Turinabol and oxandrolone: mechanisms and adverse effects

In a previous article, we compared turinabol and oxandrolone by history and status. Here, the editors focused on the pharmacology: how these molecules interact with the androgen receptor, how they are metabolized, why both damage the liver and lipids, and how their side effects differ from those of injectable testosterone.

Shared mechanism: androgen receptor

Like all anabolic-androgenic steroids, turinabol and oxandrolone act primarily through the androgen receptor (AR). The molecule enters the cell, binds to the receptor, the complex moves to the nucleus and changes gene activity. In skeletal muscles, this leads to an increase in protein synthesis and a decrease in its breakdown.

In addition to direct action through AR, anabolic steroids are likely to have anti-catabolic effects through competition with glucocorticoids. That is why oxandrolone was clinically used in states of pronounced catabolism, for example after severe burns, where it reduced the loss of muscle mass (Hart et al., 2001).

None of these steroids are truly “selective”. Androgen receptors are present in the skin, hair follicles, larynx, prostate, brain, bones, and blood cells. Therefore, the division into "anabolic" and "androgenic" effects is conditional: the degree of androgenic manifestations depends on the dose and duration, but does not disappear completely.

Compared to testosterone, both substances are not aromatase substrates, and oxandrolone as a DHT derivative is not enhanced by 5α-reductase. This changes the spectrum of side effects, but does not make it "safe": some of the risks, on the contrary, increase due to the oral route and 17α-alkylation.

Metabolism and the role of chemical modifications

Natural testosterone when taken orally is almost completely destroyed in the liver during the first passage. The methyl group in the 17α position inhibits the oxidation of the 17β-hydroxyl group, due to which the molecule retains its activity. The price of this resistance is a long and intense load on hepatocytes.

Oxandrolone is largely excreted unchanged by the kidneys, which distinguishes it from many other oral steroids. This partially explained its acceptability in clinical practice, although the requirements for monitoring liver parameters during medical use remained.

Turinabol undergoes a large number of metabolic transformations, forming numerous metabolites, some of which are excreted for a long time. The discovery of such long-lived metabolites (Sobolevsky, Rodchenkov, 2012) was the reason for repeated positive results in preserved Olympic samples.

The short half-life of oral steroids in household representations is associated with “rapid elimination” and less harm. In fact, the very nature of the 17α-alkylated molecule and the duration of exposure are more important for the liver than the half-life.

Liver: main target of toxicity

Hepatotoxicity of 17α-alkylated steroids is well described in the medical literature, in particular in the LiverTox database of the US National Institutes of Health. The most common type of lesion is cholestasis: a violation of the outflow of bile, manifested by itching, jaundice, dark urine, and an increase in bilirubin.

Less common, but more dangerous — peliosis of the liver (formation of blood-filled cavities that can rupture with internal bleeding) and liver tumors, both benign adenomas and malignant. These complications were included in the "black frame" in the Oxandrin instructions.

When comparing the two substances, it is worth remembering that for oxandrolone there is clinical data with controlled use and monitoring, and for turinabol - mostly historical and non-medical observations. This does not mean that turinabol is "safer" or "more dangerous", just that it is impossible to assess the risk more precisely. Illegal products additionally introduce uncertainty in dosage and composition.

Elevation of transaminases in people who exercise may be partially related to muscle damage, therefore, for liver evaluation, HGT, bilirubin, and alkaline phosphatase are also used. Any symptoms of jaundice or pain in the right hypochondrium require immediate medical attention.

Heart, lipids and blood

Oral 17α-alkylated steroids are particularly potent in lowering HDL—the “good” cholesterol—and raising LDL. The mechanism is associated with stimulation of hepatic lipase. Oxandrin's label specifically warned of adverse lipid profile changes, and the Endocrine Society review (Pope et al., 2014) emphasized the role of these changes in cardiovascular risk.

In addition to lipids, anabolic steroids are associated with increased blood pressure, hypertrophy and dysfunction of the myocardium, accelerated atherosclerosis. For turinabol and oxandrolone in particular, there are few long-term cardiac studies, but the mechanisms are common for the class.

Androgens stimulate erythropoiesis, so an increase in hematocrit is possible. For oral DHT derivatives, this effect is generally less pronounced than for testosterone, but it is not excluded by itself. Also, androgens can affect the blood coagulation system.

It is important that lipid changes occur "quietly" - without any symptoms. A person may feel well, while laboratory indicators indicate a significant increase in atherogenic risk.

Endocrine and other side effects

Both substances inhibit the hypothalamus-pituitary-gonadal axis by a negative feedback mechanism: LH, FSH and own testosterone decrease, spermatogenesis worsens. For some people, recovery from long-term AAS use can take months (Rahnema et al., 2014).

• In women: hoarseness of the voice, hirsutism, enlargement of the clitoris, cycle disorders; voice changes may be irreversible.
• In adolescents: risk of premature closure of bone growth zones.
• Skin and hair: acne, acceleration of androgenetic alopecia in predisposed individuals.
• Psyche: irritability, mood swings, depressive symptoms after stopping treatment.
• Interactions: oxandrolone enhances the effect of warfarin, which is described in the official instructions.

Interaction with anticoagulants is an example of an often overlooked risk. The instructions for oxandrolone warned that androgens can significantly increase the effect of warfarin and increase the risk of bleeding.

The experience of GDR is particularly revealing for women: according to Franke and Berendonk (1997), female athletes who were given turinabol developed pronounced signs of virilization. The notion that "soft" oral steroids are acceptable for women is not supported by either pharmacology or historical facts.

Editorial conclusions

Turinabol and oxandrolone act through the androgen receptor and are not aromatized, but differ in chemical modifications that determine their metabolism.

Common to both, the 17α-alkylated structure determines the main risks: hepatotoxicity from cholestasis to peliosis and tumors and a marked decrease in HDL.

Hormonal suppression, virilization in women, drug interactions, and the uncertainty of the composition of illegal products add to the picture of risks that the "soft" reputation of these substances hides.

We also advise you to familiarize yourself with our materials on liver tests during health control, on HDL and cardiovascular risk, and on the restoration of the hormonal axis after AAS.

List of used literature

1. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.
2. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
3. Hart DW, Wolf SE, Ramzy PI, et al. Anabolic effects of oxandrolone after severe burn. Ann Surg. 2001;233(4):556–564.
4. Sobolevsky T, Rodchenkov G. Detection and mass spectrometric characterization of novel long-term dehydrochloromethyltestosterone metabolites in human urine. J Steroid Biochem Mol Biol. 2012;128(3–5):121–127.
5. Franke WW, Berendonk B. Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic government. Clin Chem. 1997;43(7):1262–1279.
6. Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271–1279.
7. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Androgenic Steroids. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases.
8. Oxandrin (oxandrolone tablets). Prescribing information. U.S. Food and Drug Administration.