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SIGIS–SIAMS–SIE position statement of gender affirming hormonal treatment in transgender and non-binary people

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Abstract

Purpose

Gender Incongruence (GI) is a marked and persistent incongruence between an individual's experienced and the assigned gender at birth. In the recent years, there has been a considerable evolution and change in attitude as regards to gender nonconforming people.

Methods

According to the Italian Society of Gender, Identity and Health (SIGIS), the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE) rules, a team of experts on the topic has been nominated by a SIGIS–SIAMS–SIE Guideline Board on the basis of their recognized clinical and research expertise in the field, and coordinated by a senior author, has prepared this Position statement. Later on, the present manuscript has been submitted to the Journal of Endocrinological Investigation for the normal process of international peer reviewing after a first internal revision process made by the SIGIS–SIAMS–SIE Guideline Board.

Results

In the present document by the SIGIS–SIAMS–SIE group, we propose experts opinions concerning the psychological functioning, gender affirming hormonal treatment, safety concerns, emerging issues in transgender healthcare (sexual health, fertility issues, elderly trans people), and an Italian law overview aimed to improve gender non-conforming people care.

Conclusion

In this Position statement, we propose experts opinions concerning the psychological functioning of transgender people, the gender-affirming hormonal treatment (full/partial masculinization in assigned female at birth trans people, full/partial feminization and de-masculinization in assigned male at birth trans people), the emerging issues in transgender health care aimed to improve patient care. We have also included an overview of Italian law about gender affirming surgery and registry rectification.

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References

  1. Dakić T (2020) New perspectives on transgender health in the forthcoming 11 th revision of the international statistical classification of diseases and related health problems: an overview of gender incongruence - depathologization, considerations and recommendations for practitioners. Psychiatr Danub Summer 32(2):145–150

    Article  Google Scholar 

  2. T’Sjoen G, Arcelus J, De Vries ALC et al (2020) European Society for sexual medicine position statement “Assessment and Hormonal Management in Adolescent and Adult Trans People, With Attention for Sexual Function and Satisfaction.” J Sex Med 7(4):570–584. https://doi.org/10.1016/j.jsxm.2020.01.012

    Article  CAS  Google Scholar 

  3. Fisher AD, Castellini G, Ristori J et al (2016) Who has the worst attitudes toward sexual minorities? Comparison of transphobia and homophobia levels in gender dysphoric individuals, the general population and health care providers. J Endocrinol Invest 40(3):263–273. https://doi.org/10.1007/s40618-016-0552-3

    Article  CAS  PubMed  Google Scholar 

  4. Heylens G, Verroken C, De Cock S et al (2014) Effects of different steps in gender reassignment therapy on psychopathology: a prospective study of persons with a gender identity disorder. J Sex Med 11(1):119–126. https://doi.org/10.1111/jsm.12363

    Article  PubMed  Google Scholar 

  5. Fisher AD, Castellini G, Ristori J et al (2016) Cross-sex hormone treatment and psychobiological changes in transsexual persons: two-year follow-up data. J Clin Endocrinol Metab 101:4260–4269

    Article  CAS  PubMed  Google Scholar 

  6. Gorin-Lazard A, Baumstarck K, Boyer L et al (2012) Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study. J Sex Med 9(2):531–541. https://doi.org/10.1111/j.1743-6109.2011.02564.x

    Article  PubMed  Google Scholar 

  7. Fiorilli O, Ruocco A (2019) Psychosocial issues in transgender health and barriers to healthcare. Ital J Gender-Specif Med 5(3):123–130. https://doi.org/10.1723/3245.32146

    Article  Google Scholar 

  8. Resolution n. 21756/ 2019, GU Serie Generale n.52/2019

  9. Resolutions n. 104272/2020 and 104273/2020, GU Serie Generale n.242/2020

  10. van der Miesen AIR, Steensma TD, de Vries ALC et al (2020) Psychological functioning in transgender adolescents before and after gender-affirmative care compared with cisgender general population peers. J Adolesc Health 66(6):699–704. https://doi.org/10.1016/j.jadohealth.2019.12.018

    Article  PubMed  Google Scholar 

  11. American Psychological Association (2015) Guidelines for psychological practice with transgender and gender nonconforming people. Am Psychol 70(9):832–864. https://doi.org/10.1037/a0039906

    Article  Google Scholar 

  12. Swiglo BA, Murad MH, Schunemann HJ et al (2008) A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. J Clin Endocrinol Metab 93(3):666–673. https://doi.org/10.1210/jc.2007-1907

    Article  CAS  PubMed  Google Scholar 

  13. de Freitas LD, Léda-Rêgo G, Bezerra-Filho S et al (2020) Psychiatric disorders in individuals diagnosed with gender dysphoria: a systematic review. Psychiatry Clin Neurosci 74(2):99–104. https://doi.org/10.1111/pcn.12947

    Article  PubMed  Google Scholar 

  14. Dhejne C, Van Vlerken R, Heylens G et al (2016) Mental health and gender dysphoria: a review of the literature. Int Rev Psychiatry 28(1):44–57. https://doi.org/10.3109/09540261.2015.1115753

    Article  PubMed  Google Scholar 

  15. Clements-Nolle K, Marx R, Katz M (2006) Attempted suicide among transgender persons: the influence of gender-based discrimination and victimization. J Homosex 51(3):53–69. https://doi.org/10.1300/J082v51n03_04

