Abstract
Association between androgens and erythropoiesis has been known for more than seven decades. Androgens stimulate hematopoietic system by various mechanisms. These include stimulation of erythropoietin release, increasing bone marrow activity and iron incorporation into the red cells. Before the discovery of recombinant erythropoietin (rhEpo), androgens were used in the treatment of anemia associated with renal disease, bone marrow suppression, and hypopituitarism. Anabolism is an additional advantage of androgen therapy. Furthermore, in light of recent reports regarding adverse effects of rhEpo, the role of androgen therapy in various types of anemias should be readdressed. Polycythemia remains a known side effect of androgen therapy. In this review, we will briefly discuss the initial animal and human studies which demonstrated the role of androgens in the treatment of anemia, their mechanism of action, a detailed account of the efficacy of androgens in the treatment of various anemias, the erythropoietic side effects of androgens and finally, the relationship between hematocrit levels and cardiovascular disease.
Similar content being viewed by others
References
Vollmer EP, Gordon AS. Effect of sex and gonadotropic hormones upon the blood picture of the rat. Endocrinology 1941, 29: 828–37.
Steinglass P, Gordon AS, Charipper HA. Effect of castration and sex hormones on blood of the rat. Proc Soc Exp Biol Med 1941, 48: 169–77.
Crafts RC. Effects of hypophysectomy, castration and testosterone propionate on hemopoiesis in the adult male rat. Endocrinology 1946, 39: 401–13.
Hawkins WW, Speck E, Leonard VG. Variation of the hemoglobin level with age and sex. Blood 1954, 9: 999–1007.
Williamson CS. Influence of age and sex on hemoglobin: a spectrophotometric analysis of nine hundred and nineteen cases. Arch Intern Med 1916, 18: 505–28.
Vahlquist B. The cause of the sexual differences in erythrocyte, hemoglobin and serum iron levels in human adults. Blood 1950, 5: 874–5.
Shahidi NT, Clatanoff DV. The role of puberty in red-cell production in hereditary haemolytic anaemias. Br J Haematol 1969, 17: 335–42.
McCullagh EP, Jones R. A note on the effect of certain androgens upon red blood cell count and upon glucose tolerance. Cleve Clin Q 1941, 8: 79–84.
Kennedy BJ, Gilbertsen AS. Increased erythropoiesis induced by androgenic hormone therapy. N Engl J Med 1957, 256: 719–26.
Nutrition Canada. National survey. Ottawa: Information Canada, 1973.
Woodman R, Ferrucci L, Guralnik J. Anemia in older adults. Curr Opin Hematol 2005, 12: 123–8.
Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 2004, 104: 2263–8.
Beghé C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature. Am J Med 2004, 5: 3S-10S.
Artz AS, Fergusson D, Drinka PJ, et al. Prevalence of anemia in skilled-nursing home residents. Arch Gerontol Geriatr 2004, 39: 201–6.
Myers AM, Saunders CR, Chalmers DG. The haemoglobin level of fit elderly people. Lancet 1968, 2: 261–3.
McLennan WJ, Andrews GR, Macleod C, Caird FI. Anaemia in the elderly. Q J Med 1973, 42: 1–13.
Smith JS, Whitelaw DM. Hemoglobin values in aged men. Can Med Assoc J 1971, 105: 816–8.
Muldowney FP. The relationship of total red cell mass to lean body mass in men. Clin Sci 1956, 16: 163–70.
Forbes GB, Halloran E. The adult decline in lean body mass. Hum Biol 1976, 48: 162–73.
Lipschitz DA, Mitchell CO, Thompson C. The anemia of senescence. Am J Hematol 1981, 11: 47–54.
Gray A, Berlin JA, McKinlay JB, Longcope C. An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J Clin Epidemiol 1991, 44: 671–84.
Gray A, Feldman HA, McKinlay, Longcope C. Age, disease and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991, 73: 1016–25.
