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HISTORY
1. Oxymetholone was first introduced by Ringold et al. in 1959[1].
2. Anabolic:androgenic ratios on oxymetholone were developed from in vivo rodent studies, cited here[2]. These studies indicate that oxymetholone is as anabolic as oxandrolone, stanozolol, and less anabolic than nandrolone, but that it is more androgenic than all of them.
3. In rat and rabbit skeletal muscle androgen receptors, oxymetholone binds to the receptor extremely weakly, suggesting that it may exert its influence via metabolites or other receptors[3].
4. Oxymetholone is approved for the treatment of anemia by the FDA. It has also been studied for the treatment of HIV-induced wasting disease[4], antithrombin III deficiency[5], damaged myocardium in heart failure[6], and growth impairment in children[7].
METABOLISM
1. Oxymetholone is a 17alpha-alkyl derivative of testosterone. The 17alpha-alkyl component prevents the inactivation of the molecule via oxidation of the 17-hydroxy group into a 17-keto group, thereby slowing metabolism in the liver[8].
2. In phase I metabolism, oxymetholone is oxidized at carbon 2 (C2), reduced at C3, and hydroxylated at C17[9].
3. Oxymetholone produces more than 40 metabolites, one of which can be monitored for up to two weeks[10][11].
4. Oxymetholone’s main metabolite is mestanolone/methylandrostanolone (17alpha-methyl-DHT)[12].
5. Interestingly, fungi metabolize oxymetholone into immunosuppressant metabolites[13].
NITROGEN RETENTION
1. Oxymetholone produces more nitrogen retention than methyltestosterone[14].
HEMATOPOIESIS
1. Though it was recently suggested that androgens increase telomerase activity in hematopoietic cells[15], it remains unclear whether androgens directly raise erythropoiesis[16]. Oxymetholone increases hematopoiesis stem cell activity but does not affect telomerase or erythropoietin expression[17].
2. Still, in humans concurrent administration of oxymetholone in addition to recombinant erythropoietin significantly improves the erythropoietic effect (and increases liver enzyme values)[18].
LIPIDS
1. Within 6 weeks, oxymetholone has produced hypertriglyceridemia and hyperlipidemia in a patient (as well as cerebral thrombosis)[19].
ORGAN DAMAGE
1. Oxymetholone causes free radical-induced testicular damage that can be attenuated with the use of antioxidant compounds[20][21].
2. Cholestatic jaundice[22] and hepatitis has occurred with oxymetholone use, causing some fatalities[23].
3. After discontinuation, oxymetholone has caused peliosis hepatis[24][25].
4. Oxymetholone use is also associated with benign and malignant liver tumors (i.e. adenomas and HCC)[26].
5. Oxymetholone has caused acute renal failure due to rhabdomyolysis[27].
6. Oxymetholone can produce kidney damage (particularly to the glomeruli) in one day old rodents[28].
OTHER EFFECTS
1. There are case reports of venous thrombosis (including cerebral[29]) due to oxymetholone therapy.
2. Oxymetholone may produce insulin resistance[30].
3. Oxymetholone is not able to sustain sexual behavior of castrated rodents[31].
4. Oxymetholone appears to suppress corticosteroid production, which may cause compensatory adrenal hyperplasia[32]. This appears to indicate that unlike mesterolone, mestanolone, and methenolone, weight gain from oxymetholone may not be due to the mineralocorticoid receptors.
