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Use of Anabolic Steroids in Rehabilitation

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Use of Anabolic Steroids in Rehabilitation Use of anabolic steroids in rehabilitation M. L. TAINTER, M.D., D.Sc.,* A. ARNOLD, this field when they reported that male hormone Ph.D., A. L. BEYLER, Ph.D., H. P. DROBECK, extracts prepared from human urine produced a Ph.D., G. 0. POTTS, Ph.D., and C. H. ROTH, marked reduction in the urinary nitrogen excretion M.D., Rensselaer, New York of castrated male dogs. Later studies by these and other investigators confirmed the nitrogen-retaining It has been long known that the administration action of testosterone propionate, methyltesto- of androgens or estrogens, in addition to providing sterone, and other androgens. Other assays demon- endocrine activity, increases muscle mass and body strated their ability to increase muscle mass, kidney weight. These anabolic effects should be of value mass, and body weight. in the treatment of numerous clinical conditions. Likewise, in clinical situations the androgens However, many physicians are reluctant to employ proved useful for achieving positive nitrogen bal- the male sex hormones or androgens in women and ance and tissue build-up in conditions unrelated to children because of the possibility of inducing endocrine disorders. They were used with benefit undesirable masculinization or of precocious sexual in starvation, postsurgical recovery, chronic debili- development. Similarly the use of the female hor- tating diseases, burns, and other similar conditions mones or estrogens is often considered to be unde- characterized by nitrogen catabolism or protein sirable in males because breast engorgement and depletion. There have also been reports of the tenderness as well as suppression of testicular func- value of testosterone in combating some of the tion may occur. Therefore, combination products catabolic changes associated with the aging process. containing both androgens and estrogens have been The increasing use of corticosteroid therapy in used to minimize to a degree the disadvantages arthritis and other inflammatory conditions led to inherent in the use of either agent singly. the use of testosterone preparations to counteract However, since 1935, when the anabolic proper- the catabolic side effects of the corticoids. A similar ties of testosterone were first reported by Kochakian anticatabolic action is illustrated by the ability of and Murlin,1 our knowledge of steroidal com- androgens to relieve many of the symptoms of pounds that affect the metabolic processes has Cushings syndrome, a condition which results advanced considerably. These authors opened up from an excess of endogenous corticosteroids.2-9 Olson,19 in a report to the Council on Foods Presented at the annual meeting of the American Osteopathic Col- lege of Physical Medicine and Rehabilitation, at the Scientific Seminar and Nutrition, stated that, "Androgens play a major of the American Osteopathic Association, Miami Beach, Florida, role in stimulating growth and a positive nitrogen January 27-29, 1963. Dr. Painter is the former Director of the Sterling-Winthrop Research Institute, and is now Vice Chairman of balance, especially in adolescence." The numerous the Sterling Research Board. conditions in which androgens have been used as °Address, Sterling-Winthrop Research Institute anabolics in spite of their obvious drawbacks illus- 796/44 trate the need for an anabolic agent with fewer or ANABOLIC STEROIDS - STRUCTURAL FORMULAS minimal effects as a sex hormone. Fortunately, some research scientists believed that the anabolic and the androgenic properties of testo- sterone-like steroids might be separated by the application of synthetic chemistry to the problem. Noodrolone phenpropionate They speculated that chemical modification of the Norothondrolone 1959 1956 Durabollo 0 steroid molecule might produce compounds cap- Mow. able of exerting a useful anabolic action without androgenic or other undesirable effects. Reliable laboratory and clinical techniques for measuring C anabolic, androgenic, and other possible effects of C OH these compounds were perfected for this purpose, 113 HO-CH Osysetholone and a vast amount of synthetic work was under- Mothandrootenolono 1960 taken. Our Sterling-Winthrop Research Institute, 1960 Adroyd C0 DionaDol or for example, has synthesized and studied several Anadrol hundred new steroids with this application in mind. These anabolic steroids are related to the male sex hormone but differ in an important respect in that their predominant biologic effects are anabolic (to build up tissue) rather than androgenic. That is Stesozolol 1962 to say, these agents have a greater tendency than Winstrol androgens to stimulate constructive metabolism and to promote the formation of body protein, and Fig. I are less likely to affect the sexual organs and sexual characteristics. Experimental data in animals These compounds therefore represent a revolu- tionary advance in therapeutics and rehabilitation, Many kinds of tests are used to measure quantita- since the sex hormonal effects of the traditional tively the androgenic and anabolic