Research Article| Volume 20, ISSUE 3, P549-558, September 2000

Sex Steroids and Osteoporosis: The Role of Estrogens and Androgens

  • Robert A. Adler
    Address reprint requests to Robert A. Adler, MD, Endocrinology (111-P), McGuire Veterans Affairs Medical Center, 1201 Broad Rock Boulevard, Richmond, VA 23249.
    From the Section of Endocrinology and Metabolism, McGuire Veterans Affairs Medical Center; and the Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      Osteoporosis (low bone mass) depends on the peak bone mass attained and bone loss after the peak. Sex steroids (estrogens and androgens) have an impact on both processes. In this article the roles and mechanisms of estrogens and androgens are discussed in relation to clinical osteoporosis. Other hormones and hormonelike drugs, such as raloxifene, may be used to mimic the effects of natural sex steroids.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Barrett-Connor E.
        Postmenopausal estrogen and prevention bias.
        Ann Intern Med. 1991; 115: 455-456
        • Barrett-Connor E.
        • Kritz-Silverstein D.
        • Edelstein S.L.
        A prospective study of dehydroepi-androsterone sulfate (DHEAS) and bone mineral density in older men and women.
        Am J Epidemiol. 1993; 137: 201-206
        • Behre H.M.
        • Kliesch S.
        • Leifke E.
        • et al.
        Long-term effect of testosterone therapy on bone mineral density in hypogonadal men.
        J Clin Endocrinol Metab. 1997; 82: 2386-2390
        • Biller B.M.K.
        • Baum H.B.A.
        • Rosenthal D.L.
        • et al.
        Progressive trabecular osteopenia in women with hyperprolactinemic amenorrhea.
        J Clin Endocrinol Metab. 1992; 75: 692-697
        • Boot A.M.
        • de Ridder M.A.J.
        • Pols H.A.P.
        • et al.
        Bone mineral density in children and adolescents: Relation to puberty, calcium intake, and physical activity.
        J Clin Endocrinol Metab. 1997; 82: 57-62
        • Carani C.
        • Qin K.
        • Simoni M.
        • et al.
        Effect of testosterone and estradiol in a man with aromatase deficiency.
        N Engl J Med. 1997; 337: 91-95
        • Cauley J.A.
        • Seeley D.G.
        • Ensrud K.
        • et al.
        Estrogen replacement therapy and fractures in older women.
        Ann Intern Med. 1995; 122: 9-16
        • Cummings S.R.
        • Eckert S.
        • Kreuger K.A.
        • et al.
        The effect of raloxifene on risk of breast cancer in postmenopausal women: Results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.
        JAMA. 1999; 281: 2189-2197
        • Daniell H.W.
        Osteoporosis after orchiectomy for prostate cancer.
        J Urol. 1997; 157: 439-444
        • Delmas P.D.
        • Bjarnason N.H.
        • Mitlak B.H.
        • et al.
        Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.
        N Engl J Med. 1997; 337: 1641-1647
        • Duan Y.
        • Parfitt A.M.
        • Seeman E.
        Vertebral bone mass, size, and volumetric density in women with spinal fractures.
        J Bone Miner Res. 1999; 14: 1796-1802
        • Ettinger B.
        • Black D.M.
        • Mitlak B.H.
        • et al.
        Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.
        JAMA. 1999; 282: 637-645
        • European Foundation for Osteoporosis and the National Osteoporosis Foundation
        Consensus development statement: Who are candidates for prevention and treatment for osteoporosis?.
        Osteoporos Int. 1997; 7: 1-6
        • Finkeistein J.S.
        • Neer R.M.
        • Biller B.M.K.
        • et al.
        Osteopenia in men with a history of delayed puberty.
        N Engl J Med. 1992; 326: 600-604
        • Gallagher J.C.
        • Freeman R.
        • Baylink D.J.
        • et al.
        Tibolone prevents postmenopausal bone loss and is well-tolerated: Phase III trial results.
        J Bone Miner Res. 1999; 14: S158
        • Greendale G.A.
        • Edelstein S.
        • Barrett-Connor E.
        Endogenous sex steroids and bone mineral density in older men and women: The Rancho Bernardo Study.
        J Bone Miner Res. 1997; 12: 1833-1843
        • Greenspan S.L.
        • Neer R.M.
        • Ridgway E.C.
        • et al.
        Osteoporosis in men with hyperprolactinemic hypogonadism.
        Ann Intern Med. 1986; 104: 777-782
        • Kasperk C.H.
        • Wakley G.K.
        • Hierl T.
        • et al.
        Gonadal and adrenal androgens are potent regulators of human bone cell metabolism in vitro.
        J Bone Miner Res. 1997; 12: 464-471
        • Katznelson L.
        • Finkeistein J.S.
        • Schoenfeld D.A.
        • et al.
        Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism.
        J Clin Endocrinol Metab. 1996; 81: 4358-4365
        • Khosla S.
        • Melton L.J.
        • Atkinson E.J.
        • et al.
        Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: A key role for bioavailable estrogen.
