Reproductive BioMedicine Online
Volume 20, Issue 4 , Pages 553-558 , April 2010

Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population

  • Michaël Grynberg

      Affiliations

    • AP-HP, Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France
    • University Paris-Sud, Clamart F-92140, France
    • INSERM, U782, Clamart F-92140, France
    • Corresponding Author InformationCorresponding author.
    • ,
  • Renato Fanchin

      Affiliations

    • AP-HP, Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France
    • University Paris-Sud, Clamart F-92140, France
    • INSERM, U782, Clamart F-92140, France
    • ,
  • Geneviève Dubost

      Affiliations

    • Department of Pathology, Hôpital Foch, Suresnes, France
    • ,
  • Jean-Claude Colau

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Foch, Suresnes, France
    • ,
  • Catherine Brémont-Weil

      Affiliations

    • Department of Endocrinology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
    • ,
  • René Frydman

      Affiliations

    • AP-HP, Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, Clamart F-92141, France
    • University Paris-Sud, Clamart F-92140, France
    • INSERM, U782, Clamart F-92140, France
    • ,
  • Jean-Marc Ayoubi

      Affiliations

    • Department of Obstetrics and Gynecology, Hôpital Foch, Suresnes, France

Received 30 June 2009 ,Revised 6 August 2009 ,Accepted 2 December 2009.

