Since I consider long term hpta effects to be the most significant of the probable side effects of responsible aas use. I am trying to learn more about suppression. What causes hpta suppression? If it were estrogen, suppression could be eliminated with proper use of ancillaries. If it were the androgenic effect of steroids then non androgenic drugs such as deca would not create suppression while in reality it is a fairly suppressive drug.
I don't have time to elaborate on this right now, but suppression can occur through several mechanisms, but is largely dependant upon the drugs being used,the dose being ran, and the duration of the cycle.
If hpta health is of utmost concern, I would suggest keeping cycles to 6 weeks or less, and ideally 2-3 weekers, with twice as much time off AAS as on.
Any steroid supressed your HPTA. The stronger the steroid, the more supressive it is.
You cannot avoid supressing your HPTA. You can make it easier on your body by using HCG, preferably along with nolva, throughout your cycle, and then completely recover it by doing proper PCT after the cycle. You can also keep your cycles short and use 'weaker' steroids.
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I disagree that estrogen causes suppression.
The HPTA is a biofeedback loop that regulates hormone production in the body by reading what the body considers as homeostatic levels.
When exogenous testosterone is introduced the feedback loop reads the overload and signals the pitiuitary to cease production of certain hormones such as LH in an attempt to regain homeostasis.
Technically, testosterone shutdown by the HPTA is caused by excess testosterone. The HPTA can be compared to a thermostat. Excess heat causes the air conditioner to come on. When it returns to an acceptable temperature, the AC turns off.
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Well then you would be mostly wrong. Estrogen does cause suppression and in fact it is much more powerful than test in doing so as indicated by the fact that when an AI like arimidex is used during a short, low-mid dose test cycle, it will take almost twice as long to achieve shutdown.
Yes the body has a feedback system to control test/hormone levels, however there are also ER (estrogen receptors) in the HPTA which cause shutdown. While we are on the topic of receptors, i should mention that there is progesterone receptor mediated shutdown also and this is quite harsh as indicated by usage of tren and some of the current over the counter hormones that either escaped the ban or are being sold illegally, i suspect the latter.
As for homeostatic levels, these vary greatly and can be manipulated even without exogenous hormone therapy.
Testosterone shutdown by the HTPA could be caused by not only too much test, but any hormone that binds to the AR, ER or PR. This would include all steroids, including estrogen. Testosterone is only one of these compounds. I would not bother comparing the HTPA to a thermostat, it is much more complex than that.
ublo-Do you have any references re the data that the ai significantly reduces suppression? I was considering just useing nolva to avoid gyno and leave the est levels alone since I'm going to be bulking, but this info would probably cause me to change my mind.
Here is the one which convinced me to use AI, more specifically, Arimidex:
J Clin Endocrinol Metab. 2001 Jun;86(6):2600-6
Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men.
This in no way contradicts the fact that high doses of any androgen cause shutdown, but it does support what many are saying about using AIs during the cycle and for a short bit after. Trust, most the 'experts' who know their stuff recommend it as do I.
Hope this helps, otherwise go to pubmed and do a search with arimidex, men in the search box and you will soon find most relevant abstracts.
And the name is u,b,l,zero, not u-blo in case anyone was wondering.
I know that still itn't quite what you asked, but it is the best i could do. There are different types of suppression. Mainly from androgens and progesterones. Deca while not considered very androgenic will still lead to AR mediated shutdown in higher doses. But it will also lead to progesterone (PR) receptor mediated shutdown in addition to the AR. This is what makes higher doses of deca extremely suppressive.
The effect of having less shutdown only really takes place in the 2-3 week window, after that even high androgen levels in the (near) absence of estrogen will still lead to shutdown. I suspect that using an AI and keeping estrogen levels low allows the body to make an easier transition out of the cycle and back to natural production as one of the off signals has been circumvented. At this point, the estrogen mediated shutdown will be more sensitive to estrogen levels than if the person had done no cycle.
Wow...this is actually a question that I'm probably going to have to write a whole article on....seriously...
You know that story about the 3 blind men who each feel a different part of an elephant? One feels the ears and says "elephants are like birds" another feels the trunk and says "elephants are like snakes" and the last feels the legs and claims that "elephants are like trees." Thats what we have going on in this thread...everyone is kind of correct...but there's alot more to it...
It's really important though, as a question, and I think it should be answered as fully as possible, so I'll pitch TC the idea when I get back.
Anthony, I can't wait to see it. I'm lovin your other stuff I read here and am anxious for you to adress this issue in as comprehensive manner as you have other issues.
Great articles! (read twice!)
Post Cycle Therapy (PCT)
by Anthony Roberts
After a cycle, we have one goal: to hold onto the gains we made during the cycle. Unfortunately, this is easier said than done, because the levels of various hormones and other substances that were circulating around your body during the cycle (huge amounts of testosterone, insulin-like growth factor, growth hormone, and lower amounts of muscle-wasting glucocorticoids) are now changing. Sadly, they are making way for lower amounts of the hormones we want for building muscle, and higher amounts of the catabolic ones. What needs to be done, as quickly as possible, is to get your body to begin production of your own natural anabolic hormones, and produce less of the catabolic ones. Unfortunately, your body has other plans.
But then, so do I?
?and I?m very confident that this protocol will allow you to recover your own natural hormonal levels quickly and lose far less of the gains you worked so hard for on the cycle. This protocol, which is typically implemented after a cycle is called ?Post Cycle Therapy? or ?PCT? for short.
