Archives of Sexual Behavior

, Volume 27, Issue 2, pp 209–226 | Cite as

Endocrine Therapy of Transsexualism and Potential Complications of Long-Term Treatment

  • Walter Futterweit


Physiological principles of the interrelationship of sex hormones and their regulation are the foundation of understanding appropriate treatment of the transsexual patient. While both genetic males and females have estrogens and androgens, the quantitative sex hormone production is genetically predetermined by sex hormone production both in the gonads and via peripheral conversion of hormone precursors to sex steroids. Sex hormones exert a negative feedback on the hypothalamus and pituitary gland whereby gonadotropin-releasing hormone (GnRH), pituitary luteinizing hormone (LH), and follicle-stimulating hormone (FSH) are regulated or suppressed by the endogenous levels of these hormones. Sexhormonal therapyinduces attenuated GnRH stimulation of LH and FSH causing a reduction of serum sexhormone levels. It is clear that estrogen as well as androgen therapy have a dual role: (i) induction of feminization or virilization and (ii) suppression of the hypothalamic-pituitary-gonadal axis leading to a reduction of endogenous estradiol or testosterone secretion. Cross-sex hormonal treatment may have substantial medical side effects. The smallest dosage of hormonal therapy compatible with the above clinical aims should be used.



Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams, M. R., Kaplan, J. R., Manuck, S. B., Koritnick, D. R., Parks, J. S., Wolfe, M. S., and Clarkson, T. B. (1990). Inhibition of coronary artery atherosclerosis by 17b-estradiol on ovariectomize d monkeys: Lack of an effect of added progesterone. Arteriosclerosis 10: 1051-1057.PubMedGoogle Scholar
  2. Adlercreutz, H., and Tenhunen, R. (1970). Some aspects of the interaction between natural and synthetic female sex hormones and the liver. Am. J. Med. 49: 630-648.PubMedGoogle Scholar
  3. Aldinger, K., Ben-Menachem, Y., and Whalen, G. (1977). Focal nodular hyperplasia of the liver associated with high dosage estrogens. Arch. In t. Med. 137: 357-359.Google Scholar
  4. Ammus, S. S. (1989). The role of androgens in the treatment of hematologic disorders. Adv. Intern. Med. 34: 191-208.PubMedGoogle Scholar
  5. Anderson, A. J., Sobocinski, K. A., Freedman, D. S., Barboriak, J., Rinn, J. J., and Gruchow, H. W. (1988). Body fat distribution, plasma lipids, and lipoproteins. Arteriosclerosis 8: 88-94.PubMedGoogle Scholar
  6. Applebaum, D. M., Goldberg, A. P., Pykalisto, O. J., Brumzell, J. D., and Hazzard, W. R. (1977). Effects of estrogens on postheparin plasma lipolytic activity. Selective decline in hepatic triglyceride lipase. J. Clin. Invest. 59: 601-608.PubMedGoogle Scholar
  7. Asscheman, H., Gooren, L. J. G., Assies, J., Smits, J. P. H., and de Slegte, R. (1988). Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals. Clin. Endocrinol. 28: 583-588.Google Scholar
  8. Asscheman, H., Gooren, L. J. G., Schouten, G. J., van Kamp, G. J., and van Bezu, J. S. M. (1989a). Serum lipids in male-to-female transsexuals treated with ethinylestradiol alone or in combination with cyproterone acetate. In Cross-Gender Hormone Treatment: Side Effects and Some Metabolic Aspects, Academic Proefschrift, Vrije Universiteit Te Amsterdam, pp. 79-87.Google Scholar
  9. Asscheman, H., Gooren, L. J. G., and Eklund, P. L. E. (1989b). Mortality and morbidity in transsexual patients with cross-gender hormone treatment. Metabolism 38: 869-873.PubMedGoogle Scholar
