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Reviews in Endocrine and Metabolic Disorders

Published in:

01-09-2018

Endocrine treatment of aging transgender people

Authors: Louis J. Gooren, Guy T’Sjoen

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 3/2018

Abstract

High quality empirical data assessing morbidity and mortality and cancer incidence among transgender people are almost non-existent. Sex hormone treatment of conditions in older non-transgender people might as yet be taken as the best available analogy to hormone administration to aging transgender persons. Testosterone administration to transgender men carries little risk with regard to cardiovascular disease and cancer. A dose adaptation may be needed in men with a high hematocrit or cardiac insufficiency. In transgender men, even after breast ablation, breast cancer may occur in residual mammary tissue. Treatment with estrogens (specifically oral ethinylestradiol) of transgender women, particularly in combination with progestins, carries a significant relative risk of developing cardiovascular disease (almost a twofold incidence compared to the general population). The dose of estrogens may have to be reduced with aging. A change from oral to probably safer transdermal estrogens must be considered. Though rare, tumors of the breasts, prostate, meninges and pituitary have been encountered. Based upon the available expertise, initiation of cross-sex hormone treatment in elderly subjects is without disproportionate risks.

Hembree WC, Cohen-Kettenis P, Delemarre-van de Waal HA, Gooren LJ, Meyer WJ 3rd, Spack NP, et al. Endocrine treatment of transsexual persons: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2009;94(9):3132–54.CrossRef

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. J Clin Endocrinol Metab. 2017;102(11):3869–903. https://doi.org/10.1210/jc.2017-01658.CrossRefPubMed

Gooren LJ. Clinical practice. Care of transsexual persons N Engl J Med. 2011;364(13):1251–7.CrossRef

Tangpricha V, den Heijer M. Oestrogen and anti-androgen therapy for transgender women. Lancet Diabetes Endocrinol. 2017;5(4):291–300. https://doi.org/10.1016/S2213-8587(16)30319-9.CrossRefPubMed

Irwig MS. Testosterone therapy for transgender men. Lancet Diabetes Endocrinol. 2017;5(4):301–11. https://doi.org/10.1016/S2213-8587(16)00036-X.CrossRefPubMed

Wylie K, Knudson G, Khan SI, Bonierbale M, Watanyusakul S, Baral S. Serving transgender people: clinical care considerations and service delivery models in transgender health. Lancet. 2016;388(10042):401–11. https://doi.org/10.1016/S0140-6736(16)00682-6.CrossRefPubMed

Elamin MB, Garcia MZ, Murad MH, Erwin PJ, Montori VM. Effect of sex steroid use on cardiovascular risk in transsexual individuals: a systematic review and meta-analyses. Clin Endocrinol. 2010;72(1):1–10.CrossRef

Fabbre VD. Gender transitions in later life: the significance of time in queer aging. J Gerontol Soc Work. 2014;57(2–4):161–75. https://doi.org/10.1080/01634372.2013.855287.CrossRefPubMedPubMedCentral

Bouman WP, Claes L, Marshall E, Pinner GT, Longworth J, Maddox V, et al. Sociodemographic variables, clinical features, and the role of Preassessment cross-sex hormones in older transgender people. J Sex Med. 2016;13(4):711–9. https://doi.org/10.1016/j.jsxm.2016.01.009.CrossRefPubMed

10.

Ettner R, Wylie K. Psychological and social adjustment in older transsexual people. Maturitas. 2013;74(3):226–9. https://doi.org/10.1016/j.maturitas.2012.11.011.CrossRefPubMed

11.

Wiepjes CM, Nota NM, de Blok CJM, Klaver M, de Vries ACL, et al. The Amsterdam cohort of gender dysphoria study (1972-2015): trends in prevalence, treatment and regrets. J Sex Med. 2018;15(4):582–90.CrossRef

12.

Gooren LJ, van Trotsenburg MA, Giltay EJ, van Diest PJ. Breast cancer development in transsexual subjects receiving cross-sex hormone treatment. J Sex Med. 2013;10(12):3129–34. https://doi.org/10.1111/jsm.12319.CrossRefPubMed

13.

Gooren L, Morgentaler A. Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens. Andrologia. 2014;46(10):1156–60. https://doi.org/10.1111/and.12208.CrossRefPubMed

14.