    Article  PubMed  Google Scholar 

  16. Bauer GR, Redman N, Bradley K et al (2013) Sexual health of trans men who are gay, bisexual, or who have sex with men: results from Ontario, Canada. Int J Transgend 14:66e74. https://doi.org/10.1080/15532739.2013.791650

    Article  Google Scholar 

  17. Lawrence A, Zucker K (2012) Gender identity disorders. In: Hersen M, Beidel D (eds) Adult psychopathology and diagnosis, 6th edn. Wiley, London, pp 601–635

    Google Scholar 

  18. Gómez-Gil E, Trilla A, Salamero M et al (2009) Sociodemographic, clinical, and psychiatric characteristics of transsexuals from Spain. Arch Sex Behav 38(3):378–392. https://doi.org/10.1007/s10508-007-9307-8

    Article  PubMed  Google Scholar 

  19. Fisher AD, Bandini E, Casale H et al (2013) Sociodemographic and clinical features of gender identity disorder: an Italian multicentric evaluation. J Sex Med 10(2):408–419. https://doi.org/10.1111/j.1743-6109.2012.03006.x

    Article  PubMed  Google Scholar 

  20. Heylens G, Elaut E, Kreukels BP et al (2014) Psychiatric characteristics in transsexual individuals: multicentre study in four European countries. Br J Psychiatry J Mental Sci 204(2):151–156. https://doi.org/10.1192/bjp.bp.112.121954

    Article  Google Scholar 

  21. Fisher AD, Castellini G, Bandini E et al (2014) Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria. Sex Med. https://doi.org/10.1111/jsm.12413

    Article  Google Scholar 

  22. Bandini E, Fisher AD, Castellini G et al (2013) Gender identity disorder and eating disorders: similarities and differences in terms of body uneasiness. J Sex Med 10(4):1012–1023. https://doi.org/10.1111/jsm.12062

    Article  PubMed  Google Scholar 

  23. Gorin-Lazard A, Baumstarck K, Boyer L, Maquigneau A et al (2013) Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals. J Nerv Ment Dis 201(11):996–1000. https://doi.org/10.1097/NMD.0000000000000046

    Article  PubMed  Google Scholar 

  24. Oda H, Kinoshita T (2017) Efficacy of hormonal and mental treatments with MMPI in FtM individuals: cross-sectional and longitudinal studies. BMC Psychiatry 17(1):256. https://doi.org/10.1186/s12888-017-1423-y

    Article  PubMed  PubMed Central  Google Scholar 

  25. Fisher AD, Castellini G, Ristori J et al (2016) Cross-sex hormone treatment and psychobiological changes in transsexual persons: two-year follow-up data. J Clin Endocrinol Metab 101(11):4260–4269. https://doi.org/10.1210/jc.2016-1276

    Article  CAS  PubMed  Google Scholar 

  26. Bultynck C, Pas C, Defreyne J et al (2017) 2804Self-perception of voice in transgender persons during cross-sex hormone therapy. Laryngoscope 127(12):2796–2804. https://doi.org/10.1002/lary.26716

    Article  CAS  PubMed  Google Scholar 

  27. Ristori J, Cocchetti C, Romani A et al (2020) Brain sex differences related to gender identity development: genes or hormones? Int J Mol Sci 21(6):2123. https://doi.org/10.3390/ijms21062123

    Article  PubMed Central  Google Scholar 

  28. Costa R, Colizzi M (2016) The effect of cross-sex hormonal treatment on gender dysphoria individuals’ mental health: a systematic review. Neuropsychiatr Dis Treat 12:1953–1966. https://doi.org/10.2147/NDT.S95310

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nguyen HB, Chavez AM, Lipner E et al (2018) Gender-affirming hormone use in transgender individuals: impact on behavioral health and cognition. Curr Psychiatry Rep 20(12):110. https://doi.org/10.1007/s11920-018-0973-0

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wylie K, Knudson G, Khan SI et al (2016) Serving transgender people: clinical care considerations and service delivery models in transgender health. Lancet 388(10042):401–411. https://doi.org/10.1016/S0140-6736(16)00682-6

    Article  PubMed  Google Scholar 

  31. Budge SL (2015) Psychotherapists as gatekeepers: an evidence-based case study highlighting the role and process of letter writing for transgender clients. Psychotherapy 52(3):287

    Article  PubMed  Google Scholar 

  32. Bockting WO, Knudson G, Goldberg JM (2006) Counseling and mental health care for transgender adults and loved ones. Int J Transgenderism 9(3–4):35–82. https://doi.org/10.1300/J485v09n03_03

    Article  Google Scholar 

  33. Coleman E, Bockting W, Botzer M et al (2012) Standards of care for the health of transsexual, transgender, and gender-nonconforming people, Version 7. Int J Transgenderism 13(4):165–232. https://doi.org/10.1080/15532739.2011.700873

    Article  Google Scholar 

  34. Defreyne J, T’Sjoen G, Bouman WP et al (2018) Prospective evaluation of self-reported aggression in transgender persons. J Sex Med 15(5):768–776. https://doi.org/10.1016/j.jsxm.2018.03.079

    Article  PubMed  Google Scholar 

  35. Bess G, Stabb S (2009) The experiences of transgendered persons in psychotherapy: voices and recommendations. J Mental Health Counsel 31(3):264–282. https://doi.org/10.17744/mehc.31.3.f62415468l133w50

    Article  Google Scholar 

  36. Rachlin K (2002) Transgender Individual's Experiences of Psychotherapy, Paper presented at the American Psychological Association 109thAnnual Convention, San Francisco, CA

