Hamostaseologie 2022; 42(05): 301-307
DOI: 10.1055/a-1891-8158
Review Article

Transgender Medicine and Risk of Venous Thromboembolism

C.C. Van Bunderen*
1   Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
,
J. Leentjens*
2   Division of Vascular Medicine, Department of Internal Medicine, Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, The Netherlands
,
S. Middeldorp
2   Division of Vascular Medicine, Department of Internal Medicine, Radboud Institute of Health Sciences (RIHS), Radboud University Medical Center, Nijmegen, The Netherlands
› Institutsangaben

Abstract

Gender dysphoria refers to psychological distress that results from an incongruence between gender identity and sex assigned at birth. Administration of sex hormones is most often used as a first step to develop and maintain physical characteristics consistent with gender identity. Gender-affirming hormone treatment is considered beneficial for the quality of life and reduction of depression. However, estrogen and androgen-lowering hormone therapies used in transwomen are in particular associated with increased risk of venous thromboembolism. In this review, introduced by a clinical case, we provide an overview of the currently available medical therapies in transgender medicine, and put the associated increased risk of venous thromboembolism into perspective.

* Both authors contributed equally.




Publikationsverlauf

Eingereicht: 03. April 2022

Angenommen: 28. Juni 2022

Artikel online veröffentlicht:
02. November 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Winter S, Diamond M, Green J. et al. Transgender people: health at the margins of society. Lancet 2016; 388 (10042): 390-400
  • 2 Safer JD, Tangpricha V. Care of the transgender patient. Ann Intern Med 2019; 171 (01) ITC1-ITC16
  • 3 Aldridge Z, Patel S, Guo B. et al. Long-term effect of gender-affirming hormone treatment on depression and anxiety symptoms in transgender people: a prospective cohort study. Andrology 2021; 9 (06) 1808-1816
  • 4 Baker KE, Wilson LM, Sharma R, Dukhanin V, McArthur K, Robinson KA. Hormone therapy, mental health, and quality of life among transgender people: a systematic review. J Endocr Soc 2021; 5 (04) bvab011
  • 5 Asscheman H, T'Sjoen G, Lemaire A. et al. Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review. Andrologia 2014; 46 (07) 791-795
  • 6 Haupt C, Henke M, Kutschmar A. et al. Antiandrogen or estradiol treatment or both during hormone therapy in transitioning transgender women. Cochrane Database Syst Rev 2020; 11: CD013138
  • 7 Glintborg D, T'Sjoen G, Ravn P, Andersen MS. Management of endocrine disease: optimal feminizing hormone treatment in transgender people. Eur J Endocrinol 2021; 185 (02) R49-R63
  • 8 T'Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. Endocrinology of transgender medicine. Endocr Rev 2019; 40 (01) 97-117
  • 9 Mancini I, Rotilio A, Coati I, Seracchioli R, Martelli V, Meriggiola MC. Presentation of a meningioma in a transwoman after nine years of cyproterone acetate and estradiol intake: case report and literature review. Gynecol Endocrinol 2018; 34 (06) 456-459
  • 10 Defreyne J, Nota N, Pereira C. et al. Transient elevated serum prolactin in trans women is caused by cyproterone acetate treatment. LGBT Health 2017; 4 (05) 328-336
  • 11 Manson JE, Hsia J, Johnson KC. et al; Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349 (06) 523-534
  • 12 Braun H, Nash R, Tangpricha V, Brockman J, Ward K, Goodman M. Cancer in transgender people: evidence and methodological considerations. Epidemiol Rev 2017; 39 (01) 93-107
  • 13 de Blok CJ, Wiepjes CM, van Velzen DM. et al. Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria. Lancet Diabetes Endocrinol 2021; 9 (10) 663-670
  • 14 Baillargeon J, Urban RJ, Morgentaler A. et al. Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin Proc 2015; 90 (08) 1038-1045
  • 15 Irwig MS. Testosterone therapy for transgender men. Lancet Diabetes Endocrinol 2017; 5 (04) 301-311
  • 16 Irwig MS. Cardiovascular health in transgender people. Rev Endocr Metab Disord 2018; 19 (03) 243-251
  • 17 Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5 (04) 692-699
  • 18 Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2017; 1: CD004143
  • 19 Høibraaten E, Qvigstad E, Arnesen H, Larsen S, Wickstrøm E, Sandset PM. Increased risk of recurrent venous thromboembolism during hormone replacement therapy–results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET). Thromb Haemost 2000; 84 (06) 961-967