Gooren LJ, Giltay EJ. Men and women, so different, so similar: observations from cross-sex hormone treatment of transsexual subjects. Andrologia. 2014;46(5):570–5. https://doi.org/10.1111/and.12111.CrossRefPubMed

15.

Fuente-Martin E, Argente-Arizon P, Ros P, Argente J, Chowen JA. Sex differences in adipose tissue: it is not only a question of quantity and distribution. Adipocyte. 2013;2(3):128–34. https://doi.org/10.4161/adip.24075.CrossRefPubMedPubMedCentral

16.

Arnold AP. Mouse models for evaluating sex chromosome effects that cause sex differences in non-gonadal tissues. J Neuroendocrinol. 2009;21(4):377–86. https://doi.org/10.1111/j.1365-2826.2009.01831.x.CrossRefPubMedPubMedCentral

17.

Lucas-Herald AK, Alves-Lopes R, Montezano AC, Ahmed SF, Touyz RM. Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications. Clin Sci (Lond). 2017;131(13):1405–18. https://doi.org/10.1042/CS20170090.CrossRef

18.

Link JC, Chen X, Arnold AP, Reue K. Metabolic impact of sex chromosomes. Adipocyte. 2013;2(2):74–9. https://doi.org/10.4161/adip.23320.CrossRefPubMedPubMedCentral

19.

Straface E, Gambardella L, Brandani M, Malorni W. Sex differences at cellular level: "cells have a sex". Handb Exp Pharmacol. 2012;214:49–65. https://doi.org/10.1007/978-3-642-30726-3_3.CrossRef

20.

Weden MM, Brown RA. Historical and life course timing of the male mortality disadvantage in Europe: epidemiologic transgenderitions, evolution, and behavior. Soc Biol. 2006;53(1–2):61–80.PubMed

21.

Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev. 2003;24(3):313–40.CrossRef

22.

Oskui PM, French WJ, Herring MJ, Mayeda GS, Burstein S, Kloner RA. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. J Am Heart Assoc. 2013;2(6):e000272. https://doi.org/10.1161/JAHA.113.000272.CrossRefPubMedPubMedCentral

23.

Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635–42.CrossRef

24.

Wierckx K, Elaut E, Declercq E, Heylens G, De Cuypere G, Taes Y, et al. Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of transgender persons: a case-control study. Eur J Endocrinol. 2013;169(4):471–8. https://doi.org/10.1530/EJE-13-0493.CrossRefPubMed

25.

Gooren LJ, Wierckx K, Giltay EJ. Cardiovascular disease in transsexual persons treated with cross-sex hormones: reversal of the traditional sex difference in cardiovascular disease pattern. Eur J Endocrinol. 2014;170(6):809–19. https://doi.org/10.1530/EJE-14-0011.CrossRefPubMed

26.

Wang J, Bingaman S, Huxley VH. Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases. Am J Physiol Heart Circ Physiol. 2010;298(4):H1146–54. https://doi.org/10.1152/ajpheart.00252.2009.CrossRefPubMedPubMedCentral

27.

Kuchuk NO, van Schoor NM, Pluijm SM, Smit JH, de Ronde W, Lips P. The association of sex hormone levels with quantitative ultrasound, bone mineral density, bone turnover and osteoporotic fractures in older men and women. Clin Endocrinol. 2007;67(2):295–303. https://doi.org/10.1111/j.1365-2265.2007.02882.x.CrossRef

28.

Camacho EM, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European male ageing study. Eur J Endocrinol. 2013;168(3):445–55. https://doi.org/10.1530/EJE-12-0890.CrossRefPubMed

29.

Saylor PJ, Smith MR. Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol 2013;189(1 Suppl):S34–42; discussion S3–4. https://doi.org/10.1016/j.juro.2012.11.017 CrossRef

30.

Pye SR, Huhtaniemi IT, Finn JD, Lee DM, O'Neill TW, Tajar A, et al. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014;99(4):1357–66. https://doi.org/10.1210/jc.2013-2052.CrossRefPubMed

31.

Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, et al. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European male aging study (EMAS). J Clin Endocrinol Metab. 2012;97(5):1508–16. https://doi.org/10.1210/jc.2011-2513.CrossRefPubMed

32.

Yeap BB, Araujo AB, Wittert GA. Do low testosterone levels contribute to ill-health during male ageing? Crit Rev Clin Lab Sci. 2012;49(5–6):168–82. https://doi.org/10.3109/10408363.2012.725461.CrossRefPubMed

33.