5. Though carcinogenic, oxymetholone is not genotoxic[33].
[1] Ringold, H. J., Batres, E., Halpern, O., & Necoechea, E. (1959). Steroids. CV. 1 2-Methyl and 2-hydroxymethylene-androstane derivatives. Journal of the American Chemical Society, 81(2), 427-432. [2] DORFMAN, R. I., & KINCL, F. A. (1963). Relative potency of various steroids in an anabolic-androgenic assay using the castrated rat. Endocrinology, 72(2), 259-266. [3] SAARTOK, T., DAHLBERG, E., & GUSTAFSSON, J. Å. (1984). Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin. Endocrinology, 114(6), 2100-2106. [4] Hengge, U. R., Baumann, M., Maleba, R., Brockmeyer, N. H., & Goos, M. (1996). Oxymetholone promotes weight gain in patients with advanced human immunodeficiency virus (HIV-1) infection. British journal of nutrition, 75(1), 129-138. [5] Shibuya, A., Ninomiya, H., Nakazawa, M., Nagasawa, T., Yoda, Y., & Abe, T. (1988). Oxymetholone therapy in patients with familial antithrombin III deficiency. Thrombosis and haemostasis, 59(03), 495-497. [6] Tomoda, H. (1999). Effect of oxymetholone on left ventricular dimensions in heart failure secondary to idiopathic dilated cardiomyopathy or to mitral or aortic regurgitation. American Journal of Cardiology, 83(1), 123-125. [7] Keele, D. K., & Worley, J. W. (1967). Study of an anabolic steroid: certain effects of oxymetholone on small children. American Journal of Diseases of Children, 113(4), 422-430. [8] Schänzer, W. (1996). Metabolism of anabolic androgenic steroids. Clinical chemistry, 42(7), 1001-1020. [9] MacDonald, B. S., Sykes, P. J., Kilshaw, B. H., & Harkness, R. A. (1973). Proceedings: Metabolism of the hydroxymethylene group in the anabolic steroid, oxymetholone: isolation and identification of two major metabolites. The Journal of endocrinology, 59(2), 18. [10] Sobolevsky, T., & Rodchenkov, G. (2012). Mass spectrometric description of novel oxymetholone and desoxymethyltestosterone metabolites identified in human urine and their importance for doping control. Drug testing and analysis, 4(9), 682-691. [11] Kratena, N., Biedermann, N., Stojanovic, B., Göschl, L., Weil, M., Enev, V. S., ... & Gärtner, P. (2019). Synthesis of a human long-term oxymetholone metabolite. Steroids, 150, 108430. [12] Madrakian, T., Afkhami, A., Rahimi, M., Ahmadi, M., & Soleimani, M. (2013). Preconcentration and spectrophotometric determination of oxymetholone in the presence of its main metabolite (mestanolone) using modified maghemite nanoparticles in urine sample. Talanta, 115, 468-473. [13] Khan, N. T., Bibi, M., Yousuf, S., Qureshi, I. H., Al-Majid, A. M., Mesaik, M. A., ... & Choudhary, M. I. (2012). Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone. Chemistry Central Journal, 6(1), 153. 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The efficacy of oxymetholone in combination with erythropoietin on hematologic parameters and muscle mass in CAPD patients. International journal of clinical pharmacology and therapeutics, 48(12), 803. [19] Reeves, R. D., Morris, M. D., & Barbour, G. L. (1976). Hyperlipidemia due to oxymetholone therapy: Occurrence in a long-term hemodialysis patient. Jama, 236(5), 469-472. [20] Akbari Bazm, M., Khazaei, M., Khazaei, F., & Naseri, L. (2019). Nasturtium Officinale L. hydroalcoholic extract improved oxymetholone‐induced oxidative injury in mouse testis and sperm parameters. Andrologia, 51(7), e13294. [21] Akbari Bazm, M., Goodarzi, N., Shahrokhi, S. R., & Khazaei, M. (2020). The effects of hydroalcoholic extract of Vaccinium arctostaphylos L. on sperm parameters, oxidative injury and apoptotic changes in oxymetholone‐induced testicular toxicity in mouse. Andrologia, 52(3), e13522. [22] Wood, P., & Yin, J. L. (1994). 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Profiling of anabolic androgenic steroids and selective androgen receptor modulators for interference with adrenal steroidogenesis. Biochemical Pharmacology, 172, 113781. [33] Stoll, R. E., Holden, H. E., Barthel, C. H., & Blanchard, K. T. (1999). Oxymetholone: III. Evaluation in the p53+/-transgenic mouse model. Toxicologic pathology, 27(5), 513-518.
