This invention relates to novel non-pyrogenic steroidal erythropoietic agents, and to therapeutic compositions containing the same and methods of treatment. More particularly, the invention concerns 3.alpha.-hydroxy-5.beta.-estrane-17-one (19 nor-etiocholanolone), and 3.beta.-hydroxy-5.beta.-estrane- 17-one, and 3-substituted derivatives thereof, and their application in the stimulation of erythropoiesis.
Erythropoiesis is the process of formation of red blood cells.
The term anemia implies an abnormally low number of circulating red cells or a decreased concentration of hemoglobin in the blood. The appearance of anemia reflects either marrow failure or excessive red cell loss, or both. Marrow failure, i.e., reduced erythropoiesis, may occur as a result of a nutritional deficiency, toxic exposure, tumor invasion, or other and sometimes unknown causes.
For the treatment of anemias of bone marrow failure (hypoplastic and aplastic anemias), it has been proposed to use substances which might stimulate the marrow, such as androgens or corticosteroids. Campbell et al. U.S. Pat No. 3,383,282 discloses various 3,5-androstadiene-3,17-diol derivatives as possessing erythropoietic activity. Schmidlin et al. U.S. Pat. Nos. 3,519,659 and 3,519,660 disclose various prednisolone derivatives having antileukemia activity.
It is known that erythropoietic activity is exhibited by metabolites of certain androgenic, anabolic, or progestational steroids. Thus, Levere et al. Proceedings of a Symposium held in conjunction with the American Society of Hematology, Dec. 4, 1971, Chapter III, discloses that etiocholanolone, a human metabolite of testosterone, possesses erythropoietic activity. Jepson, ibid., Chapter II, disclosed that nandrolone (19-nortestosterone; 17-.beta.-hydroxy-19-nor-4-androsten-3-one), an anabolic steroid, possesses erythropoietic activity similar to testosterone. This substance, however, has the drawback of exhibiting androgenic side-effects. It is known in the form of its decanoate, described in DeWitt et al U.S. Pat. No. 2,998,423. Etiocholanolane possesses the substantial drawback of being a pyrogen in man.