Morley JE, Kaiser FE, Perry HM III, et al. Longitudinal changes in testosterone, luteinizing hormone and follicle-stimulating hormone in healthy older men. Metabolism 1997, 46: 410–3.
Harman SM, Metter EJ, Tobin JD, Pearson J Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001, 86: 724–31.
Ferrucci L, Maggio M, Bandinelli S, et al. Low testosterone levels and the risk of anemia in older men and women. Arch Intern Med 2006, 166: 1380–8.
Nathan DG, Gardner FH. Effects of large doses of androgen on rodent erythropoiesis and body composition. Blood 1965, 26: 411–20.
Paulo LG, Fink GD, Roh BL, Fisher JW. Effects of several androgens and steroid metabolites on erythropoietin production in the isolated perfused dog kidney. Blood 1974, 43: 39–47.
Yared K, Gagnon RF, Brox AG. Mechanisms of action of androgen treatment on the anemia of experimental chronic renal failure. J Am Soc Nephrol 1997, 8: 633A.
Schooley JC. Inhibition of erythropoietic stimulation by testosterone in polycythemic mice receiving anti-erythropoietin. Proc Soc Exp Biol Med 1966, 122: 402–3.
Fried W, Kilbridge T. Effect of testosterone and of cobalt on erythropoietin production by anephric rats. J Lab Clin Med 1969, 74: 623–9.
Alexanian R. Erythropoietin and erythropoiesis in anemic man following androgens. Blood 1969, 33: 564–72.
Shaldon S, Koch KM, Oppermann F, Patyna WD, Schoeppe W. Testosterone therapy for anaemia in maintenance dialysis. Br Med J 1971, 3: 212–5.
Mirand EA, Murphy GP. Erythropoietin activity in anephric humans given prolonged androgen treatment. J Surg Oncol 1971, 3: 59–65.
Medlinsky JT, Napier CD, Gurney CW. The use of an antiandrogen to further investigate the erythropoietic effects of androgens. J Lab Clin Med 1969, 74: 85–92.
Rishpon-Meyerstein N, Kilbridge T, Simone J, Fried W. The effect of testosterone on erythropoietin levels in anemic patients. Blood 1968, 31: 453–60.
Moriyama Y, Fisher JW. Effects of testosterone and erythropoietin on erythroid colony formation in human bone marrow cultures. Blood 1975, 45: 665–70.
Molinari PF, Rosenkrantz H. Erythropoietic activity and androgenic implications of 29 testosterone derivatives in orchiectomized rats. J Lab Clin Med 1971, 78: 399–410.
Naets JP, Wittek M. The mechanism of action of androgens on erythropoiesis. Ann N Y Acad Sci 1968, 149: 366–76.
Valladares L, Minguell J. Characterization of a nuclear receptor for testosterone in rat bone marrow. Steroids 1975, 25: 13–21.
Mulder E, Lamers-Stahlhofen GJ, van der Molen HJ. Metabolism of free and conjugated steroids by intact and hemolysed mammalian erythrocytes. Biochim Biophys Acta 1972, 260: 290–7.
Molinari PF. Erythropoietic mechanism of androgens: a critical review and clinical implications. Haematologica 1982, 67: 442–60.
Molinari PF, Esber HJ, Snyder LM. Effect of androgens on maturation and metabolism of erythroid tissue. Exp Hematol 1976, 4: 301–9.
Larner J. Intermediary metabolism and its regulation. Englewood Cliffs, NJ: Prentice Hall Inc. 1971, 228.
Molinari PF, Chung SK, Snyder LM. Variations of erythrocyte glycolysis following androgens. J Lab Clin Med 1973, 81: 443–6.
Molinari PF, Neri LL. Effect of a single oral dose of oxymetholone on the metabolism of human erythrocytes. Exp Hematol 1978, 6: 648–54.
Necheles TF, Rai US. Studies on the control of hemoglobin synthesis: the in vitro stimulating effect of a 5-beta-H steroid metabolite on heme formation in human bone marrow cells. Blood 1969, 34: 380–4.
