A comparison of 5-year administration of cyproterone acetate or leuprolide acetate in combination with estradiol in transwomen

in European Journal of Endocrinology
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  • 1 Gynecology and Physiopathology of Human Reproduction, Department of Medical and Surgical Sciences (DIMEC), S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

Correspondence should be addressed to G Gava; Email: giulia.gava2@unibo.it
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Objective

The impact of different combinations of long-term gender-affirming hormone therapy (GAHT) in transwomen (TW) is largely unknown. To assess the effects of 5-year administration of cyproterone acetate (CPA) or leuprolide acetate (Leu) plus transdermal or oral estradiol (E).

Design

Cohort study based on prospectively collected data. Fifty TW received 50 mg CPA daily orally (n = 25; CPA+E group) or 3.75 mg Leu i.m. monthly (n = 25; Leu+E group) with 1 or 2 mg E daily for 5 years. Reproductive hormones, biochemical and anthropometric parameters, body composition and bone mineral density (BMD) were assessed.

Results

LH, FSH and total testosterone levels were similarly and significantly suppressed in both groups. Prolactin increased only in the CPA+E group (P = 0.002). Fasting insulin resistance and glucose progressively increased in the CPA+E group only (treatment × time effect P = 0.002 and P = 0.043, respectively). Total cholesterol increased more in the Leu+E group than in the CPA+E group and HDL-cholesterol decreased in the CPA+E group (time × treatment interaction effect, P = 0.007). Lumbar and total body BMD increased in both groups after 3 years. No serious adverse events were recorded.

Conclusions

Both regimens were effective in suppression of T production. CPA+E worsened the metabolic profile with a slight increase in PRL levels. All subjects presented an increase in BMD regardless of treatment. These preliminary data could have clinical implications in the choice of GAHT, in particular for those TW not requiring gender-affirming surgery.

 

     European Society of Endocrinology

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  • 1

    Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th ed. Arlington, VA : American Psychiatric Publishing, 2013. ()

  • 2

    Meriggiola MC & Gava G Endocrine care of transpeople part II. A review of cross-sex hormonal treatments, outcomes and adverse effects in transwomen. Clinical Endocrinology 2015 83 607615. (https://doi.org/10.1111/cen.12754)

    • Search Google Scholar
    • Export Citation
  • 3

    Tangpricha V, Hannema SE, Irwig MS, Meyer WJ, Safer JD & Hembree WC American Association of Clinical Endocrinologists/Endocrine Society update on transgender medicine: case discussions. Endocrine Practice 2017 23 14301436.

    • Search Google Scholar
    • Export Citation
  • 4

    Meriggiola MC, Jannini EA, Lenzi A, Maggi M & Manieri C Endocrine treatment of transsexual persons: an Endocrine Society Clinical Practice Guideline: commentary from a European perspective. European Journal of Endocrinology 2010 162 831833. (https://doi.org/10.1530/EJE-09-1091)

    • Search Google Scholar
    • Export Citation
  • 5

    Asscheman H, Giltay EJ, Megens JAJ, de Ronde WP, van Trotsenburg MAA & Gooren LJG A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. European Journal of Endocrinology 2011 164 635642. (https://doi.org/10.1530/EJE-10-1038)

    • Search Google Scholar
    • Export Citation
  • 6

    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. Journal of Clinical Endocrinology and Metabolism 2012 97 44224428. (https://doi.org/10.1210/jc.2012-2030)

    • Search Google Scholar
    • Export Citation
  • 7

    Savidou I, Deutsch M, Soultati AS, Koudouras D, Kafiri G & Dourakis SP Hepatotoxicity induced by cyproterone acetate: a report of three cases. World Journal of Gastroenterology 2006 12 75517555. (https://doi.org/10.3748/wjg.v12.i46.7551)

    • Search Google Scholar
    • Export Citation
  • 8

    van Kesteren PJM, Asscheman H, Megens JAJ & Gooren LJG Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clinical Endocrinology 1997 47 337342. (https://doi.org/10.1046/j.1365-2265.1997.2601068.x)

    • Search Google Scholar
    • Export Citation
  • 9

    Cohen-Kettenis PT & Klink D Adolescents with gender dysphoria. Best Practice and Research: Clinical Endocrinology and Metabolism 2015 29 485495. (https://doi.org/10.1016/j.beem.2015.01.004)

    • Search Google Scholar
    • Export Citation
  • 10

    Wilson AC, Meethal SV, Bowen RL & Atwood CS Leuprolide acetate: a drug of diverse clinical applications. Expert Opinion on Investigational Drugs 2007 16 18511863. (https://doi.org/10.1517/13543784.16.11.1851)

    • Search Google Scholar
    • Export Citation
  • 11

    Gava G, Cerpolini S, Martelli V, Battista G, Seracchioli R & Meriggiola MC Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness. Clinical Endocrinology 2016 85 239246. (https://doi.org/10.1111/cen.13050)

    • Search Google Scholar
    • Export Citation
  • 12

    WHO | International Classification of Diseases, 11th Revision (ICD-11). WHO. (available at: http://www.who.int/classifications/icd/en/). Accessed on 25 March 2020.