  • 20 Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ 2008; 336 (7655): 1227-1231
  • 21 Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364: k4810
  • 22 Canonico M, Oger E, Plu-Bureau G. et al; Estrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007; 115 (07) 840-845
  • 23 The Women's Health Initiative Study Group. Design of the Women's Health Initiative clinical trial and observational study. Control Clin Trials 1998; 19 (01) 61-109
  • 24 Conard J. Biological coagulation findings in third-generation oral contraceptives. Hum Reprod Update 1999; 5 (06) 672-680
  • 25 Scheres LJJ, Selier NLD, Nota NM, van Diemen JJK, Cannegieter SC, den Heijer M. Effect of gender-affirming hormone use on coagulation profiles in transmen and transwomen. J Thromb Haemost 2021; 19 (04) 1029-1037
  • 26 Olié V, Canonico M, Scarabin PY. Risk of venous thrombosis with oral versus transdermal estrogen therapy among postmenopausal women. Curr Opin Hematol 2010; 17 (05) 457-463
  • 27 Getahun D, Nash R, Flanders WD. et al. Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med 2018; 169 (04) 205-213
  • 28 Totaro M, Palazzi S, Castellini C. et al. Risk of venous thromboembolism in transgender people undergoing hormone feminizing therapy: a prevalence meta-analysis and meta-regression study. Front Endocrinol (Lausanne) 2021; 12: 741866
  • 29 Khan J, Schmidt RL, Spittal MJ, Goldstein Z, Smock KJ, Greene DN. Venous thrombotic risk in transgender women undergoing estrogen therapy: a systematic review and metaanalysis. Clin Chem 2019; 65 (01) 57-66
  • 30 Wierckx K, Mueller S, Weyers S. et al. Long-term evaluation of cross-sex hormone treatment in transsexual persons. J Sex Med 2012; 9 (10) 2641-2651
  • 31 Seal LJ, Franklin S, Richards C, Shishkareva A, Sinclaire C, Barrett J. Predictive markers for mammoplasty and a comparison of side effect profiles in transwomen taking various hormonal regimens. J Clin Endocrinol Metab 2012; 97 (12) 4422-4428
  • 32 van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997; 47 (03) 337-342
  • 33 Couturaud F, Leroyer C, Julian JA. et al. Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism. Chest 2009; 136 (06) 1537-1545
  • 34 Couturaud F, Leroyer C, Tromeur C. et al. Factors that predict thrombosis in relatives of patients with venous thromboembolism. Blood 2014; 124 (13) 2124-2130
  • 35 Cushman M. Thrombophilia testing in women with venous thrombosis: the 4 P's approach. Clin Chem 2014; 60 (01) 134-137
  • 36 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 1993; 95 (03) 315-328
  • 37 Palareti G, Leali N, Coccheri S. et al; Italian Study on Complications of Oral Anticoagulant Therapy. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996; 348 (9025): 423-428
  • 38 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
  • 39 Agnelli G, Buller HR, Cohen A. et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368 (08) 699-708
  • 40 Weitz JI, Lensing AWA, Prins MH. et al; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 2017; 376 (13) 1211-1222
  • 41 Kozato A, Fox GWC, Yong PC. et al. No venous thromboembolism increase among transgender female patients remaining on estrogen for gender-affirming surgery. J Clin Endocrinol Metab 2021; 106 (04) e1586-e1590
  • 42 Hontscharuk R, Alba B, Manno C. et al. Perioperative transgender hormone management: avoiding venous thromboembolism and other complications. Plast Reconstr Surg 2021; 147 (04) 1008-1017
  • 43 Lawrence AA. Patient-reported complications and functional outcomes of male-to-female sex reassignment surgery. Arch Sex Behav 2006; 35 (06) 717-727
  • 44 Boskey ER, Taghinia AH, Ganor O. Association of surgical risk with exogenous hormone use in transgender patients: a systematic review. JAMA Surg 2019; 154 (02) 159-169
  • 45 Di Minno MN, Ambrosino P, Ageno W, Rosendaal F, Di Minno G, Dentali F. Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies. Thromb Res 2015; 135 (05) 923-932
  • 46 Simone B, De Stefano V, Leoncini E. et al. Risk of venous thromboembolism associated with single and combined effects of factor V Leiden, prothrombin 20210A and methylenetetrahydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol 2013; 28 (08) 621-647
  • 47 Grilz E, Posch F, Nopp S. et al. Relative risk of arterial and venous thromboembolism in persons with cancer vs. persons without cancer-a nationwide analysis. Eur Heart J 2021; 42 (23) 2299-2307