PHARMACOLOGICAL STUDIES IN MAN OF 11‐, 17‐, AND 21‐HYDROXY DERIVATIVES OF PROGESTERONE AND THEIR FLUORINATED ANALOGS

The oxygenated derivatives of progesterone include such highly active compounds as hydrocortisone and corticosterone, whose biological effects in experimental animals and in man have been extensively studied. Other compounds in this series, however, have been available in small amounts only, and studies of their activity in man are few.l In view of the remarkable potentiation of hydrocortisone by the substitution of a fluorine atom a t the 9a it seemed desirable to explore the metabolic activity of other 9a fluorinated steroids. Samples of the 9a fluorine derivatives of hydrocortisone, corticosterone, 1 1P-hydroxyprogesterone and 11, 17-dihydroxyprogesterone have been obtained (FIGURE 1) ; for purposes of comparison, the studies were extended to include the nontluorinated analogs and lla-hydroxyprogesterone. The intravenous route of administration was chosen as providing the most accurate basis for comparison of the small quantities of hormone available. Mefhods. These studies were carried out in the Metabolic Unit of the Peter Bent Brigham Hospital. Patients with proved Addison’s disease were allowed to come into balance on a constant diet before studies began. Sufficient time was allowed for them to return to equilibrium between the successive administration of the compounds being studied. The urinary sodium and potassium values were determined by flame photometry. The urinary glucose was estimated by the method of Renold and Froesch,’ in which the urinary reducing substances are compared before and after incubation with glucose oxidase. Other determinations were carried out as previously described? For intravenous administration the compounds were dissolved in ethanol and added to either 5 per cent dextrose in water or saline. On control days, similar infusions were given without addition of steroids. Obseroaliorzs. The effects of 25 mg. of progesterone, 1 la-hydroxyprogesterone, 1 lb-hydroxyprogesterone and 12 mg. of 9a-fluoro-ll@-hydroxyprogesterone on urinary sodium, potassium and glucose excretion were studied in a 20-year-old male with Addison’s disease. The steroids were dissolved in 20 ml. of ethanol, which wasadded to 250 cc. of 5 per cent dextrose and water. 3 , 4 ’ 5 p