Saad F, Gooren LJ. The role of testosterone in the etiology and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. J Obes Epub. 2010 Aug 10;2011

34.

Ponce OJ, Spencer-Bonilla G, Alvarez-Villalobos N, Serrano V, Singh-Ospina N, Rodriguez-Gutierrez R et al. The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: a systematic review and meta-analysis of randomized, placebo-controlled Trials J Clin Endocrinol Metab 2018 doi: https://doi.org/10.1210/jc.2018-00404.CrossRef

35.

Whitley H, Lindsey W. Sex-based differences in drug activity. Am Fam Physician. 2009;80(11):1254–8.PubMed

36.

Beierle I, Meibohm B, Derendorf H. Gender differences in pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther. 1999;37(11):529–47.PubMed

37.

Spoletini I, Vitale C, Malorni W, Rosano GM. Sex differences in drug effects: interaction with sex hormones in adult life. Handb Exp Pharmacol. 2012;214:91–105. https://doi.org/10.1007/978-3-642-30726-3_5.CrossRef

38.

Maraka S, Singh Ospina N, Rodriguez-Gutierrez R, Davidge-Pitts CJ, Nippoldt TB, Prokop LJ, et al. Sex steroids and cardiovascular outcomes in transgender individuals: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2017;102(11):3914–23. https://doi.org/10.1210/jc.2017-01643.CrossRefPubMed

39.

Goodman MP. Are all estrogens created equal? A review of oral vs. transdermal therapy. J Women's Health (Larchmt). 2012;21(2):161–9. https://doi.org/10.1089/jwh.2011.2839.CrossRef

40.

Vehkavaara S, Silveira A, Hakala-Ala-Pietila T, Virkamaki A, Hovatta O, Hamsten A, et al. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost. 2001;85(4):619–25.CrossRef

41.

Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017; https://doi.org/10.1002/14651858.CD004143.pub5.

42.

Main C, Knight B, Moxham T, Gabriel Sanchez R, Sanchez Gomez LM, Roque i, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2013;4 https://doi.org/10.1002/14651858.CD002229.pub3.

43.

Santen RJ. Menopausal hormone therapy and breast cancer. J Steroid Biochem Mol Biol. 2014;142:52–61. https://doi.org/10.1016/j.jsbmb.2013.06.010.CrossRefPubMed

44.

Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298. https://doi.org/10.1136/bmj.f5298.CrossRefPubMedPubMedCentral

45.

Wierckx K, Elaut E, Declercq E, Heylens G, De Cuypere G, Taes Y, et al. Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study. Eur J Endocrinol. 2013;169(4):471–8.CrossRef

46.

Barrett-Connor E. The Rancho Bernardo Study: 40 years studying why women have less heart disease than men and how diabetes modifies women's usual cardiac protection. Glob Heart. 2013;8(2) https://doi.org/10.1016/j.gheart.2012.12.002.CrossRef

47.

Seeman E. Clinical Review 137. Sexual dimorphism in skeletal size, density, and strength. J Clin Endocrinol Metab. 2001;86(10):4576–84.CrossRef

48.

Vanderschueren D, Laurent MR, Claessens F, Gielen E, Lagerquist MK, Vandenput L, et al. Sex steroid actions in male bone. Endoc Rev. 2014;35(6):906–60.CrossRef

49.

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. https://doi.org/10.1210/jc.2017-01642.CrossRefPubMed

50.

Callewaert F, Sinnesael M, Gielen E, Boonen S, Vanderschueren D. Skeletal sexual dimorphism: relative contribution of sex steroids, GH-IGF1. and mechanical loading J Endocrinol. 2010;207(2):127–34. https://doi.org/10.1677/JOE-10-0209.CrossRefPubMed

51.

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. https://doi.org/10.1016/j.bone.2013.01.039. CrossRefPubMed

52.

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.CrossRef

53.

Lips P, Asscheman H, Uitewaal P, Netelenbos JC, Gooren L. The effect of cross-gender hormonal treatment on bone metabolism in male-to-female transsexuals. J Bone Miner Res. 1989;4(5):657–62.CrossRef

54.

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.CrossRef

55.

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.CrossRef

56.

Lips P, van Kesteren PJ, Asscheman H, Gooren LJ. The effect of androgen treatment on bone metabolism in female-to-male transsexuals. J Bone Miner Res. 1996;11(11):1769–73.CrossRef

57.