References 

  1. American Psychiatric Association, 1994. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Washington DC.
  2. Amirikia H, Savoy-Moore RT, Sundareson AS, et al. The effects of long-term androgen treatment on the ovary. Fertil. Steril. 1986;45:202–208
  3. Bakker A, van Kesteren PJ, Gooren LJ, et al. The prevalence of transsexualism in The Netherlands. Acta Psychiatr. Scand. 2002;87:237–238
  4. Billig H, Furuta I, Hsueh AJ. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology. 1993;133:2204–2212
  5. Block E. Quantitative morphological investigations of the follicular system in women: variations at different ages. Acta Anat. 1952;14:108–123
  6. Burgess HE, Shousha S. An immunohistochemical study of the long-term effects of androgen administration on female-to-male transsexual breast: a comparison with normal female breast and male breast showing gynaecomastia. J. Pathol. 1993;170:37–43
  7. Cameron IT, O’Shea FC, Rolland JM, et al. Occult ovarian failure: a syndrome of infertility, regular menses, and elevated follicle-stimulating hormone concentrations. J. Clin. Endocrinol. Metab. 1988;67:1190–1194
  8. De Leo V, la Marca A, Lanzetta D, et al. Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF). Clin. Endocrinol. (Oxf.). 1998;49:85–89
  9. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev. 1997;18:774–800
  10. Fasouliotis SJ, Simon A, Laufer N. Evaluation and treatment of low responders in assisted reproductive technology: a challenge to meet. J. Assist. Reprod. Genet. 2000;17:357–373
  11. Futterweit W, Deligdisch L. Histopathological effects of exogenously administered testosterone in 19 female to male transsexual people. J. Clin. Endocrinol. Metab. 1986;62:16–21
  12. Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr. Rev. 1996;17:121–155
  13. The Harry Benjamin International Gender Dysphoria Association standards of care for gender identity disorders, 6th version. <http://www.hbigda.org/soc.html/> (retrieved 17.11.02).
  14. Hickok LR, Toomey C, Speroff L. A comparison of esterified estrogens with and without methyltestosterone: effects on endometrial histology and serum lipoproteins in postmenopausal women. Obstet. Gynecol. 1993;82:919–924
  15. Hillier SG, Ross GT. Effects of exogenous testosterone on ovarian weight, follicular morphology and intraovarian progesterone concentration in estrogen-primed hypophysectomized immature female rats. Biol. Reprod. 1979;20:261–268
  16. Hillier SG, Tetsuka M, Fraser HM. Location and developmental regulation of androgen receptor in primate ovary. Hum. Reprod. 1997;12:107–111
  17. Hughesdon PE. Morphology and morphogenesis of the Stein–Leventhal ovary and of so-called ‘hyperthecosis’. Obstet. Gynecol. Surv. 1982;37:59–77
  18. Jonard S, Robert Y, Cortet-Rudelli C, et al. Ultrasound examination of polycystic ovaries: is it worth counting the follicles?. Hum. Reprod. 2003;18:598–603
  19. Kase N, Kowal J, Perloff W, et al. In vitro production of androgens by a virilizing adrenal adenoma and associated polycystic ovaries. Acta Endocrinol. (Copenh.). 1963;44:15–19
  20. Key T, Appleby P, Barnes I, et al. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J. Natl. Cancer Inst. 2002;94:606–616
  21. Lathi RB, Hess AP, Tulac S, et al. Dose-dependent insulin regulation of insulin-like growth factor binding protein-1 in human endometrial stromal cells is mediated by distinct signaling pathways. J. Clin. Endocrinol. Metab. 2005;90:1599–1606
  22. Miller N, Bédard YC, Cooter NB, et al. Histological changes in the genital tract in transsexual women following androgen therapy. Histopathology. 1986;10:661–669
  23. Missmer SA, Eliassen AH, Barbieri RL, et al. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J. Natl. Cancer Inst. 2004;96:1856–1865
  24. Murray AA, Gosden RG, Allison V, et al. Effect of androgens on the development of mouse follicles growing in vitro. J. Reprod. Fertil. 1998;113:27–33
  25. Pache TD, Chadha S, Gooren LJ, et al. Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome?. Histopathology. 1991;19:445–452
  26. Perrone AM, Cerpolini S, Maria Salfi NC, et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J. Sex Med. 2009;6:3193–3200
  27. Pigny P, Merlen E, Robert Y, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J. Clin. Endocrinol. Metab. 2003;88:5957–5962
  28. Reuss ML, Kline J, Santos R, et al. Age and the ovarian follicle pool assessed with transvaginal ultrasonography. Am. J. Obstet. Gynecol. 1996;174:624–627
  29. Rose GL, Dowsett M, Mudge JE, et al. The inhibitory effects of danazol, danazol metabolites, gestrinone, and testosterone on the growth of human endometrial cells in vitro. Fertil. Steril. 1988;49:224–228
  30. Sapino A, Pietribiasi F, Godano A, et al. Effect of long-term administration of androgens on breast tissues of female-to-male transsexuals. Ann. NY Acad. Sci. 1990;586:143–145
  31. Secreto G, Fariselli G, Bandieramonte G, et al. Androgen excretion in women with a family history of breast cancer or with epithelial hyperplasia or cancer of the breast. Eur. J. Cancer Clin. Oncol. 1983;19:5–10
  32. Slagter MH, Gooren LJ, de Ronde W, et al. Serum and urine tissue kallikrein concentrations in male-to-female transsexuals treated with antiandrogens and estrogens. Clin. Chem. 2006;52:1356–1365
  33. Spinder T, Spijkstra JJ, van den Tweel JG, et al. 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. Metab. 1989;69:151–157
  34. Takayama K, Fukaya T, Sasano H, et al. Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome. Hum. Reprod. 1996;11:1387–1392
  35. Tarlatzis BC, Zepiridis L, Grimbizis G, et al. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum. Reprod. Update. 2003;9:61–76
  36. Uduwela AS, Perera MA, Aiqing L, et al. Endometrial-myometrial interface: relationship to adenomyosis and changes in pregnancy. Obstet. Gynecol. Surv. 2000;55:390–400
  37. Vendola KA, Zhou J, Adesanya OO, et al. Androgens stimulate early stages of follicular growth in the primate ovary. J. Clin. Invest. 1998;101:2622–2629
  38. Walker P, Berger J, Green R, et al. Standards of care: the hormonal and surgical sex reassignment of gender dysphoric persons. Arch. Sex Behav. 1985;14:79–90
  39. Weil SJ, Vendola K, Zhou J, et al. Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations. J. Clin. Endocrinol. Metab. 1998;83:2479–2485
  40. Weil S, Vendola K, Zhou J, et al. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J. Clin. Endocrinol. Metab. 1999;84:2951–2956
  41. World Health Organization, 1992. Mental and behavioural disorders: F64: gender identity disorders. In: International Classification of Diseases-10, vol. 1 (Chapter V).
  42. Zang H, Sahlin L, Masironi B, et al. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. J. Clin. Endocrinol. Metab. 2007;92:2169–2175

 Michaël Grynberg is a gynaecologist specializing in reproductive medicine. After spending 6months as a visiting fellow in the Department of Reproductive Medicine at Cornell University, he returned to work in France and is currently undertaking a fellowship in the Division of Reproductive Medicine at the Hôpital Antoine Béclère, Clamart, France. His scientific interests centre on the identification of clinical markers of ovarian function, the role of androgens during the folliculogenesis and the physiopathology of PCOS. In addition, he is currently a PhD student in the University Paris-Sud 11. His thesis focuses on anti-Müllerian hormone regulation in the human ovary.

PII: S1472-6483(09)00305-8

doi: 10.1016/j.rbmo.2009.12.021

Reproductive BioMedicine Online
Volume 20, Issue 4 , Pages 553-558 , April 2010

Article Tools

* Image Usage & Resolution