Why is it important to run an AI when on cycle?

[Swifto]

I've seen the theory that you do NOT need to use an AI on cycle for a while now. From newbies having read various profiles, from senior members in our community. My opinion is that this is based on poor logic and understanding. Here's why...


Its well known (atleast I think it is) that estrogen is a carcinogen. In fact, its a Group 1 IARC classified estrogen, which means it a pretty potent one really. The risks of estrogen and carcinogenic activity are then again confirmed in 'estrogen only' conraceptive treatment(s). Although the data is somewhat confusing (as some data is on estrogen+progestagen treatment), the links to various forms of cancer rates increasing is pretty clear in my book.

To quote from a paper looking at the effects of estrogen only contraceptive treatment and estorgen+progestrogen contraceptive therapy:

"Four studies (one cohort study and three large case-control studies) reported increased risk of endometrial cancer with estrogen repla***ent therapy (Cushing et al. 1998, Shapiro et al. 1998, Persson et al. 1999, Weiderpass et al. 1999), and three of these studies reported strong positive associations between risk of endometrial cancer and duration of estrogen use."

"Two of four case-control studies found that estrogen-only repla***ent therapy was associated with an increased risk of breast cancer (Heinrich et al. 1998, Magnusson et al. 1999)."

"One study found that estrogen therapy was associated with ovarian cancer (Purdie et al. 1999)."

"In 2009, IARC concluded there was sufficient evidence of the carcinogenicity of estrogen-only therapy in humans based on increased risks of endometrial cancer and ovarian cancer and limited evidence based on increased risk of breast cancer (Grosse et al. 2009). The findings for ovarian cancer were based on two meta-analyses (Greiser 2007, Zhou 2008). Since then, another meta-analysis has estimated a significant overall increase in ovarian cancer risk related to duration of use of estrogen-only therapy (Pearce et al. 2009)."

"In rodents, steroidal estrogens caused benign and malignant tumors, as well as pre-cancerous lesions, in a variety of organs, including the mammary gland and female reproductive tract (IARC 1999). Estrogenic compounds generally caused endometrial, cervical, and mammary-gland tumors in mice, mammary- and pituitary-gland tumors in rats, and kidney tumors in hamsters"

I think you get my point...

Although there is mixed data in that study, the theory that estrogen is carcinogenic is overwhelming.




So what does that all tell us? It tells us that when exposed to estrogen (steroidal) that it can cause some serious problems. Yes, these studies are done on females (I didnt miss that), but women are a hell of a lot more tolerable to estrogen than men are. Males are not designed for increased levels of estrogens at all, womens are (during pregnancy for a start). Womens levels can hit 500pg/ml, the top end of males is 50pg/ml 10x lower.

Estrogen role in males is important. Its important for GH and IGF synthesis, bone density, lipid profile, glucose uptake and utilisation, AR sensitivity and activation, immuno function, anti-inflammitory effects and a host of other benifits. Without it, we (males) would't function properly.

There are studies for and against the importance of sex hormones on CHD and mortality, but the hypothsis is plausable. Why?

- Estrogens inhibit smooth muscle proliferation and decrease smooth muscle tone

- Their effects on lipid profiles

- High-affinity estradiol receptors are present in both vascular smooth muscle and endothelium

- Estrogens enhance the release of nitric oxide and prostacyclin from endothelial cells, thus inducing vasodilation

- Estrogens exert indirect effects on the cardiovascular system through their influence on lipoprotein metabolism and the coagulation, fibrinolytic, and antioxidant systems

So one can not see the importance estrogen have on the cardiovascular system, CHD, therefore mortality rates. Here is a good solid article on estrgens links to CHD, found here.



How else does estrogen negatively effect males?

Well, recent research has confirmed its role in the most common form of cancer in males - prostate cancer. The basics of which are shown here. These are very recent findings and more research is to be done. However, the links and risks are evident and whilst DHT was thought to play as the main role (10 years ago), estrogen and also prolactin (which worsesns prostate cancer) have been shown to have positive effects on expression and proliferation in cancerous prostate cells in vitro and vivo. On the plus side Tamoxifen has been shown to inhibti expression and proliferation, much like it does in female breast cancer patients.



