Half-lives, AIs and PCT

[LeanMean]

Great thread... explains a lot but yet I have a question...

Can anyone explain the relation between the half life of a steroid and the length of a cycle? I understand the part that the steroid needs to reach a steady level in the system... but then, for how long should be in a steady level? is there a relation between the half life and the cycle's length?

Thanks in advance.

[darkrid3r]

I dont think there is, but cycle length is determined by the user.
Ester length is not, its a chemical thing.
HOWEVER there is a relationship between PCT and your longest ester.

[Hazcat]

Esters: Much more than just half-life…
by: Anthony Roberts
By the end of this article, you’re going to know:
• What an ester is and how it works
• Esters greatly impact much more than just half-life
• Esters influence the degree of a steroid’s conversion to estrogen
• Esters actually make a given steroid more or less anabolic
• Esters influence peak plasma levels of a given steroid
• Half-life/Active-life charts are all basically incorrect
Bold claims? Keep reading. I’m about to make a case for all of this being true…and by the end, you’re going to agree with me. Let’s go back a bit, first…
When I was in fifth grade I would take my math assignment home every day, and skip to the end of the was about putting the correct answer in the correct spot, and I really couldn’t see the point of understanding the process. I never understood the argument for being able to do long division…
I wondered if my teachers had ever heard of calculators.
I still spend most of my days looking for answers to questions now, and I still usually only care about the answer. But occasionally, I have an answer, and I need to go back and figure out why that answer is correct.
Let’s go back a bit more now…
An ester is essentially the thing attached to an anabolic steroid to allow it to extend its duration of effects. When you talk about “testosterone cypionate” or “testosterone enanthate” you are really talking about testosterone and an ester (cypionate or enanthate, respectively).
Not a single day goes by that I don’t receive an e-mail from somebody on their first cycle asking me about how frequently they should inject something-or-other; whether they need to inject Testosteone Cypionate every 3.5 days, or whether it’s ok to let it go to day 4. They also “know” that testosterone is just testosterone, and besides determining the active life (or half life, or whatever), the ester doesn’t actually change anything about the testosterone itself.

