Beste Aromatase Inhibitor (AI)

[Kevster]

Natuurlijk is het moeilijk om te zeggen welke nou eigelijk de beste is omdat iedere AI zijn voor en nadelen heeft. We kennen allemaal Proviron, die eigelijk niet eens een AI genoemd wordt, maar wel vaak met die bedoeling genomen wordt. Verder hebben we Letro, Aromasin en Arimidex. De ene zweer bij deze, de ander weer bij die. Vaak wordt wel geroepen dat Arimidex toch de beste is maar deze wat aan de prijzige kant is. Van de ene kant gooit het wel je oestrogeen praktisch naar nul, wat ook weer zijn nadelen heeft. Wat en waarom vindt jij dat de ene beter is dan de andere? Denk hierbij aan prijs, toepassing, halfwaarde, bijwerkingen etc. Ik ben nieuwgierig naar verschillende meningen over het gebruik van een AI tijdens een cycle, dus niet als PCT.

[GeneralIx]

Laat me eerst maar wat droge cijfers smijten. Eigenlijk hebben wij het bij AI's maar over drie namen: Anastrozole (Arimidex), Letrozole (Femara) en Exemestane.
Qua t1/2:
Exemestane 27 uur.
Letrozole: 48 uur.
Anastrozole: 46.8.

Een langere halfwaardetijd staat doorgaans in verband met stabielere bloedwaarden. Hierom zou ik dan ook zeggen dat Letro hier "the drug of choice" zou zijn. Let wel dat het verschil met Anastrozole verwaarloosbaar is, en het ook nog de vraag is of je bij consequente inname (absolute therapy compliance) echt schommelingen gaat zien tussen de verschillende producten.

De mate van onderdrukking:
PubMed Central, Table 1: Br J Cancer. 2011 March 29; 104(7): 1059?1066. Published online 2011 March 1. doi:****10.1038/bjc.2011.58

Enige wat ik wel wil benadrukken in die ratio's, is dat die niet direct vertaalbaar zijn naar mannen (de onderzoeken zijn eigenlijk alle op vrouwen gedaan). Laat staan dus dat je die resultaten van vrouwen met een veel lagere testosteronspiegel gaat vertalen naar kuurders. Niettemin lijken de verschillen tussen die middelen erg klein, waarmee het dus zeer de vraag is in hoeverre er echt een beter is op basis van deze resultaten.

Qua bijwerkingen zie ik de mensen die Letro gebruiken toch het meest klagen. Lethargie, gebrek aan libido etc. Exemestane wordt maar weinig gebruikt heb ik het idee (dat zal ook te maken hebben met de prijs), en Arimidex is de meest populaire. Probleem wat je hierbij wel in ogenschouw moet houden ook, is dat een groot gedeelte van de gebruikers zoveel stackt dat het maar de vraag is waar de bijwerkingen vandaan komen.

Er is echter, in mijn ogen, een heel belangrijk verschil tussen de Exe en de andere twee. De Exe bindt irreversibel (vandaar de term suicide inhibitor) aan het aromatase enzym. Dat wil zeggen, door deductie, dat er onmogelijk een oestrogeenrebound kan komen, gezien er niet plotseling weer allemaal aromatase-enzympjes ronddrijven. De andere twee, ana en letro, binden reversibel. Logischerwijs zou je kunnen aannemen dat het bindt, los komt, de AI gezuiverd wordt, en je nog steeds met een te hoge oestrogeenspiegel komt te zitten.

Het is lastige materie, zeker omdat er ook weinig onderzoeken zijn op mannen. Daarnaast betreffen de gekende bijwerkingen voornamelijk die van forumleden, verspreid over de boards, en die zijn wellicht niet altijd te wijten aan de AI, of overdreven, etc. etc. Er moeten dus de nodige slagen om de arm gehouden worden met dit alles.
Niettemin, als ik kon kiezen, Exemestane zonder twijfel. Ook al is het duurder dan de andere twee.

[Kevster]

De suicide inhibitie maakt Aromasin wel een stuk interessanter, Aromasin schijnt ook de enige te zijn die niet je HDL/LDL verpest. Ik lees dat letro het beste zou zijn voor het combatten van gyno, omdat deze je oestrogeen het verste terug brengt van de drie en klierweefsel kan doen slinken.

