Horm Metab Res 2002; 34(2): 87-92
DOI: 10.1055/s-2002-20521
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Impact on Lipoprotein Profile after Long-Term Testosterone Replacement in Hypogonadal Men

G.  Berg 1 , L.  Schreier 1 , G.  Geloso 2 , P.  Otero 2 , A.  Nagelberg 2 , O.  Levalle 2
  • 1 Laboratorio de Lípidos y Lipoproteínas, Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires, Argentina
  • 2 División Endocrinología, Hospital Carlos G. Durand, Buenos Aires, Argentina
Further Information

Publication History

12 March 2001

21 August 2001

Publication Date:
04 March 2002 (online)

Abstract

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 ± 0.10 mmol/l to 1.22 ± 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 ± 3.4 mg/dl to 126 ± 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.

  • 1 Kirkland R T, Keenan B S, Probstfield J L, Patsch W, Lin T L, Clayton G W, Insull W . Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence.  JAMA. 1987;  257 502-507
  • 2 Haffner S M, Mykkänen L, Valdez R A, Katz M S. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men.  J Clin Endocrinol Metab. 1993;  77 1610-1615
  • 3 Place V A. Transdermal testosterone replacement through genital skin. In: Nieschlag E, Behre HM (eds) Testosterone: action, deficiency and substitution. Berlin; Springer Verlag 1990: 165
  • 4 Jockenhövel F, Bullmann C, Schubert M, Vogel E, Reinhardt W, Reinwein D, Müller-Wieland D, Krone W. Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men.  Metabolism. 1999;  48 (5) 590-596
  • 5 Behre H M, Nieschlag E. Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester.  J Clin Endocrinol Metab. 1992;  75 1204-1210
  • 6 Zgliczynski S, Ossowski M, Slowinska-Srzednicka J, Brzezinska A, Zgliczynski W, Soszynski P, Chotkowska E, Srzednicki M, Sadowsdi Z. Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men.  Atherosclerosis. 1996;  121 35-43
  • 7 Tripathy D, Shah P, Lakshmy R, Reddy K S. Effect of testosterone replacement on whole body glucose utilisation and other cardiovascular risk factors in males with idiopathic hypogonadotrophic hypogonadism.  Horm Metab Res. 1998;  30 (10) 642-645
  • 8 Gutai J, LaPorte R, Kuller L, Dai F W, Falvo-Gerard L, Caggiula A. Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions.  Cardiology. 1981;  48 897-902
  • 9 Bagatell C J, Heiman J R, Matsumoto A M, Rivier J E, Bremner W J. Metabolic and behavioral effect of high-dose, exogenous testosterone in healthy men.  J Clin Endocrinol Metab. 1994;  79 561-567
  • 10 Sorva R, Kuusi T, Taskinen M R, Perheentupa J, Nikkila E A. Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males.  Atherosclerosis. 1988;  69 191-197
  • 11 Brinton E A. Oral estrogen replacement therapy in postmenopausal women selectively raises levels and production rates of lipoprotein A-I and lowers hepatic lipase activity without lowering the fractional catabolic rate.  Arterioscler Thromb Vasc Biol. 1996;  16 431-440
  • 12 Applebaum-Bowden D, McLean P, Steinmetz A, Fontana D, Matthys C, Warnick G R, Cheung M, Albers J J, Hazzard W R. Lipoprotein, apolipoprotein, and lipolytic enzyme changes following estrogen administration in postmenopauseal women.  J Lipid Res. 1989;  30 1895-1905
  • 13 Kuusi T, Nikkila E A, Tikkanen M J, Sipinen S. Effect of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein.  Atherosclerosis. 1985;  54 251-257
  • 14 Enholm C, Huttunen J K, Kinnunen P J, Miettinen T A, Nikkila E A. Effect of oxandrolone treatment on the activity of lipoprotein lipase, hepatic lipase and phospholipase A1 of human postheparin plasma.  N Engl J Med. 1975;  292 1314-1317
  • 15 Guendouzy K, Jaspard B, Barbaras R, Motta C, Vieu C, Marvel Y, Chap H, Perret B, Collet X. Biochemical and physical properties of remnant-HDL2 and of preβ1-HDL produced by hepatic lipase.  Biochemistry. 1999;  38 2762-2768
  • 16 Assman A G, Jabs H, Kohnert U, Nolte W, Schriewer H. LDL cholesterol determination in blood serum following precipitation of LDL with poly-vinil sulphate.  Clin Chim Acta. 1984;  140 77-83
  • 17 Warnick G R, Benderson J, Albers J J. Dextran sulfate-Mg2+ precipitation for quantitation of high-density lipoprotein cholesterol.  Clin Chem. 1982;  28 1379-1388
