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 testosterone-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. In such patients a great reduc- effects as undesired side actions. It therefore is in tion in the vital protein tissues occurs which can

791/46 50

Mg/Kg Key • 30 Control • 0.2 1.0 • 5.0 ggg 20 25.0 IM

0 0 4 8 12 18 21 Weeks Fig. 5. Growth of rhesus monkey medicated with stanozolol for 21 weeks.

be measured readily by weight loss and by the usually begin to heal, apparently due to the im- increased excretion of nitrogen in the urine. These proved local tissue nutrition and speed of protein processes lead to poor appetite and assimilation of synthesis. The clinical conditions in which these food which create a vicious cycle of deleterious compounds may often be used with benefit are changes. Many cachectic patients refuse even listed in Table II. minimal amounts of food. In such situations anabolic steroids exert a posi- TABLE II-SUGGESTED CLINICAL APPLICATIONS tive beneficial action, and they can be readily FOR ANABOLIC AGENTS demonstrated to reverse the loss of protein. They Anorexia, asthenia, general debilitation in all age groups, promote retention of potassium, phosphorus, and including the elderly calcium, and the weight gain seen comes from tissue Lassitude, low vitality build-up rather than storage of water. Preoperative therapy in debilitated and cachectic patients One of the first responses usually seen is improve- Convalescence from chronic illness, including infections Convalescence from surgery ment in appetite which is accompanied by a feeling Retarded infant and child growth or malnutrition of well-being and better mental attitude. There is Pain associated with osteoporosis increased vigor and strength, less fatigue and Senile and postmenopausal osteoporosis irritability. Often pain may diminish, particularly Decubitus ulcers and slowly healing wounds Catabolism associated with malignancy where musculoskeletal components are prominent. Catabolism due to glucocorticoid therapy Such therapy is obviously supportive rather than Kidney disease (for improvement of protein metabo- specifically curative, but it often may be a crucial lism) element in turning the balance toward recovery Calciuria, phosphaturia and in accelerating it. Severe burns Myopathies This type of benefit is of particular advantage in elderly patients with cachexia and anorexia, in underweight and malnourished adults, and in Osteoporosis is the most widespread of the patients with chronic wasting diseases of all types, metabolic bone diseases. It is an almost "physio- such as carcinoma, ulcerative colitis, broncho- logic" accompaniment of old age in both men and pulmonary disease, fractures, and arthritis. Post- women and even occurs with great frequency in operative patients are benefited by the increased comparatively young women after the menopause. speed of protein regeneration as well as by the Rehabilitative therapy of this painful and at times psychic and appetite effects. Decubitus ulcers will incapacitating disorder is of paramount importance.