When I see someone argue that an AI just isnt needed on a cycle, I think to myself, why is it not needed? Based on what? Because you haven't got gyno? The user may not experience side effects such as gyno, water retention, acne, but there estrogen level is sure as f*ck high.

Aromasin (Exemestane) at 10mg/ED will keep most people estrogen level under 50pg/ml on cycle IMO. It does me and I am sensitive to estrogenic side effects (very).

The common reason for not using an AI is, that it may limit gains made... But do they?

AI's have little impact on IGF-1 levels and Exemestane does not have any effects at all, as shown here. If IGF-1 was somewhat lowered, we also need to understand that exogenous testosterone and other anabolic steroids are going to increase IGF-1 and further negate these effects. To realise how little effect AI's have on IGF-1, read this study.To summarise; Nine young healthy men who received femara at 2.5 mg daily for 28 days had a 15% reduction in IGF-1, a 24% reduction in leptin, and a 14% increase in LDL (bad cholesterol).

As for Exemestane on lipid levels, it has far less impact than other AI's although it does not have the benificial effects of SERMs. Some data, such as this one, it has no "no clinically significant effect on the serum lipids". Another study stated, "Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels"

Here is one on young males thats slightly more applicable, this study states, "Plasma lipids and IGF-I concentrations were unaffected by treatment."

Finally, because of the LongFeedback Mechanism (google it), controlling estrogen means we can help control prolactin. So there is more of a reason to use an AI when using 19-Nors (if you experience increased PRL). I'd also keep a D2-agonist on hand though.




My advice is to keep estrogen in "normal ranges". That needs to be decided by trial and error (experimentation).

The key here is to keep it in normal ranges when "on cycle", not high off the charts and not too low. To low and we can experience a host of other side effects, from loss of labido, energy, joint problems, CNS function, anxiety and erectile dysfunction.

It needs to be balanced and the only way you're going to find out your estrogen level on cycle is BW. Have BW done when "on cycle" and taking the AI and see where you are at. Or have BW done on HRT (if you're on HRT) and see where you're at. Some doctors/endo's prescribe AI's because HRT can push estorgen high in those sensitive or estorgen dominant.

My advice is; Aromasin on cycle 10mg/ED. It can be even lower when using DHT derived steroids because of their anti-estrogenic effects. This AI dose will change with the total dose of aromotasable compounds. Put simply, if you're on compounds that aromotase - use more if you need too. 19-Nor's will also affect this dose.

[canadianbrah]

Great post!

[The Bear 79]

Its hard not 2 learn with guys like this around. Great post Swifto.

[alexISthrowed]

Sticky

[Swifto]

Thanks.

I'm still working on it.

I just added two studies to confirm two of the claims I made.

[baseline_9]

Sticky

Another top thread from AR's top brain...

[Razor]

Another great by the great!
Thanks man, will use this for my upcoming cycle

[cb714]

Swifto bring much logic to the table. You can learn a lot from this man.

As for me exemestane as of my last cycle and all future cycles. Works like a charm.

[slimshady01]

Swifto im running 750mg of test for 8 week blast then 750 and 500deca second 8 week blast..

I have 25mg Aromasin .. You recommend 12.5 ED or EOD with this cycle.. I also have 2.5 femara as backup..

need to order more Aroma!

[Swifto]

Swifto im running 750mg of test for 8 week blast then 750 and 500deca second 8 week blast..

I have 25mg Aromasin .. You recommend 12.5 ED or EOD with this cycle.. I also have 2.5 femara as backup..

need to order more Aroma!

Every day. Cabergoline on hand.

[Razor]

Every day. Cabergoline on hand.

Brief summary of Cabergoline? Never heard of it

[JohnnyVegas]

I have not used AI while on TRT of 200mg/wk Cyp, but my E2 has crept up to 36 (range <63). Doctor says Zinc may keep it from raising further.

Is it getting too high?

Do you an AI, or will it drop me too low?

