (1998). Calcif. Tissue Int. 62, 388–394.
Eastell, R., Delmas, P. D., Hodgson, S. F., Eriksen, E. F., and Mann, K. G. (1988). J. Clin. Endocrinol. Metab. 67, 741–748.
Mellish, R. W. E., Garrahan, N. J., and Compston, J. E. (1989). Bone Miner. 6, 331–338.
Eriksen, E. F., Mosekilde, L., and Melsen, F. (1985). Bone 6, 141–146.
Kimmel, D. B., Recker, R. R., Gallagher, J. C., et al. (1990). Bone Miner. 11, 217–235.
Borah, B., Gross, G. J., Dufresne, T. E., et al. (2001). Anat. Rec. (New Anat.) 265, 101–110.
Borah, B., Dufresne, T. E., Chmielewski, P. A., Johnson, T. D., Chines, A., and Manhart, M. D. (2004). Bone 34, 736–746.
Dempster, D. W., Birchman, R., Xu, R., Lindsay, R., and Shen, V. (1995). Bone 16, 157–161.
Jilka, R. L. (1998). Bone 23, 75–81.
Jilke, R. L., Hangoc, G., Girasole, G., et al. (1992). Science 257, 88–91.
Bouxsein, M. L., Myers, E. R., and Hayes, W. C. (1996). In: Osteoporosis. Marcus, R. (ed.). Academic Press, San Diego, pp. 373–393.
Vedi, S., Compstoin, J. E., Webb, A., and Tighe, J. R. (1982). Metab. Bone Dis. Rel. Res. 5, 69–74.
Darby, A. J. and Meunier, P. J. (1981). Calcif. Tissue Int. 33, 199–204.
Lips, P., Courpron, P., and Meunier, P. J. (1978). Calcif. Tissue Int. 26, 13–17.
Parfitt, A. M., Matthews, C. H. E., Villaneuva, A. R., et al. (1983). J. Clin. Invest. 72, 1396–1403.
Kleerekoper, M., Villaneuva, A. R., Stoners, J., et al. (1985). Calcif. Tiss. Res. 37, 594–597.
Elders, P. J. M., Netelenbos, J. C., Lips, P., van Ginkel, M. D., Cosman, F., and van der Stelt, P. T. (1988). Bone Miner. 5, 11–19.
Hui, S. L., Slemenda, C. W., Johnston, C. C., and Appledornm C. R. (1987). Bone Miner. 2, 141–146.
Jones, G., Nguyen, T., Sambrook, P., Kelly, P. J., and Eisman, J. A. (1994). Br. Med. J. 309, 691–695.
Morishima, A., Grumach, M. M., and Bilezikian, J. P. (1977). J. Bone Miner. Res. 12(Suppl. 1), S126.
Morishima, A., Grumbach, M. M., Simpson, E. R., Fisher, C., and Qin, K. (1995). J. Clin. Endocrinol. Metab. 80, 3689–3698.
Munooz-Torres, M., Jodar, E., Quesada, M., and Escobar-Jjiminez, F. (1995). Calcif. Tissue Int. 57, 94–96.
Murphy, S., Khaw, K.-T., Cassidy, A., and Compston, J. E. (1993). Bone Miner. 20, 133–140.
Smith, E. C., Boyd, J., Frank, G. R., et al. (1994). N. Engl. J. Med. 331, 1056–1061.
Vanderschueren, D., Boonen, S., and Bouillon, R. (1998). Bone 23, 391–394.
Parfitt, A. M. (2001). In: Osteoporosis, Vol. 1. Marcus, R., Feldman, D., and Kelsey, J. (eds.). Academic Press, Orlando, pp. 443–447.
Felix, R., Hofstetter, W., Wetterwald, A., Ceccini, M. G., and Fleisch, H. (1994). J. Cell. Biochem. 55, 340–349.
Franchimont, N., Rydziel, S., and Canalis, E. (1997). J. Clin. Invest. 100, 1797–1803.
Huges, D. E., Dai, A., Tiffee, J. C., Li, H. H., Mundy, G. R., and Boyce, B. F. (1996). Nature Med. 2, 1132–1136.
