Advertisement

Osteoporosis International

, Volume 26, Issue 1, pp 35–47 | Cite as

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study

  • E. Van CaenegemEmail author
  • K. Wierckx
  • Y. Taes
  • T. Schreiner
  • S. Vandewalle
  • K. Toye
  • J.-M. Kaufman
  • G. T’Sjoen
Original Article

Abstract

Summary

Although trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2 years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton.

Purpose

The aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2 years of hormonal therapy.

Methods

In a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2 years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4 mg daily (or transdermal 17-β estradiol 100 μg/24 h for patients >45 years old), both combined with oral cyproterone acetate 50 mg daily.

Results

Prior to CSH, trans women had lower aBMD at all measured sites (all p < 0.001), smaller cortical bone size (all p < 0.05), and lower muscle mass and strength and lean body mass (all p < 0.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all p < 0.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all p < 0.05).

Conclusions

Although trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Keywords

Bone transsexual gender dyspohria sex steroids prospective 

Notes

Acknowledgments

The authors are indebted to Griet De Cuypere, MD, PhD; Gunter Heylens, MD; Els Elaut, MSc, Birgit Van Hoorde, MSc; Steven Weyers, MD, PhD; Piet Hoebeke, MD, PhD; Stan Monstrey, MD, PhD; for referral of participants and to Jens Jacobeit, MD (Endokrinologikum, Hamburg, Germany) and Mick van Trotsenburg, MD (Vrije Universiteit, Amsterdam, the Netherlands) for their contribution to the development of the ENIGI endocrinological protocol. We thank all volunteers who participated as study subjects. We also thank Veronique Van den Bossche and Kathelyne Mertens for their excellent technical assistance. This work was supported in part by Grant G.0867.11 from the Research Foundation Flanders; Eva Van Caenegem, Sara Vandewalle, and Katrien Wierckx are holders of a PhD fellowship respectively from the Research Foundation Flanders (Eva Van Caenegem and Sara Vandewalle) and Ghent University (Katrien Wierckx).

Conflicts of interest

Eva Van Caenegem, Katrien Wierckx, Youri Taes, Thomas Schreiner, Sara Vandewalle, Kaatje Toye, Jean-Marc Kaufman, and Guy T’Sjoen declare that they have no conflict of interest.

