Preprint / Version 1

The Effects of Gender-Affirming Hormone Treatment on Transgender Musculoskeletal Health

A Protocol for a Systematic Review and Meta-Analysis

##article.authors##

  • Andrew Brown University of Brighton
  • Stephanie Moraes University of Brighton
  • Blair Hamilton Manchester Metropolitan University https://orcid.org/0000-0001-7412-1188

DOI:

https://doi.org/10.51224/SRXIV.434

Keywords:

Transgender men, Transgender women, bone, muscle, gender affirming hormone treatment

Abstract

Gender-affirming hormone treatment (GAHT) is an intervention aimed at aligning transgender individuals' hormone levels with their gender identity, thereby alleviating gender dysphoria through modifications to secondary sex characteristics. However, to effectively promote skeletal health, it is crucial to consider the potential adverse effects of GAHT. A previous meta-analysis observed no significant effect of GAHT femoral neck (FN), lumbar spine (LS) or total hip (TH) bone mineral density (BMD) in transgender women. In transgender men, LS BMD showed a significant benefit (ES: 0.04 – 0.06 g•cm-2). However, since that analysis more data have been published and updated methods of meta-analysis have been developed; therefore, an updated systematic review and meta-analysis are warranted. Methods and analysis: Literature published in English up to 31/07/24 will be retrieved by searching 3 electronic databases, cross-referencing and expert review. The primary outcome measures will be changes in FN and LS BMD and lower limb BMD. The risk of bias for each study will be assessed using the Cochrane Risk of Bias instrument for non-randomised control trials (ROBINS-I), while the strength of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. Standardised effect sizes will be calculated from each study and pooled using the inverse heterogeneity (IVhet) model. Prospero Trial Registration number: [CRD42024573102].

Metrics

Metrics Loading ...

References

References

Jones BA, Arcelus J, Bouman WP, Haycraft E. Sport and transgender people: a systematic review of the literature relating to sport participation and competitive sport policies. Sports Medicine. 2017;47(4):701-16.

Kuyper L, Wijsen C. Gender identities and gender dysphoria in the Netherlands. Archives of sexual behavior. 2014;43(2):377-85.

Statista. Share of People Identifying as Transgender, Gender Fluid, Non-binary, or Other Ways Worldwide as of 2023, by Country. https://www.statista.com/statistics/1269778/gender-identity-worldwide-country/; 2023.

Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, et al. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. International journal of transgenderism. 2012;13(4):165-232.

Wylie K, Barrett J, Besser M, Bouman WP, Bridgman M, Clayton A, et al. Good practice guidelines for the assessment and treatment of adults with gender dysphoria. Sexual and Relationship Therapy. 2014;29(2):154-214.

Arcelus J, Bouman WP, Van Den Noortgate W, Claes L, Witcomb G, Fernandez-Aranda F. Systematic review and meta-analysis of prevalence studies in transsexualism. European Psychiatry. 2015;30(6):807-15.

Aitken M, Steensma TD, Blanchard R, VanderLaan DP, Wood H, Fuentes A, et al. Evidence for an altered sex ratio in clinic‐referred adolescents with gender dysphoria. The Journal of Sexual Medicine. 2015;12(3):756-63.

De Vries A, Kreukels B, T’sjoen G, Ålgars M, Mattila A. Increase of referrals to gender identity clinics: a European trend. Transgender Healthcare in Europe Book of Abstracts. 2015:10.

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. The Journal of Clinical Endocrinology & Metabolism. 2017;102(11):3869-903.

Dhejne C, Van Vlerken R, Heylens G, Arcelus J. Mental health and gender dysphoria: A review of the literature. International Review of Psychiatry. 2016;28(1):44-57.

Murad MH, Elamin MB, Garcia MZ, Mullan RJ, Murad A, Erwin PJ, et al. Hormonal therapy and sex reassignment: A systematic review and meta‐analysis of quality of life and psychosocial outcomes. Clinical endocrinology. 2010;72(2):214-31.

White Hughto JM, Reisner SL. A systematic review of the effects of hormone therapy on psychological functioning and quality of life in transgender individuals. Transgender health. 2016;1(1):21-31.

Foster Skewis L, Bretherton I, Leemaqz SY, Zajac JD, Cheung AS. Short-term effects of gender-affirming hormone therapy on dysphoria and quality of life in transgender individuals: a prospective controlled study. Frontiers in endocrinology. 2021:919.

Wesp LM, Deutsch MB. Hormonal and surgical treatment options for transgender women and transfeminine spectrum persons. Psychiatric Clinics. 2017;40(1):99-111.