Irving RA, Mainwaring IP, Spooner PM. The regulation of haemoglobin synthesis in cultured chick blastoderms by steroids related to 5beta-androstane. Biochem J 1976, 154: 81–93.
Fisher J. Erythropoietin: physiology and pharmacology update. Exp Biol Med 2003, 228: 1–14.
Merchav S, Tatarsky I, Hochberg Z. Enhancement of erythropoiesis in vitro by human growth hormone is mediated by insulin-like growth factor 1. Br J Haematol 1988, 70: 267–1.
Miyagawa SH, Kobayashi M, Konishi N, Sato T, Ueda K. Insulin and insulin-like growth factor 1 support the proliferation of erythroid progenitor cells in bone marrow through the sharing of receptors. Br J Haematol 2000, 109: 555–62.
Muta K, Krantz SB. Apoptosis of human erythroid colony-forming cells is decreased by stem cell factor and insulin-like growth factor 1 as well as erythropoietin. J Cell Physiol 1993, 156: 264–71.
Powell DR, Rosenfeld RG, Baker BK, Liu F, Hintz RL. Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor-I (IGF-I) and IGF-II in acid-chromatographed uremic serum. J Clin Endocrinol Metab 1986, 63: 1186–92.
Goldberg AC, Trivedi B, Delmez JA, Harter HR, Daughaday WH. Uremia reduces serum insulin-like growth factor I, increases insulin like growth factor II, and modifies their serum protein binding. J Clin Endocrinol Metab 1982, 55: 1040–5.
Hagenfeldt Y, Linde K, Sjoberg HE, Zumkeller W, Arver S. Testosterone increases serum 1,25-dihydroxyvitamin D and insulin-like growth factor-I (IGF-1) in hypogonadal men. IntJ Androl 1992, 15: 93–102.
Hobbs CJ, Plymate SR, Rosen CJ, Adler RA. Testosterone administration increases insulin-like growth factor-I levels in normal men. J Clin Endocrinol Metab 1993, 77: 776–9.
Navarro JF, Mora C, Macia M, Garcia J. Randomized prospective comparison between erythropoietin and androgens in CAPD patients. Kidney Int 2002, 61: 1537–44.
Solomon LR, Hendler ED. Prospective controlled study of androgen therapy in the anemia of chronic renal disease: effects on iron kinetics. Acta Haematol 1988, 79: 12–9.
Gardner FH, Nathan DG, Piomelli S, Cummins JF. The erythrocythaemic effects of androgen. Br J Haematol 1968, 14: 611–5.
Besa EC, Gorshein D, Gardner FH. Androgens and human blood volume changes. Comparison in normal and various anemic states. Arch Intern Med 1974, 133: 418–25.
Verwilghen R, Louwagie A, Waes J, Vandenbroucke J. Anabolic agents and relative polycythaemia. Br J Haematol 1966, 12: 712–6.
Parker JP, Beirne GJ, Desai JN, Raich PC, Shahidi NT. Androgen-induced increase in red-cell 2,3-diphosphoglycerate. N Engl J Med 1972, 287: 381–3.
Mauss J, Borsch G, Bormacher K, Richter E, Leyendecker G, Nocke W. Effect of long-term testosterone enanthate administration on male reproductive function: clinical evaluation, serum FSH, LH, testosterone, and seminal fluid analyses in normal men. Acta Endocrinol (Copenh) 1975, 78: 373–84.
Alvarez-Sanchez F, Faundes A, Brache V, Leon P. Attainment and maintenance of azoospermia with combined monthly injections of depot medroxyprogesterone acetate and testosterone enanthate. Contraception 1977, 15: 635–48.
Brenner PF, Mishell DR Jr, Bernstein GS, Ortiz A. Study of medroxyprogesterone acetate and testosterone enanthate as a male contraceptive. Contraception 1977, 15: 679–91.
Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab 2008, 93: 914–9.
Bhasin S, Woodhouse L, Casaburi R, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 2005, 90: 678–88.
