DHEA: The Buffering Steroid?
DHEA may be unique among hormones for it’s lack of specificity for hormone receptor sites. Just as vitamin E has never been shown to have a specific metabolic role (it is only proved essential as a general antioxidant), DHEA may serve an equally general purpose. “DHEA is the first example of a buffer action for hormones that I know of,” states William Regelson. “It is a broad–acting hormone that only demonstrates itself under a specific set of circumstances. In that way, it is like a buffer against sudden changes in acidity or alkalinity. That is why when you get older, you’re much more vulnerable to the effects of stress. As Dehydroepiandrosterone declines with age, you are losing the buffer against the stress–related hormones. It is the buffer action that [helps prevent] us from aging.” The decrease of DHEA with age may result in gradual decline of a system for suppressing enzyme systems responsible for creating the building blocks of new cells, like lipids, nucleic acids (RNA and DNA) and sex steroids. The resulting rise in enzymatic activity in advanced age may be responsible for the proliferative events (cancer) and degenerative disease that become more frequent in advanced age. In this respect, DHEA might be best considered to be an anti–hormone, which might “De–excite” steroid–sensitive receptors that would otherwise lead to enhanced metabolic activity.

Dosage
Exact dosages for humans have not been clearly determined. Daily dosages vary from 5 to 10 mg to as much as 2000 mg, with 5, 10, 25 and 250 mg being the range for typical tablet and capsule sizes. DHEA is usually split into 2–4 daily doses, especially at the higher dosage levels. We recommend that dosage be adjusted to bring blood Dehydroepiandrosterone and DHEA–S measurements towards young–adult levels. These blood tests can be ordered by your physician (don’t forget to get your first test before you start taking DHEA).

Conclusion
Because of its generally universal function in human metabolism, DHEA is being associated with numerous human maladies. For example, DHEA has recently been found to have a highly statistically significant correlation with vertebral bone density in postmenopausal women suggesting that DHEA (and other weak androgens) may protect against osteoporosis. This, and its low toxicity, may tend to give DHEA the same panacea stigma that the antioxidants vitamin E and C suffer.

Regulatory Difficulties
In Europe, DHEA is already available as a drug in 5 and 10 mg doses (although it has been hard to obtain). It is used primarily for the treatment of menopause. In the United States, DHEA must first be approved as a drug by the FDA before it can be marketed for medical purposes. Unfortunately, this is an adversarial process (the drug companies advocating for the drug and the FDA demanding proof of efficacy and safety) which takes up to 100 million dollars and a decade to accomplish. Without a patent to restrict competition, prices cannot be raised high enough to recover the investment in the approval process. DHEA is an unpatentable substance.

References
Barrett–Connor E, Khaw KT and Yen SS. A prospective study of Dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. New England Journal of Medicine 315(24): 1519–24, 11 December 1986.
Bulbrook RD, Hayward JL and Spicer CC. Abnormal excretion of urinary steroids by women with early breast cancer. Lancet 2: 1238–40, 1962.
Bulbrook RD, Hayward JL and Spicer CC. Relation between urinary androgen and corticoid excretion and subsequent breast cancer. Lancet 2: 395–98, 1971.
Chen TT, et al. Prevention of obesity in Avy/a mice by Dehydroepiandrosterone. Lipids 12: 409–13, 1977.
Cleary MP and Fisk JF. Anti–obesity effect of two different levels of Dehydroepiandrosterone in lean and obese middle–aged female Zucker rats. International Journal of Obesity 10(3): 193–204, 1986.
Coleman DL, Leiter EH and Applezweig N. Therapeutic effects of Dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ–db/db). Endocrinology 115: 239–43, 1984.
Coleman DL, Leiter EH and Schweizer RW. Therapeutic effects of Dehydroepiandrosterone (DHEA) in diabetic mice. Diabetes 31: 830–33, 1982.
Coleman DL, Schweizer RW and Leiter EH. Effect of genetic background on the therapeutic effects of Dehydroepiandrosterone (DHEA) in diabetes–obesity mutants and in aged normal mice. Diabetes 33: 26–32, 1984.
De Peretti E and Forest MG. Pattern of plasma Dehydroepiandrosterone sulfate levels in humans from birth to adulthood: Evidence for testicular production. J Clin Endocrinol Metab 47: 572–77, 1978.
Kahn, Carol. Beyond the Double Helix: DNA and the Quest for Longevity, Times Books, 1985, page 143. A thorough and highly readable “Inside” account of DHEA research.
Loria RM, Regelson W and Padgett DA. Immune response facilitation and resistance to virus and bacterial infections with Dehydroepiandrosterone (DHEA). In: The Biologic Role of Dehydroepiandrosterone (DHEA), Mohammed Kalimi and William Regelson [Eds], page 107–130, Walter de Gruyter, New York, 1990. ISBN 3–11–012243–X.
Loria RM and Padgett DA. Androstenediol regulates systemic resistance against lethal Infections in mice. Annals of NY Academy of Sciences 685: 293–95, 1993.
Nyce JW, Magee PN, Hard GC and Schwartz AG. Inhibition of 1, 2–dimethylhydrazine–induced colon tumorigenesis in Balb/c mice by Dehydroepiandrosterone. Carcinogenesis 5: 57–62, 1984.
Orentreich N, Brind JL, Rizer RL and Vogelman JH. Age changes and sex differences in serum Dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 59: 551–55, 1984.
Pashko LL and Schwartz AG. Effect of food restriction, Dehydroepiandrosterone, or obesity on the binding of 3H–7, 12–dimethylbenz(alpha)anthracene to mouse skin DNA. J Gerontology 38: 8–12, 1983.
Schwartz AG. Inhibition of spontaneous breast cancer formation in female C3H(Avy/a) mice by long–term treatment with Dehydroepiandrosterone. Cancer Research 39: 1129–32, 1979.
Schwartz AG, Hard GC, Pashko LL, Abou–Gharbia M and Swern D. Dehydroepiandrosterone: An anti–obesity and anti–carcinogenic agent. Nutrition and Cancer 3: 46–53, 1981.
Schwartz AG, Nyce JW and Tannen RH. Inhibition of tumorigenesis and autoimmune development in mice by Dehydroepiandrosterone. Mod Aging Res 6: 177–84, 1984.
Schwartz AG, Fairman DK and Pashko LL. The Biological Significance of Dehydroepiandrosterone. In: The Biologic Role of Dehydroepiandrosterone (DHEA), Mohammed Kalimi and William Regelson [Eds], Walter de Gruyter, New York, 1990.
Yen TT, Allan JA, Pearson DV, Acton JM and Greenberg MM. Prevention of obesity in Avy/a mice by Dehydroepiandrosterone. Lipids 12: 409–13, 1977. by Ward Dean, M.D., and Steven Wm. Fowkes