Oxymetholone or Methandienone: What's the Difference

Oxymetholone and methandienone are two oral 17α-alkylated steroids that in the sports community are considered the most potent «mass-building» tablets. However, one of them still has an official medical indication, and the other — does not; one is derived from dihydrotestosterone, and the other — from testosterone. The editorial team breaks down what the real difference between them is.

Chemical structure and origin

Oxymetholone is a derivative of dihydrotestosterone (DHT). A 2-hydroxymethylene group is attached to ring A of the molecule, and at position 17α there is a methyl group that provides oral activity. Since the basis is DHT, the classic pathway of aromatization into estrogens is not characteristic of oxymetholone.

Methandienone is a derivative of testosterone with a double bond between the first and second carbon atoms and a 17α-methyl group. It is a substrate of aromatase and is converted into 17α-methylestradiol — an active estrogen that is broken down slowly in the liver.

Both substances appeared in the late 1950s — early 1960s, in the «golden era» of anabolic steroid synthesis. Methandienone was produced by the company Ciba under the name Dianabol, oxymetholone — under the names Anadrol and Anapolon.

A common feature is 17α-alkylation. It makes both compounds oral, but at the same time determines the main risks: the load on the liver and a pronounced decrease in HDL.

Medical status: anemias versus the gym

Oxymetholone is one of the few anabolic steroids that still have official FDA instructions. The drug Anadrol-50 is indicated for the treatment of anemias caused by insufficient red blood cell production: acquired or congenital aplastic anemia, myelofibrosis, hypoplastic anemias due to the intake of myelotoxic drugs.

The instructions for Anadrol-50 define doses in the range of 1–5 mg per kilogram of body weight per day, with mandatory individual selection by a doctor. They also emphasize that the effect on the blood develops gradually and that the therapy requires regular monitoring of liver tests, lipids and blood parameters.

Methandienone never had a comparable stable medical niche. In the past it was offered for various conditions associated with weight loss, but with the advent of more effective and safer treatment methods the drug went out of circulation in the USA. Today its circulation is almost entirely illegal.

It is important to understand: the presence of a medical indication for oxymetholone does not make it «safer» in sport. It is prescribed to patients with severe blood diseases, for whom the benefit outweighs the serious risks — and these risks are described in the instructions in a boxed warning.

Estrogenic effects: the paradox of oxymetholone

Methandienone is understandable from the standpoint of estrogens: it aromatizes into 17α-methylestradiol, which causes fluid retention, edema, increased blood pressure and gynecomastia.

Oxymetholone is a more complex case. As a DHT derivative, it should not aromatize, yet in the literature and clinical practice estrogenic side effects have been described, in particular gynecomastia and fluid retention. The mechanism has not been definitively clarified; a possible direct interaction with estrogen receptors or an effect of metabolites is discussed.

Fluid retention against the background of both substances explains a significant part of the rapid weight gain that users describe. After discontinuation part of this weight disappears together with fluid and glycogen.

For a person trying to assess the risk of gynecomastia, the conclusion is simple: the absence of classic aromatization does not guarantee the absence of estrogenic side effects. Oxymetholone is a clear example of the fact that the simple rule «DHT derivative = no estrogens» does not always work.

Liver, blood and heart

The instructions for Anadrol-50 contain a boxed warning about hepatic peliosis (the formation of blood-filled cavities that can rupture), liver tumors, including malignant ones, and changes in the lipid profile with an increased risk of atherosclerosis. These risks concern the class of 17α-alkylated steroids and fully extend to methandienone as well.

A characteristic property of oxymetholone is strong stimulation of erythropoiesis, which is precisely why it is used for anemias. In a healthy person this effect turns into a risk: an increase in hematocrit raises blood viscosity and the likelihood of thrombosis. Androgens stimulate the formation of red blood cells partly through an increase in erythropoietin.

Methandienone also affects the blood, but its main cardiovascular risks are associated with estrogenic fluid retention, increased blood pressure and decreased HDL. The review by Baggish et al. (2017) describes myocardial hypertrophy, a decrease in its contractile function and accelerated atherosclerosis in long-term users of anabolic steroids.

• Common:hepatotoxicity, dyslipidemia, hypertension, suppression of the hormonal axis, infertility, virilization in women.
• More characteristic of oxymetholone:erythrocytosis, the risks described in the boxed warning of the official instructions.
• More characteristic of methandienone:estrogen-mediated gynecomastia and edema, pronounced androgenic effects.

Data from clinical studies

For oxymetholone there are modern randomized studies. In particular, in the double-blind placebo-controlled study by Hengge et al. (2003) oxymetholone was studied in patients with HIV-associated wasting: it contributed to body weight gain, but in some patients an elevation of liver enzymes was observed.

These data are useful in that they show the real risk profile even under controlled conditions, with medical doses and supervision. Liver toxicity manifested even where doctors were able to monitor the patients.

For methandienone there are practically no modern randomized studies that would meet current standards. Most information about it comes from work of the 1960s–1970s, from metabolism studies for anti-doping needs (Schänzer, 1996; Schänzer et al., 2006) and from case reports.

Both substances belong to class S1 of the WADA Prohibited List. For methandienone, long-lived metabolites that extend the detection window have been described.

Editorial conclusions

Oxymetholone is a DHT derivative with an official medical indication for anemias, methandienone is a testosterone derivative without a modern medical niche. Both are 17α-alkylated and have high liver toxicity.

Methandienone causes estrogenic effects through aromatization, oxymetholone — despite the absence of classic aromatization, with a mechanism that is still being discussed. Oxymetholone especially strongly affects erythropoiesis.

The risks of both substances are documented in official documents and clinical studies, and in a non-medical context they are not offset by any health benefit.

We also recommend reading our materials «Oxymetholone vs Methandienone: what to choose and for whom», on hematocrit in athletes and on gynecomastia: causes and prevention.

References

1. U.S. Food and Drug Administration. Anadrol-50 (oxymetholone) tablets: prescribing information.
2. Hengge UR, Stocks K, Wiehler H, et al. Double-blind, randomized, placebo-controlled phase III trial of oxymetholone for the treatment of HIV wasting. AIDS. 2003;17(5):699–710.
3. Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–521.
4. 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.
5. Baggish AL, Weiner RB, Kanayama G, et al. Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation. 2017;135(21):1991–2002.
6. Schänzer W. Metabolism of anabolic androgenic steroids. Clin Chem. 1996;42(7):1001–1020.
7. Schänzer W, Geyer H, Fusshöller G, et al. Mass spectrometric identification and characterization of a new long-term metabolite of metandienone in human urine. Rapid Commun Mass Spectrom. 2006;20(15):2252–2258.