Calof O, Singh AB, Lee ML, et al. Adverse events associated with testosterone supplementation of older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol Med Sci 2005, 60: 1451–7.
Palacios A, Campfield LA, McClure RD, Steiner B, Swerdloff RS. Effect of testosterone enanthate on hematopoiesis in normal men. Fertil Steril 1983, 40: 100–4.
Jockenhovel F, Vogel E, Reinhardt W, Reinwein D. Effects of various modes of androgen substitution therapy on erythropoiesis. Eur J Med Res 1977, 2: 293–8.
Errsley AJ. Erythropoietin. N Engl J Med 1991, 324: 1339–44.
Snyder PJ, Peachey H, Berlin JA, et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 2000, 85: 2670–7.
Nicholas TA, Dean JD, Mulder H, Carnegie C, Jones NA. A novel testosterone gel formulation normalizes androgen levels in hypogonadal men with improvements in body composition and sexual function. BJU Int 2003, 91: 69–74.
Brockenbrough A, Dittrich M, Page S, Smith T, Stivelman J, Bremner W. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Am J Kidney Dis 2006, 47: 251–62.
Gurney CW, Goldwasser E, Pan C. Studies on erythropoiesis VI. Erythropoietin in human plasma. J Lab Clin Med 1957, 50: 534–42.
Eschbach JW Jr, Funk D, Adamson J, Kuhn I, Scribner BH, Finch CA. Erythropoiesis in patients with renal failure undergoing chronic dialysis. N Engl J Med 1967, 276: 653–8.
Naets JP, Wittek M. Erythropoiesis in anephric man. Lancet 1968, 1: 941–3.
Mirand EA, Murphy GP, Steeves RA, Groenewald JM, DeKlerk JN. Erythropoietin activity in anephric, allotransplanted, unilaterally nephrectomized and intact man. J Lab Clin Med 1969, 73: 121–8.
DeGowin RL, Lavender AR, Forland M, Charleston D, Gottschalk A. Erythropoiesis and erythropoietin in patients with chronic renal failure treated with hemodialysis and testosterone. Ann Intern Med 1970, 72: 913–8.
Richardson JR, Weinstein MB. Erythropoietic response of dialyzed patients to testosterone administration. Ann Intern Med 1970, 73: 403–7.
Teruel JL, Aguilera A, Marcen R, Navarro Antolin J, Garcia Otero G, Ortuno J. Androgen therapy for anaemia of chronic renal failure. Indications in the erythropoietin era. Scand J Urol Nephrol 1996, 30: 403–8.
Shaldon S, Patyna WD, Kaltwasser P, Werner E, Koch KM, Schoeppe WE. The use of testosterone in bilateral nephrectomized dialysis patients. Trans Am Soc Artif Intern Organs 1971, 17: 104–7.
Fried W, Jonasson O, Lang G, Schwartz F. The hematologic effect of androgen in uremic patients. Study of packed cell volume and erythropoietin responses. Ann Intern Med 1973, 79: 823–7.
Teruel JL, Marcen R, Navarro JF, et al. Evolution of serum erythropoietin after androgen administration to hemodialysis patients: a prospective study. Nephron 1995, 70: 282–6.
Ballal SH, Domoto DT, Polack DC, Marciulonis P, Martin KJ. Androgens potentiate the effects of EPO in the treatment of anemia of ESRD. Am J Kidney Dis 1991, 17: 29–33.
Gaughan WJ, Liss KA, Dunn SR, et al. A 6-month study of low-dose recombinant human EPO alone and in combination with androgens for the treatment of anemia in patients on chronic hemodialysis. Am J Kidney Dis 1997, 30: 495–500.
Lee MS, Ahn SH, Song JH. Effects of adjuvant androgen on anemia and nutritional parameters in chronic hemodialysis patients using low-dose recombinant human EPO. Korean J Intern Med 2002, 17: 167–73.