  10. Bagatell, C. J., Knopp, R. H., Vale, W. W., Rivier, J. E., and Bremner, W. J. (1992). Physiologic testosterone levels in normal me n suppress high-density l ipoprotein cholesterol levels. Ann. Intern. Med. 116: 967-973.PubMedGoogle Scholar
  11. Bagatell, C. J., Heiman, J. R., Matsumoto, A. M., Rivier, J. E., and Bremner, W. J. (1994). Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. J. Clin. Endocrinol. Metab. 79: 561-567.PubMedGoogle Scholar
  12. Bardin, C. W., Swerdloff, R. S., and Santen, R. J. (1991). Androgens: Risks and benefits. J. Clin. Endocrinol. Metab. 73: 4-7.PubMedGoogle Scholar
  13. Bjorntorp, P. (1991). Adipose tissue distribution and function. Int. J. Obesity 15: 67-81.Google Scholar
  14. Bradley, D. D., Wingerd, J., Petitti, D. B., Krauss, R. M., and Ramcharan, S. (1978). Serum high density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. New Engl. J. Med. 299: 17-20.PubMedGoogle Scholar
  15. Evans, D. J., Hoffman, R. G., Kalkhoff, R. K., and Kissebah, A. H. (1983). Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J. Clin. Endocrinol. Metab. 57: 304-310.PubMedGoogle Scholar
  16. Franks, S. (1989). Polycystic ovary syndrome: A changing perspective. Clin. Endocrinol. 31: 87-120.Google Scholar
  17. Friedl, K. E., Hannan, C. J., Jones, R. E., and Plymate, S. E. (1990). High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Metabolism 39: 69-77.PubMedGoogle Scholar
  18. Futterweit, W. (1980). Endocrine management of transsexual. Hormonal profiles of serum prolactin, testosterone, and estradiol. N.Y. State J. Med. 80: 1260-1264.PubMedGoogle Scholar
  19. Futterweit, W. (1984). Clinical features of polycystic ovarian disease. In Polycystic Ovarian Disease, Springer Verlag, New York, pp. 83-95.Google Scholar
  20. Futterweit, W., and Deligdisch, L. (1986). Histopathological effects of exogenously administered testosterone in 19 female-to-male transsexuals. J. Clin. Endocrinol. Metab. 62: 16-21.PubMedGoogle Scholar
  21. Futterweit, W., Gabrilove, J. L., and Smith, H., Jr. (1984). Testicular steroidogenic response to human chorionic gonadotropin of fifteen male transsexuals on chronic estrogen treatment. Metabolism. 33: 936-942.PubMedGoogle Scholar
  22. Futterweit, W., and Schwartz, I. S. (1988). Histopathology of the breasts of 12 women receiving long-term exogenous androgen therapy. Mt. Sinai J. Med. 55: 309-312.PubMedGoogle Scholar
  23. Futterweit, W., Weiss, R. A., and Fagerstrom, R. M. (1986). Endocrine evaluation of forty female-to-male transsexuals: Increased frequency of polycystic ovarian disease in female transsexualism. Arch. Sex. Behav. 15: 69-78.PubMedGoogle Scholar
  24. Futterweit, W. (1995). Pathophysiology of polycystic ovarian syndrome. In Redmond, G. P. (ed.), Androgenic Disorders, Raven Press, New York, pp. 77-166.Google Scholar
  25. Glueck, C. J., Scheel, D., Fishback, J., and Steiner, P. (1972). Estrogen-induced pancreatitis in patients with previously covert familial type V hyperlipoproteinemia. Metabolism 21: 657-666.PubMedGoogle Scholar
  26. Godsland, I. F., Gangar, K., Walton, C., Cust, M. P., Whitehead, M. I., Wynn, V., and Stevenson, J. C. (1993). Insulin resistance, secretion and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy. Metabolism 42: 846-853.PubMedGoogle Scholar
  27. Gooren, L. J. G., Assies, J., Asscheman, H., De Slegte, R., and van Kessel, H. (1988). Estrogen-induced prolactinoma in a man. J. Clin. Endocrinol. Metab. 66: 444-446.PubMedGoogle Scholar
  28. Gutai, J., LaPorte, R., Kuller, C., Dai, W., Falvo-Gerard, L., and Caggiula, A. (1981). Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions. Am. J. Cardiol. 48: 897-902.PubMedGoogle Scholar
