Cytadren ®, the U.S. brand name for the drug aminoglutethimide, is an interesting non-steroidal compound first brought to our attention several years ago by the late Dan Duchaine. It is popular with some competitive athletes who are drug tested, as in many disciplines this substance is currently not banned or tested for. CytadrenrJ inhibits the production of cortisol (by blocking the conversion of cholesterol to pregnenolone, this first step in its biosynthesis), the aromatization of androgens to estrogens and to a lesser degree the production of adrenal androgens. Its effect on cortisol production is what first brought Cytadren ® to the attention of athletes. For someone with normal cortisol levels, it is thought that a little less could actually be a good thing. This is because while androgens give your muscle cells a message to increase protein synthesis, cortisol (~ catabolic hormone) gives the exact opposite message (to breakdown amino acids). Obviously this is a process we would wish to avoid, so the use of this drug was proposed. But since Cytadren ® also inhibits androgen production (to some extent), it was typically recommended that it be used by athletes with some form of testosterone. Together with even a relatively small dose, it was thought one could shift the ratio of anabolic to catabolic hormones well in favor of the former, the goal of course being new muscle growth. Cytadren ® is also known to inhibit the aromatase enzyme, giving it a very separate second use as an effective antiestrogen to use during heavier steroid cycles. As you will see, this trait may in fact prove to be the most important one to the athlete. Its action in this regard is course very similar to that of the new antiaromatase Arimidex®. although Arimidex® seems to do the job a bit more efficiently (however it is also the more costly option).
Medically Cytadren® is used to treat estrogen dependent breast cancer as well as Cushing’s syndrome, a condition in which the body overproduces cortisol. In these arenas effective dosing regimens are well documented. When first looked at in the realm of athletics however, research was bare as to the best way to use it as a cortisol lowering anti-catabolic. It was suggested after some thought that when used for this purpose a schedule of 2 days on and 2 days off would be effective. One thing is for certain, Cytadren® cannot be taken daily if prolonged cortisol suppression were desired. Dubbed the adrenal escape phenomenon, it was shown that after ~ short period of regular use your body would react to the lowered cortisol levels and release increased amounts of another hormone, ACTH (adrenocorticotropic hormone), in response. Increased ACTH will overcome the activity of Cytadren®, resulting in your body resuming normal cortisol production (basically making the drug useless)ba, When used medically a moderate amount of hydrocortisone is often supplemented to avoid this reaction. For athletes however, it was assumed that this would probably be a counterproductive practice. Thus the 2-day on 2 day off regime was implemented as another way to delay or even avoid this response. This is only a suggested practice, and as you will see is only relevant to its use as an anti-catabolic.
In seeing exactly how an athlete might and might not benefit from this drug, we can look at studies demonstrating that the main mechanism in which this drug benefits breast cancer patients (inhibition of peripheral aromatase activity) is different from that which interferes with ~orticosteroid production65. We also see that the dosage is important in triggering each particular response. It appears that aromatase inhibition is achieved at a much lower dose than is needed to block steroid production by the adrenal gland66. While a daily dosage of 1000mg is typically needed to inhibit the demolase enzyme (the enzyme responsible for converting cholesterol to pregnenolone, and the target when reduced adrenal output is needed), maximum suppression of aromatase and estrogen levels is achieved at a dosage between 250 and 500mg (a point where adrenal steroid blockage should not be noted). There also seems to be no added benefit by adding cortisol in terms of survival/response rate among breast cancer patients, pointing to the fact that the “adrenal escape phenomenon” bears no relation at all to its abilities as an aromatase inhibitor. We find that not only do we need a very high dose (4 tablets per day) to really inhibit cortisol production, but also that there is no need for an athlete to implement a rotating dose schedule if the drug is being used as an anti-estrogen.
In effectiveness as an estrogen maintenance agent this compound rates highly. Studies have shown it capable of decreasing aromatase activity as much as 92% after administration of only 250mg, and patient response rates show aminoglutethimide to be at least us effective as tarnoxifen therapy in treating estrogen dependent cancer cells, more so under certain conaitions. However, due to its discussed broad range of activity, including the potential inhibition of not only estrogens, but corticosieroids, aldosterone and androgens as well, it is not regarded as highly in terms of patient comfort. This is not to give the impression that complaints are very common though, as aminoglutethimide still has an extremely good safety record. It has simply been pushed aside in many cases for more recently developed arid selective agents. Athletes can however still consider it to be an extremely effective remedy for estrogenic side effects should it I~e available on the black market, at least as much so as Nolvadex. As for the daily dosage when taking Cytadren® to minimize estrogenic side effects, most experiment with anywhere from 1/2 a tablet to 2 tablets per day, with one tablet of 250mg probably being the most common dosage selected.
Although many believe they have used this drug as such, few ever reach the discussed necessary four tablets per day to notice true cortisol suppression. This drug is very rarely used as an anti-catabolic in a correct manner, and those who do venture this high commonly report fatigue and discomfort, stating that the drug is intolerable for any type of prolonged use. Sadly, we are starting to realize that its original proposed use of Cytadren® as a nonsteroidal muscle-building agent does not seem a plausible one. The only instances I really have heard of this drug ever being used at such doses with any type of positive response were competitive bodybuilders partaking in highdnsed Cytadren shortly before a show. They claimed the short-term rise in androgen to corticosteroid ratio greatly aided in their abilities to bring out a shove-ready hard and dense physique, and credit the drug as genuinely being a very effective pre-contest agent. in speaking with the late Paul Borresen he summed up the pre-contest use of Cytadren nicely:
“I hive had considerahle experience with the high dose use. It makes athletes sleepy and weak. It seems to help the last ten days before a show, and this is tried and tested.”
Cytadren® is not without its side effects and warnings which are numerous. To be very succinct, these include, but are not limited to, the already mentioned possibility of fatigue, as well as dizziness, sleep disorder, apathy, depression, nausea/vomiting, stomach upset, thyroid dysfunction and liver disease. The few athletes to take it at a dosage high enough to promote cortisol suppression additionally note that reduced levels of this hormone will bring about more aches and pains in your joints when trying to lift heavy. It seems logical that this could even lead to a greatly increased susceptibility to injury, so one should be careful not to overexert during the short periods in which this drug is used in high doses. Most of the listed side effects listed here are in fact related only to high dosed regimens that inhibit the adrenal production of cortisol. arc are rarely ever reported with athletes taking one or two tablets per day in an effort to use the drug as an anti-estrogen.
Cytadren® is an expensive pharmaceutical, selling for approximately $2 per tablet on the black market. This is probably the reason its use has not become more widespread. Tris price is however still considerably less than what would be spent or7 the more recently developed antiaromatase Arimidex®, which sells for as much as $10 per tablet. Since Cytadren® is not currently being counterfeited. all preparations seen on the black market could be considered a safe buy. Although manufactured in the United Sates, the black market will generally carry the Orimeten brand name from Europe.