The Estrogenic burden on Vascular risk in male-to-female transsexuals

Current Pharmaceutical Design

Volumn 16, Issue 34, 2010, Pages 3815-3822

  Lioudaki, Eirini ^a,b   Ganotakis, Emmanuel S ^b   Mikhailidis, Dimitri P ^a   Nair, Devaki R ^c  

^a ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

^b UNIVERSITY OF CRETE   (Greece)

^c ROYAL FREE HOSPITAL   (United Kingdom)

Author keywords

Antiandrogen; Cardiovascular; Estrogen; Gender reassignment therapy; Male to female transsexuals; Transsexuals

Indexed keywords

ADIPOCYTOKINE; CREATININE; ETHINYLESTRADIOL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HOMOCYSTEINE; URIC ACID;

ARTICLE; BODY BURDEN; BODY COMPOSITION; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR RISK; CELL FUNCTION; CREATININE BLOOD LEVEL; ESTROGEN THERAPY; GLUCOSE METABOLISM; GLYCEMIC CONTROL; HUMAN; KIDNEY FUNCTION; LIPID BLOOD LEVEL; MALE TO FEMALE TRANSSEXUAL; MEDLINE; OXIDATIVE STRESS; PRIORITY JOURNAL; URIC ACID BLOOD LEVEL;

BODY COMPOSITION; ESTROGENS; FEMALE; FIBRINOLYSIS; GLUCOSE; HEMOSTASIS; HUMANS; MALE; RISK FACTORS; TRANSSEXUALISM;

EID: 79551621200     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161210794455049     Document Type: Article

References (103)

