Bone Health in the Transgender Population

  • Micol S. RothmanEmail author
  • Sean J. Iwamoto
Treating Bone loss in challenging situations
Part of the following topical collections:
  1. Treating Bone loss in challenging situations


It is well known that sex steroids, particularly estrogen, play a crucial role in the attainment and maintenance of peak bone density in all people. Transgender (trans) have been frequently observed to have low bone density prior to initiation of gender-affirming hormone therapy, while trans men generally do not. With pharmacologic estrogen, many studies show improving bone density in trans women. With pharmacologic testosterone, bone density in trans men remains largely unchanged although androgens have indirect effects on bone health via changes in fat and lean mass. Much remains unknown about best practices to optimize bone health, interpret DXA scans and assess fracture risk in trans adults.


Osteoporosis Transgender Sex steroids Body composition DXA Puberty blockade 



The authors would like to thank Prof. Dr. Guy T'Sjoen and Dr. Chantal Wiepjes for their assistance in reviewing the figures. We would also like to thank Dr. Carol Zapalowski for reviewing the manuscript.


Advanced Fellowship in Geriatrics from the Geriatric Research, Education, and Clinical Center, VA Eastern Colorado Health Care System, Rocky Mountain Regional VA Medical Center (SJI).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they no conflict of interest.

Ethical Approval


Informed Consent



  1. 1.
    Williams Institute. How many adults identify as transgender in the United States. 2016. Website:
  2. 2.
    U.S. Transgender Survey. 2015 Website:
  3. 3.
    Shires DA, Stroumsa D, Jaffee KD, Woodford MR. Primary care providers' willingness to continue gender-affirming hormone therapy for transgender patients. Fam Pract. 2018;35(5):576–81.CrossRefGoogle Scholar
  4. 4.
    Davidge-Pitts CJ, Nippoldt TB, Natt N. Endocrinology fellows’ perception of their confidence and skill level in providing transgender healthcare. Endocr Pract. 2018;24(12):1038–42.CrossRefGoogle Scholar
  5. 5.
    Paradiso C, Lally RM. Nurse practitioner knowledge, attitudes, and beliefs when caring for transgender people. Transgend Health. 2018;3(1):47–56.CrossRefGoogle Scholar
  6. 6.
    Feldman J, Brown GR, Deutsch MB, Hembree W, Meyer W, Meyer-Bahlburg HF, et al. Priorities for transgender medical and healthcare research. Curr Opin Endocrinol Diabetes Obes. 2016;23(2):180–7.CrossRefGoogle Scholar
  7. 7.
    Riggs BL, Khosla S, Melton LJ 3rd. 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(5):763–73.CrossRefGoogle Scholar
  8. 8.
    Cauley JA. Estrogen and bone health in men and women. Steroids. 2015;99(Pt A):11–5.CrossRefGoogle Scholar
  9. 9.
    Vanderschueren D, Laurent MR, Claessens F, Gielen E, Lagerquist MK, Vandenput L, et al. Sex steroid actions in male bone. Endocr Rev. 2014;35(6):906–60.CrossRefGoogle Scholar
  10. 10.
    Manolagas SC, Almeida M. Gonadal Steroids. In: Bilezikian J, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. Hoboken: Wiley; 2019.Google Scholar
  11. 11.
    Duan Y, Beck TJ, Wang XF, Seeman E. Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res. 2003;18(10):1766–74.CrossRefGoogle Scholar
  12. 12.
    Khosla S, Melton LJ 3rd, Riggs BL. The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed? J Bone Miner Res. 2011;26(3):441–51.CrossRefGoogle Scholar
  13. 13.
    Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995;80(12):3689–98.Google Scholar
  14. 14.
    Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331(16):1056–61.CrossRefGoogle Scholar
  15. 15.
    Quaynor SD, Stradtman EW Jr, Kim HG, Shen Y, Chorich LP, Schreihofer DA, et al. Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. N Engl J Med. 2013;369(2):164–71.CrossRefGoogle Scholar
  16. 16.
    Almeida M, Laurent MR, Dubois V, Claessens F, O'Brien CA, Bouillon R, et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol Rev. 2017;97(1):135–87.CrossRefGoogle Scholar
  17. 17.