Jimi, E., Ikebe, T., Takahashi, N., Hirata, M., Suda, T., and Koga, T. (1996). J. Biol. Chem. 271, 4605–4608.
Jimi, E., Nakamura, I., Ikebe, T., Takahasi, N., and Suda T. (1997). J. Bone Miner. Res. 12(Suppl.), S148.
Kimble, R. B., Srivastava, S., Ross, F. P., Mayayoshi, A., and Pacifici, R. (1996). J. Biol. Chem. 271, 28890–28897.
King, Y.-Y., Yoshida, H., Sarosi, L., et al., (1999). Nature 397, 315–323.
Poli, V., Balena, R., Fattori, E., et al. (1994). EMBO J. 13, 1189–1196.
Turner, R. T., Riggs, B. L., and Spelsberg, T. C. (1994). Endocr. Rev. 15, 175–300.
Yamate, T., Mocharla, H., Taguchi, Y., Igietseme, J. U., Manolagas, S. C., and Abe, E. (1997). Endocrinology 138, 3047–3055.
Yasuda, H., Shima, N., Nakagawa, N., et al. (1998). Proc. Natl. Acad. Sci. USA 95, 3597–3602.
Rickard, D. J., Hofbauer, L. C., Bonde, S. K., Gori, F., Spelsberg, T. C., and Riggs, B. L. (1998). J. Clin. Invest. 101, 413–422.
WHO Study Group assessment of fracture rise and its application to screening for postmenopausal osteoporosis. (1994). WHO: Geneva.
Miles, P. S., Barlays, S., Brenneman, S. K., Abbott, T. A., Barrett-Connor, E., and Siris, E. (2004). Arch. Int. Med. 164, 1113–1120.
Garnero, P., Hausherr, E., Chapuy, M.-C., et al. (1996). J. Bone Miner. Res. 11, 1531–538.
Greendale, G. and Causley, J. (2002). In: Osteoporosis, an evidence-based guide to prevention and management. Cummings, S. R. Cosman, F., and Jamal, S. A. (eds.). American College of Physicians: Philadelphia, pp. 127–150.
Lindsay, R., Hart, D. M., and Clarie, A. C. (1986). Obstet. Gynecol. 63, 759–763.
Cauley, J. A., Seeley, D. G., Ensrud, K., et al. (1995). Ann. Intern. Med. 122, 9–16.
Naessen, T., Persson, I., Adami, H. O., et al. (1990). Ann. Intern. Med. 133, 95–103.
Maxim, P., Ettinger, B., and Spitalny, G. M. (1995). Osteoporosis Int. 5, 23–29.
Weiss, N. S., Ure, C. L., Ballard, J. H., et al. (1980). N. Engl. J. Med. 303, 1195–1198.
Kiel, D. P., Felson, D. T., Anderson, J. J., et al. (1987). N. Engl. J. Med. 317, 1169–1174.
Paganini-Hill, A., Ross, R. K., Gerkins, V. R., et al. (1981). Ann. Intern. Med. 95, 28–31.
Michaëlsson, K., Baron, J. A., Farahmand, B. Y., et al. (1988). Br. Med. J. 316, 1858–1863.
Krieger, N., Kelsey, J. L., Holford, T. R., et al. (1982). Am. J. Epidemiol. 116, 114–118.
Ettinger, B., Genant, H. K., Cann, C. E. (1985). Ann. Intern. Med. 102, 319–324.
Gordon, G. S., Picchi, J., and Roof, B.S. (1973). Trans. Assoc. Am. Physicians 86, 326–332.
Hutchinson, T.A., Polansky, S. M. N., and Feinstein, A. R. (1979). Lancet ii, 706–710.
Johnson, E. R. and Specht, E. E. (1981). Am. J. Public Health 71, 138–144.
Williams, A. R., Weiss, N. S., Ure, C. L., Ballard, J., and Daling, J. R. (1982). Obstet. Gynecol. 60, 695–699.
Barrett-Conner, E. (1991). Ann. Intern. Med. 115, 455–456.
Bush, T. L., et al. for the PEPI writing group. (1996). JAMA 276, 1389–1396.
Greendale, G. A., Espeland, M. E., Slone, S., et al. (2002). Arch. Intern. Med. 162, 665–672.