Sheashaa H, Abdel-Razek W, El-Husseini A, et al. Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis. Nephron Clin Pract 2005, 99: 102–6
Teruel JL, Marcen R, Navarro-Antolin J, Aguilera A, Fernandez-Juarez G, Ortuno J. Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study. J Am Soc Nephrol 1996, 7: 140–4.
Berns JS, Rudnick MR, Cohen RM. A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis. Clin Nephrol 1992, 37: 264–7.
Daniell HW. Erythropoietin resistance during androgen deficiency. Arch Intern Med 2006, 166: 1923.
Neff MS, Goldberg J, Slifkin RF, et al. A comparison of androgens for anemia in patients on hemodialysis. N Engl J Med 1981, 304: 871–5.
Navarro JF, Mora C, Rivero A, et al. Androgens as therapy for the treatment of anemia in peritoneal dialysis (PD) patients. Perit Dial Int 1998, 18: S52.
Shahidi NT, Diamond LK. Testosterone induced remission in aplastic anemia. AMA J Dis Child 1959, 98: 293–302
Furuhjelm U, Eklund J. Treatment of aplastic anemia with anabolic steroids and corticosteroids. Ann Paediatr Fenn 1966, 12: 89–95.
O’ Gorman H. The varied pattern of aplastic anemia in childhood. Aust Paediatr J 1966, 2: 228–36.
Killander A, Lundmark KM, Sjolin S. Idiopathic aplastic anaemia in children. Results of androgen treatment. Acta Paediatr Scand 1969, 58: 10–4.
Shahidi NT, Crigler JF Jr. Evaluation of growth and of endocrine systems in testosterone-corticosteroid-treated patients with aplastic anemia. J Pediatr 1967, 70: 233–42.
Duarte L, Lopez Sandoval R, Esquivel F, Sanchez-Medal L. Androstane therapy of aplastic anaemia. Acta Haematol 1972, 47: 140–5.
Bloom GE, Diamond LK. Prognostic value of fetal hemoglobin levels in acquired aplastic anemia. N Engl J Med 1968, 278: 304–7.
Palva IP, Wasastjerna C. Treatment of aplastic anemia with methenolone. Acta Haemat 1972, 47: 13–20.
Van Hengstum M, Steenbergen J, Haanen C. Clinical course in 28 unselected patients with aplastic anaemia treated with anabolic steroids. Br J Haematol 1979, 41: 323–33.
Sacks P, Gale D, Bothwell TH, Stevens K. Oxymetholone therapy in aplastic and other refractory anaemias. S Afr Med J 1972, 46: 1607–15.
Sanchez-Medal L, Gomez-Leal A, Duarte L, Guadalupe Rico M. Anabolic androgenic steroids in the treatment of acquired aplastic anemia. Blood 1969, 34: 283–300.
Piedras J, Hernández G, López-Karpovitch X. Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes. Am J Hematol 1998, 57: 113–8.
Bacigalupo A, Chaple M, Hows J, et al. Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party. Br J Haematol 1993, 83: 145–51.
Kulkarni S, Sastry PS, Saikia TK, et al. Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) with methylprednisone and oxymethalone in aplastic anaemia. J Assoc Physicians India 1997, 45: 263–6.
Kaltwasser JP, Dix U, Schalk KP, Vogt H. Effect of androgens on the response to antithymocyte globulin in patients with aplastic anaemia. Eur J Haematol 1988, 40: 111–8.
Champlin RE, Ho WG, Feig SA, Winston DJ, Lenarsky C, Gale RP. Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial. Blood 1985, 66: 184–8.
Socie G, Gluckman E. Cure from severe aplastic anemia in vivo and late effects. Acta Haematol 2000, 103: 49–54.
Leleu X, Terriou L, Duhamel A, et al. Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens. Ann Hematol 2006, 85: 711–6.
French Cooperative Group forthe Study of Aplastic and Refractory Anemias. 1986 Androgen therapy in aplastic anaemia: a comparative study of high and low-doses and of 4 different androgens. Scand J Haematol 1986, 36: 346–52.
