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WHAT IS DESOXY DHEA AND HOW DOES IT WORK?

What is Desoxy DHEA and how does it work? By: Ben Esgro, BS,CSCS,CISSN

Desoxy (or Deoxy) DHEA is structurally similar to DHEA except for the fact that, as the name implies, an oxygen has been removed from compound (specifically at carbon #3). Although a single deoxygenation may seem to be an insignificant alteration, it notably alters the biological activity of the compound. Contrary to DHEA supplementation, which has been shown to influence both estrogen and to a lesser extent testosterone production in males [1], Deoxy DHEA acts as an anti-estrogen through unique structural interactions with the enzyme responsible for conversion of androgens to estrogens, aromatase (CYP19). To better illustrate how Deoxy DHEA works; let us first examine the structures of DHEA, Deoxy DHEA, Testosterone, and Androstenedione; the latter two of which are the primary substrates aromatase acts upon to create estrogens.

DHEA

DEOXY DHEA (R1=H, R2=CH3)

TESTOSTERONE

ANDROSTENEDIONE

To simplify our concept, let us first only focus on the rings of each of the structures illustrated above (A,B,C, D from left to right; so the A ring would be the first hexagon, B ring the second, and so on). Notice how they all have the same basic ring structures, 3 hexagons and one pentagon, this is the backbone structure of a steroid hormone. When it contains 19 carbons it is referred to as an androgen, hence the reason chemical names for androgens typically contain the word androstene (if there is a double bond) or androstane (no double bonds). If you have ever read the label for pro-hormonal products you have undoubtedly come in contact with these names before. As stated previously, the principal job of aromatase is to convert androgens to estrogens, as such, it has a high affinity for the two primary androgens Testosterone and Androstenedione. This affinity has been shown to be heavily based upon the structure of the D ring and the planarity of the A ring [2-3]. Although the attraction is strong between aromatase and the substrates Testosterone and Androstenedione, alternative structures can bind the enzyme more efficiently. This concept is referred to as competitive inhibition, where an inhibiting compound can bind to the enzyme with a greater affinity than the usual substrate thus preventing subsequent alteration to the substrate (Testosterone in this case). Again, it appears that A and D ring modifications are heavily influential upon the affinity of a compound to bind to aromatase. Specifically, a 17-carbonyl structure (D ring modification where a carbon-oxygen double bond is present) is required for tight binding to the active site of the enzyme [4], and 3-deoxy compounds (A ring modification where oxygen has been removed) have displayed higher affinities compared to the usual androgen substrates (Testosterone and Androstenedione) [2]. As you can see by observing the structure of Deoxy DHEA, it possesses BOTH of these characteristics which allows it is preferentially bind to aromatase, leaving greater circulating levels of Testosterone to exert their benefits.

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WHAT IS DESOXY DHEA AND HOW DOES IT WORK?

BOTTOM LINE

Although Deoxy DHEA is an effective competitive inhibitor of aromatase it is not nearly as potent as SERMs or other steroidal and non-steroidal suicide inhibitors [5]. The structure-activity relationships mentioned are not comprehensive as there undoubtedly exist additional structural manipulations that occur to further enhance aromatase affinity. Therefore, it is NOT an appropriate replacement to prescription compounds when heavy aromatase inhibition is required. It does however, offer a cost-effective, safe, and legal method of estrogen management as validated by independent lab tests and selected in vitro data.

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Paul M. Coates, M.R.B., Gordon M. Cragg, Mark Levine, Joel Moss, Jeffrey D. White, ed. Encyclopedia of Dietary Supplements. 2005, Marcel Dekker: New York, NY. Cepa, M.M.D.S., et al., StructureActivity Relationships of New A,D-Ring Modified Steroids as Aromatase Inhibitors: Design, Synthesis, and Biological Activity Evaluation. Journal of Medicinal Chemistry, 2005. 48(20): p. 6379-6385. Numazawa, M., et al., Role of Hydrophilic Interaction in Binding of Hydroxylated 3-Deoxy C19 Steroids to the Active Site of Aromatase. Journal of Medicinal Chemistry, 2001. 44(24): p. 4277-4283. Numazawa, M., et al., Synthesis and biochemical studies of 16- or 19-substituted androst-4-enes as aromatase inhibitors. Journal of Medicinal Chemistry, 1991. 34(8): p. 2496-2504. Numazawa, M., M. Nagaoka, and N. Sohtome, Aromatase Reaction of 3-Deoxyandrogens: Steric Mode of the C-19 Oxygenation and Cleavage of the C10C19 Bond by Human Placental Aromatase. Biochemistry, 2005. 44(32): p. 10839-10845.