414 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS hormone cream is of an order of magnitude answering the above de- scription, only a local and no sys- temic action might be expected. There is direct evidence in sup- port of the latter contention. Ei- delsberg (17) carried out a series of experiments on a cosmetic hormone cream (of 7500 I.U. per ounce of natural estrogenic substance) with the specific purpose of ascertaining the existence of any variations in the estrogen content of the urine, and in the appearance of vaginal smears following the use of such a cream. He employed fourteen subjects who ranged in age from 18 to 56 years. The hormone cream, as well as a hormone-free control cream were applied nightly for three to four months. At the end of the ex- periment, no difference was found between the two groups with re- spect to the over-all pattern of uri- nary estrogen and of the vaginal smears. From this Eidelsberg con- cluded that in the amounts used and by the method applied, the estro- genic hormones did not produce any systemic effect. Eller and Eller (5) whose work has been referred to previously, also report insignificant variations in the appearance of the vaginal smears of their subjects from this they draw the conclusion that under the condi- tions of their procedure the absorbed estrogen affects the cutaneous epi- thelium directly, rather than via the s. ystemic' route. The postulate as to a direct, local action is borne out also' by an ad hoc experiment in which the hormone cream was ap- plied to one thigh, and the hormone- free excipient to the other regener- ation and thickening of the epider- mis took place only in the former in- stance (Fig. 3). Davis (18), too, is convinced that a cosmetic hormone cream contain- ing around 7500 to 10,000 I.U. per ounce of estrone is unlikely to exert systemic action in view of the fact that the amount of estrogen ab- sorbed by the skin is far below the level required to produce such an effect. Of course, where the estrogen po- tency employed is substantially higher (as, e.g., in the several in- stances mentioned in the chapter headed "Supplementary Illustrative Data") the probability of combined topical and systemic effects must be considered. In such cases, how- ever, the pertinent formulations are no longer of a cosmetic character instead, they assume therapeutic functions in connection with the treatment of the particular patho- logical conditions involved. Parenthetically, it might be added at this point that while the topical application of estrogens produces spectacular results in a number of instances, there exists a valid physio- logical and embryological reason for this phenomenon since the several varieties of tissue susceptible to the action of estrogens have the same embryonic derivation. Thus, while the vaginal mucosa or the endome- trium is affected causally by estro- gens it must be kept in mind that the skin represents but another de- velopmental form of the same basic

?::'embryonic tissue. Another causal ?i connection between estrogenic hot- ' .: mone action and skin condition is :i!•}:" evident from the frequent occurrence ::11!i/øf atrophic skin changes during the j ! menopause. ARE HORMONE COSMETICS •': ':' DANOEROUS ? ß Occasionally one encounters in the literature warnings as to the poten- ::"tially carcinogenic action of estro- . genic hormones. Their origin ap- pears to stem from the experiments of Lacassagne (19) who showed that :!:: the administration of estrogenic hormones to young male mice from . a cancer susceptible strain, increased the rate of cancer incidence in later . life, as compared with the spontane- ous cancer incidence of the controls. In the case of mice free from suscep- ':" tibility to spontaneous mammary ::i tumors, the treatment did not elicit such a reaction. Incidentally, in order to produce this phenome- non, Lacassagne had to employ doses which are many times higher than would correspond to those ad- ministered in the most intensive es- trogen therapy, let alone in cos- metic usage. The following random quotations are given in further reference to this matter: Short (20): "Analysis of the data leads to the conclusion that no evi- dence exists that estrogenic hor- mones, given in physiological doses, have led to the development of car- cinoma in man." Geist and Salmon (21): "It is ob- viously impossible in human beings COSMETIC ASPECTS OF ESTROGENIC HORMONES 415 to administer the huge doses of es- trogens over the long periods of time that would justify comparison with the experimental production of car- cinoma in rodents. Howeve:r, the conclusion seems warranted, on the basis of these studies, that, within the limits of the dosage used in this investigation (up to 53,400,000 I.U.) there appears no evidence to justify the fear that carcinoma of the geni- tal tract may result from the thera- peutic use of estrogens." Hawkinson (22): "It is true that carcinoma can be produced in sus- ceptible animals with estrogen. This would seem significant were it not for the fact that the work has been done chiefly in the rodent, with rela- tively huge doses, and with animals having a high hereditary tendency to the development of carcinoma." Emge (23): "Evidence is accumu- lating to prove that the action of estrogenic hormones is controlled by definite biological patterns, and that their cancer-provoking faculty in small laboratory animals is strictly limited by hereditary tendencies .... We are not convinced, because es- trogen favors spontaneous mam- mary cancer in mice highly suscept- ible to this malignancy, that other species of mammalia are likewise af- fected." ß Goldzieher (3): "Warnings against the application of estrogens to the skin, lest they stimulate la- tent carcinogenic tendencies, are speculative, and not based on solidly established evidence. As a matter of fact, senile hyperkeratosis, in- cluding the pigmented variety, has