Najean Y, Pecking A. Refractory anaemia with excess of myeloblasts in the bone marrow: a clinical trial of androgens in 90 patients. Br J Haematol 1977, 37: 25–33.
Chabannon C, Molina L, Pégourié-Bandelier B, Bost M, Léger J, Hollard D. A review of 76 patients with myelodysplastic syndromes treated with danazol. Cancer 1994, 73: 3073–80.
Stadtmauer EA, Cassileth PA, Edelstein M, et al. Danazol treatment of myelodysplastic syndromes. BrJ Haematol 1991, 77: 502–8.
Katayama Y, Kojima K, Omoto E, Harada M. Androgen therapy in combination with granulocyte colony-stimulating factor and erythropoietin in a patient with refractory anemia. Int J Hematol 1996, 65: 89–92.
Tsiara SN, Chaidos A, Gouva M, et al. Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone. J Exp Clin Cancer Res 2004, 23: 47–52.
Wang JW, Ning F, Liu XD, Lou JX, Chen P, Liu B. A preliminary report on treatment of myelodysplastic syndrome with cyclosporine A and androgen. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2004, 12: 855–7.
Zhang W, Zhou F, Cao X, et al. Successful treatment of primary refractory anemia with a combination regimen of all-trans retinoic acid, calcitriol and androgen. Leuk Res 2006, 30: 935–42.
Kobaba R, Kanamaru A, Takemoto Y, Kohsaki M, Kakishita E, Nagai K. Androgen in the treatment of refractory anemia. Int J Hematol 1991, 54: 103–7.
Delamore IW, Geary CG. Aplastic anaemia, acute myeloblastic leukaemia, and oxymetholone. Br Med J 1971, 2: 743–5.
Ozdogan M, Yazicioglu G, Karadogan I, Cevikol C, Karayalcin U, Undar L. Sheehan’s syndrome associated with pancytopenia due to marrow aplasia; full recovery with hormone replacement therapy. Int J Clin Pract 2004, 58: 533–5.
Kim DY, Kim JH, ParkYJ, et al. Case of complete recovery of pancytopenia after treatment of hypopituitarism. Ann Hematol 2004, 83: 309–12.
Rudzki Z, Matynia A, Przybylik-Mazurek E, et al. Hypopituitarism and hematological abnormalities mimicking myelodysplastic syndrome. Report of four cases. Pol Arch Med Wewn 2003, 110: 1003–11.
Jepson JH, McGarry EE. Hemopoiesis in pituitary dwarfs treated with human growth hormone and testosterone. Blood 1972, 39: 238–48.
Jepson JH, McGarry EE, Lowenstein L. Erythropoietin excretion in a hypopituitary patient. Effects of testosterone and vasopressin. Arch Intern Med 1968, 122: 265–70.
Ellegala DB, Alden TD, Couture DE, Vance ML, Maartens NF, Laws ER Jr. Anemia, testosterone and pituitary adenoma in men. J Neurosurg 2003, 98: 974–7.
O’Hare JA, Rolla AP. Hemochromatosis, hypogonadism, testosterone and erythropoiesis. Ann Intern Med 1985, 102: 871–2.
West WO. The treatment of bone marrow failure with massive androgen therapy. Ohio State Med J 1965, 61: 347–55.
Thiagarajan D, Tawadros H, Dipaling S. Pure red blood cell aplasia complicating chronic lymphatic leukemia. Am J Med Sci 1983, 286: 22–7.
Lundh B, Gardner FH. The haematological response to androgens in sickle cell anaemia. Scand J Haematol 1970, 7: 389–97.
Craddock PR, Hunt FA, Rozenberg MC. The effective use of oxymetholone in the therapy of thalassaemia with anaemia. Med J Aust 1972, 2: 199–202.
Hartmann RC, Jenkins DE Jr, McKee LC, Heyssel RM. Paroxysmal nocturnal hemoglobinuria: clinical and laboratory studies relating to iron metabolism and therapy with androgen and iron. Medicine (Baltimore) 1966, 45: 331–63.