Xu K, Fu Y, Cao B, Zhao M. Association of Sex Hormones and Sex Hormone-Binding Globulin Levels With Bone Mineral Density in Adolescents Aged 12-19 Years. Front Endocrinol (Lausanne). 2022;13:891217.

Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. Journal of biological chemistry. 2010;285(33):25103-8.

Kasperk C, Helmboldt A, Börcsök I, Heuthe S, Cloos O, Niethard F, et al. Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations. Calcified tissue international. 1997;61(6):464-73.

Mohamad N-V, Soelaiman I-N, Chin K-Y. A concise review of testosterone and bone health. Clinical interventions in aging. 2016;11:1317.

Ji M-X, Yu Q. Primary osteoporosis in postmenopausal women. Chronic diseases and translational medicine. 2015;1(01):9-13.

Cole Z, Dennison E, Cooper C. Update on the treatment of post-menopausal osteoporosis. Br Med Bull. 2008;86:129-43.

Aguirre JI, Plotkin LI, Gortazar AR, Millan MM, O'Brien CA, Manolagas SC, et al. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. Journal of Biological Chemistry. 2007;282(35):25501-8.

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 Nov 1;102(11):3904-13.

Bobba R, Kalra P, Dharmalingam M. Study of Effects of Gender-Affirming Hormone Therapy on Bone Mineral Density in Individuals with Gender Dysphoria. Indian J Endocrinol Metab. 2023 Nov-Dec;27(6):486-91.

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 (Oxf). 2018 Jun;88(6):856-62.

Yun Y, Kim D, Lee ES. Effect of Cross-Sex Hormones on Body Composition, Bone Mineral Density, and Muscle Strength in Trans Women. J Bone Metab. 2021 Feb;28(1):59-66.

Doi SA, Barendregt JJ, Khan S, Thalib L, Williams GM. Advances in the meta-analysis of heterogeneous clinical trials I: the inverse variance heterogeneity model. Contemporary clinical trials. 2015;45:130-8.

Furuya-Kanamori L, Thalib L, Barendregt JJ. Meta-analysis in evidence-based healthcare: a paradigm shift away from random effects is overdue. International Journal of Evidence-Based Healthcare. 2017;15(4):152-60.

VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Annals of internal medicine. 2017;167(4):268-74.

Furuya-Kanamori L, Barendregt JJ, Doi SA. A new improved graphical and quantitative method for detecting bias in meta-analysis. International journal of evidence-based healthcare. 2018;16(4):195-203.

Garner P, Hopewell S, Chandler J, MacLehose H, Akl EA, Beyene J, et al. When and how to update systematic reviews: consensus and checklist. bmj. 2016;354:i3507.

Sarkis-Onofre R, Catalá-López F, Aromataris E, Lockwood C. How to properly use the PRISMA Statement. Systematic Reviews. 2021;10:1-3.

Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS med. 2009;6(7):e1000097.

Cohen J. Weighted kappa: nominal scale agreement with provision for scaled disagreement or partial credit. Psychology. Bulletin, 70, 213â. 1968;220.

Lee E, Dobbins M, DeCorby K, McRae L, Tirilis D, Husson H. An optimal search filter for retrieving systematic reviews and meta-analyses. BMC medical research methodology. 2012;12(1):51.

Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. bmj. 2016;355.

Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Physical therapy. 2003;83(8):713-21.

Smart NA, Waldron M, Ismail H, Giallauria F, Vigorito C, Cornelissen V, et al. Validation of a new tool for the assessment of study quality and reporting in exercise training studies: TESTEX. International journal of evidence-based healthcare. 2015;13(1):9-18.

Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. bmj. 2019;366.

Ahn S, Becker BJ. Incorporating quality scores in meta-analysis. Journal of Educational and Behavioral Statistics. 2011;36(5):555-85.

Hedges LV, Olkin I. Statistical methods for meta-analysis: Academic press; 2014.

Follmann D, Elliott P, Suh I, Cutler J. Variance imputation for overviews of clinical trials with continuous response. Journal of clinical epidemiology. 1992;45(7):769-73.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. 2003;327(7414):557-60.

Furuya-Kanamori L, Xu C, Lin L, Doan T, Chu H, Thalib L, et al. P value–driven methods were underpowered to detect publication bias: analysis of Cochrane review meta-analyses. Journal of clinical epidemiology. 2020;118:86-92.

Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from guidelinedevelopment org/handbook. 2013.

Hamilton BR, Staines K, Kelley GA, Kelley KS, Kohrt WM, Pitsiladis YP, et al. The effects of exercise on bone mineral density in men: a systematic review and meta-analysis of randomised controlled trials. 2021 [cited 2021 March 6th]; Available from: https://osf.io/e6w3v/

Downloads

Additional Files

Posted

2024-07-26