First, I?m going to tell you what anabolic hormones are typically low when a cycle ends, and which catabolic ones are high, then I?ll tell you what drugs can change that condition as fast as possible. Is all of this necessary? No, not at all. You can skip to the end of the article and look for a little chart I made - the extent of my computer skill - which has all of the dosage recommendations and compounds involved to properly recover from your cycle. I think, however, that you?ll see some very odd recommendations if you simply skip to the end, and will find yourself reading through the whole article to find out where they came from - or maybe you?ll just try to find out what?s gotten into me?
I?m not re-inventing the wheel here, and you may have seen a piece of this information elsewhere (possibly in something I?ve written, possibly somewhere else on the internet or in a magazine), but I?m sure of two things:
? You?ve never seen this PCT protocol anywhere
? This is the most effective PCT you?ll ever see
First, I?ll give you a brief explanation on the body and how it works, and why there?s a lag-time after the cessation of Anabolic Steroids before the body returns to normal. Remember, during this lag-time you lose gains, so we really need to make it as short as possible. First, we need to understand a bit of what is going on in your body, what causes it to happen naturally, and what hormones are performing what function. Don?t worry, I?ll try to make it painless.
At the age of puberty, Gonadatropin Releasing Hormone (GnRH) is increasingly released from the Hypothalamus, in turn causing the secretion of Follicle Stimulating Hormone (FSH) and Luetenizing Hormone (LH) from the pituitary, and finally the male gonads (testes) are then stimulated by those pituitary hormones (LH and FSH). (1). FSH, although generally thought to only have a role in production of sperm, actually aids the in regulation of Leydig Cell function (2), while LH directly causes the Leydig Cells in the testes to secrete androgenic hormones such as testosterone (which is causes a surge in other anabolic hormones: Insulin Like Growth Factor, Growth Hormone, etc?). Androgens do this by then targeting other tissues inside the body, either by attaching to the Androgen Receptors (AR), which are found primarily in the cytoplasm of specific cells, or by what?s known as non-receptor mediated effects. When an androgen (your own natural testosterone or an anabolic steroid you?ve injected or ingested) binds to a receptor inside the cell, it activates the transcription of specific genes. What does this mean? Don?t worry, it just means that the steroid molecule gives the cell a message to do something. In the case of testosterone, for example, one of the messages it sends to the cell is to increase nitrogen retention in your body, thus allowing you to use more of the protein you take in, and build more muscle. In the case of testosterone (or anabolic steroids in general), this transcription causes a lot of different anabolic effects to take place: an increase in IGF, a decrease in cortisol, an increase in Red Blood Cell count, and the increased protein synthesis I already told you about. This is not to say that AR binding is the only thing that causes anabolic or androgenic effects, however. Oxymetholone and Methandrostenolone (Anadrol and Dianabol) both bind very weakly to the AR yet are both highly anabolic and androgenic. The diagram below is an example of an androgen?s entry into a target cell, where it (in this case) stimulates protein synthesis, which is a major anabolic effect:
Under the control of this heightened state of androgens, you also go through androgenic development as well as anabolic development. This can be seen in puberty when males grow body hair experience voice changes, as experience genital development and growth.
Another characteristic of androgens in the body is that they are subject to what?s known as a ?negative feedback loop?. Lets review one of the first things I mentioned, ok? Your Hypothalamus secretes GnRH, thus making the pituitary secrete LH & FSH, finally in turn causing the testes to stimulate the Leydig cells to produce testosterone (by conversion of cholesterol), remember? Ok, now, once testosterone is created however, it has the ability to in turn to undergo various metabolic processes that will inhibit GnRH, which in turn inhibits the secretion of LH and FSH, and that brings a halt to natural testosterone production. Once testosterone has stopped being produced, it no longer sends this negative signal, and GnRH eventually begins to do its job again. In this way, your body prevents excess hormones from being secreted and thus maintaining homeostasis (the status quo? in this case a state where you are neither gaining nor losing muscle) (1). This negative feedback loop is partially why we use anabolic steroids?we want more testosterone for anabolic purposes (or more Anavar or whatever) than our body will let us produce (not that our bodies produce Anavar, but you get the idea). When we use that injectable testosterone, it sends the message to our body to begin the negative feedback loop and discontinue producing/secreting the hormones that cause our natural testosterone production. The chart below clearly shows this process, displaying both the negative and positive feedback system(s):
So what I?m saying is that anabolic steroids increase androgen levels in the blood, bringing a halt to GnRH, making the pituitary gland (eventually) responds by reducing the release of LH; this loss of LH has the effect of shutting down testosterone, of course, which you know is produced by the Leydig cells in the testes after they are stimulated by LH. Am I being repetitive? Yes. Do you need to understand all of this in order to understand the PCT protocol I?m about to outline? Yes. Remember, the negative feedback loop is, of course, no problem while we are on a cycle. Want more testosterone (or androgens) in your body? Fill up a few more syringes!
But all good things come to an end, and most of us choose to end our cycles at some point. At this point, while there is still some androgens floating around in us, our natural production won?t begin, and even once they are out, there may be some lag time before your body figures out that it needs to start producing its own androgens again. As I said before, this lag time is severely catabolic and it?s where you lose a lot of your gains. SO what we need to do is coax the body into quickly producing its own androgens.