Rosse WF. Treatment of paroxysmal nocturnal hemoglobinuria. Blood 1982, 60: 20–3.
Yoshimura Y, Nakayama A, Hama H, et al. Treatment of paroxysmal nocturnal hemoglobinuria with danazol. Rinsho Ketsueki 1990, 31: 1489–92.
Harrington WJ Sr, Kolodny L, Horstman LL, Jy W, Ahn YS. Danazol for paroxysmal nocturnal hemoglobinuria. Am J Hematol 1997, 54: 149–54.
Watson AJ. Adverse effects of therapy for the correction of anemia in hemodialysis patients. Semin Nephrol 1989, 9: 30–4.
Teruel JL, Lasuncion MA, Rivera M, et al. Nandrolone decanoate reduces serum lipoprotein(a) concentrations in hemodialysis patients. Am J Kidney Dis 1997, 29: 569–75.
Teruel JL, Aguilera A, Avila C, Ortuno J. Effects of androgen therapy on prostatic markers in hemodialyzed patients. Scand J Urol Nephrol 1996, 30: 129–31.
Basaria S, Dobs AS. Risks versus benefits of testosterone therapy in elderly men. Drugs Aging 1999, 15: 131–42.
Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA. Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 1999, 84: 3469–78.
Amory JK, Watts NB, Easley KA, et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 2004, 89: 503–10.
Krauss DJ, Taub HA, Lantinga LJ, Dunsky MH, Kelly CM. Risks of blood volume changes in hypogonadal men treated with testosterone enanthate for erectile impotence. J Urol 1991, 146: 1566–70.
Erslev AJ. Relative polycythemia (erythrocytosis).In: Williams WJ, Beutlere, Erslev AJ, Lichtman MA eds. Hematology. New York: McGraw-Hill Book Company. 1990, p 715–6.
Osler W. Chronic cyanosis with polycythemia and enlarged spleen; a new clinical entitiy. Am J Med Sci 1903, 126: 187–200.
Smith JR, Landaw SA. Smokers’ polycythemia. N Engl J Med 1978, 298: 6–10.
Lawrence JH, Berlin NI. Relative polycythemia — the polycythemia of stress. Yale J Biol Med 1952, 24: 498–505.
Drinka PJ, Jochen AL, Cuisinier M, Bloom R, Rudman I, Rudman D. Polycythemia as a complication of testosterone replacement therapy in nursing home men with low testosterone levels. J Am Geriatr Soc 1995, 43: 899–901.
Lowe GD, Forbes CD. Blood rheology and thrombosis. Clin Haematol 1981, 10: 343–67.
Wood JH, Kee DB. Hemorheology of the cerebral circulation in stroke. Stroke 1985, 16: 765–72.
Lowe GD, Forbes CD. Platelet aggregation, haematocrit and fibrinogen. Lancet 1985, 1: 395–6.
Harrison MJ, Pollock SS, Weisblatt E. Haematocrit and platelet aggregation. Lancet 1984, 2: 991–2.
Wannamethee G, Perry IJ, Shaper AG. Haematocrit, hypertension and risk of stroke. J Intern Med 1994, 235: 163–8.
Tohgi H, Yamanouchi H, Murakami M, Kameyama M. Importance of the hematocrit as a risk factor in cerebral infarction. Stroke 1978, 9: 369–74.
Kannel WB, Gordon T, Wolf PA, McNamara P. Hemoglobin and the risk of cerebral infarction: the Framingham Study. Stroke 1972, 3: 409–20.
Gagnon DR, Zhang TJ, Brand FN, Kannel WB. Hematocrit and the risk of cardiovascular disease — the Framingham study: a 34-year follow-up. Am Heart J 1994, 127: 674–82.
Kiyohara Y, Ueda K, Hasuo Y, et al. Hematocrit as a risk factor of cerebral infarction: long-term prospective population survey in a Japanese rural community. Stroke 1986, 17: 687–92.
