Publisher Summary A cause-effect relationship between decreasing Dehydroepiandrosterone sulfate (DHEAS) and accelerated aging, although intriguing, remains unproven. However, some animal and many epidemiologic studies are promising. Together they drive a continued quest to develop a physiologic, nonoral delivery system. Oral Dehydroepiandrosterone (DHEA) undergoes significant first-pass metabolism, which requires high doses, placing individuals at risk for side effects. Continued investigation of transdermal DHEA is needed. DHEA cream restores a hormonal milieu similar to that seen in the late follicular phase of a reproductive-age woman. Although effective, these creams require cumbersome regimens to attain adequate serum levels. Likewise, a patch is not practical, as the doses necessary would require an unacceptably large surface area. Consequently, a gel-based delivery system or a spray is the likely future solution. Oral DHEA cannot be recommended as an alternative treatment for menopausal women. Therapeutic nonoral DHEA, however, continues to hold substantial promise and is in great need of future investigation.