One of the first drugs we?ll consider for this purpose is what is typically called a SERM. Nolvadex (Tamoxifen) is a SERM (Selective Estrogen Receptor Modulator, which means that it has the ability to act as an anti-estrogen with regard to certain genes, yet also acting as an estrogen with respect to others. That?s the ?selective? part I guess. It does this by blocking gene transcription in some cases, and initiating gene transcription in others (3). Luckily for us, it has estrogenic effects on bones (meaning it increases their density), and blood lipids -meaning it lowers cholesterol-, (4)(5)as well as preventing gynocomastia by preventing estrogen gene transcription in breast tissue. However, it acts as an anti-estrogen in the pituitary, thus increasing LH and FSH, which results in an increase in testosterone. 20mgs of Nolvadex will raise your testosterone levels about 150% (6)...Nolvadex actually has quite a few applications for the steroid using athlete. First and foremost, it?s most common use is for the prevention of gynocomastia. Nolvadex does this by actually competing for the receptor site in breast tissue, and binding to it. Thus, we can safely say that the effect of tamoxifen is through estrogen receptor blockade of breast tissue (7).
Estrogen is also important for a properly functioning immune system, and not only that, but your lipid profile (both HDL and LDL) should also show marked improvement with administration of tamoxifen (34).
Nolvadex also has some important features for the steroid using athlete. In hypogonadic and infertile men given nolvadex, increases in the serum levels of LH, FSH, and most importantly, testosterone were all observed (35)It can also block a bit of estrogen in the pituitary, which is a great benefit when used with HCG (more on that later) (36)(37). The increase in testosterone Nolvadex can give someone with a dysfunctional is basically that 20mgs of Nolvadex will raise your testosterone levels about 150% (6)...Why don?t we use Clomid, another SERM? Well, basically because it takes much more to do the same thing. In comparison, it would require 150mgs of Clomid to accomplish that type of elevation in testosterone, but Nolvadex also has the added benefit of significantly increasing the LH (Leutenizing Hormone) response to LHRH (LH-releasing hormone) (6). This most likely indicates some kind of upregulation of the LH-receptors due to the anti-estrogenic effect Nolvadex has at the pituitary. Although both Nolvadex and Clomid are both SERMs, they are actually quite different. As you already know, Nolvadex is highly anti-estrogenic at the hypothalamus and pituitary, while Clomid exhibits weak estrogenic activity at the pituitary (7), which as you can guess, is less than ideal. It should be avoided for the PCT I?m suggesting?and in fact, avoided in general?it?s simply not as good as Nolvadex.
Need I even add that the 150mgs of Clomid you need to get the hormonal increase experienced with 20mgs of Nolvadex is much more expensive? So lets dump the Clomid?and no, using it along with Nolvadex will provide no ?synergy? that I?ve ever seen in any relevant study.
SO how much Nolvadex should you use during PCT? I favor using 20mgs.day, although to be totally honest, you can probably even get away with far less than that. Doses as low as 5mgs/day have proven to be as effective as 20mgs/day for certain areas of gonadal stimulation. (8) 20mgs/day, however, is a dose that myself and others have used with great success, and the research I?ve done in this area typically uses this milligram amount. SO lets stick with 20mgs/day for now.
So that effectively suggests Nolvadex can not be used at Mega-doses to get a mega-increase in your natural hormones. We can?t use huge doses of any Anti-Estrogen, actually, and expect huge increases in our natural hormones, actually. Arimidex (an Aromatase Inhibitor ?which means it stops the conversion of testosterone into estrogen-another drug used to fight breast cancer like Nolvadex) exhibits basically the same effects when .5mgs or a full 1mg is used (9) and I have even read studies where up to 10mgs/day of Arimidex is studied with no clear benefit over 1mg/day. Letrozole (another Aromatase Inhibitor) is capable of inhibiting Aromatase maximally at a mere 100mcg/day (10.). So clearly we need to add in other compounds to our PCT, because Mega-Doses of one compound will not I think it?s absurdly funny to see people recommending upwards 40-80mgs/day of Nolvadex, or a full milligram (or two!) of Arimidex, in their post-cycle or on-cycle suggestions. I?d steer very clear of listening to anyone who makes those types of recommendations?
All of this tells me that you can?t simply use mega-doses of Anti-Estrogens or SERMS to do anything more than reasonable doses. It must be, therefore, that your body can only respond with so much vigor to any one drug in those families. So lets add in another drug or two, ok? This way we can use reasonable doses of a few drugs and produce some synergy?hopefully decreasing our recovery time.
We?ll need something to go with Nolvadex, which acts in a different manner, and Human Chorionic Gonadatropin (HCG) is the clear choice here. Here?s where things get a bit controversial (no, really?I know you , because I?m pretty much the only person around (currently) who recommends HCG for Post-Cycle Therapy. Although I?m seen as Old School in this respect, really, this is a totally new paradigm for HCG use, made possible only by the inclusion of the other compounds I am introducing to you for PCT. HCG is the natural choice, as it has been used successfully to cure AAS induced (11), and this alone warrants its inclusion to our cycle.
HCG is a peptide hormone manufactured by the embryo in the early stages of pregnancy and later by the placenta to help control a pregnant woman?s hormones (can anything really be said to control a pregnant woman?s hormones except ice-cream and chocolate?). Obviously, as you can guess from the name, it is a substance that stimulates the gonads (hence: gonadotropin). It does this by initiating gene transcription that is identical to that of Luetenizing Hormone, thereby causing the Leydig Cells to produce testosterone. Sounds great right? We can stimulate LH and FSH production with our Nolvadex, and then directly stimulate the Leydig Cells as well, to produce tons of testosterone by different routes! Well...it?s not all that simple.
