For athletes familiar with prohormones and steroids, the female hormone estrogen is undoubtedly a familiar enemy. While most of us understand that estrogen is not necessarily always a harmful and worthless substance to men (in the right amounts it is necessary and beneficial), we still are aware that it must be kept under control or some pretty undesirable conditions may arise in the body.

The Evils of Estrogen
In males, higher than normal estrogen levels (or estrogen levels that are out of balance with androgen levels) can lead to several physiological disturbances. The most well known estrogen induced malady is, of course, gynecomastia (aka gyno or bitch tits). Gyno, simply put, is the growth of breast tissue in men. Usually gyno is a benign growth that is little more than a cosmetic nuisance, however it occasionally (rarely) can become malignant and lead to male breast cancer. Either way, it is something than definitely is anathema to any guy that takes pride in his physical appearance and musculature. Rock hard pecs topped off with puffy cone shaped girlie lumps are simply not for showing off - at least not in my neighborhood.

High estrogen can also promote excessive water and sodium retention, resulting in a bloated, puffy, and smooth appearance. Steroids that aromatize heavily (such as testosterone and Anadrol) are renowned for putting on lots of bodyweight. However, that body weight usually is in large part estrogen induced water retention, and certainly not all muscle.

If all this is not enough then there is the potent inhibitory effect of estrogen on the hypothalamus, resulting in a shutdown of testicular testosterone production. Science has demonstrated that perhaps the most important regulator of testosterone production in males is estrogen - produced by the conversion of testosterone (and other androgens) to estrogen in the body and the brain. Estrogen sends a signal to the hypothalamus to shut down production of a substance known as GnRH. GnRH is a hormone that stimulates the pituitary to produce luteinizing hormone (LH) which is the signal that tells the testicles to produce testosterone. Therefore, men with elevated estrogen levels will have suppressed testosterone levels and perhaps even atrophied testes. Not a pretty picture, eh?

Controlling estrogen in males
Bodybuilders who use steroids caught on years ago to drugs that control estrogen in the body. The first drugs to be utilized were estrogen receptor antagonists such as tamoxifen and clomiphene. These drugs worked by binding to the estrogen receptor like estrogens do, but unlike estrogens they are unable to translocate to the nucleus and activate estrogen responsive genes. While these drugs are somewhat effective in countering gynecomastia and testicular shut down, they still retain some estrogenic activity in certain tissues such as the liver. The result of this residual estrogenic activity can be a reduction in IGF-1 production and an increase in sex hormone binding globulin (SHBG) production. These are both undesirable side effects.

Later on, bodybuilders discovered aromatase inhibitors. These drugs work by blocking the production of estrogens in the body through binding to the enzyme aromatase. Aromatase catalyzes the transformation of aromatizable androgens (i.e. androstenedione, testosterone) into estrogens such as estrone and estradiol. By actually blocking the production of estrogens altogether, aromatase inhibitors do not share the undesirable estrogen agonist activity of estrogen receptor blockers. Instead they function as true anti-estrogens, and because of this have arisen as the most preferred compounds for combating estrogen.

6-OXO™, the first effective all natural aromatase inhibitor
Before I go into detail about 6-OXO™, I would like to give a very brief review and commentary on the current variety of estrogen blocking supplements.

The first estrogen blocking supplement to be introduced, and perhaps the most popular one to date is the isoflavone chrysin. Yes, chrysin has some good in-vitro (“test tube”) research on it that demonstrates it blocks aromatase. However, for years many experts including myself have contended that it suffers from very poor bioavailability, and therefore is ineffective in-vivo. Recently, an article has been published in a very reputable journal that substantiates this suspicion. [1] So chrysin, as promising as it once seemed, unfortunately appears to be a total bust.

After chrysin there was Indole-3-carbinol and Di-indoylmethane . These related compounds work by shifting the metabolism of estrogens away from strong estrogen compounds (16-hydroxylated) and towards weaker estrogens (2-hydroxylated). This can have benefits for women prone to breast cancer as 16-hydroxylated estrogens are quite notorious for promoting estrogen dependent breast cancer. However, there has never been any benefit demonstrated in men for reducing estrogen related effects or for increasing androgen levels. In fact, these compounds may actually REDUCE androgen levels. [2] So for males looking to reduce estrogen and raise testosterone, I-3-C and DIM are poor choices.

In addition to these aforementioned compounds there have been a slew of other compounds sold for estrogen control purposes. These include bioflavonoids such as quercitin, herbs such as Vitex Agnus Castus, and phytochemicals such as resveratrol (3,5,4’-trihydroxystilbene). None of these has ever been substantiated by any research to reduce estrogen levels or to increase testosterone levels.

6-OXO™
After years of research into natural estrogen blockers I finally discovered a compound that really truly works, in males, to both reduce estrogen and increase testosterone. Its called 6-OXO™, which is short for 3,6,17-androstenetrione.

6-OXO™ is what is known as a suicide inhibitor of aromatase. This means that 6-OXO™ binds to the aromatase enzyme in a permanent and irreversible manner, rendering it inactive. The result of this is an eventual diminishment of aromatase enzyme in the body and a concomitant reduction in estrogen levels. [3] [4] [5] [6] [7] A corresponding increase in testosterone production is usually experienced as well.[8]

It is important to note here that this deactivation of aromatase enzymes by 6-OXO™ does not mean that your body becomes permanently deficient in the ability to synthesize estrogen. Your body will react to the deficiency of enzyme by producing more enzyme to replace that which has been deactivated. Therefore, when you stop taking 6-OXO™ your aromatase enzyme level will quickly catch up to normal and full estrogen production will resume.




[1] Saarinen N et.al., “No evidence for the in vivo activity of aromatase-inhibiting flavonoids.” J Steroid Biochem Mol Biol. 2001 Sep;78(3):231-9. [3] Covey DF, Hood WF, “Enzyme-generated intermediates derived from 4-androstene-3,6,17-trione and 1,4,6-androstatriene-3,17-dione cause a time-dependent decrease in human placental aromatase activity” Endocrinology. 1981 Apr;108(4):1597-9.