ESTROGEN ASSAY IN THE HUMAN 



A NUMBER OF invcstigators have recently expressed the opinion that the 

 . therapeutic efficiency of an estrogen can only be judged by testing its 

 potency in the human. Most claims for the relative therapeutic effectiveness 

 of estrogens have been made on the basis of their activity as determined in 

 laboratory animals, principally the rat or mouse. The assumption that data 

 so obtained can be accepted for the human has resulted in considerable con- 

 fusion in the standardization of estrogen therapy. In the first place, results 

 obtained from assays differ widely, as indicated by the fact that the rat unit 

 of estrone as determined in different laboratories varies as much as several 

 thousand per cent when compared to a weighed amount of crystalline mate- 

 rial; the same holds true for assays in the mouse. The discrepancy in the assay 

 of estrogens in rat or mouse cannot be entirely accounted for by technical 

 differences in the performance of the assays, and it appears quite certain that 

 each strain of rat or mouse has a different degree of sensitivity to any one 

 estrogen. Similarly, comparisons of the potencies of different estrogens such 

 as estrone and estradiol in the same laboratory cannot be judged as the true 

 reflection of the relative therapeutic potencies of these substances, inasmuch 

 as the ratios of activity as determined by different laboratories are far from 

 constant. In a recent article a compilation of data on this subject reported by 

 a number of investigators illustrates the inconsistencies in animal assays, lead- 

 ing to the conclusion that any statement regarding the relative therapeutic 

 activity of estrogens on the basis of animal assays is liable to considerable 

 error and that assay in the human is at the present time the only hope for 

 satisfactory therapetitic standards of estrogens.^ 



Several attempts have been made to assay the activity of estrogens in humans. 

 Some investigators have utilized as an index of estrogen activity the changes 

 in the vaginal mucosa of menopausal patients following estrogen administra- 

 tion, much the same way as the castrate rodent is used.' When it is recognized, 

 however, that untreated menopausal patients have varying degrees of prolif- 

 eration of the vaginal mucosa, it does not appear that this would be a satis- 

 factory means of assay. There is a lack of evidence that the vaginal epithelium 

 of a group of menopausal women will respond to a definite amount of estrogen 

 with a sufficient degi^ee of uniformity. Furthermore, the reading of vaginal 

 smears in the human for assay purposes is liable to experimental error. 



An attempt has been made to utilize the changes in the menopausal endo- 

 metrium following estrogen administration as a means of assay.' Such a tech- 

 nique is not only cumbersome but also open to even severer criticism than that 

 mentioned above for the use of vaginal smears, inasmuch as untreated meno- 

 pausal patients may possess significant degrees of endometrial proliferation 

 and, in fact, hyperplasia.' This factor would interfere greatly with assays based 

 on endometrial changes. 



C195II 