Unfortunately, while HCG increases Testosterone, it increases estrogen as well(12). As you probably know, estrogen acts directly on the Leydig cells to effect changes in the activities of enzymes important for testosterone synthesis (13) and may actually be considered an important part of that negative feedback loop I mentioned earlier. In addition, an increase in circulating levels of LH have been shown to induce down-regulation of LH-receptors in both rodent studies (14), as well as in human studies (15); since HCG mimics LH, you can expect it to do the same. This LH downregulation can cause an increase in steroidogenic cholesterol (the cholesterol earmarked by your body for conversion into testosterone). (16). Thus, after the initial HCG induced surge in testosterone is over, if you have used enough to downregulate your LH-receptors and increase estrogen too much, then more steroidogenic cholesterol is available. This is telling me that less is being converted to testosterone. In fact, rodent models suggest that if you take a dose large enough to cause a sharp increase of plasma testosterone, you will actually desensitize your Leydig cells to your next shot, and will possibly not experience any rise in testosterone from the second dose at all, or may only experience a very slight one at best (17.). Since this is due to LH-Receptor downregulation, and that occurs in human models too, it is pretty fair to assume that if your first dose of HCG is too large, your second won?t be very effective. Unfortunately, this lack of an increase in testosterone doesn?t necessarily mean that the HCG may be unable to increase circulating levels of Estrogen (18) And remember that increase in Estrogen will (most likely) cause your body ultimately to produce less testosterone. Low LH post-cycle is not the primary cause of slow recovery, because LH generally rises to levels above baseline after a cycle much sooner than testosterone production does. This is probably because the pituitary is working very hard to get your atrophied Leydig cells to start producing testosterone again. HCG should also bring back testicular volume; I feel the need to mention this because it?s important to me and I suspect most men as well. It would also appear that HCG works very well when it?s used on men who have low levels of LH to begin with (as you would be after a cycle), as many studies on pre-pubertal boys and Hypogonadotropic Hypogonadal men would suggest (19)
This suggests that a pre-exposure to normal LH levels or gonadatropins in general is necessary for HCG-induced Leydig Cell desensitization. This, of course is not a problem for us, as we?ll be using it when LH/Gonadatropin levels are very low anyway ?we just need to stop using it before we regain normal function, or it will work against us eventually. (19) (20). Luckily, the temporary Anabolic steroid induced hypogonadism that is experienced after a cycle basically allows us to respond to HCG like anyone with low LH levels (21), and thus, as I told you, a lot of the possible inhibitory effect of HCG is not going to be relevant because there was no prior ?priming? by circulating gonadotrophins. This is great news for us, because we are going to be using HCG during PCT, when we need to get back some HPTA function, and not when we have levels of gonadatropins high enough to cause HCG-induced desensitization.
But are we still risking some inhibition and possibly delaying our recovery by using HCG? Probably not?you see, some studies in humans have shown that HCG does not actually have a direct effect on inhibiting LH release in men (22)(23), but rather (probably) works to inhibit LH secretion indirectly, simply by stimulating the production of testosterone (thus activating the negative feedback loop). Another factor involved is the induction of testicular aromatase, which raises estrogen levels, again causing inhibition. Unfortunately, yet another process, the downregulation of the Leydig Cell LH receptor itself, seems to also play a role in high dose HCG testicular desensitization. This is also done by HCG actually blocking the conversion of 17 alpha-hydroxyprogesterone (17 OHP) to testosterone (24). Nolvadex actually stops this blocking-action of HCG from taking place (25). Most likely, because of Nolvadex?s direct antiestrogenic effect and LH-upregulating effect on the Pituitary, suppression of gonadotropins via HCG is (25) almost totally stopped with concurrent administration of Nolvadex! So if we Use Nolvadex and we are only using HCG when we are low in gonadatropins, we won?t be inhibited by it at all! Right?
Well?maybe?but there?s still the issue of estrogen caused by that HCG-stimulated surge in testosterone. Well?we can use low doses (300iu or so) to avoid some of that major spike in estrogen, and thus cause far less inhibition from the HCG (26). Of course, I?d want to use a bit more HCG per injection (500iu), if I could, to get my body functioning fully more quickly, and lose less of my gains. Maybe we can get away with taking some Vitamin E with our HCG, since it increases the responsiveness of plasma testosterone levels to HCG, making them significantly higher during vitamin E administration than without it (27). So we can get a better response with our HCG by taking Vitamin E (I recommend 1,000iu/day), but that doesn?t get rid of the problem that we have, which is the estrogen increase the HCG will cause.
Lets solve that pesky estrogen problem now?.
Lets add in an Aromatase Inhibitor! Which one, though? Well, since we are already using Nolvadex, we can?t use Letrozole or Arimidex, as the Nolvadex will actually greatly decrease the blood plasma levels of them (28)!
So we have to use Aromasin (exemestane) as our AI, because it?s an aromatase inactivator, meaning it makes estrogen receptors useless, and instead of just inhibiting production (as an anti-aromatase would do) it cuts off production totally. Aromasin can also cause androgenic sides (29)(30)(31), which may help to elevate your mood while you are on PCT. This final drug in my recommended PCT can effectively remove up to about 85%+ of estrogen from your body (32). Most importantly, using Aromasin together with Nolvadex doesn?t reduce exemestane?s effectiveness (33). So now, I think the problem of ANY inhibition possible with HCG is solved, and we can use that 500iu/day dose that I wanted to use previously.
