Effects on the Male Endocrine System of Long-term Treatment with Gonadotropin-releasing Hormone Agonists and Estrogens in Male-to-Female Transsexuals

 

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Abstract

We studied hormonal changes resulting from long-term treatment with gonadotropin-releasing hormone agonist and 17β estradiol valerate in 40 healthy middle-aged male-to-female transsexuals over a period of two years. All of the participants received injections of 3.8 mg goserelin acetate every four weeks in combination with 6 mg oral 17β estradiol valerate per day for cross-sex hormone treatment for male-to-female transsexuals. There was a significant reduction in the levels of serum luteinizing hormone and follicle-stimulating hormone to the hypogonadal stage. Mean testosterone levels decreased by 97 % to 0.52 and 0.59 nmol/l after 12 months and 24 months, respectively. There was a significant reduction in dehydroepiandrosterone sulfate by 37 % after 12 months and 43 % after 24 months, and androstendione by 29 % after 12 months and 27 % after 24 months, respectively. Cortisol levels were reduced by 43 % and 50 %, respectively. Estrogen levels were significantly increased from 77.51 to 677 after 12 months and 661 pmol/l after 24 months. Sex hormone-binding globulin and corticoid-binding globulin levels were significantly increased after 12 and 24 months. There was a significant decrease in all measured androgen fractions and cortisol during long-term treatment with gonadotropin-releasing hormone agonist and 17β estradiol valerate. Apart from suppression of testicular hormone production, one possible interpretation is that treatment with long-term gonadotropin-releasing hormone agonist and 17β estradiol valerate influences adrenal hormone levels in healthy middle-aged male-to-female transsexuals. Cortisol serum levels may be decreased due to estrogen-induced increase in corticoid-binding globulin.