References

  1. 1.
    Seeman E (2001) Clinical review 137: Sexual dimorphism in skeletal size, density, and strength. J Clin Endocrinol Metab 86:4576–84PubMedCrossRefGoogle Scholar
  2. 2.
    Frost HM (1987) Bone “mass” and the “mechanostat”: a proposal. Anat Rec 219:1–9PubMedCrossRefGoogle Scholar
  3. 3.
    Nilsson M, Ohlsson C, Oden A, Mellstrom D, Lorentzon M (2012) Increased physical activity is associated with enhanced development of peak bone mass in men: a five-year longitudinal study. J Bone Miner Res 27:1206–14PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Callewaert F, Sinnesael M, Gielen E, Boonen S, Vanderschueren D (2010) Skeletal sexual dimorphism: Relative contribution of sex steroids, GH-IGF1, and mechanical loading. J Endocrinol 207:127–34PubMedCrossRefGoogle Scholar
  5. 5.
    Lapauw B, Taes Y, Bogaert V, Vanbillemont G, Goemaere S, Zmierczak HG, De Bacquer D, Kaufman JM (2009) Serum estradiol and not testosterone influences volumetric bone mineral density and modulates the impact of physical activity on bone size at the age of peak bone mass—a study in healthy male siblings. J Bone Miner Res 24:1075–85PubMedCrossRefGoogle Scholar
  6. 6.
    Elbers JM, Asscheman H, Seidell JC, Gooren LJ (1999) Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. Am J Physiol 276:E317–E325PubMedGoogle Scholar
  7. 7.
    Lapauw B, Taes Y, Simoens S, Van Caenegem E, Weyers S, Goemaere S, Toye K, Kaufman JM, T’Sjoen GG (2008) Body composition, volumetric and areal bone parameters in male-to-female transsexual persons. Bone 43:1016–21PubMedCrossRefGoogle Scholar
  8. 8.
    T’Sjoen G, Weyers S, Taes Y, Lapauw B, Toye K, Goemaere S, Kaufman JM (2009) Prevalence of low bone mass in relation to estrogen treatment and body composition in male-to-female transsexual persons. J Clin Densitom 12:306–13PubMedCrossRefGoogle Scholar
  9. 9.
    Van Caenegem E, Taes Y, Wierckx K, Vandewalle S, Toye K, Kaufman JM, Schreiner T, Haraldsen I, T’Sjoen G (2013) Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone 54:92–97PubMedCrossRefGoogle Scholar
  10. 10.
    Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A (2005) Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 113:586–92PubMedCrossRefGoogle Scholar
  11. 11.
    Haraldsen IR, Haug E, Falch J, Egeland T, Opjordsmoen S (2007) Cross-sex pattern of bone mineral density in early onset gender identity disorder. Horm Behav 52:334–43PubMedCrossRefGoogle Scholar
  12. 12.
    Mueller A, Dittrich R, Binder H, Kuehnel W, Maltaris T, Hoffmann I, Beckmann MW (2005) High dose estrogen treatment increases bone mineral density in male-to-female transsexuals receiving gonadotropin-releasing hormone agonist in the absence of testosterone. Eur J Endocrinol 153:107–13PubMedCrossRefGoogle Scholar
  13. 13.
    Mueller A, Zollver H, Kronawitter D, Oppelt PG, Claassen T, Hoffmann I, Beckmann MW, Dittrich R (2011) Body composition and bone mineral density in male-to-female transsexuals during cross-sex hormone therapy using gonadotrophin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 119:95–100PubMedCrossRefGoogle Scholar
  14. 14.
    Lips P, Asscheman H, Uitewaal P, Netelenbos JC, Gooren L (1989) The effect of cross-gender hormonal treatment on bone metabolism in male-to-female transsexuals. J Bone Miner Res 4:657–62PubMedCrossRefGoogle Scholar
  15. 15.
    Reutrakul S, Ongphiphadhanakul B, Piaseu N, Krittiyawong S, Chanprasertyothin S, Bunnag P, Rajatanavin R (1998) The effects of oestrogen exposure on bone mass in male to female transsexuals. Clin Endocrinol (Oxf) 49:811–14CrossRefGoogle Scholar
  16. 16.
    Ruetsche AG, Kneubuehl R, Birkhaeuser MH, Lippuner K (2005) Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study. Osteoporos Int 16:791–98PubMedCrossRefGoogle Scholar
  17. 17.