Lapauw B, Taes Y, Simoens S, Van Caenegem E, Weyers S, Goemaere S, et al. Body composition, volumetric and areal bone parameters in male-to-female transsexual persons. Bone. 2008;43(6):1016–21. https://doi.org/10.1016/j.bone2008.09.001.CrossRefPubMed

58.

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.CrossRef

59.

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.CrossRef

60.

Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685–705. https://doi.org/10.1146/annurev-physiol-030212-183653.CrossRefPubMed

61.

Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2008;159(3):197–202.CrossRef

62.

Braun H, Nash R, Tangpricha V, Brockman J, Ward K, Goodman M. Cancer in transgender people: evidence and methodological considerations. Epidemiol Rev. 2017;39(1):93–107. https://doi.org/10.1093/epirev/mxw003.CrossRefPubMedPubMedCentral

63.

Sonnenblick EB, Shah AD, Goldstein Z, Reisman T. Breast imaging of transgender individuals: a review. Curr Radiol Rep. 2018;6(1):1. https://doi.org/10.1007/s40134-018-0260-1.CrossRefPubMedPubMedCentral

64.

Defreyne J, Nota N, Pereira C, Schreiner T, Fisher AD, den Heijer M, et al. Transient elevated serum prolactin in transgender women is caused by Cyproterone acetate treatment. LGBT Health. 2017;4(5):328–36. https://doi.org/10.1089/lgbt.2016.0190.CrossRefPubMed

65.

Bunck MC, Debono M, Giltay EJ, Verheijen AT, Diamant M, Gooren LJ. Autonomous prolactin secretion in two male-to-female transgender patients using conventional oestrogen dosages. BMJ case reports. 2009; https://doi.org/10.1136/bcr.02.2009.1589.

66.

Ter Wengel PV, Martin E, Gooren L, Den Heijer M, Peerdeman SM. Meningiomas in three male-to-female transgender subjects using oestrogens/progestogens and review of the literature. Andrologia. 2016;48(10):1130–7. https://doi.org/10.1111/and.12550.CrossRefPubMed

67.

Bergoglio MT, Gomez-Balaguer M, Almonacid Folch E, Hurtado Murillo F, Hernandez-Mijares A. Symptomatic meningioma induced by cross-sex hormone treatment in a male-to-female transsexual. Endocrinol Nutr. 2012;60(5):264–7.CrossRef

68.

Shao T, Grossbard ML, Klein P. Breast cancer in female-to-male transsexuals: two cases with a review of physiology and management. Clin Breast Cancer. 2011;11(6):417–9.CrossRef

69.

Burcombe RJ, Makris A, Pittam M, Finer N. Breast cancer after bilateral subcutaneous mastectomy in a female-to-male trans-sexual. Breast. 2003;12(4):290–3.CrossRef

70.

Nikolic DV, Djordjevic ML, Granic M, Nikolic AT, Stanimirovic VV, Zdravkovic D, et al. Importance of revealing a rare case of breast cancer in a female to male transsexual after bilateral mastectomy. World J Surg Oncol. 2012;10:280. https://doi.org/10.1186/1477-7819-10-280.CrossRefPubMedPubMedCentral

71.

Schenck TL, Holzbach T, Zantl N, Schuhmacher C, Vogel M, Seidl S, et al. Vaginal carcinoma in a female-to-male transsexual. J Sex Med. 2010;7(8):2899–902. https://doi.org/10.1111/j.1743-6109.2009.01686.x.CrossRefPubMed

72.

Urban RR, Teng NN, Kapp DS. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance. Am J Obstet Gynecol. 2011;204(5):e9-e12.CrossRef

73.

Driak D, Samudovsky M. Cervical cancer in a female-to-male trans-sexual. Eur J Cancer. 2004;40(11):1795.CrossRef

74.

Bhattacharya RK, Khera M, Blick G, Kushner H, Miner MM. Testosterone replacement therapy among elderly males: the Testim registry in the US (TRiUS). Clin Interv Aging. 2012;7:321–30. https://doi.org/10.2147/CIA.S32036.CrossRefPubMedPubMedCentral

Title: Endocrine treatment of aging transgender people
Authors: Louis J. Gooren
Guy T’Sjoen
Publication date: 01-09-2018
Publisher: Springer US
Published in: Reviews in Endocrine and Metabolic Disorders / Issue 3/2018
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-018-9449-0

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