[Kevster]

Toch een stukje dat misschien waard is om te posten, deze komt van streroid.com.

Proviron

Mesterolone

Proviron (mesterolone) is basically an orally active DHT (Dihydrotestosterone) preparation. For comparision, we can think of some other orally prepared DHT compounds like Winstrol, Anavar, etc& Those both act very similarly in mechanism to Proviron, but a more accurate way to think of this compound is as something like "Oral Masteron." As Im sure you noticed, their anabolic/androgenic ratio is very similar.Remember, DHT is 3 to 4 times as androgenic as testosterone and is, of course, incapable of forming estrogen. Also, Proviron is quite unique in that a simple look at its 4-ring structure will show us that it is not going to be too liver toxic, since it is not c17-Alpha-Alkylated, as many orals are& this modification (lacking in Proviron) makes drugs more liver toxic. Proviron has a 1-metyhl group added, instead. Looks pretty great on paper, right? Well, as usual, things tend to look better on paper than they do in the body. Your body has a negative feedback loop which prevents your body from having too much DHT floating around(if youve been paying attention up to now from reading my other stuff, you already know this). An excess of DHT will eventually be changed into another (largely not anabolic) compound.

And of course, being a DHT-based compound, Proviron isnt going to be great for female athletes to use. Virilization (development of male sexual characteristics) is going to be a concern for women daring enough to try this stuff. My advice is that there is much better, safer compounds for female athletes and bodybuilders to use.



So lets go back to the comparison with being some sort of "Oral Masteron"& basically since Proviron is 5-alpha reduced and not capable of forming estrogen, and also has a very high affinity for binding to the aromatase enzyme (the enzyme responsible for converting all that good testosterone in your body into all that nasty estrogen). That means if you choose to take proviron with testosterone (and I know you wouldnt even be doing a cycle without including some form of testosterone) and/or any aromatizable steroid, it should actually serve to prevent estrogen build up by the aforementioned binding to the aromatase enzyme, which prevents aromatase from doing its dirty work and making a bunch of estrogen out of the other steroids you are taking. It should also be noted that Proviron also binds very well to SHBG (Sex Hormone Binding Globulin& a hormone responsible for reducing the amount of circulating free testosterone in your body)(1). As a matter of fact, in the last study I read, it bound to SHBG better than any other drug studied. Also, Id like to note that Proviron bound to the Anabolic Receptor better than any oral anabolic (except for the insanely toxic MethylTrienolone), having an ability to bind to the AR better then testosterone, but not as well as Nandrolone (1). Unfortunately, as we know, DHT also has a high affinity for binding to receptors in the scalp and prostate, causing some possible nasty side effects, like male pattern baldness and prostate enlargement. Its important to remember that DHT and DHT derived compounds are used quite successfully to treat gynocomastia, and in this area, Proviron is no different.

Lets delve into some of the positive points of this drug before we go any farther. Androgen Receptors are found in fat cells as well as muscle cells(5), and whilethey act on the AR in muscle cells to promote growth, they also act directly on the AR in fat cells to affect fat burning.(9)(3) The stronger the androgen binds to the A.R, the higher the lipolytic (fat burning) effect on adipose (fat)tissue(6)(2). As if thats not enough good news, some steroids (notably, testosterone) even increase the numbers of A.R. in muscle and fat (9)(7). Thus, if you are taking a simple stack of proviron and testosterone, youll have more of the test you shoot as free testosterone floating around building muscle (compliments of the Proviron), more androgen receptors to be bound to (compliments of your testosterone) by your Proviron, thus causing more fat loss. Testosterone and Proviron are a very nice synergistic stack, pretty nearly an "ideal" stack of an oral and injectable, because both drugs will actually act to enhance the effect of the other.

So what we have here is a steroid which can basically make other steroids more effective by preventing their conversion into estrogen, as well as increasing the amount of circulating free testosterone in your body. This of course all provides a more hardened and quality look to muscles. Proviron is very much a "synergistic" drug in this respect, and its inclusion in any cycle would definitely make all of the other steroids perform better, and provide better gains. This is all compounded by the fact that proviron is a very lipolytic (fat-burning) drug.