  37. Defreyne J, T’Sjoen G (2019) Transmasculine hormone therapy. Endocrinol Metab Clin North Am 48(2):357–375. https://doi.org/10.1016/j.ecl.2019.01.004

    Article  PubMed  Google Scholar 

  38. Hembree WC, Cohen-Kettenis PT, Gooren L et al (2017) Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society* clinical practice guideline. J Clin Endocrinol Metab 102(11):3869–3903

    Article  PubMed  Google Scholar 

  39. Pelusi C, Costantino A, Martelli V et al (2014) Effects of three different testosterone formulations in female-to-male transsexual persons. J Sex Med 11(12):3002–3011. https://doi.org/10.1111/jsm.12698

    Article  PubMed  Google Scholar 

  40. Defreyne J, Vantomme B, Van Caenegem E et al (2018) Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European Network for the Investigation of Gender Incongruence. Andrology 6(3):446–454. https://doi.org/10.1111/andr.12485

    Article  CAS  PubMed  Google Scholar 

  41. Gava G, Mancini I, Cerpolini S et al (2018) Testosterone undecanoate and testosterone enanthate injections are both effective and safe in transmen over 5 years of administration. Clin Endocrinol (Oxf) 89(6):878–886

    Article  CAS  Google Scholar 

  42. Defreyne J, Vanwonterghem Y, Collet S et al (2020) Vaginal bleeding and spotting in transgender men after initiation of testosterone therapy: a prospective cohort study (ENIGI). Int J Transgend Health 21(2):163–175. https://doi.org/10.1080/26895269.2020.1719951

    Article  PubMed  PubMed Central  Google Scholar 

  43. Meriggiola MC, Armillotta F, Costantino A et al (2008) Effects of testosterone undecanoate administered alone or in combination with letrozole or dutasteride in female to male transsexuals. J Sex Med 5(10):2442–2453

    Article  CAS  PubMed  Google Scholar 

  44. Irwig MS, Childs K, Hancock AB (2016) Effects of testosterone on the transgender male voice. Andrology 5(1):107–112. https://doi.org/10.1111/andr.12278

    Article  CAS  PubMed  Google Scholar 

  45. Wierckx K, Van de Peer F, Verhaeghe E et al (2014) Short- and long-term clinical skin effects of testosterone treatment in trans men. J Sex Med gennaio 11(1):222–229. https://doi.org/10.1111/jsm.12366

    Article  CAS  Google Scholar 

  46. Ristori J, Cocchetti C, Castellini G et al (2020) Hormonal treatment effect on sexual distress in transgender persons: 2-year follow-up data. J Sex Med 17(1):142–151. https://doi.org/10.1016/j.jsxm.2019.10.008

    Article  CAS  PubMed  Google Scholar 

  47. van Dijk D, Dekker MJHJ, Conemans EB et al (2019) Explorative prospective evaluation of short-term subjective effects of hormonal treatment in trans people-results from the european network for the investigation of gender incongruence. J Sex Med 16(8):1297–1309. https://doi.org/10.1016/j.jsxm.2019.05.009

    Article  PubMed  Google Scholar 

  48. Asscheman H, Giltay EJ, Megens JAJ et al (2011) A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol 164(4):635–642

    Article  CAS  PubMed  Google Scholar 

  49. Asscheman H, T’Sjoen G, Lemaire A et al (2014) Venous thromboembolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review. Andrologia 46(7):791–795. https://doi.org/10.1111/and.12150

    Article  CAS  PubMed  Google Scholar 

  50. Hamidi O, Davidge-Pitts CJ (2019) Transfeminine hormone therapy. Endocrinol Metab Clin North Am 48(2):341–355. https://doi.org/10.1016/j.ecl.2019.02.001

    Article  PubMed  Google Scholar 

  51. Dekker HJ, Wierckx K, Van Caenegem E et al (2016) A european network for the investigation of gender incongruence: endocrine part. J Sex Med 13(6):994–999. https://doi.org/10.1016/j.jsxm.2016.03.371

    Article  CAS  PubMed  Google Scholar 

  52. Kim JH, Yoo BW, Yang WJ (2014) Hepatic failure induced by cyproterone acetate: a case report and literature review. Can Urol Assoc J 8(5–6):E458–E461. https://doi.org/10.5489/cuaj.1753

    Article  PubMed  PubMed Central  Google Scholar 

  53. Millet N, Longworth J, Arcelus J (2016) Prevalence of anxiety symptoms and disorders in the transgender population: a systematic review of the literature. Int J Transgenderism 18(1):27–38

    Article  Google Scholar 

  54. Defreyne J, Nota N, Pereira C et al (2017) Transient elevated serum prolactin in trans women is caused by cyproterone acetate treatment. LGBT Health 4(5):328–333

    Article  PubMed  Google Scholar 

  55. Mancini I, Rotilio A, Coati I et al (2018) Presentation of a meningioma intranswoman after nine years of cyproterone acetate and estradiol intake: case report and literature review. Gynecol Endocrinol 34(6):456–459. https://doi.org/10.1080/09513590.2017.1395839

    Article  PubMed  Google Scholar 

  56. Ter Wengel PV, Martin E, Gooren L et al (2016) (2016) Meningiomas in three male-to-female transgender subjects using oestrogens/progestogens and review of the literature. Andrologia 48:1130–1137. https://doi.org/10.1111/and.12550

