1 gS Estrogen Assay in the Human 



The author has selected as an end point in the assay of estrogens in humans 

 the subjective response of menopausal patients. It is acknowledged that the 

 evaluation of such a response may be obscured by numerous uncontrolled fac- 

 tors. Nevertheless, this method has been selected for assay for a number of 

 reasons, not the least of which is the fact that the chief purpose in administer- 

 ing estrogens is to relieve the menopausal patient of her subjective symptoms. 

 Such an assay requires no special technique and a large number of patients may 

 be included in a study with little difficulty. In order to eliminate as many 

 distracting factors from this study as possible, the author has established cer- 

 tain criteria. Patients were selected who complained of moderate or severe 

 menopausal symptoms; those who had complaints which were of doubtful 

 origin or might possibly be confused wath psychic changes due to environ- 

 mental or social complications were not included in the group tested. Patients 

 were not included in the groups unless they had at least two to four hot flashes 

 daily, together with other symptoms commonly found in the menopause, such 

 as nervousness, irritability, and emotional instability. The psychic factors asso- 

 ciated with any form of therapy involving subjective sensations were reduced 

 to a miniinum by eliminating any therapeutic suggestion, such as a promise 

 of beneficial results or leading questions concerning therapeutic responses. 

 In addition, the subjective changes of all patients were evaluated by the au- 

 thor alone in as constant a manner as possible, thus eliminating differences in 

 interpretation of results which are prone to develop where a number of 

 clinicians are treating the same group of patients. Furthermore, the estrogens 

 were administered in several dosage levels in the manner which is used for 

 assaying estrogens in laboratory animals. Two synthetic estrogens, hexestrol, 

 and diethylstilbestrol, were thus assayed. 



Methods and Results 



Patients were given at different times one of three levels of the synthetic es- 

 trogen hexestrol— 1 mg., 2.5 mg. and 5 mg. daily. Diethylstilbestrol was ad- 

 ministered daily in dosages of 0.5 mg. and 1 mg. Therapy was usually started 

 by administering the highest level of hexestrol. After three weeks of treatment 

 the therapeutic response was evaluated and listed in terms of plus signs, 3+ 

 being considered the optimal response, 2^ a satisfactory response, and 1^ a 

 slight though definite response. In the evaluation of therapeutic response, the 

 disappearance of hot flashes was used as one of the most important criteria of 

 relief. Changes in nervousness, irritability, etc., were also considered in this 

 evaluation. After the first period of treatment, the dosage was dropped to the 

 next lower level and maintained in this manner for three weeks or more. After 

 the patient's response w'as evaluated at the medium level, the lowest level was 

 then administered for three or more weeks and further response noted. The 

 patients were then given the second estrogen, diethylstilbestrol, and their 

 clinical course with two dosage levels followed in a similar manner. A number 

 of patients received medication in the reverse order, first diethvlstilbestrol, 