  29. Hamalainen, E., Adlercreutz, H., Ehnholm, C., and Puska, P. (1986). Relationships of serum lipoproteins and apoproteins to sex hormones and to the sex hormone binding globulin in healthy Finnish men. Metabolism 35: 535-541.PubMedGoogle Scholar
  30. Hamburger, C. (1969). Endocrine treatment of male and female transsexualism. In Green R., and Money J. (eds.), Transsexualism and Reassignment, Johns Hopkins University Press, Baltimore, pp. 291-307.Google Scholar
  31. Jensen, J. (1991). Effects of sex steroids on serum lipids and lipoproteins. Baillier's Clin. Obstet. Gynaecol. 5: 867-887.Google Scholar
  32. Jequier, A. M., Bullimore, N. J., and Bishop, M. J. (1989). Cyproterone acetate and a small dose of oestrogen in the pre-operative management of male transsexuals. A report of three cases. Andrologia 21: 456-461.PubMedGoogle Scholar
  33. Jones, T. M., Fang, V. S., Landau, R. L., and Rosenfield, R. (1978). Direct inhibition of Leydig cell function by estradiol. J. Clin. Endocrinol. Metab. 47: 1368-1373.PubMedGoogle Scholar
  34. LaRosa, J. C. (1993). Estrogen: Risk versus benefit for the prevention of coronary heart disease. Coronary Artery Dis. 4: 588-594.Google Scholar
  35. LaRosa, J. C. (1994). Metabolic effects of estrogens and progestins. Fertil. Steril. 62(Suppl.2): 140S-146S.PubMedGoogle Scholar
  36. LaRosa, J. C. (1995). Androgens and women's health: Genetic and epidemiologic aspects of lipid metabolism. Am. J. Med. 98(Suppl. 1A): 22S-26S.PubMedGoogle Scholar
  37. Lobo, R. A., and Speroff, L. (1994). International consensus conference on postmenopausal hormone therapy and the cardiovascular system. Fertil. Steril. 62(Suppl.2): 176S-179S.Google Scholar
  38. Mant D., Villard-Mackintosh, L., Vessey, M. P., and Yeates, D. (1987). Myocardial infarction and angina pectoris in young women. J. Epidemiol. Commun. Health 41: 215-219.Google Scholar
  39. Matsumoto, A. M., Sandblom, R. E., Schoene, R. B., Lee, K. A., Giblin, E. C., Pierson, D. J., and Bremner, W. J. (1985). Testosterone replacement in hypogonadal men: Effects of obstructive sleep apnoea, respiratory drives, and sleep. Clin. Endocrinol. 22: 713-721.Google Scholar
  40. Meikle, A. W., Mazer, N. A., Moellmer, J. F., Stringham, J.D., Tolman, K. G., Sanders, S. W., and Odell, W. D. (1992). Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J. Clin. Endocrinol. Metab. 74: 623-628.PubMedGoogle Scholar
  41. Meyer, W. J., Finkelstein, J. W., Stuart, C. A., Webb, A., Smith, E. R., Payer, A. F., and Walker, P. A. (1981). Physical and hormonal evaluation of transsexual patients during hormonal therapy. Arch. Sex. Behav. 10: 347-356.PubMedGoogle Scholar
  42. Meyer, W. J., Webb, A., Stuart, C. A., Finkelstein, J. W., Lawrence, B., and Walker, P. A. (1986). Physical and hormonal evaluation of transsexual patients. A longitudinal study. Arch. Sex. Behav. 15: 121-138.PubMedGoogle Scholar
  43. Nagelberg, S. B., Laue, L., Loriaux, D. L., Liu, L., and Sherins, R. (1986). Cerebrovascular accident associated with testosterone therapy in a 21-year-old hypogonadal man. New Engl. J. Med. 314: 649-650.Google Scholar
  44. Nakao, J., Chang, W. C., Murota, S. I., and Orimo, H. (1981). Testosterone inhibits prostacyclin production by rat aortic smooth muscle cells in culture. Atherosclerosis 39: 203-209.PubMedGoogle Scholar
  45. Nestler, J. E., Clore, J. N., and Blackard, W. G. (1992). Dehydroepiandrosterone: The “missing link” between hyperinsulinemia and atherosclerosis? FASEB J. 6: 3073-3075.PubMedGoogle Scholar
  46. Neuberger, J., Nunnerly, H. B., Davis, M., Portmann, B., Laws, J. W., and Williams, R. (1980). Oral-contraceptive-associated liver tumours: Occurrence of malignancy and difficulties in diagnosis. Lancet 1: 273-276.PubMedGoogle Scholar