    King TFJ, Wat WZM, Creighton SM, Conway GS. Bone mineral density in complete androgen insensitivity syndrome and the timing of gonadectomy. Clin Endocrinol. 2017;87(2):136–40.CrossRefGoogle Scholar
  18. 18.
    Bouillon R, Bex M, Vanderschueren D, Boonen S. Estrogens are essential for male pubertal periosteal bone expansion. J Clin Endocrinol Metab. 2004;89(12):6025–9.CrossRefGoogle Scholar
  19. 19.
    Laurent M, Antonio L, Sinnesael M, Dubois V, Gielen E, Classens F, et al. Androgens and estrogens in skeletal sexual dimorphism. Asian J Androl. 2014;16(2):213–22.CrossRefGoogle Scholar
  20. 20.
    Ego S. Skeletal growth: a major determinant of Bone's structural diversity in women and men. In: Bilezikian J, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. Hoboken: Wiley; 2019.Google Scholar
  21. 21.
    Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SA, Goldstein DW, Hahn CW, et al. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest. 2016;126(3):1114–25.CrossRefGoogle Scholar
  22. 22.
    Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA, et al. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab. 2006;91(10):3908–15.CrossRefGoogle Scholar
  23. 23.
    Jankowski CM, Gozansky WS, Kittelson JM, Van Pelt RE, Schwartz RS, Kohrt WM. Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens. J Clin Endocrinol Metab. 2008;93(12):4767–73.CrossRefGoogle Scholar
  24. 24.
    Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, Ensrud KE, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial. JAMA Intern Med. 2017;177(4):471–9.CrossRefGoogle Scholar
  25. 25.
    Drake M, Khosla S. Sex steroids and the pathogenesis of osteoporosis. In: Bilezikian J, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9th ed. Hoboken: Wiley; 2019.Google Scholar
  26. 26.
    Manolagas SC. The quest for osteoporosis mechanisms and rational therapies: how far we’ve come, how much further we need to go. J Bone Miner Res. 2018;33(3):371–85.CrossRefGoogle Scholar
  27. 27.
    T’Sjoen G, Weyers S, Taes Y, Lapauw B, Toye K, Goemaere S, et al. Prevalence of low bone mass in relation to estrogen treatment and body composition in male-to-female transsexual persons. J Clin Densitom. 2009;12(3):306–13.CrossRefGoogle Scholar
  28. 28.
    Wierckx K, Mueller S, Weyers S, Van Caenegem E, Roef G, Heylens G, et al. Long-term evaluation of cross-sex hormone treatment in transsexual persons. J Sex Med. 2012;9(10):2641–51.CrossRefGoogle Scholar
  29. 29.
    Fighera TM, da Silva E, Lindenau JD, Spritzer PM. Impact of cross-sex hormone therapy on bone mineral density and body composition in transwomen. Clin Endocrinol. 2018;88(6):856–62.CrossRefGoogle Scholar
  30. 30.
    Van Caenegem E, Taes Y, Wierckx K, Vandewalle S, Toye K, Kaufman JM, et al. Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone. 2013;54(1):92–7.CrossRefGoogle Scholar
  31. 31.
    Van Caenegem E, Wierckx K, Taes Y, Schreiner T, Vandewalle S, Toye K, et al. Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study. Osteoporos Int. 2015;26(1):35–47.CrossRefGoogle Scholar
  32. 32.
    Zhu LL, Blair H, Cao J, Yuen T, Latif R, Guo L, et al. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis. Proc Natl Acad Sci U S A. 2012;109(36):14574–9.CrossRefGoogle Scholar
  33. 33.
    van Kesteren P, Lips P, Gooren LJ, Asscheman H, Megens J. Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol. 1998;48(3):347–54.CrossRefGoogle Scholar
  34. 34.
    Haraldsen IR, Haug E, Falch J, Egeland T, Opjordsmoen S. Cross-sex pattern of bone mineral density in early onset gender identity disorder. Horm Behav. 2007;52(3):334–43.CrossRefGoogle Scholar
  35. 35.
    Wiepjes CM, de Jongh RT, de Blok CJ, Vlot MC, Lips P, Twisk JW, et al. Bone safety during the first ten years of gender-affirming hormonal treatment in transwomen and transmen. J Bone Miner Res. 2018.Google Scholar
  36. 36.
    Van Caenegem E, T’Sjoen G. Bone in trans persons. Curr Opin Endocrinol Diabetes Obes. 2015;22(6):459–66.CrossRefGoogle Scholar
  37. 37.
    Wiepjes CM, Vlot MC, Klaver M, Nota NM, de Blok CJ, de Jongh RT, et al. Bone mineral density increases in trans persons after 1 year of hormonal treatment: a multicenter prospective observational study. J Bone Miner Res. 2017;32(6):1252–60.CrossRefGoogle Scholar