activities of androgens have greatly limited their use as anabolic these compounds. The objective is to select that agents. For many patients dietary measures are compound which has the least androgenic activity incapable of reversing the wasting processes associ- for a given anabolic effect. Because of limitations ated with various conditions. The weak, debilitated, of space only a few examples of these tests can be or emaciated patient is too often characterized by cited here; it is not possible to give the compara- poor food assimilation, which is usually aggravated tive data on all the steroids in the table. by poor appetite. The process of maintaining or The most commonly used test for androgenic rebuilding tissue in such patients is, at best, slow activity is to compare the amount of hypertrophy without the stimulatory action of an anabolic of the ventral prostate of rats from a range of steroid. doses of the compounds when given under stand- Although no "pure" anabolic compound has been ardized conditions. In Figure 2, from the paper found, the studies have led to the development of of Potts, Beyler, and Burnham, 11 it can be seen several substances which, unlike testosterone, have that a given dose of stanozolol produced about one strong anabolic action with relatively little sex third the amount of hypertrophy as the same hormone effect. Various degrees of separation of amount of methyltestosterone. When evaluated in these actions have been reported for the several terms of fixed amounts of hypertrophy (horizontal new steroids recently made available to the medical axis in the figure), four times as much stanozolol as profession. The first of the five new synthetic methyltestosterone are required to produce a given anabolic steroids available commercially was amount of hypertrophy, indicating that stanozolol norethandrolone ( Nilevar ) in 1956. This was fol- is only one fourth as potent an androgen as methyl- lowed by nandrolone phenpropionate (Durabolin) testosterone by this criterion. in 1959, by methandrostenolone (Dianabol) and A measure of the anabolic action is to observe oxymetholone (Adroyd and Anadrol) in 1960, and the increase in the weight of the levator ani muscle. lastly by stanozolol (Winstrol) in 1962. All these Figure 3, from the same studies, shows that twice steroids, except Durabolin, are effective orally. as large a dose of methyltestosterone as stanozolol Figure 1 depicts their structural formulas and the is needed for a given amount of gain in muscle location of changes in the structures. The circled weight. These two ratios of activity would indicate parts of the molecules indicate for each compound that stanozolol has six to eight times the relative the points of structural uniqueness. anabolic activity of methyltestosterone. In other JOURNAL A.O.A., VOL. 62, MAY 1963 797/45 ANDROGENIC ACTIVITY MYOTROPHIC ACTIVITY Response — Mg. Increase Over Control Ventral Prostate Response — Mg. Increase Over Control Levator Ani Muscle 60 60 50 50 2 w 40 z 40 w w Cf) Z 30 cc 30 20 i— 20 0 10 10 10.5 21.0 42.0 84.0 10.5 21.0 42.0 84.0 DOSE MG/KG/DAY DOSE MG/KG/DAY Fig. 2 Fig. 3 words, much more anabolic effect can be obtained from stanozolol without androgenic complications a than from methyltesterone. c•-■ The anabolic activity can also be measured by lx the amount of nitrogen retained in the body to 0 20 . METHYL- ANDROSTANOL- build up protein in test animals and by the cor- a f4 ISOXAZOLE responding increase in rate of growth or of body 1-• weight. We have found that in rats the relative METHYL- potencies as measured by nitrogen retention are TESTOSTERONE as shown in Figure 4. The ratios of activity from o0 10 NOR- METHANDIENONE these data are as shown on Table I. ETHAN- I-1 DROLON tna OXYMETHALONE TABLE I—COMPARATIVE NITROGEN RETENTION IN RATS C Methyltestosterone 1.0 STANOZOLOL 0lx Methandrostenolone 1.2 0..3 0:5 2 Oxymetholone 1.7 o yI 5 . 20 Norethandrolone 3.9 AMOUNT SUPPLEMENT, MG /RAT /DAY Stanozolol 10.0 Fig. 4 Studies on the rate of growth of monkeys, illus- order to discuss the clinical application of these trated in Figure 5, show that the gain in body therapeutic effects. weight can be approximately doubled by stanozolol in doses which did not cause masculinization. Still higher doses further increase the effects on growth The general problem in rehabilitation rate, although with some accompanying androgenic activity. Almost every serious illness or injury is apt to This selection of animal test data, obtained under produce a state of impaired nutrition and poor reliable conditions for quantitative evaluation, to- physical state by interfering with the appetite and the assimilation of food and by increasing the gether with much other similar information which breakdown of tissue, either as a result of the cannot be included here, clearly proves that marked disease processes, fever, the enforced inactivity, or and presumably useful degrees of anabolic effects all of these. Chronic and malignant diseases are can be produced by the newer synthetic steroids especially noted for the tissue wasting which in doses which do not necessarily cause sex hormone accompanies them.
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