[Swifto]

Brief summary of Cabergoline? Never heard of it

If you're ever not to sure of something, drugs.com is usually ok for basics.

http://www.drugs.com/cons/cabergoline.html

[Swifto]

I have not used AI while on TRT of 200mg/wk Cyp, but my E2 has crept up to 36 (range <63). Doctor says Zinc may keep it from raising further.

Is it getting too high?

Do you an AI, or will it drop me too low?

Its fine.

The thing is keeping it around that level "on cycle".

[JohnnyVegas]

Its fine.

The thing is keeping it around that level "on cycle".

Great, I do use an AI when I blast.

[jimmyinkedup]

Great stuff Swift.
Its time to put the foolish no need for an ai in the abscence of gyno symptoms BS to rest.
Also the more estrgogen = more gains being prudent notion needs to disappear as well.

[slimshady01]

Every day. Cabergoline on hand.

Ok I'll order lots of more aromasin !

I have caber for when I add the deca . I go .5 every 3 with that.

[The Bear 79]

Great stuff Swift.
Its time to put the foolish no need for an ai in the abscence of gyno symptoms BS to rest.
Also the more estrgogen = more gains being prudent notion needs to disappear as well.

Couldn't agree mor. I luv the guys that say "AI's r so expensive", the 1st thing that come 2 mind is "imagine how expensive Gyno. surgery is gona b"

[jimmyinkedup]

Also along these lines I recall recently reading something about estrogen and its role in prostate cancer. Traditional treatment was using anti androgen therapy but now more and more its believed that the resulting estrogen was primarily to blame - not the primary or resulting androgen. Basically they have been one step off the mark in treatment protocols if this is indeed true (which seems to be the case.)
Have u heard or read anything on this Swift?

[Swifto]

Also along these lines I recall recently reading something about estrogen and its role in prostate cancer. Traditional treatment was using anti androgen therapy but now more and more its believed that the resulting estrogen was primarily to blame - not the primary androgen. Basically they have been one step off the mark in treatment protocols if this is indeed true (which seems to be the case.)
Have u heard or read anything on this Swift?

Yes, moreso than DHT is.

[cb714]

Couldn't agree mor. I luv the guys that say "AI's r so expensive", the 1st thing that come 2 mind is "imagine how expensive Gyno. surgery is gona b"

I see that all the time... if it's expensive for those guys they should think twice about cycling. Feel like saying save your money and come back when you have enough. You can't put a price on safety and results.

[Swifto]

I will dig up some data on Tamoxifen reducing cancerous cell proliferation in prostate cancer Jimmy.

[Swifto]

J Cell Biochem. 2007 Nov 1;102(4):899-911.

Estrogen and prostate cancer: an eclipsed truth in an androgen-dominated scenario.

Carruba G.
Source

Experimental Oncology, Department of Oncology, M. Ascoli Cancer Center, ARNAS-Civico, Palermo, Italy. [email protected]
Abstract