Now, as if all of this werent enough, lets talk about how Proviron affects your HPTA (Hypothalamic-Pituitary-Testicular-Axis)& the thing that regulates the male hormonal system. When a reasonable dose of this stuff is given (100-150mgs/day), it had no depressing effect on low or normal serum FSH and LH levels (6). Follicle Stimulating Hormone (FSH) and Leutenizing Hormone (LH) are two hormones which send a signal to your testes to produce testosterone. Good news for people considering it for PCT is that it can even raise your LH (10)! Thus, by not suppressing those hormones and maybe even raising some, your normal testosterone levels will remain intact. This points to a novel use for this compound during Post-Cycyle-Therapy for a non-suppressive "bridge" between cycles. In fact, in yet another study, administration of Proviron (basically the same dose as in the last study) produced no changes in steroids, thyroid hormones, gonadotropins nor PRL (Prolactin Levels& you want those to remain low). (8).

Unfortunately, this stuff is not too hot on its own. Its a good drug for inclusion in a cycle containing testosterone and other armoatizable steroids, and its a good drug for a possible "bridge" between cycles. Alone, however, as an androgenic or anabolic agent, its effects have been very weak in both studies (9), as well as in the experience of everyone I spoke to about it. This may be due to the addition of the 1-methyl-group to DHT, which makes this stuff orally active. Whatever the case, as a stand alone anabolic or androgenic compound, its not too impressive.

This drug is a rare find on the American Black Market, and many Underground Labs dont even produce it, but if you can find it, Id say that you shouldnt be paying more than .50cents for each 50mg tab.

Proviron (Mesterolone) Profile

[1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one]
Molecular Weight: 304.4716
Molecular Formula: C20H32O2
Melting Point: N/A
Manufacturer: Schering
Release Date: 1960
Effective Dose: 25-200mgs/day
Active Life: up to 12 hours
Detection Time: 5-6weeks
Androgenic: Anabolic Ratio:30-40/100-150

References:



Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin.Endocrinology. 1984 Jun;114(6):2100-6.
APMIS. 2000 Dec;108(12):838-46.
(Xu X, et al. "The effects of androgens on the regulation of lipolysis in adipose precursor cells." Endocrinology 1990 Feb;126(2):1229 ).
J Anim Sci. 1992 Nov;70(11):3381-90.
Am J Physiol. 1998 Jun;274(6 Pt 1):C1645-52.
The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men.Int J Gynaecol Obstet. 1988 Feb;26(1):121-8.
J Appl. Physiol.94 1153-61 2003
Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure.Horm Metab Res. 1984 Sep;16(9):492-7.
[Androgen substitution in the andrological disease picture] Andrologia. 1983 May-Jun;15(3):283-6. German.
The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study). Methods Find Exp Clin Pharmacol. 1984 Jun;6(6):331-7.


Read more: Provirone - Steroid .com

[Kevster]

Nog een interessant stukje van 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.

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).

Conclusion

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.

References:

1 Clin Cancer Res. 2005 Apr 15;11(8):2809-21.
2. J Clin Endocrinol Metab. 1995 Sep;80(9):2658-60.
3.[Clinical aspects of estrogen and bone metabolism] Clin Calcium. 2002 Sep;12(9):1246-51. Japanese.
4. Science, Vol 283, Issue 5406, 1277-1278 , 26 February 1999
5. J Clin Endocrinol Metab 2000 Jul;85(7):2370-7, "Estrogen Suppression in Males"
6. Fertil Steril. 1978 Mar;29(3):320-7
7. J Clin Endocrinol Metab. 2004 Mar;89(3):1174-80
8. J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):85-91.
9. The Oncologist, Vol. 9, No. 2, 126–136, April 2004
10. Zilembo N., Noberasco C., Bajetta E., Martinetti A., Mariani L., Orefici S. Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor. Br. J. Cancer, 72: 1007-1012, 1995
11.Clinical Cancer Research Vol. 10, 1943-1948, March 2004
12.The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5951-5956
Copyright © 2003 by The Endocrine Society

[AESTHETICS]

De suicide inhibitie maakt Aromasin wel een stuk interessanter, Aromasin schijnt ook de enige te zijn die niet je HDL/LDL verpest. Ik lees dat letro het beste zou zijn voor het combatten van gyno, omdat deze je oestrogeen het verste terug brengt van de drie en klierweefsel kan doen slinken.

juist maar de sides van letro is wel lastig ....

