578 



PHYSIOLOGY OF GONADS 



noticeable loss of edema by the 4th or 5th 

 day followed by rapid involution and re- 

 duction of the turgid folds of skin to loose, 

 flabby wrinkles within about 10 days. When 

 estrogen and progesterone are given con- 

 currently to a castrated monkey from the 

 beginning of treatment edema does not ap- 

 pear but the sexual skin regains its normal 

 color. In fact, progesterone alone, like es- 

 trogen, can restore the color to the sexual 

 skin of castrated adult monkeys (Hisaw, 

 Greep and Fevold, 1937; Hisaw, 1942). 



The interaction of estrogen and i)ro- 

 gesterone on the sexual skin of rhesus mon- 

 keys can best be demonstrated by the reac- 

 tion of the skin of the sexual area in 

 adolescent animals. The most striking effect 

 and probably the most important is the 

 sequence of events initiated by a single 

 dose of progesterone when given to an ani- 

 mal on continuous estrogen treatment. Un- 

 der such treatment a full response of the 

 sexual skin is obtained by the end of 20 

 days. If at this time 1 mg. progesterone is 

 given in a single dose and the estrogen 

 treatment continued uninterruptedly, the 

 first indication of an effect of the luteal hor- 

 mone is a slight loss of edema and color of 

 the sexual skin on the 4th or 5th day there- 

 after. The sexual skin is markedly reduced 

 by the 8th day, almost gone by the 9th, and 

 at the end of about a fortnight regains its 

 ability to respond to estrogen as shown by 

 a return of color and swelling. However, the 

 most remarkable eventuation of such treat- 

 ment is menstruation which usually begins 

 on about the 10th day (Hisaw, 1942). 



Involution of the sexual skin and men- 

 struation following a single injection of 

 progesterone also have been produced in the 

 baboon by Gillman (1940a). He found that 

 5 mg. progesterone, when given on the 8th 

 day of a normal menstrual cycle, would 

 cause an appreciable loss of edema of the 

 swollen perineal sexual skin by the day after 

 injection. This was followed by a progres- 

 sive involution of the perineum until the 

 13th day and swelling was re-initiated by 

 the end of the 15th day. Reduction of the 

 sexual skin at this dosage of progesterone 

 was not associated with menstruation. How- 

 ever, when tlie dose was increased to 20 mg. 

 both deturgescence of the sexual skin and 

 menstruation occurred. These effects pro- 



duced by progesterone in the presence of 

 endogenous estrogen have much in common 

 with those described above as occurring in 

 castrated monkeys on continuous estrogen 

 treatments. 



IX. Menstruation 



An experimental ai^proach to the physi- 

 ology of menstruation dates from the ob- 

 servations of Allen (1927) that uterine 

 bleeding would occur in castrated monkeys 

 following the discontinuance of an estrogen 

 treatment. He suggested that normal men- 

 struation is due to a fluctuation in estrogen 

 secretion and proposed the "estrogen-with- 

 drawal" theory to account for the observed 

 facts. This concept led to an extensive in- 

 vestigation of the effects of estrogens on the 

 endometrium and of conditions that modify 

 their action. It was soon found that in both 

 castrated monkeys and human beings there 

 was a quantitative relationship between the 

 dosage of estrogen given and the mainte- 

 nance of the endometrium. Bleeding oc- 

 curred during treatment when the daily dose 

 of estrogen was small, but with larger doses 

 a point was reached at which the injections 

 could be continued for months or even years 

 without bleeding (Werner and Collier, 1933; 

 Zuckerman, 1937b, d). 



Estrogen also will inliihit i)ostop('rative 

 bleeding which usually follows total castra- 

 tion, provided the ovaries are removed be- 

 fore or soon after ovulation (Hartman. 

 1934). With the advent of a corpus luteum 

 and development of a progestational endo- 

 metrium it becomes progressively more diffi- 

 cult, following castration, to prevent men- 

 struation by injecting estrogen. Similar 

 results are obtained when estrogen is given 

 during a normal menstrual cycle. Small 

 doses may not prevent the onset of men- 

 struation, but if continued, subsequent men- 

 strual periods are delayed (Corner, 1935). 

 Large doses when given during the luteal 

 phase of the cycle do not disturb the normal 

 menstrual rhythm, but may do so if the 

 treatment is started during the follicular 

 phase (Zuckerman, 1935. 1936a). 



Progesterone, in contrast with estrogen, 

 will prevent menstruation from an endome- 

 trium representative of any stage of the nor- 

 mal cycle. It will delay onset of the next men- 

 ses even when the treatment is started only 