    Article  PubMed  Google Scholar 

  57. Gava G, Cerpolini S, Martelli V et al (2016) Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness. Clin Endocrinol (Oxf) 85:239–246. https://doi.org/10.1111/cen.13050

    Article  CAS  Google Scholar 

  58. Dittrich R, Binder H, Cupisti S et al (2005) Endocrine treatment of maleto-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 113(10):586–592

    Article  CAS  PubMed  Google Scholar 

  59. Gava G, Mancini I, Alvisi S et al (2020) A comparison of 5-year administration of cyproterone acetate or leuprolide acetate in combination with estradiol in transwomen. Eur J Endocrinol 183(6):561–569. https://doi.org/10.1530/EJE-20-0370

    Article  CAS  PubMed  Google Scholar 

  60. Angus LM, Nolan BJ, Zajac JD et al (2020) A systematic review of antiandrogens and feminization in transgender women. Clin Endocrinol 00:1–10. https://doi.org/10.1111/cen.14329Jun2020

    Article  Google Scholar 

  61. Stevenson MO, Wixon N, Safer JD (2016) Scalp hair regrowth in hormone-treated transgender woman. Transgend Health 1(1):202–204

    Article  PubMed  PubMed Central  Google Scholar 

  62. Irwig MS (2020) Is there a role for 5alpha-reductase inhibitors in transgender individuals? Andrology. https://doi.org/10.1111/andr.12881 (Online ahead of print)

    Article  PubMed  Google Scholar 

  63. Prior JC (2019) Progesterone is important for transgender women’s therapy—applying evidence for the benefits of progesterone in ciswomen. J Clin Endocrinol Metab 104(4):1181–1186

    Article  PubMed  Google Scholar 

  64. Jain J, Kwan D, Forcier M (2019) Medroxyprogesterone acetate in gender-affirming therapy for transwomen: results from a retrospective study. J Clin Endocrinol Metab 104(11):5148–5156

    Article  PubMed  Google Scholar 

  65. T’Sjoen G, Arcelus J, Gooren L et al (2019) Endocrinology of Transgender Medicine. Endocr Rev 40(1):97–117. https://doi.org/10.1210/er.2018-00011

    Article  PubMed  Google Scholar 

  66. de Blok CJM, Staphorsius AS, Wiepjes CM et al (2019) Frequency, determinants, and satisfaction of breast augmentation in trans women receiving hormone treatment. J Sex Med 17(2):342–348. https://doi.org/10.1016/j.jsxm.2019.10.021

    Article  CAS  PubMed  Google Scholar 

  67. Giltay EJ, Fonk JC, von Blomberg BM et al (2000) In vivo effects of sex steroids on lymphocyte respon-siveness and immunoglobulin levels in humans. J Clin EndocrinolMetab 85:1648–1657. https://doi.org/10.1210/jcem.85.4.6562

    Article  CAS  Google Scholar 

  68. Klaver M, de Blok CJM, Wiepjes CM et al (2018) Changes in regional body fat, lean body mass and body shape in trans persons using cross-sex hormonal therapy: results from a multicenter prospective study. Eur J Endocrinol 178(2):163–171. https://doi.org/10.1530/EJE-17-0496

    Article  CAS  PubMed  Google Scholar 

  69. Bultynck C, Pas C, Defreyne J et al (2017) Self-perception of voice in transgender persons during cross-sex hormone therapy. Laryngoscope 127(12):2796–2804. https://doi.org/10.1002/lary.26716

    Article  CAS  PubMed  Google Scholar 

  70. Meyer WJ III, Webb A, Stuart CA et al (1986) Physical and hormonal evaluation of transsexual patients: a longitudinal study. Arch Sex Behav 15(2):121–138. https://doi.org/10.1007/BF01542220

    Article  PubMed  Google Scholar 

  71. Defreyne J, Elaut E, Kreukels B et al (2020) Sexual desire changes in transgender individuals upon initiation of hormone treatment: results from the Investigation of gender incongruence. J Sex Med 17(4):812–825. https://doi.org/10.1016/j.jsxm.2019.12.020

    Article  CAS  PubMed  Google Scholar 

  72. Cocchetti C, Ristori J, Romani A (2020) Hormonal treatment strategies tailored to non-binary transgender individuals. J Clin Med 9(6):1609. https://doi.org/10.3390/jcm9061609

    Article  CAS  PubMed Central  Google Scholar 

  73. Rachner TD, Coleman R, Hadji P et al (2018) Bone health during endocrine therapy for cancer. Lancet Diabetes Endocrinol 6:901–910. https://doi.org/10.1016/S2213-8587(18)30047-0

    Article  CAS  PubMed  Google Scholar 

  74. Martin KA, Anderson RR, Chang RJ et al (2018) Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 103:1233–1257. https://doi.org/10.1210/jc.2018-00241

    Article  PubMed  Google Scholar 

  75. Unluhizarci K, Ozel D, Tanriverdi F et al (2009) A comparison between finasteride, flutamide, and finasteride plus flutamide combination in the treatment of hirsutism. J Endocrinol Invest 32:37–40. https://doi.org/10.1007/BF03345676

    Article  CAS  PubMed  Google Scholar 

  76. Gava G, Armillotta F, Pillastrini P et al (2021) A randomized double-blind placebo-controlled pilot trial on the effects of testosterone undecanoate plus dutasteride or placebo on muscle strength, body composition, and metabolic profile in transmen. J Sex Med. https://doi.org/10.1016/j.jsxm.2020.12.015