        J Clin Endocrinol Metab. 1998; 83: 2266-2274
        • Kiel D.P.
        • Felson D.T.
        • Anderson J.J.
        • et al.
        Hip fracture and the use of estrogens in postmenopausal women: The Framingham Study.
        N Engl J Med. 1987; 317: 1169-1174
        • Lindsay R.
        The role of estrogen in the prevention of osteoporosis.
        Endocrinol Metab Clin North Am. 1998; 27: 399-409
        • Lindsay R.
        • Tohme J.
        Estrogen treatment of patients with established postmenopausal osteoporosis.
        Obstet Gynecol. 1990; 76: 290-295
        • Love R.R.
        • Mazess R.B.
        • Barden H.S.
        • et al.
        Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer.
        N Engl J Med. 1992; 326: 852-856
        • Lufkin E.G.
        • Wahner H.W.
        • O’Fallon W.M.
        • et al.
        Treatment of postmenopausal osteoporosis with transdermal estrogen.
        Ann Intern Med. 1992; 117: 1-9
        • Manolagas S.C.
        • Jilka R.L.
        Bone marrow, cytokines, and bone remodeling.
        N Engl J Med. 1995; 332: 305-311
        • The Writing Group for the PEPI
        Effects of hormone therapy on bone mineral density: Results from the postmenopausal estrogen/progestin interventions (PEPI) trial.
        JAMA. 1996; 276: 1389-1396
        • Morales A.J.
        • Nolan J.J.
        • Nelson J.C.
        • et al.
        Effects of replacement dose of dehydroepian-drosterone in men and women of advancing age.
        J Clin Endocrinol Metab. 1994; 78: 1360-1367
        • Nachtigall L.E.
        • Nachtigall R.H.
        • Nachtigall R.D.
        • et al.
        Estrogen replacement therapy. I. A 10-year prospective study in the relationship to osteoporosis.
        Obstet Gynecol. 1979; 53: 277-281
        • Naessen T.
        • Persson I.
        • Adama H.O.
        • et al.
        Hormone replacement therapy and the risk for a first hip fracture: A prospective population-based cohort study.
        Ann Intern Med. 1990; 113: 95-103
        • Prestwood K.M.
        • Pilbeam C.C.
        • Burleson J.A.
        • et al.
        The short term effects of conjugated estrogen on bone turnover in older women.
        J Clin Endocrinol Metab. 1994; 79: 366-371
        • Reid I.R.
        • Wattie D.J.
        • Evans M.C.
        • et al.
        Testosterone therapy in glucocorticoid-treated men.
        Arch Intern Med. 1996; 156: 1173-1177
        • Riggs B.L.
        • Khosla S.
        • Melton LJ I.I.I.
        A unitary model for involutional osteoporosis: Estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men.
        J Bone Miner Res. 1998; 13: 763-773
        • Rosen C.J.
        • Kessenich C.R.
        The pathophysiology and treatment of postmenopausal osteoporosis.
        Endocrinol Metab Clin North Am. 1997; 26: 295-311
        • Slemenda C.W.
        • Longcope C.
        • Shou L.
        • et al.
        Sex steroids and bone mass in older men: Positive associations with serum estrogens and negative associations with androgens.
        J Clin Invest. 1997; 100: 1755-1759
        • Smith E.P.
        • Boyd J.
        • Frank G.R.
        • et al.
        Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man.
        N Engl J Med. 1994; 331: 1056-1061
        • Snyder P.J.
        • Peachey H.
        • Hannoush P.
        • et al.
        Effect of testosterone treatment on bone mineral density in men over 65 years of age.
        J Clin Endocrinol Metab. 1999; 84: 1966-1972
        • Stepan J.J.
        • Lachman M.
        • Zverina J.
        • et al.
        Castrated men exhibit bone loss: Effect of calcitonin treatment on biochemical indices of bone remodeling.
        J Clin Endocrinol Metab. 1989; 69: 523-527
        • Waibel-Treber S.
        • Minne H.W.
        • Scharia S.H.
        • et al.
        Reversible bone loss in women treated with GnRH agonists for endometriosis and uterine leiomyoma.
        Hum Reprod. 1989; 4: 384-388
        • Warren M.P.
        Hormonal influences on the establishment of peak bone mass.
        in: Rosen C.J. Glowacki J. Bilezekian J.P. The Aging Skeleton. Academic Press, San Diego1999: 115
        • Watts N.B.
        • Notelovitz
        • Timmons M.C.
        • et al.
        Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid lipoprotein profiles in surgical menopause.
        Obstet Gynecol. 1995; 85: 529-537
        • Wild R.A.
        • Buchanan J.R.
        • Myers C.
        • et al.
        Declining adrenal androgens: An association with bone loss in aging women.
        Proc Soc Exp Biol Med. 1987; 186: 355-360
        • Young N.
        • Formica C.
        • Szmukler G.
        • et al.
        Bone density at weight-bearing and nonweight-bearing sites in ballet dancers: The effects of exercise, hypogonadism, and body weight.
        J Clin Endocrinol Metab. 1994; 78: 449-454