JOURNAL A.O.A., VOL. 62, MAY 1963 799/47 To date, investigators working with the various activity of the anabolic agent used and the dosage, hormonal and anabolic agents have been unable to sex, age, duration of therapy, and individual suscep- demonstrate radiologic evidence of bone reminer- tibility. Virilization is seldom seen with stanozolol alization, that is, actual reversal of osteoporosis when given in the recommended dosage because once it is established and well advanced. This is of its low androgenic activity. The dosage may be probably because short-term studies have been con- decreased or discontinued in any rare instance of ducted on a process (remineralization ) which appearance of disturbing masculinizing effects. normally occurs slowly, and because of the diffi- Should virilization occur with the more andro- culty of demonstrating changes in bone density genic anabolic agents, decreasing the dose or dis- by roentgenographic measures. Despite this gap in continuing the drug will reverse the adverse our findings, these agents seem to produce well symptoms, except for occasional residual hirsutism defined clinical benefits in patients who have a or deepening of the voice. The latter occurs if it is deficiency of calcified bone due to a defect in the permitted to persist for a prolonged time so that formation of bone matrix. permanent organic changes can take place. This Heaney12 recently reported on combined cal- residual deepening of the voice has not been cium balance and radioactive turnover studies on reported to date with stanozolol, owing to its patients with acute disuse osteoporosis treated with considerably lower order of androgenicity at ana- anabolic agents, including stanozolol. These patients bolic levels. Furthermore, this agent rarely produces prior to treatment had persistent hypercalciuria and scanty menses in women receiving 4 mg. daily. To were in strongly negative calcium balance. They date no cases of amenorrhea have been reported as responded to the anabolic therapy with a striking occurring with this low dosage. When amenorrhea improvement in the calcium balance and consider- has been caused by larger doses, the menses have able decrease in bone resorption. returned promptly when the dosage was reduced. Benefits which frequently have been reported by Animal studies of the effect of the anabolic agents investigators who use anabolic agents in treating on the testes reveal that anabolic steroids suppress osteoporosis include relief of pain, such as low-back testicular function by inhibition of gonadotropin pain; increased strength and well-being; increased release from the pituitary to an extent which is mobility; prevention of loss of height which would parallel to their degree of androgenicity, rather result from extensive collapse of the vertebrae— than to their anabolic potency. Thus with stanozolol a condition noted in untreated patients having there is little if any such indirect testicular suppres- advanced osteoporosis; and prevention of new frac- sion. tures, such as of the neck of the femur. In addition, muscle tenderness and spasm associated with osteoporosis are relieved in the majority of patients. This Nonendocrine side effects • The major side effects latter benefit may not be due to a direct protein of a nonendocrine nature observed with the use of anabolic effect, but to the ability of the drug to certain of these anabolic agents consist of (1) increase tissue calcium levels and thus prevent edema, such as pitting edema of the lower legs due muscle irritability. These applications are sum- to sodium and water retention, and (2) liver changes marized in Table III. with clinical jaundice. The liver effect is a choles- tatic jaundice occurring gradually after a varying amount of norethandrolone, and to a less extent

TABLE III-ANABOLIC EFFECTS IN OSTEOPOROSIS following methandrostenolone. Liver function tests Relief of pain, such as of low-back pain which may have altered results during the use Increased strength and well-being of all anabolic agents include the Bromsulphalein Increased mobility (BSP) retention test. However, it should be noted Gain in weight that an increase in the BSP retention during ana- Prevention of loss of height resulting from extensive col- bolic steroid therapy may merely represent compe- lapse of vertebrae noted in untreated patients No new fractures, such as neck of femur tition by the steroid for hepatic excretory sites, and Induces nitrogen and mineral retention (calcium and thus any elevation may not be indicative of hepatic phosphorus) with postulated consequent development of disease. new protein matrix It is interesting to note that Ohlenschlager13 studied 86 patients with severe, moderate, or slight liver damage, such as hepatitis and cirrhosis, who Side effects from anabolic steroids were given 15 mg. of stanozolol daily over a period of 5 weeks, an amount far in excess of the recom- - Endocrine side effects • The incidence of viriliza- mended 4 to 6 mg. dose. Paper-electrophoretic tion, as characterized by such symptoms as hirsu- examinations, determinations of total protein, tism, acne, voice changes, enlargement of the clitoris, Bromsulphalein tests, serum lability tests, erythro- or scanty menses, depends upon the androgenic cyte sedimentation rates, and recording of body

800/48 AG. 6. COMPARATIVE ACTIONS OF ORAL ANABOLIC STEROIDS Based on animal studies

Winstrol Adroyd/Anadrol Dianabol Nilevar (stanozolol) (oxymetholone) (methandrostenolone) (norethandrolone)

N2 retention 10 X M.T. 1.75 X M.T. 1.2 X M.T. 3.9 X M.T.

N2 retention Ratio •!..4 Androgenic 30 8.75 3.4 20 ID "= 2 Anticatabolic Equal to _2 O activity 8 X M.T. M .T. 8 X M.T.

Equal to Equal to Myotrophic activity 2 X M.T. M .T. M .T. 2 X M.T.

Androgenic activity 0.33 M.T. 0.2 M.T. 0.35 M.T. 0.19 M.T.

