6-OXO – The First Effective All-Natural Aromatase Inhibitor
by Patrick Arnold
Pat is responsible for launching several major product and innovation in the prohormone industry through LPJ Research and Ergopharm, including the first to release androstenedione, 1-AD, 6-OXO, 4-androstenediol, and 19-norandrostenediol. In addition, he is responsible for bringing innovative delivery systems to the prohormone market including HPB cyclodextrin, bioadhesive technology for sustained release, and sustained release sprays.
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. 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 compounsds 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. 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.
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?„?.
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. A corresponding increase in testosterone production is usually experienced as well.
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.
When and how you should use 6-OXO?„?
There are two main situations where 6-OXO?„? can come in useful. The first situation is in combating estrogen elevation while taking aromatizable prohormones or steroids. Aromatizable prohormones/ steroids include testosterone, testosterone precursors (4-androstenedione, 4-androstenediol), nortestosterone, nortestosterone precursors (19-nor-4-androstenedione, 19-nor-4-androstenediol), and synthetic anabolic steroids such as oxymetholone (Anadrol?®) and methandrostenolone (Dianabol).
The second situation where 6-OXO?„? stands very useful is in restoring full endogenous testosterone production after a cycle of prohormones or steroids. Prohormones and steroids act as replacements for natural testosterone, and as a consequence, prolonged usage of these substances results in the body resetting the level of its own natural testosterone production. Your body does this by adjusting the activity of the hypothalamic pituitary testicular axis, or HPTA. The HPTA acts like a thermostat that constantly adjusts the body’s production of testosterone to maintain a certain level in the blood. The hypothalamus is the primary sensor in this system, and it responds to both androgens (i.e. testosterone, DHT) and estrogens (derived from aromatization of androgens). The hypothalamus is so sensitive to estrogens in fact that administration of an estrogen blocker can often result in a very substantial surge in testosterone production. This is why steroid using bodybuilders take products such as Clomiphene (an estrogen receptor antagonist) and Anastrazole (an aromatase inhibitor) after cycles to jump-start their suppressed testicular testosterone production. Now, with the introduction of 6-OXO?„?, there is a natural – over the counter alternative available to these prescription only drugs.
Okay, am I saying that one has to be a prohormone or steroid user to find 6-OXO?„? useful? Certainly not! Even if you never touch prohormones/steroids you can obtain a very substantial and beneficial increase in natural testosterone production by taking nothing but 6-OXO?„?. For those that are wary of hormonal supplements and their effects on the bodies endocrine balance, yet still want to obtain the benefits of increased testosterone levels, 6-OXO?„? offers a very safe and effective alternative.
So how does one use 6-OXO?„?? If you are using it to combat estrogen during a cycle of aromatizable steroids then you can take it every day of your cycle, once a day (preferably with your evening meal) at a dosage of 200-600 mg. If you are using it to jump-start your testosterone production after a cycle of prohormones (or just to increase your own natural production in a clean state) then you would also take 200-600mg of 6-OXO?„? once a day, for a period of 3-6 weeks.
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.
2 Wilson, V.S., et al., .Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.??? Environ Health Perspect, 1999. 107(5):377-384.
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.
4 Numazawa M, Mutsumi A, Tachibana M, ???Mechanism for aromatase inactivation by a suicide substrate, androst-4-ene-3,6,17-trione. The 4 beta, 5 beta-epoxy-19-oxo derivative as a reactive electrophile irreversibly binding to the active site??? Biochem Pharmacol. 1996 Oct 25;52(8): 1253-9.
5 Numazawa M, Midzuhashi K, Nagaoka M, ???Metabolic aspects of the 1 beta-proton and the 19-methyl group of androst-4-ene-3,6,17-trione during aromatization by placental microsomes and inactivation of aromatase??? Biochem Pharmacol. 1994 Feb 11;47(4):717-26.
6 Numazawa M, Tsuji M, Mutsumi A, ???Studies on aromatase inhibition with 4-androstene-3,6, 17-trione: its 3 beta-reduction and time-dependent irreversible binding to aromatase with human placental microsomes???.J Steroid Biochem. 1987 Sep;28(3):337-44.
7 Marsh DA, Brodie HJ, Garrett W, Tsai-Morris CH, Brodie AM, ???Aromatase inhibitors. Synthesis and biological activity of androstenedione derivatives??? J Med Chem. 1985 Jun;28(6): 788-95.
8 Booth JE ???Effects of the aromatization inhibitor androst-4-ene-3,6,17-trione on sexual differentiation induced by testosterone in the neonatally castrated rat??? J Endocrinol. 1978 Oct;79 (1):69-76.
9 Levy H et.al, ???The inhibition by metopirone of 11beta and 19-hydroxylations of androst-4-ene-3,17-dione in bovine adrenal perfusion??? Steroids. 1965; 5:479-493.
10 Tan L et al., ???De novo biosynthesis of 6 beta-hydroperoxyandrostenedione in human placental microsomes.??? Biochem Biophys Res Commun. 1984 Feb 14;118(3):805-13.