    • Search Google Scholar
    • Export Citation
  • 13

    Fanelli F, Gambineri A, Belluomo I, Repaci A, Di Lallo VD, Di Dalmazi G, Mezzullo M, Prontera O, Cuomo G & Zanotti L et al. Androgen profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS) in healthy normal-weight ovulatory and anovulatory late adolescent and young women. Journal of Clinical Endocrinology and Metabolism 2013 98 30583067. (https://doi.org/10.1210/jc.2013-1381)

    • Search Google Scholar
    • Export Citation
  • 14

    Bartsch W, Horst HJ, Becker H & Nehse G Sex hormone binding globulin binding capacity, testosterone, 5alpha-dihydrotestosterone, oestradiol and prolactin in plasma of patients with prostatic carcinoma under various types of hormonal treatment. Acta Endocrinologica 1977 85 650664. (https://doi.org/10.1530/acta.0.0850650)

    • Search Google Scholar
    • Export Citation
  • 15

    Gooren LJ, Harmsen-Louman W & van Kessel H Follow-up of prolactin levels in long-term oestrogen-treated male-to-female transsexuals with regard to prolactinoma induction. Clinical Endocrinology 1985 22 201207. (https://doi.org/10.1111/j.1365-2265.1985.tb01081.x)

    • Search Google Scholar
    • Export Citation
  • 16

    Asscheman H, Gooren LJ, Assies J, Smits JP & de Slegte R Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals. Clinical Endocrinology 1988 28 583588. (https://doi.org/10.1111/j.1365-2265.1988.tb03849.x)

    • Search Google Scholar
    • Export Citation
  • 17

    Cunha FS, Domenice S, Câmara VL, Sircili MHP, Gooren LJG, Mendonça BB & Costa EMF Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy. Andrologia 2015 47 680684. (https://doi.org/10.1111/and.12317)

    • Search Google Scholar
    • Export Citation
  • 18

    García-Malpartida K, Martín-Gorgojo A, Rocha M, Gómez-Balaguer M & Hernández-Mijares A Prolactinoma induced by estrogen and cyproterone acetate in a male-to-female transsexual. Fertility and Sterility 2010 94 1097.e131097.e15. (https://doi.org/10.1016/j.fertnstert.2010.01.076)

    • Search Google Scholar
    • Export Citation
  • 19

    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 2009 bcr0220091589. (https://doi.org/10.1136/bcr.02.2009.1589)

    • Search Google Scholar
    • Export Citation
  • 20

    Sathyapalan T, González S & Atkin SL Effect of long-term, high-dose estrogen treatment on prolactin levels: a retrospective analysis. Climacteric 2009 12 427430. (https://doi.org/10.1080/13697130902929559)

    • Search Google Scholar
    • Export Citation
  • 21

    Colizzi M, Costa R, Scaramuzzi F, Palumbo C, Tyropani M, Pace V, Quagliarella L, Brescia F, Natilla LC & Loverro G et al. Concomitant psychiatric problems and hormonal treatment induced metabolic syndrome in gender dysphoria individuals: a 2 year follow-up study. Journal of Psychosomatic Research 2015 78 399406. (https://doi.org/10.1016/j.jpsychores.2015.02.001)

    • Search Google Scholar
    • Export Citation
  • 22

    Giltay EJ, Gooren LJ, Emeis JJ, Kooistra T & Stehouwer CD Oral, but not transdermal, administration of estrogens lowers tissue-type plasminogen activator levels in humans without affecting endothelial synthesis. Arteriosclerosis, Thrombosis, and Vascular Biology 2000 20 13961403. (https://doi.org/10.1161/01.atv.20.5.1396)

    • Search Google Scholar
    • Export Citation
  • 23

    Smith MR, Lee H, McGovern F, Fallon MA, Goode M, Zietman AL & Finkelstein JS Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome. Cancer 2008 112 21882194. (https://doi.org/10.1002/cncr.23440)

    • Search Google Scholar
    • Export Citation
  • 24

    Poyet P & Labrie F Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate. Molecular and Cellular Endocrinology 1985 42 283288. (https://doi.org/10.1016/0303-7207(8590059-0)

    • Search Google Scholar
    • Export Citation
  • 25

    Ott J, Aust S, Promberger R, Huber JC & Kaufmann U Cross‐sex hormone therapy alters the serum lipid profile: a retrospective cohort study in 169 transsexuals. Journal of Sexual Medicine 2011 8 23612369. (https://doi.org/10.1111/j.1743-6109.2011.02311.x)