2 °3 .Progestational •.5 activity None Detectable Highly active a Estrogenic activity None Weakly active

Methyltestosterone weight were carried out on all the patients dur- Contraindications ing the course of disorder. With suitable therapy and in spite of the continued use of stanozolol, 10 The only condition which can be considered a con- of the 15 patients with cirrhosis of the liver showed traindication to the use of anabolic agents is cancer improvement in the serum lability tests, Bromsul- of the prostate, although stanozolol, owing to its phalein tests, and serum-protein relationship in the mild or weak androgenic activity, has been used electrophoretic diagrams. In the remaining 5 pain the presence of this disorder by a number of tients with cirrhosis, there were signs neither of investigators. Unlike the estrogens, which have a improvement nor of deterioration during and after carcinogenic effect when administered experiment- discontinuing administration of this anabolic agent. ally to animals, the androgens and anabolic agents have never been incriminated as producing cancer. In the entire series of 86 patients with pre-existing Concerning the use of anabolic agents in preg- damage to the liver parenchyma, the investigator nancy, no preparation with detectable androgenic reported that no hyperbilirubinemia, no rise in activity should be administered to pregnant women Bromsulphalein values, nor any pathologic shift of since there is a risk that their babies may have the the serum-protein fractions were found. In none of adrenogenital syndrome. This is not a deformity in the patients could any deterioration of liver func- the usual sense of the term, but female children in tion due to the product be observed, even though particular are apt to be born with pronounced male it was administered in doses which were two and characteristics which may respond poorly to later one-half to three and three-quarter times those treatment. For this reason, such steroids should not usually recommended. Additional stanozolol studies be given to patients with amenorrhea unless it has on cirrhosis of the liver are currently in progress been established that this is not due to pregnancy. in the United States. In summary, one can state that obstructive Selection of compounds jaundice and hepatic damage which at times occur with certain anabolic agents have not been observed The choice of an anabolic agent depends upon its to date during the use of stanozolol. (1) anabolic or nitrogen-retaining activity, (2) its

JOURNAL A.O.A., VOL. 62, MAY 1963 801/49 FIG. 7. CLINICALLY AVAILABLE ANABOLIC AGENTS

Generic name Availability Dosage

Nilevar—Searle Adults: Ora/—usually 20-30 mg. daily. May give up to I00 mg. daily, although mild androgen effects may be present 10 mg. unscored tablets (oral) Norethandrolone Intramuscular-25 mg. daily; dosage essentially the same 0.25 mg./drop (oral) as oral 25 mg./cc. (intramuscular) Children: 0.5 mg. per kg. or 0.25 mg. per lb. of body weight

Durabolin—Organon Adults: 50 mg., then 25-50 mg. intramuscularly, weekly for 12 weeks 25 mg./cc. Nandrolone Children 2 to 13 yrs.: 25 mg. intramuscularly, every 2-4 weeks phenpropionate (intramuscular) 50 mg./cc. (intramuscular) Infants: Half childrens dose

FIG. 8. CLINICALLY AVAILABLE ANABOLIC AGENTS

Generic name Availability Dosage

Adults: 5-10 mg. daily for 7-21 days; occasionally 30 mg. daily; single course should not exceed 90 days

Infants and children up to 6 yrs.: 1.25-5 mg. daily for 7-21 days Short term Rx Adroyd—Parke, Davis Children over 6 yrs.: 5-10 mg. 2.5, 5, and 10 mg. daily for 7-21 days scored tablets (oral) Children up to 6 yrs.: 1.25-5 mg. Oxymetholone daily up to 90 days Refractory underweight Children 6 yrs. to puberty: 2.5-5 or malnutrition mg. daily up to 90 days

Adolescents: 5-10 mg. daily up to 90 days

Anadrol—Syntex ( Adults: Usually 7.5 mg. daily; may use up to 15 mg. daily 2.5 mg. tablets Children to 12 yrs.: 2.5-5 mg. daily; should not be continued . (oral) beyond a 30-day period

anticatabolic activity, and (3) undesired activities Furthermore, it has the advantages of having no which may produce side effects, such as (a) andro- progestational or estrogenic activity. In addition, genic activity, (b) progestational activity, (c) estro- no other preparation possesses greater absolute genic activity, and (d) salt and water retaining anabolic activity as well as anticatabolic activity. activities. Figure 6 summarizes the comparative At present there are available for therapeutic data on the currently available oral anabolic prep- use five anabolic steroids, of which two may be arations. given intramuscularly and four orally. Data perti- From the aforementioned pharmacologic data as nent to specific availability and dosage are con- well as from clinical reports, one can conclude that tained in Figures 7, 8, and 9. stanozolol is the anabolic preparation which provides the greatest relative degree of protein build- Summary up, with the highest anabolic to androgenic ratio of all the available oral anabolic preparations. Within the past 6 years, five agents with strong

