224 John Rock 



Furthermore, in recent years there have been two Hnes of investigation 

 with plant extracts, leading to reports of possible inactivation of gonado- 

 tropins by: (1) a postulated descnsitization of the ovary to gonadotropins by 

 lithospermum (9, 10); and (2) interaction of quinones from the Indian garden 

 pea with gonadotropin so as to nullify the latter (9, 1 1). 



III. INHIBITION OF OVULATION BY THE 19-NOR STEROIDS 



Since none of the methods mentioned above seemed to offer a satisfactory 

 solution to the problem of fertility control, and since, in harmony with the 

 long-recognized ovulation-inhibiting action of progesterone recently re- 

 affirmed (12-14)*, certain artificial progestins, the so-called 19-nor steroids, 

 had also been found by Pincus and his associates (14, 17, 18) to inhibit ovula- 

 tion in animals, Dr. Garcia and I were fortunate to obtain these steroidal 

 substances from Dr. Pincus. Oral administration in women on cycle-days 

 5 through 25 showed that these steroids had the same ovulation-suppressant 

 effect as in laboratory animals (14, 19-23). Some of them, however, were 

 more potent than others. One of them in particular, 17a-ethinyl-5(10)- 

 estraeneolone, possessed such a high degree of ovulation-inhibitory, as well 

 as other qualities, that it was chosen for use in large-scale field studies organ- 

 ized by Dr. Pincus, first in Puerto Rico and later in Haiti (8, 24-33). 



It was unfortunate, perhaps, that we were supplied with the best prepara- 

 tions first. Our enthusiasm for some of the later, less effective ones was 

 insufficient to encourage us to utilize our patients in the way animal experi- 

 menters so easily do their subjects. Possibly, therefore, some of the conclusions 

 suggested by our negative results with the newer preparations derive only 

 from a sample that is deficient in the number of cases as well as in variety of 

 dosage. Presently, I shall discuss our experiences with several of these steroids 

 of various degrees of efiicacy. 



First, I wish to state that Dr. Pincus provided not only the material and 

 the motivation for these projects, but he also organized them. For the tables 

 to be shown in connection with the field studies, Dr. Pincus compiled the 

 data derived from the clinical observations which Dr. Garcia and I, together 

 with several physicians in the island areas, were able to supply. 



A. Nature of the Ovulation-inhibiting Steroidal Substances 



Certain of these synthetic steroids, the so-called 19-nor steroids, are shown 

 in Fig. 1 in relationship to the naturally occurring hormones, progesterone 

 and testosterone.! The nortestosterones, norethindrone (Norlutin — Parke- 

 Davis) and norethandrolone (Nilevar — Searle) were found to be very effective, 



* The ovulation-inhibiting function of the corpus luteum had been recognized even 

 long before the isolation of progesterone (6, 15, 16). 



t Although ovulation is also inhibited by these naturally occurring hormones, as well 

 as by estrogens in both natural and synthetic form, their use for this purpose is undesirable. 



