GREGORY PINCUS 
Undoubtedly the most active experimental work has been 
with steroidal inhibitors of ovulation acting via the hypothala- 
mus. Our re-investigation of the effect of progesterone in 
inhibiting ovulation in the rabbit was followed by the discovery 
of certain synthetic steroids, known as 19-norsteroids, which 
show progesterone-like activity when taken orally. Subsequently 
many studies of these and related anti-gonadotropic steroids 
have been carried out on animals. In a study of several hundred 
steroids in the rabbit, we have to date found 67 active com- 
pounds, and with a different series of steroids Kincl and Dorf- 
man have found approximately 50 active compounds, but only 
a few of these compounds exhibited sufficient activity to be of 
possible practical importance. 
The comparative potency of these compounds as ovulation 
inhibitors in women has so far not been examined in detail, 
but we have had some evidence that substances shown in the 
rabbit to be more active when administered orally than by 
injection are excellent oral ovulation inhibitors in women}, In 
women, the compound most extensively studied has been 
norethynodrel. It is ordinarily administered in combination 
with an oestrogen in a preparation called Enovid. This com- 
bination effects adequate control of the endometrial blood 
vessels, thus avoiding bleeding during medication. On with- 
drawal of the medication, a menstrual flow follows in one to 
several days. Thus by employing a medication regimen requir- 
ing the taking of a single tablet each day for 20 days beginning 
on the fifth day of the menstrual cycle, an average cycle length 
of 28 days has been attained. Furthermore, with faithful 
following of this regimen, a remarkable succession of regular 
menstrual cycles may be attained year after year. Ina five-year 
period of study of volunteer subjects taking Enovid, it was 
found that, although the first few cycles might be short, with 
premature bleeding, the endometrium soon accommodated to 
the medication, and thereafter short cycles with premature 
bleeding were relatively infrequent. Such bleeding occurred 
more frequently at low dosages of Enovid (2-5 mg. per day). 
When the dosage of Enovid is 5 or 10 mg. per day, the frequency 
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