PHYSIOLOGIC EFFECTIVENESS OF ORAL PROGESTERONE*

Abstract

IT HAS been assumed for many years that ingested progesterone is physiologically ineffective because of partial destruction by gastric secretions and direct absorption into the portal circulation with subsequent immediate conjugation and deactivation in the liver. This belief has apparently been perpetuated on the basis of experimental studies in animals. The literature fails to disclose adequate studies of the physiologic action of progesterone administered orally to the human patient. Extensive search for some mode of administration other than parenteral has led to the synthesis of anhydrohydroxyprogesterone. Progesterone prepared in a vehicle suitable for absorption from mucous membranes has proved effective (1). Bickers (2), in a study of the comparison of intramuscular, oral and sublingual routes of administration of progesterone and anhydrohydroxyprogesterone, recently reported the results of six cycles during which oral free progesterone was administered in doses of 80 mg. per day for five days without estrogen priming. In none of the six cycles did withdrawal bleeding occur, but endometrial biopsy specimens are reported to have shown transitional endometrium in three, and fair progestational effect in three cycles. The endometrial changes were interpreted as evidence of effectiveness of the ingested progesterone, although withdrawal bleeding did not occur. We are unable to confirm Bickers' interpretation in this study because withdrawal bleeding was the rule rather than the exception in our series in spite of absence of progestational transformation of the endometrium. Progestational endometrium was found in only one instance after therapy.