    Article  PubMed  Google Scholar 

  77. Ingprasert S, Tanglertsampa C, Tangphianphan N (2016) Efficacy and safety of minoxidil 3% lotion for beard enhancement: a randomized, double-masked, placebo-controlled study. J Dermatol 43:968–969. https://doi.org/10.1111/1346-8138.13312

    Article  PubMed  Google Scholar 

  78. Dickersin K, Munro MG, Clark M (2007) Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding: a randomized controlled trial. OBSTET Gynecol 110:1279–1289. https://doi.org/10.1097/01.AOG.0000292083.97478.38

    Article  PubMed  Google Scholar 

  79. Francis A, Jasani S, Bachmann G (2018) Contraceptive challenges and the transgender individual. Womens Midlife Health 4:12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Elamin MB, Garcia MZ, Murad MH et al (2010) (2010) Effect of sex steroid use on cardiovascular risk in transsexual individuals: a systematic review and meta-analyses. Clin Endocrinol (Oxf) 72(1):1–10. https://doi.org/10.1111/j.1365-2265.2009.03632.x

    Article  CAS  Google Scholar 

  81. Berra M, Armillotta L, D’Emidio F et al (2006) Testosterone decreases adiponectin levels in female to male transsexuals. Asian J Androl 8(6):725–729. https://doi.org/10.1111/j.1745-7262.2006.00204.x

    Article  CAS  PubMed  Google Scholar 

  82. Van Velzen DM, Al P, Klaver M et al (2019) Cardiometabolic effects of testosterone in transmen and estrogen plus cyproterone acetate in transwomen. J Clin Endocrinol Metab 104(6):1937–1947. https://doi.org/10.1210/jc.2018-02138

    Article  PubMed  Google Scholar 

  83. Cocchetti C, Castellini G, Iacuaniello D et al (2021) Does gender-affirming hormonal treatment affect 30-year cardiovascular risk in transgender persons? A two-year prospective European study (ENIGI). J Sex Med. https://doi.org/10.1016/j.jsxm.2021.01.185

    Article  PubMed  Google Scholar 

  84. Maraka S, Singh Ospina N, Rodriguez-Gutierrez R et al (2017) Sex steroids and cardiovascular outcomes in transgender individuals: a systematic review and meta-analysis. J Clin Endocrinol Metab 102:3914–3923. https://doi.org/10.1210/jc.2017-01643

    Article  PubMed  Google Scholar 

  85. Getahun D, Nash R, Flanders WD et al (2018) Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med 169:205–213. https://doi.org/10.7326/M17-2785

    Article  PubMed  PubMed Central  Google Scholar 

  86. Defreyne J, Vantomme B, Van Caenegem E et al (2018) Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European network for the investigation of gender incongruence. Andrology 6:446–454. https://doi.org/10.1111/andr.12485

    Article  CAS  PubMed  Google Scholar 

  87. Van Caenegem E, Wierckx K, Taes Y et al (2015) 2015) Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective casecontrolled study (ENIGI. Eur J Endocrinol 172(2):163–171. https://doi.org/10.1530/EJE-14-0586

    Article  CAS  PubMed  Google Scholar 

  88. Turner A, Chen TC, Barber TW et al (2004) Testosterone increases bone mineral density in female-to-male transsexuals: a case series of 15 subjects. Clin Endocrinol (Oxf) 61(5):560–566. https://doi.org/10.1111/j.1365-2265.2004.02125.x

    Article  CAS  Google Scholar 

  89. van Kesteren P, Lips P, Gooren LJG et al (1998) Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol (Oxf) 48(3):347–354. https://doi.org/10.1046/j.1365-2265.1998.00396.x

    Article  Google Scholar 

  90. Elbers JMH, Giltay EJ, Teerlink T et al (2003) Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin Endocrinol (Oxf) 58(5):562–571. https://doi.org/10.1046/j.1365-2265.2003.01753.x

    Article  CAS  Google Scholar 

  91. Murad MH, Elamin MB, Garcia MZ et al (2010) Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes. Clin Endocrinol (Oxf) 72(2):214–231. https://doi.org/10.1111/j.1365-2265.2009.03625.x

    Article  Google Scholar 

  92. Maraka S, Singh Ospina N, Rodriguez-Gutierrez R, Davidge-Pitts CJ, Nippoldt TB, Prokop LJ, Murad MH (2017) Sex steroids and cardiovascular outcomes in transgender individuals: a systematic review and meta-analysis. J Clin Endocrinol Metab 102(11):3914–3923. https://doi.org/10.1210/jc.2017-01643

    Article  PubMed  Google Scholar 

  93. Getahun D, Nash R, Flanders WD et al (2018) Cross-sex hormones and acute cardiovascular events in transgender persons: a cohort study. Ann Intern Med 169(4):205–213. https://doi.org/10.7326/M17-2785

    Article  PubMed  PubMed Central  Google Scholar 

  94. Alzahrani T, Nguyen T, Ryan A et al (2019) Cardiovascular disease risk factors and myocardial infarction in the transgender population. Circ Cardiovasc Qual Outcomes 12(4):e005597. https://doi.org/10.1161/CIRCOUTCOMES.119.005597

    Article  PubMed  Google Scholar 

  95. Khan J, Schmidt RL, Spittal MJ et al (2019) Venous thrombotic risk in transgender women undergoing estrogen therapy: a systematic review and metaanalysis. Clin Chem 65(1):57–66. https://doi.org/10.1373/clinchem.2018.288316