Niazi GA, Awada A, al Rajeh S, Larbi E. Hematological values and their assessment as risk factor in Saudi patients with stroke. Acta Neurol Scand 1994, 89: 439–45.
Tohgi H, Yamanouchi H, Murakami M, Kameyama M. Importance of the hematocrit as a risk factor in cerebral infarction. Stroke 1978, 9: 369–74.
Lowe GD, Jaap AJ, Forbes CD. Relation of atrial fibrillation and high haematocrit to mortality in acute stroke. Lancet 1983, 1: 784–6.
Harrison MJ, Pollock S, Kendall BE, Marshall J. Effect of haematocrit on carotid stenosis and cerebral infarction. Lancet 1981, 2: 114–5.
Spiess BD, Ley C, Body SC, et al. Hematocrit value on intensive care unit entry influences the frequency of Q-wave myocardial infarction after coronary artery bypass grafting: the Institutions of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group. J Thorac Cardiovasc Surg 1998, 116: 460–7.
Goubali A, Voukiklaris G, Kritsikis S, Viliotou F, Stamatis D. Relation of hematocrit values to coronary heart disease, arterial hypertension, and respiratory impairment in occupational and population groups of the Athens area. Angiology 1995, 46: 719–25.
Melina G, Colivicchi F, Bevilacqua E, Mangnanimi S, Melina D. Blood pressure variations, hemorheological determinants and platelet aggregation in hypertensive patients with unstable angina. Clin Exp Hypertens 1995, 17: 1145–56.
Fuchs J, Pinhas A, Davidson E, Rotenberg Z, Agmon J, Weinberger I. Plasma viscosity, fibrinogen and haematocrit in the course of unstable angina. Eur Heart J 1990, 11: 1029–32.
Mares M, Bertolo C, Terribile V, Girolami A. Hemorheological study in patients with coronary artery disease. Cardiology 1991, 78: 111–6.
Burch GE, DePasquale NP. The hematocrit in patients with myocardial infarction. JAMA 1962, 180: 62–3.
Sorlie PD, Garcia-Palmieri MR, Costas R Jr, Havlik RJ. Hematocrit and risk of coronary heart disease: the Puerto Rico Health Program. Am Heart J 1981, 101: 456–61.
Carter C, McGee D, Reed D,Yano K, Stemmermann G. Hematocrit and the risk of coronary heart disease: the Honolulu Heart Program. Am Heart J 1983, 105: 674–9.
Nishikido N, Kobayashi T, Kashiwazaki H. Hematocrit correlates with blood pressure in young male office workers. Ind Health 1999, 37: 76–81.
Vriz O, Nesbitt S, Krause L, Majahalme S, Lu H, Julius S. Smoking is associated with higher cardiovascular risk in young women than in men: the Tecumseh Blood Pressure Study. J Hypertens 1997, 15: 127–34.
Erikssen G, Thaulow E, Sandvik L, Stormorken H, Erikssen J. Haematocrit: a predictor of cardiovascular mortality? J Intern Med 1993, 234: 493–9.
Campbell MJ, Elwood PC, Mackean J, Waters WE. Mortality, haemoglobin level and haematocrit in women. J Chronic Dis 1985, 38: 881–9.
Brown DW, Giles WH, Croft JB. Hematocrit and the risk of coronary heart disease mortality. Am Heart J 2001, 142: 657–63.
T’Sjoen GG, Beguin Y, Feyen E, Rubens R, Kaufman J-M, Gooren L. Influence of exogenous oestrogen or (anti-) androgen administration on soluble transferring receptor in human plasma. J Endocrinol 2005, 186: 61–7.
Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab 2008, 93: 914–9.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shahani, S., Braga-Basaria, M., Maggio, M. et al. Androgens and erythropoiesis: Past and present. J Endocrinol Invest 32, 704–716 (2009). https://doi.org/10.1007/BF03345745
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03345745