Prostate cancer is the commonest non-skin cancer in men. Incidence and mortality rates of this tumor vary strikingly throughout the world. Although several factors have been implicated to explain this remarkable variation, lifestyle and dietary factors may play a dominant role, with sex hormones behaving as intermediaries between exogenous factors and molecular targets in development and progression of prostate cancer. Human prostate cancer is generally considered a paradigm of androgen-dependent tumor; however, estrogen role in both normal and malignant prostate appears to be equally important. The association between plasma androgens and prostate cancer remains contradictory and mostly not compatible with the androgen hypothesis. Similar evidence apply to estrogens, although the ratio of androgen to estrogen in plasma declines with age. Apart from methodological problems, a major issue is to what extent circulating hormones can be considered representative of their intraprostatic levels. Both nontumoral and malignant human prostate tissues and cells are endowed with key enzymes of steroid metabolism, including 17betahydroxysteroid dehydrogenase (17betaHSD), 5beta-reductase, 3alpha/3betaHSD, and aromatase. A divergent expression and/or activity of these enzymes may eventually lead to a differential prostate accumulation of steroid derivatives having distinct biological activities, as it occurs for hydroxylated estrogens in the human breast. Locally produced or metabolically transformed estrogens may differently affect proliferative activity of prostate cancer cells. Aberrant aromatase expression and activity has been reported in prostate tumor tissues and cells, implying that androgen aromatization to estrogens may play a role in prostate carcinogenesis or tumor progression. Interestingly, many genes encoding for steroid enzymes are polymorphic, although only a few studies have supported their relation with risk of prostate cancer. In animal model systems estrogens, combined with androgens, appear to be required for the malignant transformation of prostate epithelial cells. Although the mechanisms underlying the hormonal induction of prostate cancer in experimental animals remain uncertain, there is however evidence to support the assumption that long term administration of androgens and estrogens results in an estrogenic milieu in rat prostates and in the ensuing development of dysplasia and cancer. Both androgen and estrogen have been reported to stimulate proliferation of cultured prostate cancer cells, primarily through receptor-mediated effects. As for estrogens, the two major receptor types, ERalpha and ERbeta, are expressed in both normal and diseased human prostate, though with a different cellular localization. Since these two receptors are different in terms of ligand binding, heterodimerization, transactivation, and estrogen response element activity, it is likely that an imbalance of their expression may be critical to determine the ultimate estrogen effects on prostate cancer cells. In prostate cancer, ERbeta activation appears to limit cell proliferation directly or through ERalpha inhibition, and loss of ERbeta has been consistently associated with tumor progression. Several splicing variants of both ERalpha and ERbeta exist. Little is known about their expression and function in the human prostate, although reciprocal regulation and interaction with gene promoter both warrant further investigation. In summary, although multiple consistent evidence suggests that estrogens are critical players in human prostate cancer, their role has been only recently reconsidered, being eclipsed for years by an androgen-dominated interest.

(c) 2007 Wiley-Liss, Inc.

PMID:
17786930
[PubMed - indexed for MEDLINE]


Also information on ER-subtypes.

Further reading: Further reading: http://www.medscape.com/viewarticle/742985 (new 2011 study).

[slimshady01]

I see that all the time... if it's expensive for those guys they should think twice about cycling. Feel like saying save your money and come back when you have enough. You can't put a price on safety and results.

AIs are cheap as crap if you know the good places to get them and i would make sure they are Pharma brand.. Generic is key for prices!

[slimshady01]

YOu got me worried now about high E and cancer.. When i was on Propecia for 8 years "no gear" i had random blood tests and my E was close to 200 every time with a high range of 70. I never felt any sides but that means nothing from what i see.

[Swifto]

YOu got me worried now about high E and cancer.. When i was on Propecia for 8 years "no gear" i had random blood tests and my E was close to 200 every time with a high range of 70. I never felt any sides but that means nothing from what i see.

There are risks with everything we do in this sport.

Just because you have had high estrogen, it doesn't mean your going to get cancer, it means the chances were higher when you had a high level.

Now its normal, I wouldn't worry

The key here is to keep it in normal ranges when "on cycle", not high off the charts and not too low. It needs to be balanced and the only way you're going to find out your estrogen level on cycle is BW. Have BW done when "on cycle" and taking the AI and see where you are at.

[slimshady01]

its probably been how now for a while.. I havent ran it last few cycles and decided to go on self TRT for better quality of life "had very low free test my whole life yet no doc wanted to do crap"... cruising i was going 150-200mg a week, i bet on that i was high.. my body seems very prone to high estrogen with the many blood tests i have had in my last 15 years.

[songdog]

Good job Swifto I love reading your threads always learn something.

[HitIt]

bump ... good read

[Swifto]

I'm still editing on it, so its probably woth reading again in 3 days!

[JohnnyVegas]

Best thread in a while. Thanks for the info.

[dtob]

Great post !

[analovz]

Thanks for sharing Swifto...you are precious to us!

[DeadlyD]

Swift, in your opinion how does arimadex stack up to aromasin ?

[Swifto]

Swift, in your opinion how does arimadex stack up to aromasin ?

Its fine if its all you have available.

Rather that then nothing.

Aromasin > Arimidex > Letro (for on cycle estrogen control)

Arimidex can be harsh on some causing lipid, labido and joint issues. Its actually directly tooxic to the joints as well.