With this PCT, there will be a rapid increase in LH, FSH, and testosterone, as well as almost a complete block on all the factors that could be causing your natural hormones to be delayed in returning to baseline. For this reason, I feel that the second your cycle is over is when you should start this PCT (a week after your last shot, or the day after your last pill is fine). Remember, waiting for some of the extra androgens you?ve been taking to leave your body is nonsensical, as we want to start recovery as soon as possible to retain maximum gains. There is no evidence to suggest waiting any length of time after your cycle is over will increase PCT effectiveness?it simply prolongs the time you aren?t doing anything positive to regain your natural hormones. And how long do we run this for? Well?we need to stop the HCG relatively soon for reasons discussed earlier. But the Nolvadex, and Aromasin can be used for awhile longer. Ideally, we?d be getting weekly blood work, but we could also get it done monthly, and just running this PCT until we see our natural hormones restored?but weekly bloodwork isn?t really an option for most of us. Failing the option of monitoring recovery with blood-work, I?m going to give you my best thoughts on the time you should be running your PCT. It?s important to note I haven?t discussed nutrition or other compounds that may be beneficial?this is because in this article, I am primarily concerned with the restoration of hormonal function, nothing else. And with no further delays, here are my recommendations for PCT:
Week Nolvadex HCG Aromasin Vitamin E
1 20mgs/day 500iu/day 20mgs/day 1,000iu/day
2 20mgs/day 500iu/day 20mgs/day 1,000iu/day
3 20mgs/day 500iu/day 20mgs/day 1,000iu/day
4 20mgs/day 20mgs/day
Rationale for the Use of Aromasin with Tamoxifen During Post Cycle Therapy
Aromasin (Exemestane) is one of those weird compounds that nobody really knows what to do with. What we generally hear about it makes it very uninteresting?It?s a third generation Aromatase Inhibitor (AI) just like Arimidex (Anastrozole) and Femera (Letrozole). Both of those two drugs are very efficient at stopping the conversion of androgens into estrogen, and since we have them, why bother with Aromasin? It?s a little harder to get than the other two commonly used aromatase inhibitors, because it?s not in high demand, and there?s never been a readily apparent advantage to using it. And I mean?lets face it: It?s awkward-sounding. Aromasin doesn?t have much of a ring to it, and exemestane is even worse. Arimidex has a bunch of cool abbreviations ("A-dex" or just ?dex) and even Letrozole is just "Letro" to most people. Where?s the cool nickname for
Aromasin/exemestane? A-Sin? E-Stane? It just doesn?t work. It?s the black sheep of AIs. And why do we even need it when we have Letrozole, which is by far the most efficient AI for stopping aromatization (the process by which your body converts testosterone into estrogen)? Letro can reduce estrogen levels by 98% or greater; clinically a dose as low as 100mcgs has been shown to provide maximum aromatase inhibition (2)!
So why would we need any other AIs? Well, first of all, estrogen is necessary for healthy joints (3) as well as a healthy immune system (4). So getting rid of 98% of the estrogen in your body for an extended period of time may not be the best of ideas. This may be useful on an extreme cutting cycle, leading up to a bodybuilding contest, or if you are particularly prone to gyno, but certainly can?t be used safely for extended periods of time without compromising your joints and immune system.
That leaves us with Arimidex, which isn?t as potent as Letrozole, but at .5mgs/day will still get rid of around half (50%) of the estrogen in your body. Problem solved, right? Use Arimidex on your typical cycles, and if you are very prone to gyno or are getting ready for a contest, use Letro.
But what about Post Cycle Therapy (PCT)?
I think at this point most people are sold on the use of Nolvadex (Tamoxifen Citrate) instead of Clomid for post cycle therapy (PCT), since both compete estrogen at the receptor site, both increase serum test levels, and both drugs may also alter blood lipid profiles favorably (6). But since 20mgs of Tamoxifen is equal to 150mgs of clomid for purposes of testosterone elevation, FSH and LH, but Tamoxifen doesn?t decrease the LH response to LHRH (6) I think most people agree to Nolvadex?s superiority for PCT.
Aromasin with Nolvadex
I?ve always been in favor of using Nolvadex during PCT, along with an AI, because reducing estrogen levels has been positively correlated with an increase in testosterone (7) so in my mind, it?s be beneficial to increase testosterone by as many mechanisms as possible while trying to recover your endogenous testosterone levels after a cycle. SO which AI do we use? Letro or A-dex? Well, why don?t we just keep using whichever one we used during the cycle, and add in some Nolvadex? Unfortunately, Nolvadex will significantly reduce the blood plasma levels of both Letrozole as well as Arimidex (8). So if we choose to use one of them with our Nolvadex on PCT, we?re throwing away a bit of money as the Nolvadex will be reducing their effectiveness.
This, of course, is where Aromasin comes in, at 20-25mgs/day.
Aromasin, at that dose, will raise your testosterone levels by about 60%, and also help out your free to bound testosterone ratio by lowering levels of Sex Hormone Binding Globulin (SHBG), by about 20% (12)?SHBG is that nasty enzyme that binds to testosterone and renders it useless for building muscle. But what about using it along with Nolvadex for PCT?
Difference Between Type-I and Type-II Aromatase Inhibitors
To understand why Aromasin may be useful in conjunction with Nolvadex while both Letro and A-dex suffer reduced effectiveness, we?ll need to first understand the differences between a Type-I and Type-II Aromatase Inhibitor. Type I inhibitors (like Aromasin) are actually steroidal compounds, while type II inhibitors (like Letro and A-dex) are non-steroidal drugs. Hence, androgenic side effects are very possible with Type-I AIs, and they should probably be avoided by women. Of course, there are some similarities between the two types of AIs?both type I & type II AIs mimic normal substrates (essentially androgens), allowing them to compete with the substrate for access to the binding site on the aromatase enzyme. After this binding, the next step is where things differ greatly for the two different types of AI?s. In the case of a type-I AI, the noncompetitive inhibitor will bind, and the enzyme initiates a sequence of hydroxylation; this hydroxylation produces an unbreakable covalent bond between the inhibitor and the enzyme protein. Now, enzyme activity is permanently blocked; even if all unattached inhibitor is removed. Aromatase enzyme activity can only be restored by new enzyme synthesis. Now, on the other hand, competitive inhibitors, called type II AI?s, reversibly bind to the active enzyme site, and one of two things can happen: 1.) either no enzyme activity is triggered or 2.) the enzyme is somehow triggered without effect. The type II inhibitor can now actually disassociate from the binding site, eventually allowing renewed competition between the inhibitor and the substrate for binding to the site. This means that the effectiveness of competitive aromatase inhibitors depends on the relative concentrations and affinities of both the inhibitor and the substrate, while this is not so for noncompetitive inhibitors. Aromasin is a type-I inhibitor, meaning that once it has done its job, and deactivated the aromatase enzyme, we don?t need it anymore. Letrozole and Arimidex actually need to remain present to continue their effects. This is possibly why Nolvadex does not alter the pharmacokinetics of Aromasin (11).
