228 



John Rock 



Because of the highly probable "feedback" of progesterone-suppression 

 of LH, it seems very likely that the strongly progestational Enovid exerts the 

 same influence. The gonadotropin-depressant action of norethynodrel, both 

 in animalsand in women, has been demonstrated by several other investigators 

 (38, 39). 



C. Indices of Ovulation-Suppression with Enovid and Norlutin 



The effect of Enovid, as of Norlutin (norethindrone), on pregnanediol 

 excretion is at least very suggestive of inhibition of ovulation. As shown in 

 Table 3, the average premedication pregnanediol excretion in 40 ovulatory 



Table 3. Effects of 17a-ETHINYL-19-NORTESTOSTERO>4E (I) and 17a-ETHINYL-5(10)-ESTRA- 

 ENEOLONE (II) UPON CYCLE LENGTHS, INDICES OF OVULATION, AND StEROID OUTPUT IN 



Normally Ovulating Women 



* 10-40 mg/day. ** 10-20 mg/day. 



cycles was 3.4 mg per day. With each of the two administered steroids, the 

 average pregnanediol output was found to be only about 10% of this pre- 

 treatment value (20). 



Absence of secreted progesterone is also reflected in the atypy of response 

 in the other common indices of postovulatory corpus-luteum activity. Since 

 in each of these tests the normal critical effect is due to progesterone, 

 and the two artificial steroids are called "progestins" because of the fact that 

 their action resembles that of progesterone, it is not surprising that inferences 

 from temperature graphs, endometrial biopsies, and vaginal smears, although 

 somewhat less exact, are similar to those from biochemical assay of an 

 excreted product of progesterone itself (22). 



In order to obtain more direct evidence of the effect of these steroids on 

 ovulation, a careful study was made of the ovaries of women who had taken 

 Norlutin (norethindrone) for one to 3 cycles before required laparotomy (20, 

 22). Whether operation took place late in the medicated cycle or early in 

 the next untreated cycle, there was no evidence of corpus-luteum formation. 

 More recently, these observations have been repeated with Enovid both by 

 our own group (40) and by the Japanese investigator, Matsumoto (41). In 

 neither of the two series was there any morphologic sign of recent ovulation. 



