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Sex steroids play an important role in skin morphology and physiology. To evaluate the specific effects of sex steroids, the thickness of each skin layer was measured in intact and gonadectomized (GDX) male and female mice, as well as in GDX animals treated for 3 wk with 17beta-estradiol (E2), dihydrotestosterone (DHT), or their precursor dehydroepiandrosterone (DHEA). Morphological analysis shows that the dorsal skin of intact male is thicker than in the female, whereas the epidermis and hypodermis are thicker in the female. After GDX, epidermal thickness decreases only in the female to become similar to that of the intact male. Epidermal thickness in GDX animals of both sexes increases after E2 treatment to a value similar to that of intact females, whereas an increase is observed only in females after DHEA treatment. Both DHEA and DHT increased dermal thickness whereas E2, DHT, and DHEA markedly reduced hypodermal thickness in GDX animals of both sexes. Under all conditions, the hypodermis remains thicker in females. GDX triggers a rapid hair growth from telogen to anagen with a thicker hair shaft diameter in females. This data shows that DHT, E2, and DHEA exert specific effects on the different skin layers and appendages.

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The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.

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