44 



Gregory Pincus and Anne P. Merrill 



oral progestational activity of 17a-ctliinyl-19-nortcstostcrone (XLVI) was 

 first reported by Hertz et al. (7). We reported in extenso (2, 3, 4) on the 

 progestational, ovulation-inhibiting, deciduomagenic and other properties 

 of four 17a-alkyl-19-norsteroids (XLVI, XLII, XLIII and LXII), as well as 

 on their effects on ovulation and various menstrual cycle phenomena in 

 women (2, 8, 9, 10). Of the compounds listed in Fig. 9, all save XLIV are 

 potent ovulation inhibitors. Among the higher alkyl derivatives of 19- 

 nortestosterone (Fig. 10), significant ovulation inhibition at fairly low 

 dosages is exhibited on subcutaneous injection, but all the compounds of 

 high potency by this route are much less active by the oral route (cf. LI, LIII, 



LW 



SQ -10,2,0.4 



AcC ^OAc 

 SQ~I0,2 



HCCH, 



SQ-IO 



C,H, 



SQ-10,2 



Fig. II. Miscellaneous 19-norsteroids. (Dosage in milligrams. SQ = subcutaneous injection; 



O = by gavage.) 



LIV and LV). Certain miscellaneous 19-norsteroids listed in Fig. 11 are 

 either marginally active or of low potency. Finally, the shifting of the ring A 

 double bond from the 4, 5 to the 5, 10 position may reduce the ovulation- 

 inhibiting activity by subcutaneous administration (cf. LXII and XLVI; 

 LXIII and XLIII; LXIV and LII), but highly potent activity is exhibited by 

 the one compound (LXII) tested orally. 



We have presented in the foregoing figures a list of sixty-four steroid 

 compounds indicated as ovulation inhibitors in the rabbit. One hundred and 

 twenty-three additional steroid compounds have been submitted to this test, 

 with negative results. In Table 1 we list the numbers tested in various classi- 

 fications and the percentages of active compounds. It is clear that the largest 

 proportion of active compounds is in the group of 19-norsteroids, with the 

 1 7-hydroxyprogesterone derivatives ranking next. These percentage figures 



