6 OXO is made by Ergopharm, the makers of the popular 1-AD before it was taken off the market when the Prohormone ban was implemented. One of the first estrogen blockers that was quite popular previously is Chrysin. It is promoted in bodybuilding to be an effective inhibitor of an enzyme known as aromatase which causes the conversion of testosterone into estradiol and androstenedione into estrone.
In many in vitro (artificial environment) studies, chrysin has been shown to be a very potent and natural inhibitor of human estrogen aromatase. Its ability to inhibit the aromatization of androstenedione and testosterone to estrogen has been well demonstrated in lab tests. However, in real life environments, Chrysin falls short of the promising results in vitro studies have demonstrated. I won't go in detail about it here, but you can read more about Chrysin in this article.
6-OXO (3,6,17-androstenetrione) is a natural estrogen blocker that reduces estrogen and increases testosterone levels. 6 OXO reduces estrogen by inhibiting aromatase, which is an enzyme of the cytochrome P450 superfamily that aromatizes androgens and produces estrogens. 6 OXO is a suicide inhibitor of aromatase, and when it binds to aromatase, the binding is irreversible [1]. When aromatase is inhibited, it follows that estrogen is also reduced, and there is a corresponding increase in testosterone.
Side note: You can read 6-OXO user reviews here. If you've used Ergopharm 6-OXO, you may also wish to share your feedback and review as well.
6-OXO and Estrogen
I'm sure most know what Estrogen is. It functions as the primary female sex hormone, but it is also present in males as well. However, higher than normal levels of estrogen can cause unwanted problems in men, with gynecomastia (or gyno) being the most well known. There are a slew of potential health problems when estrogen is out of balance. Testosterone levels decrease with age, but what you may not be aware of is that with age, some men also experience an increase in their estrogen levels as well, which leads to a testosterone / estrogen imbalance.
An increase in levels of estrogen can also cause a reduction in testosterone, leading to fatigue, increased body fat, lower sex drive, loss of muscle, and enlarged prostate - all undesirable side effects. The rise in estrogen and decrease in testosterone also increases men's risk of heart attack and stroke. Probably one of the more complained about problems is the lack of sex drive. High levels of estrogen also can lead to water retention leading to a bloated and smooth appearance - not something bodybuilders want.
Aromatase is an enzyme that converts testosterone into estrogen. As men age, their body produce more aromatase, which leads to higher levels of estrogen. By inhibiting the aromatase, there will be a decline in estrogen levels and usually a corresponding increase in free testosterone levels. What's the significance of "free testosterone" you ask? When testosterone is produced, it does not circulate freely in the blood. In fact almost 100% of the total testosterone is bound to proteins in the blood. The tiny fraction that is not bound is the free testosterone, and this is the bioactive component of testosterone. [1] Testosterone can be converted to DHT (dihydrotestosterone) or alternatively, it can be converted to estadiol by the aromatase enzyme.
This is exactly where 6OXO comes into play - it inhibits the aromatase enzyme, so that the aromatase can no longer convert testosterone to estrogen. 6 OXO has been shown to irreversibly bind to the aromatase enzyme thus decreasing estradiol levels, and also increase free testosterone, and DHT levels. [1]
6 OXO Clinical Study & 6 OXO Side Effects
There aren't many studies done on 6-OXO, but there is one double blind clinical study published in the Journal of the International Society of Sports Nutrition, which is a peer reviewed publication, and it is worth mentioning. This study was performed specifically to test the aromatase inhibiting ability of 6 OXO, its clinical safety, and to determine its effects on the hormone levels in the body. This 6 OXO study was a 8 week trial supplementing either a 300mg/day or 600mg/day of 6OXO that involved 16 healthy, active males. The subjects had an average age of 26.6 years, an average height of 180cm, average body weight of 87.3kg, and average body fat of 14.9%.