1. Standards of care: the hormonal and surgical sex reassignment of gender dysphoric persons. Harry benjamin international gender dysphonia association. Arch Sex Behav 1985; 14: 79-90.
2. Gooren L. Hormone treatment of the adult transsexual patient. Horm Res 2005; 64 (Suppl 2): 31-6.
3. 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: 3467-73.
4. Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow- up study of 14 786 middle-aged men and women in Finland. Circulation 1999; 99: 1165-72.
5. Hanes DS, Weir MR, Sowers JR. Gender considerations in hypertension pathophysiology and treatment. Am J Med 1996; 101: 10S- 21S.
6. Skafar DF, Xu R, Morales J, et al. Clinical review 91: Female sex hormones and cardiovascular disease in women. J Clin Endocrinol Metab 1997; 82: 3913-8.
7. Crook D, Godsland IF, Hull J, Stevenson JC. Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up. Br J Obstet Gynaecol 1997; 104: 298-304.
8. Stevenson JC, Crook D, Godsland IF, et al. Hormone replacement therapy and the cardiovascular system. Nonlipid effects. Drugs 1994; 47 (Suppl 2): 35-41.
9. Perseghin G, Scifo P, Pagliato E, et al. Gender factors affect fatty acids-induced insulin resistance in nonobese humans: effects of oral steroidal contraception. J Clin Endocrinol Metab 2001; 86: 3188-96.
10. Byington RP, Furberg CD, Herrington DM, et al. Effect of estrogen plus progestin on progression of carotid atherosclerosis in postmenopausal women with heart disease: HERS B-mode substudy. Arterioscler Thromb Vasc Biol 2002; 22: 1692-7.
11. Herrington DM, Reboussin DM, Brosnihan KB, et al. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med 2000; 343: 522-9.
12. Lamon-Fava S, Herrington DM, Reboussin DM, et al. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women. Atherosclerosis 2009; 205: 325-30.
13. Hodis HN, Mack WJ, Azen SP, et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med 2003; 349: 535-45.
14. Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA 2002; 288: 2432-40.
15. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/ progestin Replacement Study follow-up (HERS II). JAMA 2002; 288: 49-57.
16. Schulman SP, Thiemann DR, Ouyang P, et al. Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina. J Am Coll Cardiol 2002; 39: 231-7.
17. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998; 280: 605-13.
18. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33.
19. Lobo RA. Postmenopausal hormones and coronary artery disease: potential benefits and risks. Climacteric 2007; 10 (Suppl 2): 21-6.
20. Hodis HN, Mack WJ. Coronary heart disease and hormone replacement therapy after the menopause. Climacteric 2009; 12 (Suppl 1): 71-5.
21. Lobo RA. The risk of stroke in postmenopausal women receiving hormonal therapy. Climacteric 2009; 12 (Suppl 1): 81-5.
22. The Coronary Drug Project. Findings leading to discontinuation of the 2.5-mg day estrogen group. The coronary Drug Project Research Group. JAMA 1973; 226: 652-7.
23. Wild RA. Obesity, lipids, cardiovascular risk, and androgen excess. Am J Med 1995; 98: 27S-32S.
24. Alexandersen P, Haarbo J, Christiansen C. The relationship of natural androgens to coronary heart disease in males: a review. Atherosclerosis 1996; 125: 1-13.
25. Nath A, Sitruk-Ware R. Different cardiovascular effects of progestins according to structure and activity. Climacteric 2009; 12 (Suppl 1): 96-101.
26. Kintzel PE, Chase SL, Schultz LM, O'Rourke TJ. Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy 2008; 28: 1511-22.
27. Traish AM, Saad F, Feeley RJ, Guay A. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 2009; 30: 477-94.
28. Choong K, Basaria S. Emerging cardiometabolic complications of androgen deprivation therapy. Aging Male 13: 1-9.
29. Elbers JM, Giltay EJ, Teerlink T, et al. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects. Clin Endocrinol (Oxf) 2003; 58: 562-71.
30. New G, Berry KL, Cameron JD, et al. Long-term oestrogen treatment does not alter systemic arterial compliance and haemodynamics in biological males. Coron Artery Dis 2000; 11: 253-9.
31. Giltay EJ, Elbers JM, Gooren LJ, et al. Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: modulation by cross-sex hormone administration. Arterioscler Thromb Vasc Biol 1998; 18: 1716-22.
32. New G, Timmins KL, Duffy SJ, et al. Long-term estrogen therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol 1997; 29: 1437-44.
33. Wilson R, Jenkins C, Miller H, Carr S. The effect of oestrogen on cytokine and antioxidant levels in male to female transsexual patients. Maturitas 2006; 55: 14-8.
34. Giltay EJ, Verhoef P, Gooren LJ, et al. Oral and transdermal estrogens both lower plasma total homocysteine in male-to-female transsexuals. Atherosclerosis 2003; 168: 139-46.
35. Elamin MB, Garcia MZ, Murad MH, et al. Effect of sex steroid use on cardiovascular risk in transsexual individuals: a systematic review and meta-analyses. Clin Endocrinol (Oxf) 2010; 72: 1-10.
36. Giltay EJ, Lambert J, Gooren LJ, et al. Sex steroids, insulin, and arterial stiffness in women and Men. Hypertension 1999; 34: 590-7.
37. Resmini E, Andraghetti G, Rebora A, et al. Leptin, ghrelin, and adiponectin evaluation in transsexual subjects during hormonal treatments. J Androl 2008; 29: 580-5.