Why use Arimidex when Aromasin is so widely available and cheap?

[Macon_Bacon]

Its fine if its all you have available.

Rather that then nothing.

Aromasin > Arimidex > Letro (for on cycle estrogen control)

Arimidex can be harsh on some causing lipid, labido and joint issues. Its actually directly tooxic to the joints as well.

Why use Arimidex when Aromasin is so widely available and cheap?

I thought I had read in a pct post that aromasin is a suicide inhibitor to estrogen (thus killing all of it in your system) while arimidex will just inhibit the estrogen from binding to receptors (decreasing estrogen effects by 80%, this is just from memory so might be wrong). Above you stated we wanted some estrogen but not above 50ng/ml. Long story short, why doesn't aromasin completely deplete estrogen levels?

[Swifto]

I thought I had read in a pct post that aromasin is a suicide inhibitor to estrogen (thus killing all of it in your system) while arimidex will just inhibit the estrogen from binding to receptors (decreasing estrogen effects by 80%, this is just from memory so might be wrong). Above you stated we wanted some estrogen but not above 50ng/ml. Long story short, why doesn't aromasin completely deplete estrogen levels?

Its a suicide inhibitor, so it attaches to the aromotase enzyme and kils it, stopping it from becoming active again.

The dose of the AI is important. 10mg/ED is inhibitive enough for most people to use "on cycle" and keep estrogen in normal ranges. Some will need more, some less.

I never said Aromasin will destroy "80% of estrogen", Anthony Roberts (Conners) said that looking at its effects in females (not males) whilst not taking age into account as well. AI's do not effect males as they do females when looking at estrogen suppression.

The study I posted above looking at IGF-1 levels (showing no impact) when using Aromasin also looks at estrogen levels, have a read of it.

[DeadlyD]

Its fine if its all you have available.

Rather that then nothing.

Aromasin > Arimidex > Letro (for on cycle estrogen control)

Arimidex can be harsh on some causing lipid, labido and joint issues. Its actually directly tooxic to the joints as well.

Why use Arimidex when Aromasin is so widely available and cheap?

With the last order of test i got he threw in a bottle of 1mg caps of adex for free.

[Sgt. Hartman]

When I see someone argue that an AI just isnt needed on a cycle, I think to myself, why is it not needed? Based on what? Because you haven't got gyno? The user may not experience side effects such as gyno, water retention, acne, but there estrogen level is sure as f*ck high.

You already know about this Swifto but I'll post it anyway for others to give a real life example.

Long story short I was running a conservative test dose and noticed my nipples were a little sensitive. I didn't think much of it but went and had blood work done anyway. Estradiol was in the mid 300's, over 6 times the top end of my reference range. I didn't have any lumps or gyno, no acne at all, no excessive water retention or any other estrogen related sides, only slightly sensitive nipples. I'd imagine if my E would have been below 300 or so I probably wouldn't have had any sides at all, all the while not knowing that I had extremely dangerous estrogen levels.

Lesson learned: don't ever assume your estrogen levels are in check just because you don't have estrogen related sides.

[BigBadWolf]

You already know about this Swifto but I'll post it anyway for others to give a real life example.

Running about 500mg test with 12.5mg exemestane ED I noticed my nipples were a little sensitive. I doubled the AI dose and nothing changed, didn't get any worse but still a little sensitive so I upped it again and still had no change. I suspected that my research chem exemestane was probably bunk and went and had blood work done. Estradiol was in the mid 300's, over 6 times the top end of my reference range. I didn't have any lumps or gyno, no acne at all, no excessive water retention or any other estrogen related sides, only slightly sensitive nipples. I'd imagine if my E would have been below 300 or so I probably wouldn't have had any sides at all, all the while not knowing that I had extremely dangerous estrogen levels.

Two lessons learned: don't trust research chems, and don't ever assume your estrogen levels are in check just because you don't have estrogen related sides.

Damn!! I know you can't say but damn, where did you get your exemestane? Pm me, I'm off to get bloodwork !!