    Sosa M, Jodar E, Arbelo E, Dominguez C, Saavedra P, Torres A, Salido E, de Tejada MJ, Hernandez D (2003) Bone mass, bone turnover, vitamin D, and estrogen receptor gene polymorphisms in male to female transsexuals: Effects of estrogenic treatment on bone metabolism of the male. J Clin Densitom 6:297–304PubMedCrossRefGoogle Scholar
  18. 18.
    Van Kesteren P, Lips P, Gooren LJ, Asscheman H, Megens J (1998) Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol (Oxf) 48:347–54CrossRefGoogle Scholar
  19. 19.
    Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ (2011) A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 164:635–42PubMedCrossRefGoogle Scholar
  20. 20.
    Coleman E, Bockting W, Botzer M, Cohen-Kettenis PT, De Cuypere G, Feldman J, Fraser L, Green J, Knudson G, Meyer W, Adler R, Brown G, Ehrbar R, Ettner R, Eyler E, Garofalo R, Karasic D, Lev AI, Mayer G, Meyer-Bahlburg H, Hall BP, Pfaefflin F, Rachlin K, Robinson B, Schechter L, Tangpricha V, van Trotsenburg M, Vitale A, Winter S, Whittle S, Wylie K, Zucker K (2011) Standards of care for the health of transsexual, transgender and gender nonconforming people. 7th edition. Int J Transgenderism 13:165–232CrossRefGoogle Scholar
  21. 21.
    Kreukels BP, Haraldsen IR, De Cuypere G, Richter-Appelt H, Gijs L, Cohen-Kettenis PT (2012) A European network for the investigation of gender incongruence: the ENIGI initiative. Eur Psychiatry 27:445–50PubMedCrossRefGoogle Scholar
  22. 22.
    Baecke JA, Burema J, Frijters JE (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 36:936–42PubMedGoogle Scholar
  23. 23.
    Van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ (1997) Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 47:337–342CrossRefGoogle Scholar
  24. 24.
    Fiers T, Casetta B, Bernaert B et al (2012) Development of a highly sensitive method for the quantification of estrone and estradiol in serum by liquid chromatography tandem mass spectrometry without derivatization. J Chromatogr B Analyt Technol Biomed Life Sci 893–894:57–62PubMedCrossRefGoogle Scholar
  25. 25.
    Kanis JA, Bianchi G, Bilezikian JP, Kaufman JM, Khosla S, Orwoll E, Seeman E (2011) Towards a diagnostic and therapeutic consensus in male osteoporosis. Osteoporos Int 22:2789–98PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Gunter KB, Almstedt HC, Janz KF (2012) Physical activity in childhood may be the key to optimizing lifespan skeletal health. Exerc Sport Sci Rev 40:13–21PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Delvaux K, Lefevre J, Philippaerts R, Dequeker J, Thomis M, Vanreusel B, Claessens A, Eynde BV, Beunen G, Lysens R (2001) Bone mass and lifetime physical activity in Flemish males: a 27-year follow-up study. Med Sci Sports Exerc 33:1868–75PubMedCrossRefGoogle Scholar
  28. 28.
    Fujiyoshi A, Polgreen LE, Hurley DL, Gross MD, Sidney S, Jacobs DR Jr (2013) A cross-sectional association between bone mineral density and parathyroid hormone and other biomarkers in community-dwelling young adults: the CARDIA study. J Clin Endocrinol Metab 98:4038–46PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Chaitou A, Boutroy S, Vilayphiou N, Munoz F, Delmas PD, Chapurlat R, Szulc P (2010) Association between bone turnover rate and bone microarchitecture in men: the STRAMBO study. J Bone Miner Res 25:2313–23PubMedCrossRefGoogle Scholar
  30. 30.
    Kanis JA, Johnell O, Oden A, Johansson H, Eisman LC, Fujiwara S, KrogerH MCEV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Smoking and fracture risk: a meta-analysis. OsteoporosInt 16:155–162CrossRefGoogle Scholar
  31. 31.
    Khosla S, Oursler MJ, Monroe DG (2012) Estrogen and the skeleton. Trends Endocrinol Metab 23:576–81PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Varsavsky M, Reyes-Garcia R, Garcia-Martin A, Rozas-Moreno P, Rocio GR, Munoz-Torres M (2014) Bone turnover markers in patients with prostate carcinoma: Influence of sex steroids levels. J Bone Miner Metab 32:65–70PubMedCrossRefGoogle Scholar
  33. 33.