38. Yahyaoui R, Esteva I, Haro-Mora JJ, et al. Effect of long-term administration of cross-sex hormone therapy on serum and urinary uric acid in transsexual persons. J Clin Endocrinol Metab 2008; 93: 2230-3.
39. Giltay EJ, Hoogeveen EK, Elbers JM, et al. Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females. J Clin Endocrinol Metab 1998; 83: 550-3.
40. Canonico M, Scarabin PY. Hormone therapy and risk of venous thromboembolism among postmenopausal women. Climacteric 2009; 12 (Suppl 1): 76-80.
41. Wilson R, Spiers A, Ewan J, et al. Effects of high dose oestrogen therapy on circulating inflammatory markers. Maturitas 2009; 62: 281-6.
42. Giltay EJ, Gooren LJ, Emeis JJ, et al. Oral, but not transdermal, administration of estrogens lowers tissue-type plasminogen activator levels in humans without affecting endothelial synthesis. Arterioscler Thromb Vasc Biol 2000; 20: 1396-403.
43. Toorians AW, Thomassen MC, Zweegman S, et al. Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people. J Clin Endocrinol Metab 2003; 88: 5723-9.
44. Rodeghiero F, Tosetto A. Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism. Ann Intern Med 1999; 130: 643-50.
45. Rosing J, Middeldorp S, Curvers J, et al. Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study. Lancet 1999; 354: 2036-40.
46. Lowe GD, Upton MN, Rumley A, et al. Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional population survey. Thromb Haemost 2001; 86: 550-6.
47. Liang YL, Teede H, Shiel LM, et al. Effects of oestrogen and progesterone on age-related changes in arteries of postmenopausal women. Clin Exp Pharmacol Physiol 1997; 24: 457-9.
48. McGrath BP, Liang YL, Teede H, et al. Age-related deterioration in arterial structure and function in postmenopausal women: impact of hormone replacement therapy. Arterioscler Thromb Vasc Biol 1998; 18: 1149-56.
49. Rajkumar C, Kingwell BA, Cameron JD, et al. Hormonal therapy increases arterial compliance in postmenopausal women. J Am Coll Cardiol 1997; 30: 350-6.
50. Hayward CS, Knight DC, Wren BG, Kelly RP. Effect of hormone replacement therapy on non-invasive cardiovascular haemodynamics. J Hypertens 1997; 15: 987-93.
51. McCrohon JA, Walters WA, Robinson JT, et al. Arterial reactivity is enhanced in genetic males taking high dose estrogens. J Am Coll Cardiol 1997; 29: 1432-6.
52. Wright J, Hutchison A. Cardiovascular disease in patients with chronic kidney disease. Vasc Health Risk Manag 2009; 5: 713-22.
53. van Kesteren P, Lips P, Gooren LJ, et al. Long-term follow-up of bone mineral density and bone metabolism in transsexuals treated with cross-sex hormones. Clin Endocrinol (Oxf) 1998; 48: 347-54.
54. Maltais ML, Desroches J, Dionne IJ. Changes in muscle mass and strength after menopause. J Musculoskelet Neuronal Interact 2009; 9: 186-97.
55. T'Sjoen G, Weyers S, Taes Y, et al. Prevalence of low bone mass in relation to estrogen treatment and body composition in male-tofemale transsexual persons. J Clin Densitom 2009; 12: 306-13.
56. Zhou J, Austin RC. Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms. Biofactors 2009; 35: 120-9.
57. Jacobsen DW, Gatautis VJ, Green R, et al. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem 1994; 40: 873-81.
58. Wu LL, Wu J, Hunt SC, et al. Plasma homocyst(e)ine as a risk factor for early familial coronary artery disease. Clin Chem 1994; 40: 552-61.
59. Nygard O, Vollset SE, Refsum H, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA 1995; 274: 1526-33.
60. Morris MS, Jacques PF, Selhub J, Rosenberg IH. Total homocysteine and estrogen status indicators in the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2000; 152: 140-8.
61. Hak AE, Polderman KH, Westendorp IC, et al. Increased plasma homocysteine after menopause. Atherosclerosis 2000; 149: 163-8.
62. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008; 359: 1811-21.
63. Strasak A, Ruttmann E, Brant L, et al. Serum uric acid and risk of cardiovascular mortality: a prospective long-term study of 83,683 Austrian men. Clin Chem 2008; 54: 273-84.
64. Strasak AM, Kelleher CC, Brant LJ, et al. Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study. Int J Cardiol 2008; 125: 232-9.
65. Edwards NL. The role of hyperuricemia in vascular disorders. Curr Opin Rheumatol 2009; 21: 132-7.
66. Nicholls A, Snaith ML, Scott JT. Effect of oestrogen therapy on plasma and urinary levels of uric acid. Br Med J 1973; 1: 449-51.
67. Anton FM, Garcia Puig J, Ramos T, et al. Sex differences in uric acid metabolism in adults: evidence for a lack of influence of estradiol-17 beta (E2) on the renal handling of urate. Metabolism 1986; 35: 343-8.
68. Mikhailidis DP, Press M. The importance of treating multiple cardiometabolic risk factors in patients with Type 2 diabetes. Expert Opin Pharmacother 2007; 8: 3009-20.
69. Athyros VG, Tziomalos K, Karagiannis A, et al. Should adipokines be considered in the choice of the treatment of obesity-related health problems? Curr Drug Targets 2010; 11: 122-35.
70. Paraskevas KI, Liapis CD, Mikhailidis DP. Leptin: a promising therapeutic target with pleiotropic action besides body weight regulation. Curr Drug Targets 2006; 7: 761-71.
71. Poulakou MV, Paraskevas KI, Wilson MR, et al. Apolipoprotein J and leptin levels in patients with coronary heart disease. In Vivo 2008; 22: 537-42.