I just don’t have the heart to tell them that everything they think they know about esters…namely that they only influence the half-life and active life…is probably just plain wrong.
I’m going to make a case for different rates of testosterone conversion to estrogen based on different esters…and I’m also going to make a case for different testosterones (depending on ester) actually having differing anabolic potential. I also think this is applicable to virtually all steroids that aromatize and probably to all steroids that are able to convert to DHT or something 5a-Reduced.
Let’s take a look at some anecdotal evidence first, then I’ll give you some studies, and wrap it up with some nice little charts, which will tell you exactly which testosterones do what. First, the problem, as I see it:
Testosterone Propionate bloats me (and everyone else) less than Testosterone Enanthate. But…we often hear (and repeat) that “Testosterone is Testosterone” (especially on the internet, in steroid books, and in all the bodybuilding rags). But if test is test, then why do we see different effects from different esters? We gain more weight, have more water retention, and bloat much more with longer testosterone esters. This also seems to apply to the Nandrolones, as most people find Nandrolone Phenylpropionate (NPP) bloats them less than Nandrolone Decanoate (Deca). On the other hand, using a long ester with Masteron or Trenbolone doesn’t add any bloating at all.
What the hell is going on here?
By the end of this article you’ll think that testosterone is not just testosterone anymore, and you’ll know why using the propionate ester will bloat you less than the enanthate ester. But don’t just skip to the end…without understanding, the answers are as meaningless as the answers I was turning in to my fifth grade math teacher. Besides, you’ll wanna look smart next time someone asks you “why”, right?
But before I get into why everything you know about esters is probably wrong, let’s take a further look into this stuff and see what we’re missing.
And we’re going to start with the idea (and history) of the ester…
The first anabolic steroid that scientists added an ester to was testosterone. Straight testosterone is absorbed easily during oral administration but is pretty much destroyed by the liver soon after. So the injectable (or “parenternal”) route, for testosterone, was considered far superior, despite the inconvenience of having to inject (unestrified) testosterone every day.
Until that point, testosterone was the only game in town for androgen therapy. Then in 1953, 19-nortestosterone was discovered. And furthermore, it was discovered that an oral dose of 60mgs/kg/day of 19-nortestosterone was needed for the same results as 7mgs/kg/day of the injectable (non-estered) version. So an oral, in this case (19-nortestosterone with no alkylation or methylation) requires a dose of about 8.5x the same drug given by injection (without ester), to elicit the same results (Anabolic Steroids and Sports). I think this is about right. If you were to down a bottle of testosterone suspension you’d likely need to be drinking a bottle a day to see any kind of decent results. On the other hand, you’d only need 100mgs a day if you were injecting it. E
Therefore, we don’t see unaltered (non-estered) testosterone available as an oral formula. The best (oral) solution is to use 17- alkylated derivatives of testosterone (such as methyltestosterone), which are considerably more resistant to destruction in the liver; although, the potential for hepatotoxicity is much higher with this modification. So there is a way to take testosterone (or any steroid) and make it orally useful. But, of course, there is a way to make injecting them more convenient also, and that is to add an ester.
Adding an ester delays the amount of time that it takes for the steroid to leave the body, although peak concentrations are realized (with both long as well as short esters) within a day or two at most.
Different testosterone preparations and the years they became available for clinical use: 1940 = su**ermal testosterone pellet implants, 1954 =intramuscular testosterone enanthate, 1977 = oral testosterone undecanoate, 1992 = scrotal testosterone patch, 1995 and 1998 = transdermal testosterone patches, 2002 = transdermal testosterone gels, 2004 = buccal testosterone and intramuscular testosterone undecanoate Adapted from: Human Reproduction Update Advance Access originally published online on August 5, 2004 Human Reproduction Update 2004 10(5):409-419; doi:10.1093/humupd/dmh035
The esterification of the testosterone molecule at the 17-ß-hydroxy position makes the molecule hydrophobic (hydro means water, and phobic means “scared of”…just like any other phobia) and extends its duration of action. This means you don’t need daily injections of testosterone suspension, but rather, you can choose to utilize an estrified version. Although there were implants available previously (ouch!), testosterone propionate and enanthate were the first ones to widely be used clinically. You can see the 17th position on this diagram (where it says “17” of course)
Testosterone , estrified
It is the slow release of the hydrophobic testosterone ester from its oily depot in the muscle that accounts for its extended duration. The longer the side chain, the greater the hydrophobicity of the ester and the greater the duration of action. Thus testosterone enanthate with its longer side chain has a longer duration of action than testosterone propionate. The more carbons an ester has, typically, the longer it will take to release the parent hormone into the bloodstream. Esters have even been used to make steroids orally available (notably with Primobolan tabs and Testosterone capsules- Methenolone Acetate and Testosterone Undecanoate respectively).
However, testosterone undecanoate capsules are not nearly as effective as testosterone injections, based on both real world as well as clinical evidence, Primobolan tabs don’t stack up well against the injectable version, and and Trenbolone is roughly 100x more anabolic when you inject it instead of taking it orally:
Comparison of the relative anabolic potency of oral (po) vs. injectable (sc) dosing of Trenbolone on LABC muscle. (Toxicol. Sci., Dec 2002; 70: 202 - 211.)
Whether taken orally or injected, an esterfied steroid molecule is temporarily deactivated. In an injection, the ester chain temporarily blocks the 17-ß position, making binding to the androgen receptor is impossible. When the compound enters the bloodstream, esterase enzymes cleave off (hydrolyze) the ester, thus restoring the functional hydroxyl (OH) group at the 17-ß position, enabling the drug to attach to the androgen receptor and exert its effects.

[Hazcat]