Before we close the book on Aromasin, it?s worth noting that you can (and should) still use one of the non-steroidal AIs during your cycle to reduce estrogen, if necessary. When you are ready for PCT, you can then switch over to Aromasin and still experience the full effects of an AI, since there is no cross-over tolerance experienced between steroidal and non-steroidal AIs (9). Since Aromasin is about 65% efficient at suppressing estrogen (10), it?s certainly a very powerful agent, especially considering you won?t experience reduced effectiveness because of your concurrent use of Nolvadex or from any sort of tolerance developed by using other AIs on your cycle(9). There is also a decent amount of preclinical data suggesting that Aromasin has a beneficial effect on bone mineral metabolism that is not seen with non-steroidal agents, and it may also have beneficial effects on lipid metabolism that are not found in the non-steroidal Letro and A-dex (9).
Finally, as we?re going to be using Nolvadex for PCT anyway, and we ought to be using an AI with it for maximum recovery?I think Aromasin- considering it?s compatibility with Nolvadex and beneficial effects on bone mineral content and lipid profile, has finally stopped being the black sheep of AIs and found a home in our cycles.
Tamoxifen may prevent breast cancer
Well-known drug helps women with high risk of disease, study finds
Updated: 5:55 p.m. ET Nov. 15, 2005
WASHINGTON - Women at high risk for breast cancer who take the well-known drug tamoxifen can reduce their long-term risk of developing the disease, according to a new study released Tuesday.
Researchers found that women who took tamoxifen, sold as a generic and by AstraZeneca Plc under the brand Nolvadex, for up to five years were about 43 percent less likely to get breast cancer than those who took a placebo.
Out of 6,681 women taking the drug, 145 have developed cancer since the study began in 1992, compared with 250 cases in 6,707 women assigned to placebo, according to scientists at the Pittsburgh-based research network that conducted the trial with funding from the National Cancer Institute.
"This final analysis confirms that tamoxifen reduces the risk of invasive breast cancer in both pre- and post-menopausal women at increased risk for the disease," they said in a statement.
While a number of new medicines have been shown to treat the disease, such as Genentech Inc. and Roche's Herceptin and others, only tamoxifen has U.S.-approval to prevent it in high-risk women.
Researchers at the National Surgical Adjuvant Breast and Bowel Project network studied women at least 60 years old or who were between ages 35 and 59 with a high risk, such as having an mother or sister who had been diagnosed or experiencing breast lumps that were then tested.
About 17 out of every 1,000 women who are over 60 may develop the disease within five years, they said.
Breast cancer is one of the leading cancers among U.S. women. More than 200,000 are diagnosed and another roughly 40,000 die from it each year, according to the American Cancer Society.
Some women took the drug for up to five years, others for less time before researchers told participants in 1998 if they were taking tamoxifen and allowed them to opt for the drug. At that time, findings showed it could reduce cancer risk by 49 percent, and researchers have continued to follow the patients.
"There is proof of a benefit from tamoxifen beyond the time a woman is taking the pills," said Dr. Leslie Ford, co-author of the study and associate director for NCI's Division of Cancer Prevention.
They also found women taking tamoxifen experienced fewer broken bones than those taking placebo. Eighty women on the drug reported a hip, wrist or spine fracture compared with 116 reports from those on the placebo.
The earlier results also found tamoxifen increased the risk of cancer in the uterus lining as well as blood clots in the lungs and major veins. These new findings showed no statistically significant change, researchers said, although the rate of lung blood clots was 11 percent lower and uterine cancer was about 29 percent higher than in 1998.
Other possible side-effects, including stroke and cataracts, remained about the same as long as patients did not take the drug longer than five years, which could increase possible problems, researchers said.
The group is also studying tamoxifen's ability to prevent the disease in comparison to raloxifene, an osteoporosis drug sold under the brand Evista by Eli Lilly and Co.. Those results are due next spring.
European researchers are also studying AstraZenaca's new breast cancer treatment Arimidex, or anastrazole, for prevention.
Like tamoxifen, both drugs also work by blocking the hormone estrogen.
Copyright 2005 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content is expressly prohibited without the prior written consent of Reuters.
? 2005 MSNBC.com
Those are a couple of great reads...I can't wait for the book to come out!
i fully believe running an AI greatly aids your recovery come PCT time. no references to studies or journals to back that up.....just my own personal experiences/observations when using aromatizing gear, both with and without an AI during the cycle. some bros echo that sentiment...others do not. you just have to try it and find out for yourself.
Study Shows That Arimidex Boosts Testosterone
Estrogen suppression in males: metabolic effects.
J Clin Endocrinol Metab 2000 Jul;85(7):2370-7 (ISSN: 0021-972X)
Mauras N; O'Brien KO; Klein KO; Hayes V firstname.lastname@example.org.