802/50 FIG. 9. CLINICALLY AVAILABLE ANABOLIC AGENTS

Generic name Availability Dosage

Adults: 5 mg. daily. For more rapid or intense effect, 10 mg. Dianabol—Ciba daily may be given for 3 weeks; then reduce usually to 2.5-5 mg. daily for maintenance Methandrostenolone 2.5 and 5 mg. scored tablets Intermittent therapy is recommended when given over (oral) long periods. Thus, after 6 weeks treatment, there should I be an interval of 2-4 weeks before resuming therapy

Winstrol—Winthrop Adults: 6 mg. daily. For long-term use in young women, 4 mg. Stanozolol 2 mg. scored may be adequate. tablets Preschool children: 2 mg. daily ( 1/2 tablet twice daily) (oral)

anabolic activity — norethandrolone, nandrolone therefore seem to be the agent of choice in clinical phenpropionate, methandrostenolone, oxymetho- situations where anabolic therapy is needed. lone, and stanozolol—were added to the physicians armamentarium. They differ from one another in 1. Kochakian, C. D., and Marlin, J. R.: Effect of male hormone their therapeutic activities, that is, nitrogen reten- on protein and energy metabolism of castrate dogs. J. Nutrition 10:437-459, Oct. 1935. tion, anticatabolic, and myotrophic activities, as 2. Camerino, B., and Sala, G.: Anabolic steroids. Progress in well as in the undesired properties of virilization, Drug Research 2:71-134, 1960. 3. Berczeller, P. H., and Kupperman, H. S.: Anabolic steroids. of sodium and water retention, and of the presence Clin. Pharmacol. Therap. 1:464-482, July-Aug. 1960. or absence of progestational and estrogenic activ- 4. Cooper, I. S., et al.: Testosterone propionate as a nitrogen- sparing agent after spinal cord injury. J. Am. M. A. 145:549-553, ities. Feb. 24, 1951. 5. Forsyth, B. T.: Effect of testosterone propionate at various pro- The marked therapeutic effects of the anabolic tein and calorie intakes in malnutrition after trauma. J. Lab. Clin. agents in patients with cachexia, osteoporosis, Med. 43:732-740, May 1954. 6. Reifenstein, E. C., Jr.: Rationale for use of anabolic steroids selected malignancies, and so forth, and in those in controlling adverse effects of corticoid hormones upon protein and receiving prolonged corticosteroid or ACTH ther- osseous tissues. South. M. J. 49:933-960, Sept. 1956. 7. Drill, V. A.: Pharmacology in medicine. Ed. 2. McGraw-Hill apy justify their use in those patients requiring Book Co., New York, 1958. general tonic, hematopoietic, and anticatabolic ef- 8. Beckman, H.: Drugs: their nature, action and use. W. B. Saunders Co., Philadelphia, 1958. fects. 9. Dorfman, R. I., and Shipley, R. A.: Androgens; biochemistry, Evidence indicates that the most recently intro- physiology and clinical significance. John Wiley Sons, New York, 1956. duced agent, stanozolol, provides the greatest ana- 10. Olson, R. E.: Role of hormones in protein metabolism; report to the council on foods and nutrition. J. Am. M. A. 164:1758-1765, bolic activity and possesses the highest anabolic-to- Aug. 17, 1957. androgenic ratio of all the available oral anabolic 11. Potts, G. 0., Beyler, A. L., and Burnham, D. F.: Myotrophic and androgenic activities of androstanazole; new heterocyclic steroid. preparations. It also has the advantages of having Proc. Soc. Ever. Biol. Med. 103:383-384, Feb. 1960. no progestational or estrogenic activity. In addition, 12. Heaney, R. P.: Radiocalcium metabolism in disuse osteoporosis in man. Am. J. Med. 33:188-200, Aug. 1962. no other preparation possesses greater myotrophic 13. Ohlenschlager, G.: Liver tolerance and stromba. Puls (Ger- and anticatabolic potency. This compound would many) 3:6 (No. 3) 1962.

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