    Taxel P, Fall PM, Albertsen PC, Downset RD, Trahiotis M, Zimmerman J, Ohannessian C, Raisz LG (2002) The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. J Clin Endocrinol Metab 87:4907–13PubMedCrossRefGoogle Scholar
  34. 34.
    Eriksson S, Eriksson A, Stege R, Carlstrom K (1995) Bone mineral density in patients with prostatic cancer treated with orchidectomy and with estrogens. Calcif Tissue Int 57:97–99PubMedCrossRefGoogle Scholar
  35. 35.
    Smith MR, Morton RA, Barnette KG, Sieber PR, Malkowicz SB, Rodrigez D, Hancock ML, Steiner MS (2013) Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer. J Urol 189:S45–50PubMedCrossRefGoogle Scholar
  36. 36.
    Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1553–60PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Reid IR, Bolland MJ, Grey A (2014) Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 11(383(9912)):146–55CrossRefGoogle Scholar
  38. 38.
    Lorentzon M, Swanson C, Andersson N, Mellstrom D, Ohlsson C (2005) Free testosterone is a positive, whereas free estradiol is a negative, predictor of cortical bone size in young Swedish men: the GOOD study. J Bone Miner Res 20:1334–41PubMedCrossRefGoogle Scholar
  39. 39.
    Rinaldi G, Wisniewski CA, Setty NG, Leboff MS (2011) Peripheral quantitative computed tomography: Optimization of reproducibility measures of bone density, geometry, and strength at the radius and tibia. J Clin Densitom 14:367–73PubMedCrossRefGoogle Scholar
  40. 40.
    Duckham RL, Frank AW, Johnston JD, Olszynski WP, Kontulainen SA (2013) Monitoring time interval for pQCT-derived bone outcomes in postmenopausal women. Osteoporos Int 24:1917–22PubMedCrossRefGoogle Scholar
  41. 41.
    Marjanovic EJ, Ward KA, Adams JE (2009) The impact of accurate positioning on measurements made by peripheral QCT in the distal radius. OsteoporosInt 20:1207–1214CrossRefGoogle Scholar
  42. 42.
    Yu EW, Bouxsein M, Roy AE, Baldwin C, Cange A, Neer RM, Kaplan LM, Finkelstein JS (2013) Bone loss after bariatric surgery: Discordant results between DXA and QCT bone density. J Bone Miner ResGoogle Scholar
  43. 43.
    Goemaere S, Van Pottelbergh I, Zmierczak H, Toye K, Daems M, Demuynck R, Myny H, De Bacquer D, Kaufman JM (2001) Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: No major role of sex steroid status. Bone 29:286–91PubMedCrossRefGoogle Scholar
  44. 44.
    Svensson J, Moverare-Skrtic S, Windahl S, Swanson C, Sjogren K (2010) Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways. J Mol Endocrinol 45:45–57PubMedCrossRefGoogle Scholar
  45. 45.
    Leung KC, Johannsson G, Leong GM, Ho KK (2004) Estrogen regulation of growth hormone action. Endocr Rev 25:693–721PubMedCrossRefGoogle Scholar
  46. 46.
    Elbers JM, Asscheman H, Seidell JC, Frolich M, Meinders AE, Gooren LJ (1997) Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals. J Clin Endocrinol Metab 82:3267–70PubMedGoogle Scholar
  47. 47.
    Finkelstein JS, Lee H, Burnett-Bowie S-AAM, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ (2013) Gonadal steroids and body composition, strength, and sexual function in men. NEJM 369:1011–1022PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD (2002) Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87:1586–92PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • E. Van Caenegem
    • 1
    • 2
    Email author
  • K. Wierckx
    • 1
    • 2
  • Y. Taes
    • 1
  • T. Schreiner
    • 2
    • 3
  • S. Vandewalle
    • 1
  • K. Toye
    • 1
  • J.-M. Kaufman
    • 1
  • G. T’Sjoen
    • 1
    • 2
    • 4
  1. 1.Department of EndocrinologyGhent University HospitalGhentBelgium
  2. 2.European Network for the Investigation of Gender Incongruence (ENIGI)GhentBelgium
  3. 3.Department of Endocrinology, RikshospitaletOslo University HospitalOsloNorway
  4. 4.Center for Sexology and Gender problemsGhent University HospitalGhentBelgium

Personalised recommendations