72. Elbers JM, Asscheman H, Seidell JC, et al. Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals. J Clin Endocrinol Metab 1997; 82: 3267-70.
73. Saad MF, Damani S, Gingerich RL, et al. Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab 1997; 82: 579-84.
74. Kohrt WM, Landt M, Birge SJ, Jr. Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women. J Clin Endocrinol Metab 1996; 81: 3980-5.
75. Giltay EJ, Gooren LJ, Emeis JJ, et al. Oral ethinyl estradiol, but not transdermal 17beta-estradiol, increases plasma C-reactive protein levels in men. Thromb Haemost 2000; 84: 359-60.
76. Ozden S, Dildar K, Kadir YH, Gulizar K. The effects of hormone replacement therapy on lipid peroxidation and antioxidant status. Maturitas 2001; 38: 165-70.
77. Vongpatanasin W, Tuncel M, Wang Z, et al. Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women. J Am Coll Cardiol 2003; 41: 1358-63.
78. Prelevic GM, Kwong P, Byrne DJ, et al. A cross-sectional study of the effects of hormon replacement therapy on the cardiovascular disease risk profile in healthy postmenopausal women. Fertil Steril 2002; 77: 945-51.
79. Asscheman H, Gooren LJ, Eklund PL. Mortality and morbidity in transsexual patients with cross-gender hormone treatment. Metabolism 1989; 38: 869-73.
80. van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997; 47: 337-42.
81. Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 2009; 5: 673-81.
82. Siroen MP, Teerlink T, Nijveldt RJ, et al. The clinical significance of asymmetric dimethylarginine. Annu Rev Nutr 2006; 26: 203-28.
83. Post MS, Verhoeven MO, van der Mooren MJ, et al. Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo- controlled 12-week study in healthy early postmenopausal women. J Clin Endocrinol Metab 2003; 88: 4221-6.
84. Teerlink T, Neele SJ, de Jong S, et al. Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. Clin Sci (Lond) 2003; 105: 67-71.
85. Verhoeven MO, Hemelaar M, van der Mooren MJ, et al. Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study. J Intern Med 2006; 259: 199-208.
86. Rosselli M, Imthurm B, Macas E, et al. Circulating nitrite/nitrate levels increase with follicular development: indirect evidence for estradiol mediated NO release. Biochem Biophys Res Commun 1994; 202: 1543-52.
87. Cicinelli E, Ignarro LJ, Schonauer LM, et al. Effects of short-term transdermal estradiol administration on plasma levels of nitric oxide in postmenopausal women. Fertil Steril 1998; 69: 58-61.
88. Akcay T, Dincer Y, Kayali R, et al. Effects of hormone replacement therapy on lipid peroxides and oxidation system in postmenopausal women. J Toxicol Environ Health A 2000; 59: 1-5.
89. Eilertsen AL, Hoibraaten E, Os I, et al. The effects of oral and transdermal hormone replacement therapy on C-reactive protein levels and other inflammatory markers in women with high risk of thrombosis. Maturitas 2005; 52: 111-8.
90. Athyros VG, Mikhailidis DP, Liberopoulos EN, et al. Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: a subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Nephrol Dial Transplant 2007; 22: 118-27.
91. Karagiannis A, Mikhailidis DP, Tziomalos K, et al. Serum uric acid as an independent predictor of early death after acute stroke. Circ J 2007; 71: 1120-7.
92. Tsouli SG, Liberopoulos EN, Mikhailidis DP, et al. Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism 2006; 55: 1293-301.
93. Barrett-Connor E, Bush TL. Estrogen and coronary heart disease in women. JAMA 1991; 265: 1861-7.
94. Hodis HN, Mack WJ. Postmenopausal hormone therapy and cardiovascular disease in perspective. Clin Obstet Gynecol 2008; 51: 564-80.
95. Mikkola AK, Ruutu ML, Aro JL, et al. Parenteral polyoestradiol phosphate vs orchidectomy in the treatment of advanced prostatic cancer. Efficacy and cardiovascular complications: a 2-year followup report of a national, prospective prostatic cancer study. Finnprostate Group. Br J Urol 1998; 82: 63-8.
96. Hedlund PO, Ala-Opas M, Brekkan E, et al. Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer -- Scandinavian Prostatic Cancer Group (SPCG) Study No. 5. Scand J Urol Nephrol 2002; 36: 405-13.
97. Tivesten A, Hulthe J, Wallenfeldt K, et al. Circulating estradiol is an independent predictor of progression of carotid artery intimamedia thickness in middle-aged men. J Clin Endocrinol Metab 2006; 91: 4433-7.
98. Lehtimaki T, Kunnas TA, Mattila KM, et al. Coronary artery wall atherosclerosis in relation to the estrogen receptor 1 gene polymorphism: an autopsy study. J Mol Med 2002; 80: 176-80.
99. Shearman AM, Cupples LA, Demissie S, et al. Association between estrogen receptor alpha gene variation and cardiovascular disease. JAMA 2003; 290: 2263-70.
100. Phillips GB. Is atherosclerotic cardiovascular disease an endocrinological disorder? The estrogen-androgen paradox. J Clin Endocrinol Metab 2005; 90: 2708-11.
101. Maggio M, Basaria S. Welcoming low testosterone as a cardiovascular risk factor. Int J Impot Res 2009; 21: 261-4.
102. Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ. Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat. Diabetes Care 2004; 27: 861-8.
103. Brand JS, van der Schouw YT. Testosterone, SHBG and cardiovascular health in postmenopausal women. Int J Impot Res 2010; [Epub ahead of print].