    Article  CAS  PubMed  Google Scholar 

  96. Kotamarti VS, Nicolas Greige G, Adee JH et al (2021) Risk for venous thromboembolism in transgender patients undergoing cross-sex hormone treatment: a systematic review. J Sex Med 18(7):1280–1291. https://doi.org/10.1016/j.jsxm.2021.04.006

    Article  CAS  PubMed  Google Scholar 

  97. Van Caenegem E, Taes Y, Wierckx K et al (2013) Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone 54(1):92–97. https://doi.org/10.1016/j.bone.2013.01.039

    Article  PubMed  Google Scholar 

  98. Wiepjes CM, Vlot MC, Klaver M et al (2017) Bone mineral density increases in trans persons after 1 year of hormonal treatment: a multicenter prospective observational study. J Bone Miner Res 32:1252–1260. https://doi.org/10.1002/jbmr.3102

    Article  CAS  PubMed  Google Scholar 

  99. Singh-Ospina N, Maraka S, Rodriguez-Gutierrez R et al (2017) Effect of sex steroids on the bone health of transgender individuals: a systematic review and meta-analysis. J Clin Endocrinol Metab 102:3904–3913. https://doi.org/10.1210/jc.2017-01642

    Article  PubMed  Google Scholar 

  100. Rothman MS, Iwamoto SJ (2019) Bone health in the transgender population. Clin Rev Bone Miner Metab 17(2):77–85. https://doi.org/10.1007/s12018-019-09261-3

    Article  PubMed  PubMed Central  Google Scholar 

  101. Nota NM, Wiepjes CM, de Blok CJM et al (2018) The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment. Brain 141(7):2047–2054

    Article  PubMed  Google Scholar 

  102. Gil M, Oliva B, Timoner J et al (2011) Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a populationbased cohort study. Br J Clin Pharmacol 72:965–968. https://doi.org/10.1111/j.1365-2125.2011.04031.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gomez AM, Ðỗ L, Ratliff A et al (2020) Contraceptive beliefs, needs, and care experiences among transgender and nonbinary young adults. J Adolesc Health 67(4):597–602. https://doi.org/10.1016/j.jadohealth.2020.03.003

    Article  PubMed  Google Scholar 

  104. Mirabella M, Giovanardi G, Fortunato A et al (2020) The Body I live in perceptions and meanings of body dissatisfaction in young transgender adults: a qualitative study. J Clin Med 9:3733. https://doi.org/10.3390/jcm9113733

    Article  PubMed Central  Google Scholar 

  105. Abern L, Maguire K (2018) Contraception knowledge in transgender individuals: are we doing enough? Obstet Gynecol 131:65S. https://doi.org/10.1097/01.AOG.0000533319.47797.7e

    Article  Google Scholar 

  106. Porsch LM, Dayananda I, Dean G et al (2016) An exploratory study of transgender New Yorkers’ Use of sexual health services and interest in receiving services at planned parenthood of New York city. Transgend Health 1:231e7. https://doi.org/10.1089/trgh.2016.0032

    Article  Google Scholar 

  107. Reisner SL, Perkovich B, Mimiaga MJ et al (2010) A mixed methods study of the sexual health needs of New England transmen who have sex with nontransgender men. AIDS Patient Care STDS 24:501e13

    Article  Google Scholar 

  108. Tishelman AC, Sutter ME, Chen D et al (2019) Health care provider perceptions of fertility preservation barriers and challenges with transgender patients and families: qualitative responses to an international survey. J Assist Reprod Genet 36:579e88

    Article  Google Scholar 

  109. Gomez AM, Wapman M et al (2017) Under (implicit) pressure: young black and latina women’s perceptions of contraceptive care. Contraception 96:221e6. https://doi.org/10.1016/j.contraception.2017.07.007

    Article  Google Scholar 

  110. Light AD, Obedin-Maliver J, Sevelius JM et al (2014) Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol 124:1120e7. https://doi.org/10.1097/AOG.0000000000000540

    Article  CAS  Google Scholar 

  111. Mancini I, Alvisi S, Gava G et al (2021) Contraception across transgender. Int J Impot Res. https://doi.org/10.1038/s41443-021-00412-z

    Article  Google Scholar 

  112. Light A, Wang LF, Zeymo A, Gomez-Lobo V (2018) Family planning and contraception use in transgender men. Contraception 98(4):266–269. https://doi.org/10.1016/j.contraception.2018.06.006

    Article  PubMed  Google Scholar 

  113. Auer MK, Fuss J, Nieder TO et al (2018) Desire to have children among transgender people in germany: a cross-sectional multi-center study. J Sex Med 15(5):757–767. https://doi.org/10.1016/j.jsxm.2018.03.083

    Article  PubMed  Google Scholar 

  114. von Doussa H, Power J, Riggs D et al (2015) Imagining parenthood: the possibilities and experiences of parenthood among transgender people. Cult Health Sex 17(9):1119–1131. https://doi.org/10.1080/13691058.2015.1042919

    Article  Google Scholar 

  115. Defreyne J, Van Schuylenbergh J, Motmans J et al (2020) Parental desire and fertility preservation in assigned male at birth transgender people living in Belgium. Int J Transgend Health 21(1):45–57. https://doi.org/10.1080/15532739.2019.1692750

    Article  PubMed  PubMed Central  Google Scholar 

  116. T’Sjoen G, Van Caenegem E, Wierckx K et al (2013) Transgenderism and reproduction. Curr Opin Endocrinol Diabetes Obes 20(6):575–579. https://doi.org/10.1097/01.med.0000436184.42554.b7