Cauley, J. A., Black, D. M., Barrett-Connor, E., et al. (2001). Am. J. Med. 110, 442–450.
Hochberg, M. C. (1998). In: Osteoporosis, an evidence-based guide to prevention and management. Cummings, S. R. Cosman, F., and Jamal, S. A. (eds.). American College of Physicians Women’s Health Series, Philadelphia, pp. 181–195.
Hosking, D., Chilvers, C. E., Christiansen, C., et al. (1998). N. Engl. J. Med. 338, 485–489.
Nieves, J. (1998). In: Osteoporosis, an evidence-based guide to prevention and management. Cummings, S. R. Cosman, F., and Jamal, S. A. (eds.). American College of Physicians Women’s Health Series, Philadelphia, pp. 85–108.
Cosman, F. (1998). In: Osteoporosis, an evidence-based guide to prevention and management. Cummings, S. R. Cosman, F., and Jamal, S. A. (eds.). American College of Physicians Women’s Health Series, Philadelphia, pp. 151–167.
Silverman, S. L. (1998). In: Osteoporosis, an evidence-based guide to prevention and management. Cummings, S. R. Cosman, F., and Jamal, S. A. (eds.). American College of Physicians Women’s Health Series, Philadelphia, pp. 197–208.
Cummings, S. R., Karpf, D. B., Harris, F., et al. (2002). Am. J. Med. 112, 281–289.
Sarkar, S., Mitlak, B., Wong, M., et al. (2002). J. Bone Miner. Res. 17, 1–10.
Li, Z., Meredith, M. P., and Hoseyni, M. S. (2001). Stats. Med. 20, 3175–3188.
Delmas, P. D. (2002). Lancet 359, 2018–2026.
Eastell, R., Barton, I., Hannon, R. A., Chines, A., Garnero, P., and Delmas, P. D. (2003). J. Bone Miner. Res. 18, 1051–1056.
Garnero, P., Sornay-Rendu, E., Chapuy, M. C., and Delmas, P. D. (1995). J. Bone Miner. Res. 11, 337–349.
Roux, C., Seena, E., Eastern, R., et al. (2004). Clin. Med. Res. Opinion 20, 433–439.
Greendale, G. A., Espeland, M., Slone, S., Marcus, R., and Barrett-Connor, E. (2002). Arch. Intern. Med. 162, 665–672.
Greendale, G. A., Edelstein, S., and Barrett-Connor, E. (1997). J. Bone Miner. Res. 12, 1833–1843.
Cummings, S. R., Browne, W. S., Bauer, D., et al. (1998). N. Engl. J. Med. 339, 733–738.
Weiss, S. R., Ellman, H., and Dolker, M. (1999). Obstet. Gynecol. 94, 330–336.
Prestwood, K. M., Kenny, A. M., Unson, C., and Kulldorff, M. (2000). J. Clin. Endocr. Metab. 85, 4462–4469.
Lindsay, R., Gallagher, J. C., Kleerekoper, M., Pickar, J. H. (2002). JAMA 287, 2668–2676.
Recker, R. R., Davies, K. M., Dowd, R. M., and Heaney, R. (1999). Ann. Intern. Med. 130, 897–904.
Cummings, S. R., Yankov, V., Ensrud, K., et al. (2003). J. Bone Miner. Res. 18(Suppl 2), 1207.
Lindsay, R., Hart, D. M., MacLean, A., Clark, A. C., Kraszewski, A., and Garwood, J. (1978). Lancet i, 1325–1327.
Christiansen, C., Christiansenm M. S., and Transbol, I. (1981). Lancet i, 459–461.
Felson, D. T., Zhang, Y., Hannan, M. T., Kiel, D. P., Wilson, P. W., and Anderson, J. J. (1993). N. Engl. J. Med. 329, 1141–1146.
Yates, J., Barrett-Connor, E., Barias, S., Cheny, J., Miller, P. D., and Siris, E. (2002). Obstet. Gynecol. 103, 440–446.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lindsay, R. Hormones and bone health in postmenopausal women. Endocr 24, 223–230 (2004). https://doi.org/10.1385/ENDO:24:3:223
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/ENDO:24:3:223