  47. Prior, J. C., Vigna, Y. M., and Watson, D. (1989). Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism. Arch. Sex. Behav. 18: 49-57.PubMedGoogle Scholar
  48. Sacks, F. M., and Walsh, B. W. (1990). The effects of reproductive hormones on serum lipoproteins: Unresolved issues in biology and clinical practice. Ann. N.Y. Acad. Sci. 592: 273-285.Google Scholar
  49. Schmidt, G. (1977). Hepatocellular carcinoma. A possible complication of oral contraceptive steroids. Med. J. Australia 1: 215-220.PubMedGoogle Scholar
  50. Schneider, B. K., Pickett, C. K., Zwillich, C. W., Weil, J. V., McDermott, M. T., Santen, R. J., Varano, L. A., and White, D. P. (1986). Influence of testosterone on breathing during sleep. J. Appl. Physiol. 61: 618-623.PubMedGoogle Scholar
  51. Shahidi, N. T. (1973). Androgens and erythropoiesis. New Engl. J. Med. 289: 73-80.Google Scholar
  52. Snyder, P. J., and Lawrence, D. A. (1980). Treatment of male hypogonadism with testosterone enanthate. J. Clin. Endocrinol. Metab. 51: 1335-1339.PubMedGoogle Scholar
  53. Sorva, R., Kuusi, T., Dunket, L., and Taskinen, M. R. (1988). Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes. J. Clin. Endocrinol. Metab. 66: 408-413.PubMedGoogle Scholar
  54. Stefanick, M. L., Williams, P. T., Krauss, R. M., Terry, R. B., Vranizan, K. M., and Wood, P. D. (1987). Relationship of plasma estradiol, testosterone, and sex hormone-binding globulin with lipoproteins, apolipoproteins, and high-density lipoprotein subfractions in men. J. Clin. Endocrinol. Metab. 64: 723-729.PubMedGoogle Scholar
  55. Stern, M. P., and Haffner, S. M. (1986). Body fat distribution and hyperinsulinemia as risk factors for diabetes and cardiovascular disease. Arteriosclerosis 6: 123-130.PubMedGoogle Scholar
  56. Terry, R. B., Wood, P. D., Haskell, W. L., Stefanick, M. L., and Krauss, R. M. (1989). Regional adiposity in relation to plasma lipids, lipoproteins and subfraction mass in men. J. Clin. Endocrinol. Metab. 68: 191-199.PubMedGoogle Scholar
  57. Thompson, P. D., Cullinane, E. M., Sady, S. P., Chevenent, C., Saritelli, A. L., Sady, M. A., and Herbert, R. H. (1989). Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. J. Am. Med. Assoc. 261: 1165-1168.Google Scholar
  58. Tikkanen, M. J., Nikkila, E. A., Kussi, S., and Sipinen, S. (1982). High density lipoprotein-2 and hepatic lipase: Reciprocal changes produced by estrogen and norgestrel. J. Clin. Endocrinol. Metab. 54: 1113-1117.PubMedGoogle Scholar
  59. Tribble, D. L., and Krauss, R. M. (1993). HDL and coronary artery disease. Adv. Intern. Med. 38: 1-29.PubMedGoogle Scholar
  60. Wallentin, L., and Varenhorst, E. (1980). Plasma lipoproteins during treatment with cyproterone acetate in men with prostatic carcinoma. J. Clin. Endocrin ol. Metab. 51: 1118-1122.Google Scholar
  61. Walton, C., Godsland, I. F., Proudler, A. J., Wynn, V., and Stevenson, J. C. (1993). The effects of the menopause on insulin sensitivity, secretion and elimination in non-obese healthy women. Eur. J. Clin. Invest. 23: 466-473.PubMedGoogle Scholar
  62. Webb, O. L., Laskarzewski, P. M., and Glueck, C. J. (1984). Severe depression of high-density lipoprotein cholesterol levels in weight lifters and body builders by self administered exogenous testosterone and anabolic-androgenic steroids. Metabolism 33: 971-975.PubMedGoogle Scholar
  63. Xu, X., De Pergola, G., and Bjorntorp, P. (1991). Testosterone increases lipolysis and the number of b-adrenoceptors in male adipocytes. Endocrinology 128: 379-382.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Walter Futterweit

There are no affiliations available

Personalised recommendations