The effects of short-term and long-term testosterone supplementation on blood viscosity and erythrocyte deformability in healthy adult mice.

Testosterone treatment induces erythrocytosis that could potentially affect blood viscosity and cardiovascular risk. We thus investigated the effects of testosterone administration on blood viscosity and erythrocyte deformability using mouse models. Blood viscosity, erythrocyte deformability, and hematocrits were measured in normal male and female mice, as well as in females and castrated males after short-term (2 wk) and long-term (5-7 mo) testosterone intervention (50 mg/kg, weekly). Castrated males for long-term intervention were studied in parallel with the normal males to assess the effect of long-term testosterone deprivation. An additional short-term intervention study was conducted in females with a lower testosterone dose (5 mg/kg). Our results indicate no rheological difference among normal males, females, and castrated males at steady-state. Short-term high-dose testosterone increased hematocrit and whole-blood viscosity in both females and castrated males. This effect diminished after long-term treatment, in association with increased erythrocyte deformability in the testosterone-treated mice, suggesting the presence of adaptive mechanism. Considering that cardiovascular events in human trials are seen early after intervention, rheological changes as potential mediator of vascular events warrant further investigation.

[1]  Ying Li,et al.  Increased whole blood viscosity is associated with silent cerebral infarction. , 2015, Clinical hemorheology and microcirculation.

[2]  M. Lagerquist,et al.  The effect of estrogen on bone requires ERα in nonhematopoietic cells but is enhanced by ERα in hematopoietic cells. , 2014, American journal of physiology. Endocrinology and metabolism.

[3]  T. Travison,et al.  Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[4]  S. Greenland,et al.  Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men , 2014, PloS one.

[5]  G. Hankey,et al.  In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality. , 2014, The Journal of clinical endocrinology and metabolism.

[6]  G. Grunwald,et al.  Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. , 2013, JAMA.

[7]  O. Baskurt,et al.  Blood rheology and aging , 2013, Journal of geriatric cardiology : JGC.

[8]  O. Rouaud,et al.  A J-shaped association between plasma testosterone and risk of ischemic arterial event in elderly men: the French 3C cohort study. , 2013, Maturitas.

[9]  D. Delev,et al.  Effect of Testosterone Propionate on Erythropoiesis after Experimental Orchiectomy , 2013, Folia medica.

[10]  D. Moon,et al.  Effect of testosterone undecanoate on hematological profiles, blood lipid and viscosity and plasma testosterone level in castrated rabbits. , 2013, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[11]  T. Travison,et al.  Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells , 2013, Aging cell.

[12]  Z. Kamenov,et al.  Testosterone replacement therapy improves erythrocyte membrane lipid composition in hypogonadal men , 2012, The aging male : the official journal of the International Society for the Study of the Aging Male.

[13]  R. Rosenson,et al.  Importance of Blood Rheology in the Pathophysiology of Atherothrombosis , 2012, Cardiovascular Drugs and Therapy.

[14]  T. Travison,et al.  Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. , 2010, The Journal of clinical endocrinology and metabolism.

[15]  A. Jette,et al.  Adverse events associated with testosterone administration. , 2010, The New England journal of medicine.

[16]  R. Rosenson,et al.  Cardiovascular Risks of Anemia Correction with Erythrocyte Stimulating Agents: Should Blood Viscosity Be Monitored for Risk Assessment? , 2010, Cardiovascular Drugs and Therapy.

[17]  Ping Song,et al.  AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice , 2010, The Journal of Biological Chemistry.

[18]  Broulík Pd The effect of castration and androgen treatment on glomerular volume in mice. , 2009 .

[19]  L. Maffei,et al.  Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men , 2009, The Journal of Steroid Biochemistry and Molecular Biology.

[20]  R. Vasan,et al.  The impact of assay quality and reference ranges on clinical decision making in the diagnosis of androgen disorders , 2008, Steroids.

[21]  A. Dobs,et al.  Effect of methyl testosterone administration on plasma viscosity in postmenopausal women , 2002, Clinical endocrinology.

[22]  R. Francis,et al.  Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. , 1996, Bone.

[23]  G. Gorodeski Impact of the menopause on the epidemiology and risk factors of coronary artery heart disease in women , 1994, Experimental Gerontology.

[24]  G. Bartosz,et al.  The effect of donor age on the packing susceptibility of erythrocytes , 1988, Mechanisms of Ageing and Development.

[25]  G. Biasi,et al.  Arterial and venous blood viscosity in ischemic lower limbs in patients affected by peripheral obliterative arterial disease. , 1979, The Journal of cardiovascular surgery.

[26]  J. Naets,et al.  THE MECHANISM OF ACTION OF ANDROGENS ON ERYTHROPOIESIS * , 1965, Annals of the New York Academy of Sciences.

[27]  M. Gassmann,et al.  Scientific Heading: RED CELLS Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity , 2003 .

[28]  H S Borovetz,et al.  Red blood cell aging and risk of cardiovascular diseases. , 1998, Clinical hemorheology and microcirculation.

[29]  P. Broulik,et al.  The effect of castration and androgen treatment on glomerular volume in mice. , 1983, Experimental and clinical endocrinology.

[30]  P. L. la Celle,et al.  Blood viscosity and thrombosis: clinical considerations. , 1982, Progress in hemostasis and thrombosis.

[31]  Lacelle Pl,et al.  Blood viscosity and thrombosis: clinical considerations. , 1982 .