Skip to main content

Advertisement

Log in

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

  • Published:
Archives of Sexual Behavior Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • Ammus, S. S. (1989). The role of androgens in the treatment of hematologic disorders. Adv. Intern. Med. 34: 191-208.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Bardin, C. W., Swerdloff, R. S., and Santen, R. J. (1991). Androgens: Risks and benefits. J. Clin. Endocrinol. Metab. 73: 4-7.

    PubMed  Google Scholar 

  • Bjorntorp, P. (1991). Adipose tissue distribution and function. Int. J. Obesity 15: 67-81.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Franks, S. (1989). Polycystic ovary syndrome: A changing perspective. Clin. Endocrinol. 31: 87-120.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Futterweit, W. (1980). Endocrine management of transsexual. Hormonal profiles of serum prolactin, testosterone, and estradiol. N.Y. State J. Med. 80: 1260-1264.

    PubMed  Google Scholar 

  • Futterweit, W. (1984). Clinical features of polycystic ovarian disease. In Polycystic Ovarian Disease, Springer Verlag, New York, pp. 83-95.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Futterweit, W. (1995). Pathophysiology of polycystic ovarian syndrome. In Redmond, G. P. (ed.), Androgenic Disorders, Raven Press, New York, pp. 77-166.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • Jensen, J. (1991). Effects of sex steroids on serum lipids and lipoproteins. Baillier's Clin. Obstet. Gynaecol. 5: 867-887.

    Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • LaRosa, J. C. (1993). Estrogen: Risk versus benefit for the prevention of coronary heart disease. Coronary Artery Dis. 4: 588-594.

    Google Scholar 

  • LaRosa, J. C. (1994). Metabolic effects of estrogens and progestins. Fertil. Steril. 62(Suppl.2): 140S-146S.

    PubMed  Google Scholar 

  • LaRosa, J. C. (1995). Androgens and women's health: Genetic and epidemiologic aspects of lipid metabolism. Am. J. Med. 98(Suppl. 1A): 22S-26S.

    PubMed  Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • Nestler, J. E., Clore, J. N., and Blackard, W. G. (1992). Dehydroepiandrosterone: The “missing link” between hyperinsulinemia and atherosclerosis? FASEB J. 6: 3073-3075.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • Schmidt, G. (1977). Hepatocellular carcinoma. A possible complication of oral contraceptive steroids. Med. J. Australia 1: 215-220.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Shahidi, N. T. (1973). Androgens and erythropoiesis. New Engl. J. Med. 289: 73-80.

    Google Scholar 

  • Snyder, P. J., and Lawrence, D. A. (1980). Treatment of male hypogonadism with testosterone enanthate. J. Clin. Endocrinol. Metab. 51: 1335-1339.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • Tribble, D. L., and Krauss, R. M. (1993). HDL and coronary artery disease. Adv. Intern. Med. 38: 1-29.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Futterweit, W. Endocrine Therapy of Transsexualism and Potential Complications of Long-Term Treatment. Arch Sex Behav 27, 209–226 (1998). https://doi.org/10.1023/A:1018638715498

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018638715498

Navigation