Orally Active steroids
So now that we’ve taken a look at some different oral and injectable steroids, and their structures, you can see exactly what I’m talking about with the idea of adding an ester (in the parenternal box) versus the box showing the oral. You can see the long faty acid chain at the end, which we already know delays release of the hormone.
But that’s not all the ester does…
In 1954, a researcher named Reifstein and his colleagues compared an injection of Testosterone Propionate with Testosterone Enanthate, and they found that the injection of testosterone propionate resulted in nitrogen retention of 1.02g/day with a total measurable anabolic activity of 12 days, while the Enanthate version resulted in nitrogen retention of 1.76g/day and had a total measurable anabolic activity of 33 days. (1). Therefore, a 200mg shot of Testosterone (long ester) is going to have a greater overall anabolic effect than a 200mg shot of a short ester. That’s actually kind of common sense, isn’t it?
So does that mean that the ester effects the anabolic ability of the actual steroid. Well, yes, that would seem to be the case. If a steroid hangs out in your body for a longer amount of time, and helps you retain more nitrogen, then its overall anabolic effect would be greater. Granted, they’re studying a single injection- but with a typical injection schedule of testosterone propionate, as compared to testosterone enanthate, most people gain more weight from the enanthate version. Think about it; experience tells us that with an every other day injection schedule of 100mgs of testosterone propionate versus 400mgs/week of testosterone enanthate, most people gain more weight from the enanthate. Yet, the actual amount of injected (pure) testosterone is virtually the same, even when you subtract the weight of the ester.
Here’s my position, S-P-E-L-L-E-D out for you:
Testosterone, depending on the ester, will give you different effects in a variety of areas. Yeah, I’m saying the ester will have it’s own effect on how the testosterone is metabolized and used by your body. And that will give you different effects, depending on the ester you choose.
Testosterone
I thought testosterone is testosterone? Isn’t that what they say on the internet? If you hear it on a steroid forum, isn’t it true? Well, research dating as far back as 1954 says no. In fact, (primate) research as recent as this decade seems to say the same thing. Alright, I can hear the pubmed-scientists and keyboard-cowboys all over the internet shouting in protest right now. I know that primate studies aren’t perfect, but they’re offering us a clue as to why we all gain more weight on the longer esters versus the shorter esters. And in this case, they offer us a perfect- even elegant – explanation.
Why do we need an explanation for this? Well, because for literally decades we’ve been using short esters for cutting cycles and long esters for bulking cycles, and for all that time we’ve also been claiming that “testosterone is testosterone” regardless of ester. If we actually believed that last “fact”, we’d just be using the longest esters all the time, because they’re more cost effective per bottle. But we don’t; and we see different effects on water retention, gyno, weight gain, and other parameters, depending on the ester lengths.
Here’s what scientists found out when they examined different ester lengths:
Testosterone ester length can (and does) influence suppression of the gonadal axis, effects on anabolic parameters, and lipid metabolism. (2)
Furthermore, they reassure us that their results are most likely transferable to human males. Further-furthermore (I made that up), their research indicates that esters influence conversion to estrogen. (2) And when you think about what experience tells us, doesn’t that agree with the real world? Don’t people get gyno more frequently, more water retention, and higher bodyweight gains with longer esters? When is the last time you saw someone using a short ester and still need an anti-estrogen? And more estrogen also means more hypothalamic-pituitary-testicular axis suppression, because of the body’s negative feedback loop. Haven’t we always known that long esters suppress you more than short ones? It’s not just the time they are in the body, but also the amount that they convert to estrogen. Do the math if you don’t believe me…it can’t just be the extra couple days that long esters are active in the body. It’s the estrogen conversion.
Thus - the amount you suppress your natural hormonal system, the potential anabolic effect, and the effects on lipids, are all influenced by the ester length. Esters are not just something that delays the release of the hormone into the body…their length plays a crucial role in what degree the steroid actually performs certain functions.
I know it goes against everything that is typically said about esters, but think about it…don’t we use different testosterone esters (in the real world) for different things….long esters for bulking and short esters for cutting? I’m presenting new information
Alright…let me tell you about a study now. Scientists (real ones, with lab coats and everything) examined 3 different testosterone preperations with different ester lengths. What they found was that the shortest ester provided the highest peak levels of testosterone, followed by the medium length ester, and the lowest peak level was found with the longest ester. Even a two- to threefold higher dose of the shortest acting ester studied did not fully achieve the effects of longer esters concerning gonadal and metabolic functions. (2) Did I mention that the amount of pure testosterone (minus the ester) was the same in all injections? So what does that tell us?

The ester influences far more than just the release time and active life of the parent hormone.Estradiol levels were significantly higher with the longest ester. Yes…Using longer estered testosterone will cause a higher rise in estrogen. And, although the same total amount of testosterone was injected in all groups, the group using the longest acting version gained the most weight.