  38. 38.
    Singh-Ospina N, Maraka S, Rodriguez-Gutierrez R, Davidge-Pitts C, Nippoldt TB, Prokop LJ, et al. Effect of sex steroids on the bone health of transgender individuals: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2017;102(11):3904–13.CrossRefGoogle Scholar
  39. 39.
    Van Caenegem E, Wierckx K, Taes Y, Schreiner T, Vandewalle S, Toye K, et al. Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case-controlled study (ENIGI). Eur J Endocrinol. 2015;172(2):163–71.CrossRefGoogle Scholar
  40. 40.
    Van Caenegem E, Wierckx K, Taes Y, Dedecker D, Van de Peer F, Toye K, et al. Bone mass, bone geometry, and body composition in female-to-male transsexual persons after long-term cross-sex hormonal therapy. J Clin Endocrinol Metab. 2012;97(7):2503–11.CrossRefGoogle Scholar
  41. 41.
    Turner A, Chen TC, Barber TW, Malabanan AO, Holick MF, Tangpricha V. Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects. Clin Endocrinol. 2004;61(5):560–6.CrossRefGoogle Scholar
  42. 42.
    Mueller A, Haeberle L, Zollver H, Claassen T, Kronawitter D, Oppelt PG, et al. Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals. J Sex Med. 2010;7(9):3190–8.CrossRefGoogle Scholar
  43. 43.
    Elbers JM, Asscheman H, Seidell JC, Megens JA, Gooren LJ. Long-term testosterone administration increases visceral fat in female to male transsexuals. J Clin Endocrinol Metab. 1997;82(7):2044–7.Google Scholar
  44. 44.
    van Kesteren P, Lips P, Deville W, Popp-Snijders C, Asscheman H, Megens J, et al. The effect of one-year cross-sex hormonal treatment on bone metabolism and serum insulin-like growth factor-1 in transsexuals. J Clin Endocrinol Metab. 1996;81(6):2227–32.Google Scholar
  45. 45.
    Broulik PD, Urbanek V, Libansky P. Eighteen-year effect of androgen therapy on bone mineral density in trans(gender) men. Horm Metab Res. 2018;50(2):133–7.CrossRefGoogle Scholar
  46. 46.
    Ruetsche AG, Kneubuehl R, Birkhaeuser MH, Lippuner K. Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study. Osteoporos Int. 2005;16(7):791–8.CrossRefGoogle Scholar
  47. 47.
    Bruder JM, Ma JZ, Basler JW, Welch MD. Prevalence of osteopenia and osteoporosis by central and peripheral bone mineral density in men with prostate cancer during androgen-deprivation therapy. Urology. 2006;67(1):152–5.CrossRefGoogle Scholar
  48. 48.
    Panagiotakopoulos L. Transgender medicine - puberty suppression. Rev Endocr Metab Disord. 2018;19(3):221–5.CrossRefGoogle Scholar
  49. 49.
    Klink D, Caris M, Heijboer A, van Trotsenburg M, Rotteveel J. Bone mass in young adulthood following gonadotropin-releasing hormone analog treatment and cross-sex hormone treatment in adolescents with gender dysphoria. J Clin Endocrinol Metab. 2015;100(2):E270–5.CrossRefGoogle Scholar
  50. 50.
    Vlot MC, Klink DT, den Heijer M, Blankenstein MA, Rotteveel J, Heijboer AC. Effect of pubertal suppression and cross-sex hormone therapy on bone turnover markers and bone mineral apparent density (BMAD) in transgender adolescents. Bone. 2017;95:11–9.CrossRefGoogle Scholar
  51. 51.
    Tack LJW, Craen M, Lapauw B, Goemaere S, Toye K, Kaufman JM, et al. Proandrogenic and antiandrogenic progestins in transgender youth: differential effects on body composition and bone metabolism. J Clin Endocrinol Metab. 2018;103(6):2147–56.CrossRefGoogle Scholar
  52. 52.
    Sedlak CA, Roller CG, van Dulmen M, Alharbi HA, Sanata JD, Leifson MA, et al. Transgender individuals and osteoporosis prevention. Orthop Nurs. 2017;36(4):259–68.CrossRefGoogle Scholar
  53. 53. Accessed 2/26, 2019.
  54. 54.
    Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline. Endocr Pract. 2017;23:1437.CrossRefGoogle Scholar
  55. 55.
    Hammond I, Lentle B, van den Berg L, Vitols-McKay M. Gender identity and bone densitometry. Can Assoc Radiol J. 2017;68(3):267–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Endocrinology, Metabolism & DiabetesUniversity of Colorado School of MedicineAuroraUSA
  2. 2.Division of EndocrinologyRocky Mountain Regional VA Medical CenterAuroraUSA

Personalised recommendations