Studies on the Creatinuria Due to Methylated Steroids 1

Abstract

We reported in 1941 that the oral administration of methyl testosterone caused a. marked increase of creatine excretion in sexually undeveloped dwarfs (1). Simultaneously, Samuels, Henschel, and Keys (2) discovered that the same effects occurred in normal men. Since then Tager (3), Werner and West (4), and others (5, 6, 7) have observed that creatinuria followed the use of methyl testosterone in various conditions. The present paper deals with further studies we have made to determine the nature of the changes which occur in the creatinecreatinine metabolism. METHODSThe observations we are reporting were made principally on sexually undeveloped dwarfs between the ages of 11 and 22 years because we were at the same time studying the protein anabolic effects of steroids in this group of patients. It is probable that the dwarfism and sexual infantilism were due to pituitary deficiency in most instances, although this diagnosis cannot be proved in all cases. The fact that methyl testosterone has identical effects on the creatine metabolism in normal individuals and in patients of either sex suffering from other disturbances has been amply demonstrated by Samuels, ourselves, and other workers.All patients received "low creatine" diets containing no meat or fish, and not over 1000 ml. of milk daily, furnishing 30 mgm. or less of creatine. During each study, the diet was constant in respect to the content of protein, carbohydrate, and fat. Twenty-four-hour specimens of urine were collected over dilute HCI and analyzed daily by the method of Benedict and Myers (8), using a Klett photoelectric colorimeter for the readings. In presenting the results of the first 24 days of treatment, we employed the method of "sliding averages" using 5-day periods to compute the daily outputs. By this method, the average of days 1 to 5 inclusive are shown as the output for the third day, which is the middle of the period; the average of days 2 to 6 inclusive are recorded as the 4th day; 3 to 7 as the 5th day, etc.2 The values recorded for the excretion after the first month of treatment are averages for periods of 10 days or longer. To emphasize the early changes, the time intervals of one day are shown on the abscissae of the chart for the first month; but to conserve-space, the same interval represents one month in the remainder of the chart. This causes the rise in the curve of excretion after the first month to appear more abrupt than it actually is.It is seen from this chart that after treatment with methyl testosterone is begun there is a latent period varying from approximately 4 to 16 days before the excretion of creatine increases. During this period, the output of creatine apparently decreases in some cases. The creatinine curves are more irregular than those of creatine, but in many instances, there also appears to be a decreased output during the early period of (Col. U. S. A.). The contents of this paper have been reported from time to time in the minutes of the Committee on the Metabolic Aspects of Convalescence.2 By this m...

Effects of Thyroid on Creatine Metabolism With a Discussion of the Mechanism of Storage and Excretion of Creatine Bodies 1

“…contrasted the type of curve observed with that found when patients are treated with methyl testosterone (13). (Compare Figures 2 and 3).…”

“…The total creatine + creatinine was decreased in one case and increased slightly in the other. These results are illustrated graphically in Figure 1 (13).…”

“…Changes in the rate of synthesis of creatine from its precursors It has been shown that the synthesis of creatine is increased by the administration of methyl testosterone ( 13,14). Other conditions which might affect this synthesis have not been fully investigated.…”

Studies on Amino Acid Metabolism. Ii. Blood Glycine and Total Amino Acids in Various Pathological Conditions, With Observations on the Effects of Intravenously Administered Glycine 1

“…The elevated glycine and total blood amino acids in one patient with myasthenia gravis who was receiving methyltestosterone may be referable to the anabolic effects of this hormone (56).…”

Experimental Use of Testosterone Compounds in Premature Infants

“…5 terone tended to promote hypercreatinuria whereas propionate decreased it. 4 It is now felt that the fundamental effects are the same. The apparent discrepancy in creatine metabolism is merely ascribable to the fact that in the case of methyl testosterone administration the nitrogen retention is so profound as to cause a spilling over of creatine.…”