6-OXO Test Booster Reviewed: Potent Aromatase Inhibitor?
Note: 6-OXO has been discontinued (so much for “legally available for a long time to come!”).
“…we truly believe that we have developed the most effective and safest testosterone booster ever. Best of all, this product is both natural and non-hormonal, so it is and will remain legally available for a long time to come!! The Era Of Prohormones Is Over. The Era Of 6-OXO Has Begun!”
It’s true: the “era” of prohormones is over in the United States. Prohormones were banned as of January 2005. This left various “orphan” supplements used in prohormone cycles behind, in search of new applications. 6-OXO (4-Androstene-3,6,17-trione) was one of the best known, and a core ingredient of many prohormone cycles.
6-OXO is a suicide inhibitor of the aromatase enzyme, which converts the “male” hormone testosterone, into the “female” hormone estradiol (an estrogen). This is what made it a valuable addition to a prohormone cycle…It could be used on-cycle, if aromatizable compounds were being used; or following a cycle, for facilitating recovery of natural testosterone production (post-cycle therapy or “PCT”).
Understanding prohormones and the role of anti-estrogens
Normal testosterone production is controlled by the Hypothalamic-Pituitary-Testicular Axis (HPTA). The signal (GnRH) begins in the brain (hypothalamus). GnRH in turn signals the pituitary to release luteinizing hormone (LH); which signals the testes to produce testosterone. Testosterone and estrogen—produced from aromatization of testosterone—act back on the hypothalamus to modulate the release of GnRH. This process is known as “feedback inhibition” and maintains hormonal balance.
This balance is affected by prohormones (and anabolic steroids), which provide an outside source of excess hormones. If aromatizable compounds are being used, this can lead to excess estrogen as well—which can cause undesirable side effects such as gynecomastia (“bitch tits”).
The excess hormones also shut down natural testosterone production. After the cycle is over, it takes some time before natural production is fully restored. The goal of PCT is to enhance the recovery process, and facilitate the retention of the gains made on-cycle.
Anti-estrogens have a vital role to play in both situations. Controlling estrogen on-cycle helps to minimize side effects. Controlling estrogen synthesis during the post-cycle period helps make the most of limited testosterone production, while reducing feedback inhibition from aromatization.
Now that prohormones are illegal, 6-OXO is being marketed as a standalone supplement for increasing testosterone. Does it actually boost testosterone levels when taken solo?
The answer is a qualified “yes.” Studies on a prescription aromatase inhibitor (AI), anastrozole, have shown that the concept is valid…AIs, in fact, have the potential to be used as an alternative to hormone replacement therapy.
This makes 6-OXO an attractive prospect for boosting testosterone—especially for men who have low testosterone, yet not low enough to qualify for prescription testosterone replacement therapy (such as Androgel or Testim).
6-OXO itself has been shown to raise testosterone in two separate trials: the first was a small, unpublished clinical study conducted by a private company (Human Performance Specialists, Inc.); the second, a formal study performed at Baylor University.
The first study is not publicly available or peer-reviewed, and only selected highlights are published on ErgoPharm’s web site. The second, however, has been published in the Journal of the International Society of Sports Nutrition, so we can look at the results in detail.
In the Baylor study, the test subjects—who were healthy, “recreationally active” males—took either 300 mg or 600 mg of 6-OXO over a period of 8 weeks. By the end of the test period, there were similar, and significant, increases in free testosterone, DHT (an active testosterone metabolite) and the T/E (testosterone to estrogen) ratio for both groups. Even better, there were no adverse effects on markers of clinical safety.
In short, 6-OXO works for increasing testosterone and appears to be perfectly safe. So at this point, you might be asking why I used the word “qualified” earlier?
This is because most men want to increase their testosterone levels to experience the known physiological benefits: more muscle, less body fat and increased libido. As it turns out, the study authors also measured changes in body composition, and concluded that there were no significant changes.
“In regard to body composition, neither dose of 6-OXO demonstrated any significant improvement in fat mass or fat-free mass over the course of the study. Even with significant increases in FT and DHT, this furthers indicates that 6-OXO supplemented at these dosages for eight weeks did not decrease fat mass or cause an anabolic response by increasing muscle mass.”
Anecdotal reports on the use of 6-OXO bear this out: many users taking it as a standalone supplement report minimal changes in body composition or other “quality of life” measures that normally accrue from testosterone replacement therapy.
Why? It’s an interesting question. In his review of 6-OXO in “Bodybuilding Revealed,” supplement guru Will Brink opined:
“The almost universal negative feedback is puzzling. My hunch is that there needs to be a high enough increase in testosterone to hit some physiological threshold for people to see real changes in body composition.”
There may be another explanation, however. Daniel Rohle is the lead author of the Baylor study, and additional details about it are available in his thesis. This point was puzzling to the Baylor team too, but Rohle’s hypothesis was based on the chemical nature of 6-OXO.
“This lack of change even at higher testosterone levels can probably be attributed to 6OXOTM‘s chemical structure. By being chemically similar to testosterone, it could interact with testosterone in a competitive fashion not only at the aromatase enzyme but also at the androgen receptor in muscles. Competition at the androgen receptor would decrease testosterone’s ability to bind to the receptor and stimulate muscle growth. This would explain the lack of increased muscle mass with increased testosterone concentrations.” (p. 62)
Is it possible that 6-OXO can both raise testosterone…and interfere with testosterone, all at the same time? It’s a plausible hypothesis: a study on exemestane, another prescription aromatase inhibitor that’s chemically similar to 6-OXO, showed that a prominent metabolite, 17-hydroxyexemestane, binds quite strongly to androgen receptors. This isn’t proof, of course, but it does lend support to the possibility.
So where does this leave us?
6-OXO has a solid reputation for use during/following prohormone cycles. While prohormones are currently illegal, it’s still quite possible to obtain various pro-hormonal and “designer steroid” supplements that have (for now) not been subjected to government action…in short, 6-OXO is still of use for those considering cycles of these compounds.
It certainly works to raise testosterone as a standalone supplement, but its effectiveness for making testosterone-related changes in body composition is debatable—at least during shorter term use. It may be that longer, more dedicated use is needed to bring about noticeable changes.