    • Search Google Scholar
    • Export Citation
  • 26

    Denti L, Pasolini G, Cortellini P, Sanfelici L, Benedetti R, Cecchetti A, Ferretti S, Bruschieri L, Ablondi F & Valenti G Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH). Atherosclerosis 2000 152 159166. (https://doi.org/10.1016/s0021-9150(9900442-6)

    • Search Google Scholar
    • Export Citation
  • 27

    Elbers JMH, Giltay EJ, Teerlink T, Scheffer PG, Asscheman H, Seidell JC & Gooren LJG Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clinical Endocrinology 2003 58 562571. (https://doi.org/10.1046/j.1365-2265.2003.01753.x)

    • Search Google Scholar
    • Export Citation
  • 28

    Shadid S, Abosi-Appeadu K, De Maertelaere AS, Defreyne J, Veldeman L, Holst JJ, Lapauw B, Vilsbøll T & T’Sjoen G Effects of gender-affirming hormone therapy on insulin sensitivity and incretin responses in transgender people. Diabetes Care 2020 43 411417. (https://doi.org/10.2337/dc19-1061)

    • Search Google Scholar
    • Export Citation
  • 29

    Elbers JM, Asscheman H, Seidell JC & Gooren LJ Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals. American Journal of Physiology 1999 276 E317E 325. (https://doi.org/10.1152/ajpendo.1999.276.2.E317)

    • Search Google Scholar
    • Export Citation
  • 30

    Mueller A, Zollver H, Kronawitter D, Oppelt PG, Claassen T, Hoffmann I, Beckmann MW & Dittrich R Body composition and bone mineral density in male-to-female transsexuals during cross-sex hormone therapy using gonadotrophin-releasing hormone agonist. Experimental and Clinical Endocrinology and Diabetes 2011 119 95100. (https://doi.org/10.1055/s-0030-1255074)

    • Search Google Scholar
    • Export Citation
  • 31

    Gooren LJ Olympic sports and transsexuals. Asian Journal of Andrology 2008 10 427432. (https://doi.org/10.1111/j.1745-7262.2008.00378.x)

    • Search Google Scholar
    • Export Citation
  • 32

    Gooren L Hormone treatment of the adult transsexual patient. Hormone Research 2005 64 (Supplement 2) 3136. (https://doi.org/10.1159/000087751)

    • Search Google Scholar
    • Export Citation
  • 33

    Klaver M, Dekker MJHJ, de Mutsert R, Twisk JWR & den Heijer M Cross-sex hormone therapy in transgender persons affects total body weight, body fat and lean body mass: a meta-analysis. Andrologia 2017 49 e12660. (https://doi.org/10.1111/and.12660)

    • Search Google Scholar
    • Export Citation
  • 34

    Wierckx K, Van Caenegem E, Schreiner T, Haraldsen I, Fisher AD, Toye K, Kaufman JM & T’Sjoen G Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European network for the investigation of gender incongruence. Journal of Sexual Medicine 2014 11 19992011. (https://doi.org/10.1111/jsm.12571)

    • Search Google Scholar
    • Export Citation
  • 35

    Barros Almeida Leite C, Di Renzo L, Sinibaldi Salimei P, Gualtieri P, Madalozo Schieferdecker ME, Vilela RM, Ghizoni Teive HA, Frehner C, Taconeli CA & Cabral A et al. Lean body mass: reference values for Italian population between 18 to 88 years old. European Review for Medical and Pharmacological Sciences 2018 22 78917898. (https://doi.org/10.26355/eurrev_201811_16415)

    • Search Google Scholar
    • Export Citation
  • 36

    Van Caenegem E, Wierckx K, Taes Y, Schreiner T, Vandewalle S, Toye K, Kaufman JM & T’Sjoen G Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study . Osteoporosis International 2015 26 3547. (https://doi.org/10.1007/s00198-014-2805-3)

    • Search Google Scholar
    • Export Citation
  • 37

    Wiepjes CM, de Jongh RT, de Blok CJ, Vlot MC, Lips P, Twisk JW & den Heijer M Bone safety during the first ten years of gender‐affirming hormonal treatment in transwomen and transmen. Journal of Bone and Mineral Research 2019 34 447454. (https://doi.org/10.1002/jbmr.3612)

    • Search Google Scholar
    • Export Citation
  • 38

    Singh-Ospina N, Maraka S, Rodriguez-Gutierrez R, Davidge-Pitts C, Nippoldt TB, Prokop LJ & Murad MH Effect of sex steroids on the bone health of transgender individuals: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 2017 102 39043913. (https://doi.org/10.1210/jc.2017-01642)

    • Search Google Scholar
    • Export Citation