EFFECT OF TOPICAL HORMONES ON SKIN 561 such as gynecomastia in men and resumption of uterine bleeding in postmenopausal women. Apparently the application of pharmacologic quantities of hormones to the skin yields unique results which cannot be predicted from know- ledge of their usual physiologic and systemic effects. It is becoming evident that cutaneous pathways of metabolism for steroids exist and that much remains to be learned of their integumentary fate (4-8). It is clear, however, that hasty generalizations drawn from "expected results" can be misleading. The reliance on topically applied female hormones to alleviate the defects of aging skin undoubtedly draws support from this type of reasoning. With regard to the practical implications of our studies, it is of course most encouraging to have achieved even these modest changes on skin which was already markedly damaged. This strongly suggests that prophylaxis might well yield even more satisfactory results. It is conceivable that application of the appropriate steroid begun rather early in life, particularly in light skinned, susceptible individuals, might not only enhance their appearance in later years but also afford protec- tion against the development of cutaneous epitheliomas. SUMMARY The characteristic structural changes which typify aged skin, both in protected and actinically damaged areas, can be modified by the topical application of steroidal hormones. Androgenic compounds exert an ameliorative effect, restoring the gross and microscopic archi- tecture toward a more youthful integument. Hair growth is stimulated, sweat secretion increased and, in some instances, the sagging and fine wrinkling of senescence effaced. The microscopic improvement is even more uniform and striking, particularly in the epidermis where the dis- orderly cytologic and histologic alterations are reversed. The "benefi- cial" effects of topical estrogen have not been confirmed, and such substances exert no appreciable activity on human skin. Corticosteroid action is diametrically opposite to that of the androgens, and topical administration accentuates the degradative changes. ACKNOWLEDGMENT Particular appreciation is acknowledged to the administration (Raymond S. Groller, Director) and the residents of Riverview Home for the Aged who participated in this study. (Received November 14, 1966)

562 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS REFERENCES (1) Montagna, W., Formisano, V., and Kligman, A.M. Hormonal factors in aging. Hor- monal Steroids, Biochemistry, Pharmacology and Therapeutics: Proceedings of the First International Congress on Hormonal Steroids. Vol. 1, pp 559-568, Academic Press, New York, 1964. (2) Papa, C. M. and Kligman, A.M. The effect of topical steroids on the aged human axilla, in Montagna, W., Advances in Biology of Skin-Aging, Pergamon Press, New York, 1965. (3) Formisano, V., and Kligman, A.M., Modification of human aged skin by sex steroids. (In press) (4) Wotiz, H. H., Mescon, H., Doppel, H., and Lemon, H. M., The in vitro metabolism of testosterone by human skin, J. Invest. Dermatol., 20, 113 (1956). (5) Baillie, A. H., Calman, K. C., and Milne, J. A., Histochemical distribution of hydroxy- steroid dehydrogenases in human skin, Brit. J. Dermtaol. 77, 610 (1965). (6) Gomez, E. C., and Hsia, S.C., Studies in cutaneous metabolism of testosterone 4-C x• Federation Proc., 25,282 (1966). (7) Hsia, S. L., Witten, V. H., and Hao, Y. L., In vitro metabolic studies of hydrocortisone- 4-C •4 in human skin. J. Invest. Dermatol. 43,407 (1964). (8) Frost, P., Weinstein, G. D., and Hsia, S. L. Metabolism of estradiol-17 B and estrone in human skin. Ibid., 46, 584 (1966).