408 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS tween the active and the control sides. 4. The active side was recog- nized by observing various degrees of dilatation of the blood vessels, an increase in simple cellular elements, a greater succulence of the derma, as well as a betterment of the elastic tissue. There appeared to be no es- sential changes in the basophilic strands when the final sections re- moved at the conclusion of the ex- periment were compared with the original sections of the skin. Gross examination indicated also a tendency toward the diminution of senile pigmentation or freckling. Moreover, it could be shown by a comparatively simple experiment that skin areas treated with the hor- mone cream developed a greater avidity for taking up fluids (phys- iological saline) than the control areas. In two more recent publications, Goldzieher (3) reported upon the topical application of hormone creams to senile skin. He used one preparation assayed at 10,000 I.U. to the ounce, and another one con- taining the synthetic estrogen, di- ethylstilbestrol (1 milligram per ounce). With biopsies taken from both the treated and untreated areas (of the inner surfaces of the thighs and forearms) he found •triking changes following a daily applica- tion of the hormone-bearing oint- ments over a period of six weeks. There was evidence of a regenera- tion of the surface epithelium. There were also significant changes in the mesoderm thus the water content of the estrogen-treated site waõ greater, the number and size of the capillaries seemed increased, the bundles of collagenous fibers ap- peared less fragmented, and the elastic fibrils were more numerous. No such changes were elicited with the hormone-free ointment base. It is argued that topical applica- tion ofestrogens affects the skin to a much greater degree than oral or parenteral administration because by the latter modes of administra- tion substantial amounts are lost for the skin through excretion, through inactivation by the liver, through attraction to the genital and mammary tissues, and through dilution by body fluids. In Goldzie- her's opinion, the demonstrated ab- sorption and utilization by the skin of topically applied estrogens opens a new field of therapy applicable to skin conditions not only induced by a hormone deficiency, but also to those involving other pathologic changes. Jaff• (4) who reported earlier upon the treatment with follicular hormones of dermatoses of ovarian origin states that the stimulating effect upon the regeneration of the epithelium is in evidence also in the case of a healthy skin. He advo- cates, therefore, the application of a hormone cream in those cases (of flabbiness, etc.) where its positive action is likely to produce the ap- pearance of a younger skin, owing to an improved skin tone and to an in- tensified capillary circulation. He indicates his awareness of the tern-

COSMETIC ASPECTS OF ESTROGENIC HORMONES 409 Figure 1.--Average response of senile female skin to continuous application of ointment containing 242 international units of estrogen per gram (7500 international units per ounce). A, Biopsy specimen of the skin of the back before treatment. Note the thin epidermis, the absence of pegs and the cubvidal cells of the basal cell layer B, biopsy specimen of the skin of the back after application of an estrogen-free ointment for thirty days. There are thickening of the epidermis, greater cellulacity and slight wariness of the basal cell layer C, biopsy specimen after application of estrogenic ointment for thirty days. Note the increased sizes of the epidermal cells and the pronounced wariness of the basal cell layer, indicating prolifera- tire activity. (Reproduced from the paper by Eller and Eller in the Archives of Dermatology and $yphilology, 59, 449 (1949).)