  • 18 Warnick G R. Measurement and clinical significance of high density lipoprotein cholesterol: subclases. In: Rifai N, Warnick GR, Dominiczak MH (ed) Handbook of lipoprotein testing. AACC Press 1997: 251-266
  • 19 Castelli W P. Epidemiology of coronary heart disease. The Framingham Study.  Am J Med. 1984;  76 4-12
  • 20 Hattori Y, Susuki M, Tsuchima M, Yoshida M, Tokunaga Y, Wang Y, Zhao D, Takeuchi M, Hara Y, Ryomoto K I, Ikebuchi M, Kishioka H, Mannami T, Baba S, Harano Y. Development of approximate formula for LDLcholesterol, LDLapoB and LDLcholesterol/LDL apoB as indices of hyperapobetaliporoteinemia and small dense LDL.  Atherosclerosis. 1998;  138 289-299
  • 21 Capell W H, Zambon A, Austin M A, Brunzell J D, Hokanson J E. Compositional differences of LDL particles in normal subjects with LDL subclass phenotype A and LDL subclass phenotype B.  Arterioscler Thromb Vasc Biol. 1996;  16 1040-1046
  • 22 Berg G, Siseles N, González A I, Contreras Ortiz O, Tempone A, Wikinski R. Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins.  Menopause. 2001;  8 (2) 51-57
  • 23 Wang C, Eyre D R, Clark R, Kleinberg D, Newman C, Iranmanesh A, Veldhuis J, Dudley R E, Berman N, Davidson T, Barstow T J, Sinow R, Alexander G, Swerdloff R S. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men-a clinical research center study.  J Clin Endocrinol Metab. 1996;  81 3654-3662
  • 24 Sih R, Morley J E, Kaiser F E, Perry III H M , Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial.  J Clin Endocrinol Metab. 1997;  82 1661-1667
  • 25 Burris A S, Banks S M, Carter C S, Davidson T M, Sherins R J. A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men.  J Androl. 1992;  13 297-304
  • 26 Goldberg R B, Rabin D, Alexander A N, Doelle G C, Getz G S. Suppression of plasma testosterone leads to an increase in serum total and high density lipoprotein cholesterol and apoproteins-A-1 and B.  J Clin Endocrinol Metab. 1992;  116 967-973
  • 27 Partsch C J, Weinbauer G F, Fang R, Nieschlag E. Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate.  Eur J Endocrinol. 1995;  132 514-519
  • 28 Tan K CB, Shiu S WM, Kung A WC. Alterations in hepatic lipase and lipoprotein subfractions with transdermal testosterone replacement therapy.  Clin Endocrinol. 1999;  51 765-769
  • 29 Haffner S M, Kushwaha R S, Foster D M, Applebaum-Bowden D, Hazzard R W. Studies on metabolic mechanism of reduced high density lipoprotein during anabolic steroid therapy.  Metabolism. 1983;  32 413-420
  • 30 Roheim P S, Aszatalos B F. Clinical significance of lipoprotein size and risk for coronary atherosclerosis.  Clin Chem. 1995;  41/1 147-152
  • 31 Arver S, Dobs A S, Meikle A W, Caramelli K E, Rajaram L, Sanders S W, Mazer N A. : Long-term efficacy and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men.  Clin Endocrinol. 1997;  47 727-737
  • 32 Castelli W P, Garrison R J, Wilson P W, Abbott R D, Kalousdian S, Kannel W B. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study.  JAMA. 1986;  256 2835-2838
  • 33 Dobs A, Bachorik P, Arver S, Meikle A, Sanders S, Caramelli K, Mazer N. Interrelationships among lipoprotein levels, sex hormones, anthropometric parameters, and age in hypogonadal men treated for 1 year with a permeation-enhanced testosterone transdermal system.  J Clin Endocrinol Metab. 2001;  86 1026-1033
  • 34 Tchernof A, Labrie F, Bélanger A, Prud'homme D, Bouchard C, Tremblay A, Nadeau A, Després J P. Relationship between endogenous steroid hormone, sex hormone-binding globulin and lipoprotein levels in men: contribution of visceral obesity, insulin levels and other metabolic variables.  Atherosclerosis. 1997;  133 235-244
  • 35 Marin P, Holmäng S, Jansson L, Sjöström L, Kvist H, Holm G, Lindstedt G, Björntorp P. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men.  Int J Obes. 1992;  16 991-997
  • 36 Tchernof A, Labrie F, Bélanger A, Després J P. Obesity and metabolic complications: contribution of dehydroepiandrosterone and other steroid hormones.  J Endocrinol. 1996;  150 S155-S164
  • 37 Tenover J S. Effects of testosterone supplementation in the aging male.  J Clin Endocrinol Metab. 1992;  75 1092-1098

Gabriela Berg

Lab. Lípidos y Lipoproteínas · Dto. Bioquímica Clínica, Fac. Farmacia y Bioquímica · Universidad de Buenos Aires

Junín 956 (C1113AAD) · Buenos Aires · Argentina

Phone: + 54 (11) 4964-8297

Fax: + 54 (11) 4508-3645

Email: gaberg@dbc.ffyb.uba.ar

    >