A-dex during pct? Anyone?

[WilliamH.Bonney]

Originally Posted by access

Your slightly mistaken here sorry William.

Arimidex does not effect estradiol greatly at all. It does reduce it somewhat but not significantly whereas it DOES raise endogenous test levels and this is why I raised the issue that it has been trialed as a "form" of test replacement in hypogonadal men rather than direct test replacement.

See below as reference:

Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels.

Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C.
Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

As men age, serum testosterone levels decrease, a factor that may contribute to some aspects of age-related physiological deterioration. Although androgen replacement has been shown to have beneficial effects in frankly hypogonadal men, its use in elderly men with borderline hypogonadism is controversial. Furthermore, current testosterone replacement methods have important limitations. We investigated the ability of the orally administered aromatase inhibitor, anastrozole, to increase endogenous testosterone production in 37 elderly men (aged 62-74 yr) with screening serum testosterone levels less than 350 ng/dl. Subjects were randomized in a double-blind fashion to the following 12-wk oral regimens: group 1: anastrozole 1 mg daily (n = 12); group 2: anastrozole 1 mg twice weekly (n = 11); and group 3: placebo daily (n = 14). Hormone levels, quality of life (MOS Short-Form Health Survey), sexual function (International Index of Erectile Function), benign prostate hyperplasia severity (American Urological Association Symptom Index Score), prostate-specific antigen, and measures of safety were compared among groups. Mean +/- SD bioavailable testosterone increased from 99 +/- 31 to 207 +/- 65 ng/dl in group 1 and from 115 +/- 37 to 178 +/- 55 ng/dl in group 2 (P < 0.001 vs. placebo for both groups and P = 0.054 group 1 vs. group 2). Total testosterone levels increased from 343 +/- 61 to 572 +/- 139 ng/dl in group 1 and from 397 +/- 106 to 520 +/- 91 ng/dl in group 2 (P < 0.001 vs. placebo for both groups and P = 0.012 group 1 vs. group 2). Serum estradiol levels decreased from 26 +/- 8 to 17 +/- 6 pg/ml in group 1 and from 27 +/- 8 to 17 +/- 5 pg/ml in group 2 (P < 0.001 vs. placebo for both groups and P = NS group 1 vs. group 2). Serum LH levels increased from 5.1 +/- 4.8 to 7.9 +/- 6.5 U/liter and from 4.1 +/- 1.6 to 7.2 +/- 2.8 U/liter in groups 1 and 2, respectively (P = 0.007 group 1 vs. placebo, P = 0.003 group 2 vs. placebo, and P = NS group 1 vs. group 2). Scores for hematocrit, MOS Short-Form Health Survey, International Index of Erectile Function, and American Urological Association Symptom Index Score did not change. Serum prostate-specific antigen levels increased in group 2 only (1.7 +/- 1.0 to 2.2 +/- 1.5 ng/ml, P = 0.031, compared with placebo). These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Serum estradiol levels decrease modestly but remain within the normal male range. The physiological consequences of these changes remain to be determined.

Either way we agree that running an AI for 2-3 weeks after last test shot does have it's advantages and this is what Haz initally made mention of and you initially seemed to dispute but perhaps this was due to the confliction on exactly when PCT commences.

I'm not really sure what you are arguing here, and I'm not really sure where I am mistaken. So lets go through it, and no I'm not trying to start a pissing match. I think we are agreeing on more than we are disagreeing on.

Arimidex is not a "form" of testosterone replacement. There are no forms of testosterone replacement. Arimidex is a "form" of treatment for hypogonadism. As I stated before only exogenous testosterone can be used to replace endogenous testosterone. Maybe I'm being a little too anal about your terminology, but from my perspective the way you state this makes it incorrect.

If you re-read my previous post I never stated to what degree Arimidex decreased estradiol. In the abstract you posted the decrease in estradiol in both groups one & two are approximately 37%. I would call this a significant decrease when you take into consideration the powerful ability of estradiol to inhibit the secretion of LH and FSH. Which in some of the literature I have read can be around 1000 fold that of testosterone.

However, I find the exact numbers of estadiol levels stated in the abstract to be a moot point. What we are focusing on is, as stated in the abstract, "These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels." In my previous post I agreed that arimidex raises testosterone levels. But it does this through the inhibition of aromatase, which lowers estradiol. Testosterone levels would not be raised without this effect. It seems to me, you are under the impression that arimidex works by more than one mechanism to raise testosterone levels. So I'm saying it doesn't matter to what degree arimidex lowers estradiol, only that it does, and that is why it works to raise testosterone.

[hazcat]

I have to agree that an AI's action works through preventing the formation of estradiol that shuts down natural testosterone production. In a very simplistic explanation...natural testosterone production is controlled by a negative feedback loop.

As natural testosterone rises in the body it is continously converted to estrodiol except for a small active amount. As the body produces more and more testosterone more estrodiol accumulates and receptors in the body recognize at a certain level that there is too much estrodiol. This stimulates the male body to shut down natural testosterone production. With less testosterone in the body less is available to convert to estrodiol. As the estrodiol levels drop the male body recognizes this decrease which indirectly stimulates the production of testosterone again. This cycle repeats itself over and over throughout our lives.

In the study the elderly male with low testoterone levels. They had an AI administered that helped to reduce the estrodiol levels which in turn signaled their body to increase endogenous testosterone production.

I believe we all can agree that once our cycle is complete it can be beneficial to run an AI to keep estrodiol levels in check and enhance the body to begin it's own production of testosterone. If any male even those that are "natural" ran a low dose of an AI you would see an increase in testosterone. Doing this would take months and months of AI dosing adjustments that would more than likely never end. With that thought in mind I do believe an AI can be beneficial particularly in the early phases of pct. I would also offer that gradual decrease in the AI could be beneficial during the initial phase of hcg, clomid and/or nolvadex usage. Hcg will cause spikes as the natural mechanisms of testosterone are stimulated. An AI could be beneficial in buffering this spike from aromatizing. It would take a lot of blood work to see when those spikes occur and when the AI should be increased and decreased which is down to the point of splitting hairs. I'm not gyno prone so I don't run an AI nearly as often as others but I do use them and I do use them in a tapering out dosage even part way into nolva use. I stop all all AI's in late pct and run only the nolva toward the end.

I like arimidex throughout the cycle when running products with great aromatizing tendencies. I switch to Exemestane (Aromasin) which I believe gives superior results in pct. I reserve letro to incipient phases of gyno symptoms. Several articles have been written on this topic and I wish I could produce them for you. This is a great thread and deserves the articles to explain but I just don't time to look them up again right now. If you care to do a little leg work, one of them was by the controversial but entertaining writer Anthony Roberts. If I find it I'll post it up here in a little while.
I'm short on time now but hope to continue this discussion soon. I really enjoy learning from all. Keep up the good work everyone!!!!

[hazcat]

I found this on my computer. I'm not certain where I got it. It's a long read but interesting if you're into this type of thing

by Anthony Roberts -- 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.

So 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 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.

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?

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.

[dashizzle]

AWESOME read, thanks.