    Article  PubMed  Google Scholar 

  117. WHO (2021) WHO laboratory manual for the examination and processing of human semen, 6th edn. World Health Organization, Geneva

    Google Scholar 

  118. Hamada A, Kingsberg S, Wierckx K et al (2015) (2015) Semen characteristics of transwomen referred for sperm banking before sex transition: a case series. Andrologia 47:832–838

    Article  CAS  PubMed  Google Scholar 

  119. Li K, Rodriguez D, Gabrielsen JS et al (2018) Sperm cryopreservation of transgender individuals: trends and findings in the past decade. Andrology 6:860–864. https://doi.org/10.1111/andr.12527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Adeleye AJ, Reid G, Kao CN et al (2019) Semen parameters among transgender women with a history of hormonal treatment. Urology 124:136–141. https://doi.org/10.1016/j.urology.2018.10.005

    Article  PubMed  Google Scholar 

  121. Baba T, Endo T, Honnma H et al (2007) Association between polycystic ovary syndrome and female-to-male transsexuality. Hum Reprod 22(4):1011–1016. https://doi.org/10.1093/humrep/del474

    Article  PubMed  Google Scholar 

  122. Spinder T, Spijkstra JJ, van den Tweel JG et al (1989) The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects. J Clin Endocrinol Meta 69(1):151–157. https://doi.org/10.1210/jcem-69-1-151

    Article  CAS  Google Scholar 

  123. Ikeda K, Baba T, Noguchi H et al (2013) Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology. Hum Reprod 28(2):453–461. https://doi.org/10.1093/humrep/des385

    Article  CAS  PubMed  Google Scholar 

  124. Maxwell S, Noyes N, Keefe D et al (2017) Pregnancy outcomes after fertility preservation in transgender men. Obstet Gynecol 129(6):1031–1034. https://doi.org/10.1097/AOG.0000000000002036

    Article  PubMed  Google Scholar 

  125. Armuand G, Dhejne C, Olofsson JI et al (2017) Transgender men’s experiences of fertility preservation: a qualitative study. Hum Reprod 32:383–390. https://doi.org/10.1093/humrep/dew323

    Article  CAS  PubMed  Google Scholar 

  126. Gooren LJ, T’Sjoen G et al (2018) (2018) Endocrine treatment of aging transgender people. Rev Endocr Metab Disord 19:253–262. https://doi.org/10.1007/s11154-018-9449-0

    Article  CAS  PubMed  Google Scholar 

  127. Van Caenegem E, Taes Y, Wierckx K et al (2013) Low bone mass is prevalent in male-to-female transsexual persons before the start of cross-sex hormonal therapy and gonadectomy. Bone 54:92–97. https://doi.org/10.1016/j.bone.2013.01.039

    Article  PubMed  Google Scholar 

  128. Wiepjes CM, Jm de Blok C, Staphorsius AS et al (2020) Fracture risk in trans women and trans men using long-term gender-affirming hormonal treatment: a nationwide cohort study. J Bone Miner Res 35(1):64–70. https://doi.org/10.1002/jbmr.3862

    Article  PubMed  Google Scholar 

  129. Shao T, Grossbard ML, Klein P (2011) Breast cancer in female-tomaletranssexuals: two cases with a review of physiology and management. Clin Breast Cancer 11(6):417–419. https://doi.org/10.1016/j.clbc.2011.06.006

    Article  PubMed  Google Scholar 

  130. Burcombe RJ, Makris A, Pittam M et al (2003) Breast cancer after bilateral subcutaneous mastectomy in a female-to-male transsexual. Breast 12(4):290–293. https://doi.org/10.1016/s0960-9776(03)00033-x

    Article  CAS  PubMed  Google Scholar 

  131. Marjoribanks J, Farquhar C, Roberts H et al (2017) Longterm hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD004143.pub5

    Article  PubMed  PubMed Central  Google Scholar 

  132. Bergoglio MT, Gomez-Balaguer M, Almonacid Folch E et al (2013) Symptomatic meningioma induced by cross-sex hormone treatment in a male-to-female transsexual. Endocrinol Nutr 60(5):264–267. https://doi.org/10.1016/j.endonu.2012.07.004

    Article  PubMed  Google Scholar 

  133. Stegeman BH, de Bastos M, Rosendaal FR et al (2013) Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ 347:f5298. https://doi.org/10.1136/bmj.f5298

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Andrology, Women’s Endocrinology and Gender Incongruence Unit, Florence University Hospital, Viale Pieraccini 6, 50139, Florence, Italy

    A. D. Fisher, C. Cocchetti & J. Ristori

  2. Laboratory of Seminology, Sperm Bank “Loredana Gandini”, Department of Experimental Medicine, Sapienza University of Rome, 00185, Rome, Italy

    G. Senofonte & F. Lombardo

  3. Studio Legale Avv. Giovanni Guercio, Via Antonio Mordini, 14, 00195, Rome, Italy

    G. Guercio

  4. Department of Dynamic and Clinical Psychology, and Health Studies, Sapienza University of Rome, Via degli Apuli 1, 00185, Roma, Italy

    V. Lingiardi & A. M. Speranza

  5. Gynecology and Physiopathology of Human Reproduction, Department of Medical and Surgical Sciences (DIMEC), IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy

    M. C. Meriggiola

  6. Gender Identity Development Service, Hospital S. Camillo-Forlanini, Rome, Italy

    M. Mosconi

  7. Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy

    G. Motta

  8. Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy

    M. Pierdominici

  9. Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, Viale Pieraccini 6, 50139, Florence, Italy

    M. Maggi

  10. Endocrinology Unit, Medical Department, Maggiore-Bellaria Hospital, Azienda-Usl, Bologna, Italy

    G. Corona

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  1. A. D. Fisher
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Appendices

Appendix 1

An Italian law overview

Law n.164 of 1982

The procedure of gender reassignment, for those who wish to undertake it, is regulated by Law n.164/1982.

