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buff guy curlingOxandrolone is a derivative of dihydrotestosterone (DHT) that was introduced by Searle in 1964 under the trade name Anavar. Oxandrolone has very low androgen receptor binding affinity but a long half-life makes it reasonably potent1. Embedded in the A-ring is an oxygen atom at the 2-position forming what is referred to as a heterocycle. Since it is a DHT derivative, and due to the presence of the heterocycle, oxandrolone cannot be converted to estrogenic metabolites through aromatization. Also, since it is already 5-alpha reduced, oxandrolone cannot be reduced further by 5-alpha reductase. Due to the presence of the oxygen atom in the A-ring, this steroid is not deactivated by 3-alpha hydroxysteroid dehydrogenase (3HSD) in skeletal muscle2. 3HSD is an enzyme that is found in skeletal muscle that rapidly deactivates circulating DHT rendering it inactive. This steroid does not bind to sex hormone binding globulin (SHBG) so the entire circulating quantity can be considered to be in the “free/active” state.

Oxandrolone has been shown, like most androgens, to decrease SHBG levels which may result in estrogenic side effects due to higher free levels of estrogens (3). For years, people were under the erroneous assumption that because oxandrolone does not convert to estrogen it would not shut down natural testosterone production. However, we now know that androgens as well as estrogens reduce luteinizing hormone which results in reduced natural testosterone production over time. In fact, a study by Sheffield-Moore et al. demonstrated that a dose of only 15 mg/day in healthy young men for five days reduced total and free testosterone levels (5).

There is no evidence in the literature that oxandrolone interacts with the progesterone receptor, but it is likely that oxandrolone has significant anti-cortisol effects (4). Oxandrolone increases nitrogen retention both through the anabolic effect of activating androgen receptor but also through antagonism of the catabolic effects of cortisol (4,5,6). Cortisol is the major stress hormone produced by the body and one of its actions is to break down muscle tissue to produce glucose during times of stress.

Oxandrolone is often used by women because it is considered to be weak, however, it can still produce androgenic side effects such as acne, hair loss, deepening of the voice, facial and body hair growth and enlargement of the clitoris. High doses of oxandrolone are needed, particularly by men, to notice any appreciable mass gains while strength gains seem to come more easily. Doses of 20 to 50 mg are common though doses twice this amount are often used. Oxandrolone is expensive and the high doses needed often preclude its use. In addition, it tends to be less available on the black market than methandrostenolone or oxymetholone.

Oxandrolone increases free and bound cortisol levels, most likely due to its actions as a cortisol receptor antagonist (7). Additionally, oxandrolone decreases thyroid binding globulin concentrations pretty severely with large increases in thyroxine-binding prealbumin resulting in increased T3 uptake (7). This correlates with the belief that oxandrolone is beneficial in a “cutting stack”. Further evidence comes from studies showing a 4 pound decrease in fat mass with a gain of 7 pounds of lean mass over the course of 12 weeks of treatment with only 20 mg (10 mg, twice daily) of oxandrolone (8). There is also evidence in the literature that oxandrolone enhances ketogenesis (9).

Though oxandrolone is C-17 alpha alkylated, the literature and practical experience shows this steroid to be fairly benign with regard to liver toxicity. Of course, higher doses will increase the risk of liver toxicity.

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1. Feldkoren BI, Andersson S. Anabolic-androgenic steroid interaction with rat androgen receptor in vivo and in vitro: a comparative study. J Steroid Biochem Mol Biol, 2005;94(5):481-7.

2. Schanzer W: Metabolism of anabolic androgenic steroids. Clin Chem, 1996;42(7):1001-20.

3. Wasserman P, Segal-Maurer S, Rubin D. Low sex hormone-binding globulin and testosterone levels in association with erectile dysfunction among human immunodeficiency virus-infected men receiving testosterone and oxandrolone. J Sex Med, 2008;5(1):241-7.

4. Zhao J, Bauman WA, Huang R, Caplan AJ, Cardozo C. Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner. Steroids, 2004;69(5):357-66.

5. Sheffield-Moore M, Urban RJ, Wolf SE, Jiang J, Catlin DH, Herndon DN, Wolfe RR, Ferrando AA: Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab, 1999;84(8):2705-11.

6. Sheffield-Moore M, Wolfe RR, Gore DC, Wolf SE, Ferrer DM, Ferrando AA: Combined effects of hyperaminoacidemia and oxandrolone on skeletal muscle protein synthesis. Am J Physiol Endocrinol Metab, 2000;278(2):E273-9.

7. Barbosa J, Seal US, Doe RP: Effects of anabolic steroids on hormone-binding proteins, serum cortisol and serum nonprotein-bound cortisol. J Clin Endocrinol Metab, 1971;32(2):232-40.

8. Schroeder ET, Zheng L, Ong MD, Martinez C, Flores C, Stewart Y, Azen C, Sattler FR: Effects of androgen therapy on adipose tissue and metabolism in older men. J Clin Endocrinol Metab, 2004;89(10):4863-72.

9. Vega GL, Clarenbach JJ, Dunn F, Grundy SM. Oxandrolone enhances hepatic ketogenesis in adult men. J Investig Med, 2008;56(7):920-4.