References

• 1 Koutsilieris M, Mitsiades C, Dimopoulos T, Ioannidis A, Ntounis A, Lambou T. A combination therapy of dexamethasone and somatostatin analog reintroduces objective clinical responses to LHRH analog in androgen ablation-refractory prostate cancer patients.  J Clin Endocrinol Metab. 2001;  86 5729-5736
  CrossrefPubMedGoogle Scholar
• 2 Oka H, Negoro H, Sugino Y, Iwamura H, Moroi S, Kawakita M. Change of serum adrenal androgens in prostatic cancer patients after bilateral orchidectomy or LHRH agonist treatment; in Japanese.  Hinyokika Kiyo. 2003;  49 521-525
  PubMedGoogle Scholar
• 3 Eri L M, Haug E, Tveter K J. Effects on the endocrine system of long-term treatment with the luteinizing hormone-releasing hormone agonist leuprolide in patients with benign prostatic hyperplasia.  Scand J Clin Lab Invest. 1996;  56 319-325
  PubMedGoogle Scholar
• 4 Philip P A, Carmichael J, Tonkin K. et al . Hormonal treatment of pancreatic carcinoma: a phase II study of LHRH agonist goserelin plus hydrocortisone.  Br J Cancer. 1993;  67 379-382
  PubMedGoogle Scholar
• 5 Scher H I, Kelly W K. Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer.  J Clin Oncol. 1993;  11 1566-1572
  PubMedGoogle Scholar
• 6 Kitahara S, Umeda H, Yano M. et al . Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer.  Endocr J. 1999;  46 659-664
  PubMedGoogle Scholar
• 7 Spetz A C, Hammar M, Lindberg B, Spangberg A, Varenhorst E,. Scandinavian Prostatic Cancer Group-5 Trial Study . Prospective evaluation of hot flashes during treatment with parenteral estrogen or complete androgen ablation for metastatic carcinoma of the prostate.  J Urol. 2001;  166 517-520
  CrossrefPubMedGoogle Scholar
• 8 Gerber G S, Zagaja G P, Ray P S, Rukstalis D B. Transdermal estrogen in the treatment of hot flushes in men with prostate cancer.  Urology. 2000;  55 97-101
  CrossrefPubMedGoogle Scholar
• 9 Fiet J, Dore J C, Go A L, Ojasoo T, Raynaud J P. Multivariate analysis of plasma hormones in patients with metastatic prostate cancer receiving combined LHRH-analog and antiandrogen therapy.  Prostate. 1993;  23 291-313
  PubMedGoogle Scholar
• 10 Ayub M, Levell M J. Suppression of plasma androgens by the antiandrogen flutamide in prostatic cancer patients treated with Zoladex, a GnRH analogue.  Clin Endocrinol (Oxf). 1990;  32 329-339
  PubMedGoogle Scholar
• 11 Hamburger C. Endocrine treatment of male and female transsexualism. In: Green R, Money J (eds) Transsexualism and Sex Reassignment. Baltimore; Johns Hopkins Press 1969: 291-307
  Google Scholar
• 12 Harry Benjamin International Gender Dysphoria Association .The Harry Benjamin International Gender Dysphoria Association standards of care for gender identity disorders, 6th version (November 17th, 2001). http://http://www.hbigda.org/soc.html. Retrieved 2002
  Google Scholar
• 13 Moore E, Wisniewski A, Dobs A. Endocrine treatment of transsexual people: a review of treatment regimens, outcomes, and adverse effects.  J Clin Endocrinol Metab. 2003;  88 3467-3473
  CrossrefPubMedGoogle Scholar
• 14 Levy A, Crown A, Reid R. Endocrine intervention for transsexuals.  Clin Endocrinol. 2003;  59 409-418
  CrossrefPubMedGoogle Scholar
• 15 Futterweit W. Endocrine management of transsexual: hormonal profiles of serum prolactin, testosterone, and estradiol.  N Y State J Med. 1980;  80 1260-1264
  PubMedGoogle Scholar
• 16 Asscheman H, Gooren L, Assies J, Smith J, De Slegte R. Prolactin levels and pituitary enlargement in hormone-treated male to female transsexual people.  Clin Endocrinol (Oxf). 1988;  28 583-588
  PubMedGoogle Scholar
• 17 Gooren L, Assies J, Asscheman H, de Slegte R, van Kessel H. Estrogen-induced prolactinoma in a man.  J Clin Endocrinol Metab. 1988;  66 444-446
  CrossrefPubMedGoogle Scholar
• 18 Asscheman H, Gooren L, Eklund P. Mortality and morbidity in transsexual patients with cross-gender hormone treatment.  Metabolism. 1989;  38 869-873
  CrossrefPubMedGoogle Scholar
• 19 Van Kesteren P, Asscheman H, Megens J, Gooren L. Mortality and morbidity in transsexual subjects treated with cross-sex hormones.  Clin Endocrinol (Oxf). 1997;  47 337-342
  CrossrefPubMedGoogle Scholar
• 20 Michel A, Mormont C, Legros J. A psycho-endocrinological overview of transsexualism.  Eur J Endocrinol. 2001;  145 365-376
  CrossrefPubMedGoogle Scholar
• 21 Khosla S, Melton L J 3rd, Atkinson E J, O’Fallon W M, Klee G G, Riggs B L. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen.  J Clin Endocrinol Metab. 1998;  83 2266-2274
  CrossrefPubMedGoogle Scholar
• 22 Vermeulen A, Kaufman J M, Goemaere S, van Pottelberg I. Estradiol in elderly men.  Aging Male. 2002;  5 98-102
  PubMedGoogle Scholar
• 23 Carreau S, Bourguiba S, Marie E. Testicular and blood steroid levels in aged men.  Reprod Biol. 2004;  4 299-304
  PubMedGoogle Scholar
• 24 Tyrell J B, Aron D C, Forsham P H. Glucocorticoids and adrenal androgens. In: Greenspan FS (ed) Basic and clinical endocrinology, 3rd ed. Englewood Cliffs, New Jersey; Prentice-Hall 1991: 323-362
  Google Scholar
• 25 Gregg D W, Allen M C, Nett T M. Estradiol-induced increase in number of gonadotropin-releasing hormone receptors in cultured ovine pituitary cells.  Biol Reprod. 1990;  43 1032-1036
  CrossrefPubMedGoogle Scholar
• 26 Dall’Asta C, Ballare E, Mantovani G. et al . Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma.  Horm Metab Res. 2004;  36 578-583
  Article in Thieme ConnectPubMedGoogle Scholar
• 27 Miyamura N, Tsutsumi A, Senokuchi H. et al . A case of ACTH-independent macronodular adrenal hyperplasia: simultaneous expression of several aberrant hormone receptors in the adrenal gland.  Endocr J. 2003;  50 333-340
  CrossrefPubMedGoogle Scholar
• 28 Aedo A R, Landgren B M, Diczfalusy E. Pharmacokinetics and biotransformation of orally administered oestrone sulphate and oestradiol valerate in postmenopausal women.  Maturitas. 1990;  12 333-343
  CrossrefPubMedGoogle Scholar
• 29 Kuhl H. Pharmacology of estradiol and estriol.  Menopause Rev. 2000;  5 23-44
  PubMedGoogle Scholar
• 30 Lin A D, Chen K K, Lin A T. et al . Antiandrogen-associated hepatotoxicity in the management of advanced prostate cancer.  J Chin Med Assoc. 2003;  66 735-740
  PubMedGoogle Scholar
• 31 Adlercreutz H, Tenhunen R. Some aspects of the interaction between natural and synthetic female sex hormones and the liver.  Am J Med. 1970;  49 630-648
  PubMedGoogle Scholar
• 32 Aldinger K, Ben Menachem Y, Whalen G. Focal nodular hyperplasia of the liver associated with high-dosage estrogens.  Arch Intern Med. 1977;  137 357-359
  CrossrefPubMedGoogle Scholar
• 33 Mueller A, Dittrich R, Binder H, Kühnel W, Maltaris T, Hoffmann I, Beckmann M W. High Dose Estrogen Treatment Increases Bone Mineral Density in Male to Female Transsexuals Receiving Gonadotropin-Releasing Hormone Agonist in the Absence of Testosterone.  Eur J Endocrinol. 2005;  153 107-113
  CrossrefPubMedGoogle Scholar

Andreas Mueller

Department of Obstetrics and Gynecology · Erlangen University Hospital

Universitätsstrasse 21-23 · 91054 Erlangen · Germany

Phone: +49 (9131) 853 35 53

Fax: +49 (9131) 853 35 52

Email: andreas.mueller@gyn.imed.uni-erlangen.de