PREGNENOLONE ACETATE ! 35 7...:'• ' •. •'½:'•.,•,- •'z•,•, -:½' '"'•.," -•T' . . ---% :,:r' 3 • ... .: .. .. . . . -e ... ..-•. •, •..•, .. ½, • •.-• • . :-- ...:• ....... - :...::' .•. •e.. ß -.•. . •:......•: : . . :,'• . R L 4:-...•, .. ...... •. ..... • •. ,•.. ,. --•..:.•?,•. •?' 5. - % :•: ...:•, .-.. .. ...,. ... -.. :.:.•:-• .? .•½ • .--• ,.•..-• •,,..• ...... •:. • •'•:•½• • '5: ..: . :. '• Figure 8.--Closeup of another subject treated for three months--this one received pregnenolone cream on the right. between the test and control sides on histological examination. Closeups of the two sides of another patient's face, this one treated with the preg- nenolone cream on the right, are shown in Fig. 8. Here again the marked plumping and smoothing as a result of subcutaneous edema is particularly apparent. Another group of university dermatologists (18) conducted a double- blind half-face study which was continued for at least three months in seventy-nine patients. The results are compared in Fig. 9, in which the distribution of the degree of improvement for the two sides of the face is shown. Many of these women had been using some form of cosmetic cream previously, so that the response to the control cream, which was labeled "B," was negligible, and only seven of the seventy-nine reported moderate improvement with no marked improvement on the control side. By contrast, sixteen reported marked improvement and an additional thirty-seven moderate improvement on the side where cream "A," con- taining pregnenolone, was used so that fifty-three out of the seventy- nine, or 67 per cent, observed a significant improvement with the test cream. The diffbrence between these results was statistically highly significant. These investigators made the following observations: "A. The compound is completely nontoxic, both locally to the skin itself and systemically, with no evidence of systemic absorption whatever. B. On the average, ten days to two weeks is required for the hy- drating effect to be evidenced after beginning use. While our patients were given the application once daily, a small group used the pregnenolone

136 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Subjects 50' 40- ne 30- 20- I0- O- CREAM A with pregnenolone IMPROVEMENT Rating I Marked 3 M Moderate 2 • Slight I o CREAM B control base 1.77+-0.10 Mean Improvement 0)'5 ñ 0.07 Figure 9.--Improvement after three months of treatment in double blind half-face tests. acetate twice daily and it would appear that this offers some advantages as far as hydrating effects are concerned. C. The majority of patients were able to determine themselves which side contained the pregnenolone acetate, not only by appearance, but also by a feeling of fullness of that side." A number of other clinical studies and consumer tests of this product have been carried out, all of which confirm that pregnenolone has a hy- drating effect upon the skin, resulting in a smoother, plumper appearance and increased feeling of firmness. In general, the more aged the skin, the more dramatic the results a few tests which were conducted in younger persons bothered by problems unrelated to skin aging were inconclusive. D•scuss•oN It is interesting to theorize on the mechanism of action of pregnenolone on the skin and its relationship to local estrogenic activity, particularly in the light of several other findings which have recently been reported. With pregnenolone, we have found asteroid with marked dermal activity which possesses no hormonal activity systemically. This was clearly shown by Hornburger, et al. (19) in their paper on "The Use of Hairless Mice for Study of Cosmetics," in which a number of steroids, including testosterone and ethisterone, were compared with estrogens both alone and combined with progesterone, for their dermal effects. Pregnenolone and 2-methoxy estradiol were included in