1 gS Estrogen Assay in the Human 



apparent paradox can be explained by the fact that the patients were first 

 administered the higher level. Those who failed to respond did not receive 

 the 2.5 mg. daily dose. The seven patients who failed to respond to the 2.5 mg. 

 daily dose had received some beneficial results when they were given 5 mg. 

 daily. 



In regard to the toxic manifestations of this therapy, which is of considerable 

 interest inasmuch as the unpleasant symptoms following oral administration 

 of these estrogens are considered to be their greatest disadvantage, it appears 

 that hexestrol is significantly less toxic than diethylstilbestrol, although the 

 incidence of toxic reactions from hexestrol administration is appreciable. Ad- 

 ditional data seem indicated on this phase of the study before definite con- 

 clusions can be drawn as to the relative toxicity of these estrogens. 



Discussion 



By the use of different dosage levels, a satisfactory evaluation of the therapeutic 

 potency of estrogens can be obtained by using the relief of menopausal symp- 

 toms as an end point. Nonspecific factors are minimized by the proper selec- 

 tion and handling of patients. With the use of the technique described above, 

 there is no need for control with either untreated patients or patients who 

 receive placebo medication inasmuch as each dosage level controls the next. 

 The psychic factor of administering some form of medication is thus reduced. 

 In this regard, the author has observed a number of patients who responded 

 equally well on all levels of estrogens and who when placed on placebo medica- 

 tion also responded satisfactorily. The data obtained from these were not in- 

 cluded in the tables since the inclusion of this type of patient in a group for 

 study renders results less significant statistically. With the use of multiple 

 dosage levels it is not necessary for statistical purposes to treat a large series of 

 patients receiving a single dosage since, as can be noted from the two tables, 

 these is some cancellation of experimental error at the different levels. Thus, 

 in table 1, 2.5 mg. hexestrol seems somewhat superior to 0.5 mg. hexestrol, 

 but 5 mg. hexestrol is somewhat inferior to 1 mg. diethylstilbestrol. It is also 

 expected that any new estrogen can be easily compared in potency to estrogens 

 which have already been tested by this assay method. Furthermore, the mini- 

 mal therapeutic dose can readily be determined by the use of multiple dosage 

 levels. 



The results of this study are not in accord with those of Bishop and co- 

 workers^ regarding the relative therapeutic activity of hexestrol and diethyl- 

 stilbestrol. These workers report that these compounds are almost equal in 

 potency. My results indicate that hexestrol is one-fifth as effective as diethylstil- 

 bestrol. In addition, they claim hexestrol to be relatively free of untoward 

 reactions. In my hands hexestrol appears to be less toxic than diethylstilbes- 

 trol in equivalent therapeutic doses, although the incidence of unpleasant 

 symptoms is sufficiently high to warrant caution in its use. 