The subjects were given either a 300mg or a 600mg dose of 6OXO each day for a period of 8 weeks. Blood and urine samples were taken at start, 1, 3, 8, and 11 week time periods (the last 11 week sampling is after a 3 week washout period). Of these samples, total testosterone, free testosterone, DHT, estradiol, LH (leutinizing hormone), GH (growth hormone) and several other hormones were analyzed.
Below are some highlights of the findings of this 6 OXO study:
6 OXO did not exhibit any significant improvement in body fat mass, or lean mass over the 8 week study period - meaning no changes in muscle mass or fat mass was observed from using 6 OXO
The researchers stated that "6-OXO supplemented at these dosages for eight weeks did not decrease fat mass or cause an anabolic response by increasing muscle mass."
Free testosterone and DHT had significant increases during the trial period
For the 300mg dose group, free testosterone increased 90%, and DHT increased 192% (rather significant increase in DHT I'd say)
For the 600mg dose group, free testosterone increased 84%, and DHT increased 265%
At the end of the 11th week, after 3 weeks of washout period, all levels of these stated hormones have returned to normal base levels
Estrone levels increased 22% for the 300mg dose group, and increased 52% for the 600mg dose group (estrone is one the 3 estrogens).
Estradiol levels increased 27% for the 300mg dose group, and increased 12% for the 600mg dose group (estradiol is one the 3 estrogens).
Surprisingly, as you can see from above, the 300mg dose group had a slightly higher increase in free testosterone (90% compared to 84%), while the 600mg dose group had a significantly higher increase in DHT (265% compared to 192% for the 300mg group). This brings to light the fact that there isn't any additional benefit to be had consuming 600mg 6OXO daily compared to 300mg, and as concluded by the researchers: "for free testosterone, DHT there were no significant differences between groups, suggesting 300 mg and 600 mg of 6-OXO to be equally as effective in increasing androgen levels.
Also, from the above results, we see that estrogen levels also increased slightly while taking 6-OXO, slightly more so for the 600mg group compared to the 300mg dose group. These results suggest that aromatase activity is not completely inhibited by 6-oxo during the 8 week trial period. The study states:
However, our results suggest the contrary; 6-OXO does elevate testosterone and DHT levels without the complete inhibition of serum aromatase activity. As a result, it is conceivable that the apparent testosterone aromatization occurring was in part responsible for the observed elevations in estradiol and estrone.
So what does this mean? Considering that Ergopharm 6OXO is by no means a cheap supplement, you'd be better off taking 300mg dose per day instead of 600mg. With 300mg dose, you receive the same level of free testosterone increase. You'll save yourself some money, and will probably have a slightly lower chance of hair loss, as the 600mg dose increased DHT levels by 265% - yes, DHT causes hair loss. As you can see, there really is no additional benefit of supplementing more than 300mg of 6-OXO.
Because DHT is a testosterone metabolite, it only makes sense that as your testosterone levels increase, so will the DHT levels. This is the very reason, why some users of 6-OXO have reported increase in hair loss while taking 6oxo. So, if hair is important to you, and if you have a family history of hair loss, you may be at a higher risk of increased hair loss while taking 6-oxo.
The study found 6-OXO at the studied dosages, for a 8 week period appears to be safe, and at the same time, there were no adverse side effects reported by the subjects.
So what can we get from all of this? Several key points:
6-OXO is an effective inhibitor of the enzyme aromatase; however, it does not completely inhibit aromatase activities
Supplementing 6-OXO leads to significant increases in free testosterone, DHT, and also slight increases in estradiol and estrone (presumably from the fact that aromatase activity is not 100% inhibited)
There's no additional benefit of doubling the dose of 6oxo from 300mg to 600mg - in fact, supplementing with 600mg had increased DHT significantly more, and slightly increased estrogen levels over the 300mg dose
Supplementing 6 OXO appears to be clinically safe, with no adverse side effects reported; however, increased hair loss is a possible side effect of 6-oxo
1. J Steroid Biochem. 1987 Sep;28(3):337-44.
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.
Numazawa M, Tsuji M, Mutsumi A.
Tohoku College of Pharmacy, Sendai, Japan.