[Hazcat]

(Estrogen)
Also of interest in this study is that even though testosterone was used for 28 weeks in a row, the shortest ester allowed the most rapid return of natural hormonal levels. Sperm count also remained highest with the shortest ester, and lipid profiles were worse with the longer acting testosterone. And once again, even though this was only a primate study, the authors believe these results are transferable to human males…and bodybuilders who have used different esters for different goals will confirm this as well.
The identifiable pattern of exposure and degree of aromatization and estrogen, rather than overall exposure to testosterone, determined the differing effects of the different esters. Longer esters cause a higher rise in estrogen (even when the total dose of testosterone is identical). That’s why we all get more water retention on testosterone enanthate, while testosterone propionate doesn’t cause much if any. This is the explanation that we have been waiting for…because I know that even when people say “test is test” they don’t really believe it- or we’d be seeing short ester bulking cycles and long-ester cutting cycles.
Oh…and if this weren’t the case, then why is it that people almost always talk about using an anti-estrogen with long estered testosterone and not usually with the short estered variety?
Have I mentioned that testosterone’s effect on Growth Hormone and IGF-I (two very anabolic hormones) are also dependant on aromatization to estrogen? Again, this is why we gain more muscle with the long estered tests. (3, 4, 5). This means that you actually get far more anabolism from the longer estered testosterones, because the increased conversion to estrogen will provide a greater elevation in your GH and IGF-1 levels. And many other positive effects of testosterone are actually dependent on it’s conversion to estrogen as well. (6, 7, 8)
But does this apply across the board, to esterfied (aromatizable/DHT-convertible) hormones other than testosterone?
It probably does…in fact I’m pretty much positive that it does. Let’s take a look at the 19-nortestosterone derived family of anabolics, specifically Nandrolone.
When comparing different preparations of Nandrolone, many of these similar properties were found when a long ester (decanoate) was compared with a short one (Phenylpropionate).Peak plasma levels are higher with the shorter esters, suppression is greater with longer esters, and so on. (9,10) Of course, with Nandrolone (compared with testosterone) the degree of suppression is pretty harsh regardless of the actual ester used…but still, you can see more lengthy suppression with the longer ester. And another study also shows a higher anabolic effect when longer nandrolone esters are compared with short ones (11,12). Basically, what I’m saying here is that we’re seeing the same thing with different Nandrolone esters as we saw with testosterone esters; more imnportantly, the scientific research confirms what we know to be true in our own cycles, and also gives support for my explanation as to why this is happening.
It’s the ester length! And it sure as hell isn’t just affecting the half-life! Well….it’s likely that the release of the parent hormone is subject to different aromatization levels based on it’s release time…but still, the end result is that the ester is greatly influencing the actual effects because of this.
Unfortunately, in this study, only one injection was used…but again, we know that people who’ve used Nandrolone Phenylpropionate get less bloating then when they’ve used Nandrolone Decanoate.
Let’s go back to the other two drugs I mentioned earlier, namely the long estered versions of Trenbolone and Masteron. It doesn’t matter what ester you use with them, because neither of them convert to estrogen at all. In fact, since one is already derived from DHT, and the other isn’t subject to 5a-reduction, neither “convert” to DHT at all.
Dihydrotestosterone
In order for a hormone to become the dihydro version, is must be 5alpha-reduced (or already exist as such). Does ester length also influence 5a-Reduction? I suspect it may. But in this case, I would imagine that the long esters convert less readily to DHT (though I guess I could be wrong).
If I’m right, then it would seem to give us another explanation of why we gain less weight on short esters…DHT is a potent androgen, but a disappointing anabolic, due to deactivation by the 3-alpha Hydroxysteroid Dehydrogenase enzyme. Increased conversion to DHT in short esters inversely correlated with a decreased conversion to estrogen would provide us with a neat, bow-wrapped, conclusion to all of this. I tend to think that the fact that ester length doesn’t have any real effect on 1. non-aromatizing androgens which also 2. can’t be further 5a-reduced – gives us strong inductive evidence to believe that there is more DHT conversion with short esters. Unfortunately, the research doesn’t give me 100% reassurance on the DHT-thing (however, the estrogen thing regarding esters is set-in-stone- gospel now, as far as I’m concerned). There is, however, some strong evidence in medical journals to support my thoughts on this (13, 14, 15, 16).
I’m speculating that short esters convert to more (not-really-very-anabolic) DHT, and that would also give us a clue as to why stuff like testosterone propionate is better at getting us a nice hard physique than testosterone enanthate. It fits…I just can’t be 100% sure on it. But I hope you joined me in that logical leap…because it sure gives us a safe landing on the other side, doesn’t it? I think this modulation and difference depending on ester in DHT levels is much more modest than those we see with estrogen levels (depending on ester).