[GeneralIx]

Was al bang voor het proviron gekut. 1-Methyl groep is volgens mij ook levergiftig.
Dan, waarom geen proviron?
1) Er is geen enkel bewijs in de literatuur dat ik ooit heb mogen aanschouwen dat proviron als AI fungeert middels binding aan het aromatase-enzym.
2) Het SHBG verhaal is onzin. Oestrogeen bindt losser dan testosteron (7x uit mijn hoofd) aan SHBG. Als er dus een hormoon van de SHBG gewipt gaat worden door een binding aan SHBG (waar ik ook geen data van heb gezien), zal dat eerder oestrogeen betreffen dan testosteron. Dit heeft weer een hoger SHBG tot gevolg, en daarmee een lagere testosteronspiegel. Daarnaast staat ter discussie of je op een gegeven dosis provi wel genoeg hebt ronddrijven in je bloed om kruiscompetitie te faciliteren.
3) Het al dan niet loswippen van test van de SHBG is irrelevant, gegeven genoeg oestrogeenrepressie. Je hebt immers enorm suprafysiologische concentraties test ronddrijven, en zolang je je oestrogeen niet uit de klauwen laat lopen, blijft je SHBG op je natuurlijke niveau, waarmee je dus totaal geen last hebt van het al dan niet binden van test aan SHBG.

[GeneralIx]

Zit op de bb, dus even gescheiden posts om te voorkomen dat ik per ongeluk alles kwijt ben.

Over BR. AI in de nakuur wegens hoger test? Joh. Stapel nolva en een AI in je nakuur, en je testosteron komt gegarandeerd ver uit boven je natuurlijke niveau. En wat geeft stoppen dan? Een rebound. Niet aan te raden dus.
Dan het punt over "letro is baas". Zever. Letro onderdrukte meer oestrogeen dan de Ana of Exe. Maar klinisch significant? Staat zeer te bezien. We hebben het over een tot twee procentpunt verschil in de niveaus bij VROUWEN. Denk je echt dat je met een enorm veelvoud aan testosteron die marginale verschillen terug gaat zien? Ik vraag het me zeer af.
Daarnaast vergeet BR de veiligheid van de SI. Gegarandeerd geen rebound via aromatase op korte termijn vs mogelijke onwijze rebound op extreem korte termijn.

[Kevster]

Interessante redenering.

Enig idee waarom de zogenaamde provi hype zo hardnekkig is en waarom guru's met toch wel enig aanzien dit blijven roepen?

[GeneralIx]

Nope.

[Toph]

Misschien een domme vraag, maar waar is een AI goed voor als je tamoxifen als nakuur hebt? (hebben de meeste toch?) Daarmee hebben de oestrogenen toch al geen functie gezien de receptorblokkade?

[scoobydoo]

Misschien een domme vraag, maar waar is een AI goed voor als je tamoxifen als nakuur hebt? (hebben de meeste toch?) Daarmee hebben de oestrogenen toch al geen functie gezien de receptorblokkade?

Misschien om de whiplash van het stoppen met tamoxifen te voorkomen.

[Toph]

Misschien om de whiplash van het stoppen met tamoxifen te voorkomen.

Heb er totaal geen verstand van, maar zou het dan niet handiger zijn om tamoxifen langzaam af te bouwen?

[GeneralIx]

Er zijn meer oestrogeenreceptoren in je lichaam actief dan die waar tamo zo graag op hect (borstweefsel). Daarnaast is de beperkende factor bij de nakuur voornamelijk een hoog oestrogeen en dat wil je voorkomen.

[Toph]

Er zijn meer oestrogeenreceptoren in je lichaam actief dan die waar tamo zo graag op hect (borstweefsel). Daarnaast is de beperkende factor bij de nakuur voornamelijk een hoog oestrogeen en dat wil je voorkomen.

Ah, wist niet dat tamoxifen maar beperkte binding had met verschillende oestrogeen receptoren. Sterker nog, ik weet niet eens hoeveel verschillende oestro receptoren er zijn Maareh, ik zie het niet vaak langskomen in kuurvoorstellen, of zie ik dat verkeerd.