ESTROGEN AND PROGESTERONE 



58c 



drastic destruction of endometrial struc- 

 tures occurs when both estrogen and proges- 

 terone are given for several months. Not 

 only are the coiled arteries destroyed but 

 also the glands and the luminal epithelium. 

 All that remains is a modified stroma pene- 

 trated by a few small blood and lymph ves- 

 sels and scattered glandular rudiments along 

 the myometrium (Fig. 9.13). Yet, in spite 

 of this, bleeding follows discontinuance of 

 the treatment. 



These observations prove conclusively 

 that the spiral arteries of the endometrium 

 do not hold the solution to the menstrual 

 process. However, the descriptive account 

 by Markee of the events that take place in 

 the endometrium during the cycle remains 

 one of the major contributions to our knowl- 

 edge of the primate endometrium. Phelps 

 (1946) also made a very careful study of the 

 vascular changes in intraocular endometrial 

 transplants in ovariectomized monkeys re- 

 ceiving estrogen and progesterone, and con- 

 cluded that the primary function of the 

 coiled arteries is concerned with vasculari- 

 zation of the implantation site of a develop- 

 ing embryo. 



There also is reason for doul^ting that 

 ischemia is a determining factor in the 

 menstrual process. That constriction of the 

 endometrial vessels does occur is well estab- 

 lished, but that tissue destruction and bleed- 

 ing are consequences of prolonged anoxemia 

 may be questioned. The endometrium 

 around the internal cervical os as seen in 

 incised exteriorized uteri (Fig. 9.7) contains 

 very few coiled arteries and does not take 

 part in the periodic blushing and blanching 

 of the fundus, but instead remains blood-red 

 even during menstruation. Also, certain 

 tongues of endometrium in a uterine fistula 

 may become crowded by their neighbors to 

 an extent of being partly or completely de- 

 prived of blood, yet they do not bleed even 

 though their unfavorable situation leads to 

 deterioration within a few days. 



Emmel, Worthington and Allen (1941) 

 attempted to induce menstruation in mon- 

 keys by operative ischemia. Circulation to 

 the fundus of the uterus was interrupted by 

 means of a tourniquet for periods of 1 to 8V4 

 hours, and in two instances for 19 hours. 

 This procedure did not precijiitate uterine 



bleeding nor did it hasten the onset of an 

 expected bleeding following estrogen with- 

 drawal. In fact, when the uterus was de- 

 prived of blood for periods longer than 3 

 hours impairment of the bleeding response 

 to estrogen withdrawal was observed, and 

 19 hours of ischemia caused atrophy of the 

 uterus without bleeding. 



It also has been reported that a toxic sub- 

 stance formed in the endometrium is re- 

 sponsible for menstruation. This menstrual 

 toxin is supposed to be present in the endo- 

 metrium just previous to and during men- 

 struation, and to be a substance resembling 

 or identical with necrosin, a material found 

 in pleural exudate following an inflamma- 

 tory reaction (Smith and Smith, 1951). 

 Zondek (1953) reports that menstrual blood, 

 when obtained under relatively sterile con- 

 ditions, is no more toxic to experimental 

 animals than sterile tissue extracts. He also 

 found that death of animals given injections 

 of menstrual blood was due to bacteremia, 

 an effect that could be prevented by giving 

 antibiotics. Nor was he able to demonstrate 

 a toxic substance in the premenstrual or 

 menstrual endometrium. It might be men- 

 tioned in this connection that endometrial 

 tissue destroyed by experimental ischemia 

 in the experiments by Emmel, Worthington 

 and Allen (1941), obviously did not influ- 

 ence menstruation nor did involuting endo- 

 metrial tissue in uterine fistulae (p. 564). 

 Therefore, the presence of a specific toxin 

 that may induce menstruation has not been 

 conclusively demonstrated. 



Regardless of the specific cause of men- 

 struation, the evidence shows that it can 

 occur in the absence of coiled arteries, en- 

 dometrial glands, or surface mucosa, and is 

 unrelated to the thickness of the endome- 

 trium. This statement is based on condi- 

 tions that have been experimentally induced 

 in the monkey and they strongly indicate 

 that menstruation, whatever the cause, is a 

 stromal phenomenon. This view seems to be 

 in agreement with the observations reported 

 by Bartelmez in his elegant studies of the 

 morphology of the endometrium of both 

 monkeys and the human being. He empha- 

 sizes changes taking place in the connective 

 tissue elements of the stroma and points out 

 that much less tissue is lost at menstruation 