To sum everything up in a nice neat package:
• Longer esters are more anabolic than shorter ones
• Shorter esters cause less water retention
• Longer esters cause more gonadal suppression
• Shorter esters cause a higher peak plasma level
• Most of this is only applicable to steroids that are estrified, aromatizable, and able to convert to DHT
I think I’ve made a pretty reasonable case for esters influencing far more than just active-life or half-life…and I think we’re about to see a new paradigm in the use of esters for different reasons.
I rest my case.

References:
1. Reifenstein, et. al. Studies comparing the effects of certain testosterone esters in man.J Am Geriatr Soc. 1954 May;2(5):293-8.. PMID: 13162731
2. Journal of Andrology, Vol. 24, No. 5, September/October 2003 Copyright © American Society of Andrology Pharmacokinetics and Degree of Aromatization Rather Than Total Dose of Different Preparations Determine the Effects of Testosterone: A Nonhuman Primate Study in Macaca fascicularisGERHARD F. WEINBAUER*, CARL-JOACHIM PARTSCH, MICHAEL ZITZMANN, STEFAN SCHLATT AND EBERHARD NIESCHLAG
3. Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M, Smith ER 1993 Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. J Clin Endocrinol Metab 76:996–1001
4. Eakman GD, Dallas JS, Ponder SW, Keenan BS 1996 The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion. J Clin Endocrinol Metab 81:1217–1223
5. [Veldhuis JD, Metzger DL, Martha Jr PM, Mauras N, Kerrigan JR, Keenan B, Rogol AD, Pincus SM 1997 Estrogen and testosterone, but not a nonaromatizable androgen, direct network integration of the hypothalamo-somatotrope (growth hormone)-insulin-like growth factor I axis in the human: evidence from pubertal pathophysiology and sex-steroid hormone replacement. J Clin Endocrinol Metab 82:3414–3420
6. The role of aromatization in testosterone supplementation: Effects on cognition in older men M. M. Cherrier, A. M. Matsumoto, J. K. Amory, S. Ahmed, W. Bremner, E. R. Peskind, M. A. Raskind, M. Johnson, and S. Craft Neurology, Jan 2005; 64: 290 – 296
7. The Complex Role of Estrogens in Inflammation Rainer H. Straub Endocr. Rev., Aug 2007; 28: 521 – 574
8. The Protective Effects of Estrogen on the Cardiovascular SystemMichael E. Mendelsohn and Richard H. Karas N. Engl. J. Med., Jun 1999; 340: 1801 - 1811.
9. Pharmacokinetics and Pharmacodynamics of Nandrolone Esters in Oil Vehicle: Effects of Ester, Injection Site and Injection VolumeCharles F. Minto, Christopher Howe, Susan Wishart, Ann J. Conway, and David J. HandelsmanJ. Pharmacol. Exp. Ther., Apr 1997; 281: 93.
10. Belkien, L., Schurmeyer, T., Hano, R., Gunnarson, P. O. and Nieschlag, E.: Pharmacokinetics of 19-nortestosterone esters in normal men. J. Steroid Biochem. 5: 623-629, 1985
11. 1. Chaudry, M.A.Q.; James, K.C.; et al. J. Pharm. Pharmac., 1976, 28, 882-885
12. Chaudry, M.A.Q.; James, K.C. J. Med. Chem., 1974, 17, 157-161.
13. Comparison of testosterone, dihydrotestosterone, luteinizing hormone, and follicle-stimulating hormone in serum after injection of testosterone enanthate of testosterone cypionate.Fertil Steril. 1980 Feb;33(2):201-3.
14. Behre HM, Nieschlag E. Comparative pharmacokinetics of testosterone esters. In: Nieschlag E, Behre HM, eds. Testosterone: Action, Deficiency, Substitution. 2nd ed. Berlin: Springer;1998:329-348.
15. Pharmacokinetic properties of testosterone propionate in normal menM Fujioka, Y Shinohara, S Baba, M Irie, and K Inoue J. Clin. Endocrinol. Metab., Dec 1986; 63: 1361 – 1364
16. Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthateCJ Partsch, GF Weinbauer, R Fang, and E NieschlagEur. J. Endocrinol., Apr 1995; 132: 514 - 519.