ANTICATABOLIC AND ANABOLIC STRATEGIES AFTER BURNS & TRAUMA

Anabolic steroids refer to the parent hormone testosterone or its derivatives. The fact that testosterone increases protein synthesis was determined in the 1940’s while studying its androgenic or masculinizing properties. One of its tissue growth properties was production of red blood cells and anemia was the early indication for testosterone use.

In the 1950’s testosterone was used for debilitating disease and osteoporosis using its anabolic properties. Abuse in the body building and strength sports began shortly after.

The mechanism of action of the testosterone is its action on cell androgenic receptors (1970’s) which in lean mass tissue leads to cell amino acid influx and increased protein synthesis.

Because of its clinical potential anabolic steroids were developed for medicine. Exogenously administered testosterone has a very short half life (10 minutes) being cleared rapidly by the liver, and its initial use was mainly for its masculinizing properties in a hypogonadal state

Modifications in the steroid molecule was found to increase activity time and also anabolic potency. A 17 alpha methyl configuration for oral drugs and a 17 beta ester modification for parenteral agents are the now standard modifications..

The quality of a testosterone analog is based on the ratio of anabolic to androgenic activity, the higher the better.

ANABOLIC STEROIDS (HISTORY)

Testosterone and its derivatives
Anabolic properties noted in the 1940’s
Androgen receptors found in cytosol (1960’s)
Attempt to increase anabolism (use of anabolic to androgenic ratio to judge new drugs)
Derivatives

- oral are 17 alpha alkated

- parenteral are 17 beta esters

Most cleared by the liver (concern for hepatotoxicity)

Anabolic Steroids (Use in Medicine)

Use for hypogonadism debilitating disease (1950’s)
Abuse in strength sports (1950’s)
Use for anemia, osteoporosis, protect bone marrow from radiation (1960’s)
Use for lean mass loss and for wound healing (1960’s, 1970’s)
Increased abuse resulting in decreased clinical use
Resurgence of use 1990’s for AIDS and now burns, wounds

The decrease in use in clinical medicine was caused not only by concerns of abuse and toxicity, but also

Current Use

restore and maintain lean body mass
decrease lean mass loss
increase wound healing (all stages)

Testosterone levels are decreased immediately after severe trauma or critical illness and throughout the recovery period, eliminating another anabolic stimulus during a period of catabolism. Exogenously administered (oral or parenteral) testosterone is rapidly metabolized in the liver, resulting in a half-life of approximately 10 minutes, which is not practical for clinical use. Slow-release testosterone can be injected, but androgenic effects leading to hirsutism, hypersexualism, and mood changes may occur. Anabolic activity is only modest compared with the testosterone analogs.

TESTOSTERONE

produced mainly by testis in males and by adrenal gland in females
conversion of adrenal precursor androsteindione to testosterone in liver
both androgenic and anabolic activity via androgenic receptors
modest androgenic activity
endogenous levels decrease with adult age (or chronic illness)
male muscle 100 times more responsive than female muscle to testosterone
high doses given exogenously will increase anabolism but short half life
metabolized by the liver

Currently testosterone is used primarily to treat hypergonadism and more recently to decrease osteoporosis and progressive debility in aging males.

Oxandrolone (Bio-Technology General Corp., Iselin, NJ) is a 17b -hydroxy-17a -methyl ester of testosterone which is cleared primarily by the kidney. Hepatotoxicity is minimal, even at doses higher than the 20mg/d recommended by the FDA. Oxandrolone is the only steroid in which a carbon atom within the phenanthrene nucleus has been replaced by oxygen. This alteration appears to be responsible for its potent anabolic activity, which is 5 to 10 times that of methyltestosterone. In addition, its androgenic effect is considerably less than testosterone, minimizing this complication common to other testosterone derivatives. The increased anabolic activity and decreased androgenic (masculinizing) activity , markedly increases its clinical value. Oxandrolone is given orally, with 99% bioavailability. It is protein-bound in plasma with a biologic life of 9 hours, and the current cost for 20mg is about $30.00.

Oxandrolone is the only oral anabolic steroid that is FDA approved for restoration of weight loss after severe trauma, major surgical procedures, or infections. Weight gain is primarily lean body mass.

Clinical trials conducted on a variety of patient populations, including patients with chronic hepatitis, AIDS, and severe burns have demonstrated a significant weight gain, mainly muscle, (4/month). This lean mass gain is 4 times that seen with optimum nutrition alone. Of significant interest is the fact that the drug significantly decreased the mortality of chronic hepatitis reflecting its lack of liver toxicity. Also, oxandrolone has been shown to markedly attenuate post burn catabolism. As with other anabolic agents, adequate calorie and protein intake is necessary for an optimum effect. The anabolic effect is dose-dependent, with a 20-mg daily dose being about 5 to 10 times more potent than 2.5 mg/d. The main contraindications for oxandrolone use are the presence of carcinoma of the male breast or prostate as these tumors have androgenic receptors.

Anabolic Activity of 17 Derivatives
Agent	Androgenic: Anabolic Activity	Indications	Hepatotoxicity
Testosterone	1:1	Hypogonadism
Nandrolone	1:4 - 1:25	Anemia	Moderate to severe
Oxymetholone	1:3	Anemia	Severe
Oxandrolone	1:3 - 1:13	Loss of body weight from injury or infection	Mild, rare

Oxandrolone is the only anabolic steroid which has been studied and found to be safe and effective in the burn patient.