According to the aforementioned law “, when it is necessary to adapt the sexual characteristics through surgical treatment, the Court authorizes it with a judgment” and, “once done the authorized treatment, orders the rectification of sex attribution” (article 3).

According to this rule, therefore, the judge can issue an order for the Registry to rectify the birth certificate only after the surgical intervention has been carried out.

First jurisprudence without appointment of the C.T.U. (Court expert in the subject) in the surgical interventions’ authorization phase and in the Registry’s correction phase

Law 164/82, in Article 2 paragraph 4, provides the possibility (not the obligation) for the judge to appoint a technical consultant (C.T.U.) who certifies the psycho-sexual conditions of the person.

Unfortunately, what was supposed to be just a “possibility”, from 1982 (year of entry into force of the law) until 1996, became the case law in use by the Italian Courts which appointed this technical consultancy without wondering whether this auxiliary activity (expensive in terms of time, embarrassment and costs) was actually “necessary”.

With a petition of the writer, who pointed out that, in the presence of a certified psycho-sexual report or, better, drafted by a public hospital, there was no “need” to appoint another expert who would have done nothing but confirm what his colleagues had already certified, in 1996 the Court of Rome ruled favorably, avoiding for the first time the appointment of this expert.

Case law on rectification of the Registry without the need of phalloplasty

Another obstacle to be faced (again in the absolute silence of the law) was the erroneous interpretation of Law 164/1982 for people subjected to transition from female to male (FtM). The Courts in the absence of total reconstruction of the genital organs (penis and testicles) refused the registry correction.

Once again the current legislation is ambiguous: art.3 paragraph 2 of the Law requires the authorized treatment to be carried out in order as to obtain the rectification of the birth certificate, but it does not clarify what this “authorized treatment” consists of. The Courts, therefore, for more than 20 years rejected the application substantially, because the male sexual organs were not reconstructed. As a matter of fact, the problem consisted in establishing whether the rectification of the Registry was allowed after a hysterectomy with bilateral oophorectomy and mastectomy, even in the absence of a phalloplasty.

The modifications of the physical sexual characteristics should represent only the tool for completing a pathway of the personality that already exists and which is the actual prerequisite for rectification. Therefore, when the Court had already ascertained the existence of a male personality (so-called psychological or behavioral sex) opposed to the biological sex and has authorized with a sentence the modification of the female sexual characteristics, this must be considered sufficient for the modification of the personal data without the full acquisition of the characteristics of the other sex (penis and testicles).

Genesis of the Registry rectification without any surgery

Taking in consideration that the current legislation must obey to the requirements of health protection as a constitutionally guaranteed right (Constitutional Court n.161/1985 and n.170/2014), it is, therefore, impossible to oblige a person to undergo surgery if it may prove to be harmful or, simply, not desired or not necessary for the achievement of the psycho-physical wellbeing and/or health of that person.

The keyword, therefore, lies in the term “necessary” indicated by the reference standards, and surgery is not, in fact, necessary, whenever the person experiences his or her body with balance and satisfaction, regardless of their physic and/or behavioral sex.

The Court of Rome (October 18 1997), in a case sponsored by the writer, for the first time affirmed the principle that Law No. 164/82 does not imply surgical treatment as an indispensable prerequisite for rectification, but only provides that such intervention must be authorized, when necessary.

Of the same and ultimate opinion is again the Court of Rome, with a judgment of March 22 2011 that state that “…the person has reached such a level of integration of its genitals with its own body image that she can live satisfactorily both personally and in relationships with others"; "… this sexual identity notion therefore takes into account not only external sexual characteristics, but also psychological and social elements, so that it defines the gender as a complex data of personality …”. This milestone sentence was followed by many other Italian Courts (among which Rovereto in 2013, Siena in 2013, Messina in 2014).

Finally, the High Court on July 20, 2015 (15138/15), with a sentence considered of a measure that has been defined as of "historical" importance, declared that there is no need of surgical modification of genitals to obtain the correction of sex and name.

The Supreme Court's ruling on the gender identity problem (DIG), interprets surgery not as the solution, but only as a possible aid, where necessary, for the well-being of the person. An interpretation that does not take account of this evolution, according to the Court, "ends up betraying the rationale of the law" and "the choice to undergo surgical modification of genitals can only be an expressive choice of the inviolable rights of the person, expendable only if there are superior interests to be protected". Since the current legislation does not indicate what such superior interests might be, "the public interest does not require the sacrifice of the right to the preservation of one's psycho-physical integrity". Moreover, a different interpretation would be in stark contrast to the constitutionally guaranteed principle of the impossibility of imposing on anyone any health treatment that violates human dignity, as it is unnecessary or, quite simply, unwished.

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Fisher, A.D., Senofonte, G., Cocchetti, C. et al. SIGIS–SIAMS–SIE position statement of gender affirming hormonal treatment in transgender and non-binary people. J Endocrinol Invest 45, 657–673 (2022). https://doi.org/10.1007/s40618-021-01694-2

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