We have shown that testosterone (T) deficiency per se is associated with marked catabolic effects on protein, calcium metabolism, and body composition in men independent of changes in GH or insulin-like growth factor I production. It is not clear,,however, whether estrogens have a major role in whole body anabolism in males. We investigated the metabolic effects of selective estrogen suppression in the male using a potent aromatase inhibitor, Arimidex (Anastrozole). First, a dose-response study of 12 males (mean age, 16.1 +/- 0.3 yr) was conducted, and blood withdrawn at baseline and after 10 days of oral Arimidex given as two different doses (either 0.5 or 1 mg) in random order with a 14-day washout in between. A sensitive estradiol (E2) assay showed an approximately 50% decrease in E2
concentrations with either of the two doses; hence, a 1-mg dose was selected for other studies. Subsequently, eight males (aged 15-22 yr; four adults and four late pubertal) had isotopic infusions of [(13)C]leucine and (42)Ca/(44)Ca, indirect calorimetry, dual energy x-ray absorptiometry, isokinetic dynamometry, and growth factors measurements performed before and after 10 weeks of daily doses of Arimidex. Contrary to the effects of T withdrawal, there were no significant changes in body composition (body mass index, fat mass, and fat-free mass) after estrogen suppression or in rates of protein synthesis or degradation; carbohydrate, lipid, or protein oxidation; muscle strength; calcium kinetics; or bone growth factors concentrations. However, E2 concentrations decreased 48% (P = 0.006), with
no significant change in mean and peak GH concentrations, but with an 18% decrease in plasma insulin-like growth factor I concentrations. There was a 58% increase in serum T (P = 0.0001), sex hormone-binding globulin did not change, whereas LH and FSH concentrations increased (P < 0.02, both). Serum bone markers, osteocalcin and bone alkaline phosphatase concentrations, and
rates of bone calcium deposition and resorption did not change. In conclusion, these data suggest that in the male 1) estrogens do not contribute significantly to the changes in body composition and protein
synthesis observed with changing androgen levels; 2) estrogen is a main regulator of the gonadal-pituitary feedback for the gonadotropin axis; and 3) this level of aromatase inhibition does not negatively impact either kinetically measured rates of bone calcium turnover or indirect markers of bone calcium turnover, at least in the short term. Further studies will provide valuable information on whether timed aromatase inhibition can be useful in increasing the height potential of pubertal boys with profound
growth retardation without the confounding negative effects of gonadal androgen suppression.
Clomid, Nolvadex and Testosterone Stimulation
By: William Llewellyn
I have received a lot of heat lately about my preference for Nolvadex over Clomid, which I hold for all purposes of use (in the bodybuilding world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting drug, and as a testosterone-stimulating compound. Most people use Nolvadex to combat gynecomastia over Clomid anyway, so that is an easy sell.
And for cholesterol, well, most bodybuilders unfortunately pay little attention to this important issue, so by way of disinterest, another easy opinion to discuss. But when it comes to using Nolvadex for increasing endogenous testosterone release, bodybuilders just do not want to hear it. They only seem to want Clomid. I can only guess that this is based on a long rooted misunderstanding of the actions of the two drugs. In this article I would therefore like to discuss the specifics for these two agents, and explain clearly the usefulness of Nolvadex for the specific purpose of increasing testosterone production.
Clomid and Nolvadex
I am not sure how Clomid and Nolvadex became so separated in the minds of bodybuilders. They certainly should not be. Clomid and Nolvadex are both anti-estrogens belonging to the same group of triphenylethylene compounds. They are structurally related and specifically classified as selective estrogen receptor modulators (SERMs) with mixed agonistic and antagonistic properties. This means that in certain tissues they can block the effects of estrogen, by altering the binding capacity of the receptor, while in others they can act as actual estrogens, activating the receptor.
In men, both of these drugs act as anti-estrogens in their capacity to oppose the negative feedback of estrogens on the hypothalamus and stimulate the heightened release of GnRH (Gonadotropin Releasing Hormone). LH output by the pituitary will be increased as a result, which in turn can increase the level of testosterone by the testes. Both drugs do this, but for some reason bodybuilders persist in thinking that Clomid is the only drug good at stimulating testosterone. What you will find with a little investigation however is that not only is Nolvadex useful for the same purpose, it should actually be the preferred agent of the two.
Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using Nolvadex instead of Clomid for increasing testosterone levels (1). Here, researchers looked the effects of Nolvadex and Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant.
What was found, just in the early parts of the study, was quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum testosterone levels to 142% of baseline, which was on par with the effect of 150mg of Clomid daily for the same duration (the testosterone increase was slightly, but not significantly, better for Clomid). We must remember though that this is the effect of three 50mg tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the Nolvadex side.
Pituitary Sensitivity to GnRH
But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response.
The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The tests showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment).
As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.
The Estrogen Clomid
The above discrepancies are likely explained by differences in the estrogenic nature of the two compounds. The researchers' clearly support this theory when commenting in their paper, "The difference in response might be attributable to the weak intrinsic estrogenic effect of Clomid, which in this study manifested itself by an increase in transcortin and testosterone/estradiol-binding globulin [SHBG] levels; this increase was not observed after tamoxifen treatment". In reviewing other theories later in the paper, such as interference by increased androgen or estrogen levels, they persist in noting that increases in these hormones were similar with both drug treatments, and state that," ?a role of the intrinsic estrogenic activity of Clomid which is practically absent in Tamoxifen seems the most probable explanation".
Although these two are related anti-estrogens, they appear to act very differently at different sites of action. Nolvadex seems to be strongly anti-estrogenic at both the hypothalamus and pituitary, which is in contrast to Clomid, which although a strong anti-estrogen at the hypothalamus, seems to exhibit weak estrogenic activity at the pituitary. To find further support for this we can look at an in-vitro animal study published in the American Journal of Physiology in February 1981 (2).
This paper looks at the effects of Clomid and Nolvadex on the GnRH stimulated release of LH from cultured rat pituitary cells. In this paper, it was noted that incubating cells with Clomid had a direct estrogenic effect on cultured pituitary cell sensitivity, exerting a weaker but still significant effect compared to estradiol. Nolvadex on the other hand did not have any significant effect on LH response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.
To summarize the above research succinctly, Nolvadex is the more purely anti-estrogenic of the two drugs, at least where the HPTA (Hypothalamic-Pituitary-Testicular Axis) is concerned. This fact enables Nolvadex to offer the male bodybuilder certain advantages over Clomid.
This is especially true at times when we are looking to restore a balanced HPTA, and would not want to desensitize the pituitary to GnRH. This could perhaps slow recovery to some extent, as the pituitary would require higher amounts of hypothalamic GnRH in the presence of Clomid in order to get the same level of LH stimulation.
Nolvadex also seems preferred from long-term use, for those who find anti-estrogens effective enough at raising testosterone levels to warrant using as anabolics. Here Nolvadex would seem to provide a better and more stable increase in testosterone levels, and likely will offer a similar or greater effect than Clomid for considerably less money. The potential rise in SHBG levels with Clomid, supported by other research (3), is also cause for concern, as this might work to allow for comparably less free active testosterone compared to Nolvadex as well.
Ultimately both drugs are effective anti-estrogens for the prevention of gyno and elevation of endogenous testosterone, however the above research provides enough evidence for me to choose Nolvadex every time.
Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen, Comhaire. Fertil and Steril 29 (1978) 320-7
Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro. Adashi EY, Hsueh AJ, Bambino TH, Yen SS. Am J Physiol 1981 Feb;240(2):E125-30
The effect of clomiphene citrate on sex hormone binding globulin in normospermic and oligozoospermic men. Adamopoulos, Kapolla et al. Int J Androl 4 (1981) 639-45
An important consideration when planning a steroid cycle, in particular the timing of dosing to be administered, is the active half-life of the drug being employed. The half -life may be defined as the time (t) the level is half of the starting level of a given compound; at time 2t, the level is a quarter of the starting level, and at time 3t, the level is an eighth of the starting level, and so on.
This information is vital in the timing of the dosing when attempting to achieve a more stable blood concentration, which leads to greater overall results and maintenance of gains. Some fluctuations of concentration levels are acceptable, and are also mostly unavoidable, but should be kept to a minimum.
Basically every drug has a half life, steroids included. If for example, you were to inject 200mg of Decadurabolin once weekly, for 6 weeks, how would you know when you were "off"? Would you be "off" when you had finished your last dose? You would be able to calculate this from the half life of Deca. The half life of Deca is around 14 days. This means that 14 days from your last shot of 200mg of Deca, your blood levels of Deca will contain 100mg of the steroid. Another 14 days from then, i.e. 28 days from last dose, your blood levels will contain 50mg of the steroid. This amount then keeps halving every 14 days. Therefore you can clearly see that when you finish your cycle, even though you are not putting any steroids into your body, you may think that you are now "off", however you still have, and will still have for some time after your last dose, "active" blood levels of the steroid. Therefore you can plan what to use, how long for, and how long off your cycle, based on these half life's.
Below a list of half-life's of the most commonly used steroids, esters and ancillary compounds.
Oral steroids Drug Active half-life
Anadrol / Anapolan50 (oxymetholone) 8 to 9 hours
Anavar (oxandrolone) 9 hours
Dianabol (methandrostenolone, methandienone) 4.5 to 6 hours
Methyltestosterone 4 days
(tablets or depot taken orally) 9 hours
Depot steroids Drug Active half-life
Deca-durabolin (Nandrolone decanate) 14 days
Equipoise 14 days
Finaject (trenbolone acetate) 3 days
Primobolan (methenolone enanthate) 10.5 days
Sustanon or Omnadren 15 to 18 days
Testosterone Cypionate 12 days
Testosterone Enanthate 10.5 days
Testosterone Propionate 4.5 days
Testosterone Suspension 1 day
Winstrol (stanozolol) 1 day
Steroid esters Drug Active half-life
Formate 1.5 days
Acetate 3 days
Propionate 2 days
Phenylpropionate 4.5 days
Butyrate 6 days
Valerate 7.5 days
Hexanoate 9 days
Caproate 9 days
Isocaproate 9 days
Heptanoate 10.5 days
Enanthate 10.5 days
Octanoate 12 days
Cypionate 12 days
Nonanoate 13.5 days
Decanoate 15 days
Undecanoate 16.5 days
Ancillaries Drug Active half-life
Arimidex 3 days
Clenbuterol 1.5 days
Clomid 5 days
Cytadren 6 hours
Ephedrine 6 hours
T3 10 hours
Anthony Roberts (or others), Re your pct protocol. It seems overly general to recommend this 1 week after last shot of injectable. It does not appear that you advise paying any attention to half life of various gear. While 1 week might be great if I've been on nothing but Test Suspension but on the other hand if I've been on something like Deca starting pct after 1 week seems like a very bad idea since the aas levels won't be down enough to allow anything to prompt endogenous test for many more weeks. Even takeing a modest cycle of Test Enanthate 500 week for a mere 6 weeks, one week after last shot still puts me at a level of well over 900. My levels won't get under 100 for approx 6 weeks after my last injection.