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  1. #1
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    To much letro in cycle?

    I am currently in my 7th week of Test E - 500mg & EQ - 400mg. I think i might be restricting my gains a bit too much with my letro dose. I already had a few gyno issues before steroid use so i wanted to be on the safe side. I decided to run 1.25mg ED. My sex drive is below average. Still capable but not as horny as i would like to be, or should be considering the situation. Should i lower the dose? If so, what too? Thanks everyone. Also, one thing has me slighty worried in that i haven't experienced much in the way of side effects... if any.

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    Bump. Anyone?

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    I have posted this before but I was doing 1.25 mg Letro ed and I think it smoked my sex drive....I was also on 500 mg prop with winnie and gh and my libido went to zero.

  4. #4
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    .50ED should be sufficient. If you notice any swelling or soreness, up the dose again, and you'll not Gain any gyno, don't worry.

  5. #5
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    1.25mg EOD.............. Are you running Nolva as well?

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    I think 0.2ml ED would be fine
    That works out as 0.5mg ED

    I would try that for a few days and see how that effects you

    It still seems strange to me that you've got bigger but not stronger

  7. #7
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    Quote Originally Posted by TheMudMan
    1.25mg EOD.............. Are you running Nolva as well?
    Yes. 20mg ED. Could i jump straight into 1.25mg EOD?

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    yeah, going straight onto 1.25mg EOD shouldn't give you any problems

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    Quote Originally Posted by MatrixGuy
    Yes. 20mg ED. Could i jump straight into 1.25mg EOD?
    You're going to take Letrozole and Tamoxifen together? Not a Great Idea.

    Impact of Tamoxifen on the Pharmacokinetics and Endocrine Effects of the Aromatase Inhibitor Letrozole in Postmenopausal Women with Breast Cancer

    M. Dowsett2, C. Pfister, S. R. D. Johnston, D. W. Miles, S. J. Houston, J. A. Verbeek, H. Gundacker, A. Sioufi and I. E. Smith


    Departments of Biochemistry and Medicine, Royal Marsden Hospital, London SW3 6JJ, United Kingdom [M. D., S. R. D. J., I. E. S.]; Novartis Pharma AG Clinical Research, CH-4002 Basel, Switzerland [C. P., J. A. V., H. G.]; Department of Clinical Oncology, Thomas/Guy House, Guy’s Hospital, London SE1 9RT, United Kingdom [D. W. M., S. J. H.]; and Novartis Pharma SA, 92500 Rueil-Malmaison, France [A. S.]

    This study examined whether the addition of tamoxifen to the treatment regimen of patients with advanced breast cancer being treated with the aromatase inhibitor letrozole led to any pharmacokinetic or pharmacodynamic interaction. Twelve of 17 patients completed the core period of the trial in which 2.5 mg/day letrozole was administered alone for 6 weeks and in combination with 20 mg/day tamoxifen for the subsequent 6 weeks. Patients responding to treatment continued on the combination until progression of disease or any other reason for discontinuation. Plasma levels of letrozole were measured at the end of the 6-week periods of treatment with letrozole alone and the combination and once more between 4 and 8 months on combination therapy. No further measurements were done thereafter. Hormone levels were measured at 2-week intervals throughout the core period. Marked suppression of estradiol, estrone, and estrone sulfate occurred with letrozole treatment, and this was not significantly affected by the addition of tamoxifen. However, plasma levels of letrozole were reduced by a mean 37.6% during combination therapy (P < 0.0001), and this reduction persisted after 4–8 months of combination therapy. Letrozole is the first drug to be described in which this pharmacokinetic interaction occurs with tamoxifen. The mechanism is likely to be a consequence of an induction of letrozole-metabolizing enzymes by tamoxifen but was not further addressed in this study. It is possible that the antitumor efficacy of letrozole may be affected. Thus, sequential therapy may be preferable with these two drugs. It is not known whether tamoxifen interacts with other members of this class of drugs or with other drugs in combination.

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    so your saying he could lower the letro and discontinue the nolva? or what

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    Quote Originally Posted by TheMudMan
    1.25mg EOD..............
    Incorrect. Both the dosage as well as the EOD reccomendation are incorrect.

    First, regarding the reccomendation of "1.25mg" it's way too much. You can use 100mcgs/day for maximum inhibition of aromatase:

    J Clin Endocrinol Metab. 1995 Sep;80(9):2658-60.



    Use of ultrasensitive recombinant cell bioassay to measure estrogen levels in women with breast cancer receiving the aromatase inhibitor, letrozole.

    Klein KO, Demers LM, Santner SJ, Baron J, Cutler GB Jr, Santen RJ.

    Children's Hospital of Orange County, California 92668, USA.

    The development of well tolerated, potent, specific, and nontoxic aromatase inhibitors for the treatment of postmenopausal women with estrogen-dependent breast cancer has been a major goal of recent studies. The third generation inhibitors now under investigation are nearly 10,000-fold more potent than first generation compounds. Currently available RIAs for plasma estradiol lack sufficient sensitivity to measure levels during aromatase inhibition and, thus, to assess drug potency precisely. The availability of an ultrasensitive bioassay for estradiol provided the opportunity to accurately assess the potency of a new third generation triazole aromatase inhibitor, letrozole (CGS 20267). We used this assay to measure estradiol levels in 14 women with metastatic breast cancer given letrozole at doses of 100 micrograms to 5.0 mg/day over a 12-week period. The lack of differences between doses and sampling times allowed pooling of data. Basal estradiol levels of 7.2 +/- 1.9 pmol/L (mean +/- SEM, 1.95 +/- 0.52 pg/mL) fell to 0.26 +/- 0.11 pmol/L (0.07 +/- 0.03 pg/mL) during the first 6 weeks of therapy and to 0.48 +/- 0.18 pmol/L (0.13 +/- 0.05 pg/mL) during the second 6 weeks of therapy. Although plasma estradiol levels measured by RIA were significantly correlated with levels measured by bioassay (r = 0.79; P < 0.01), the degree of suppression assessed by the bioassay (95 +/- 2% after 6 weeks) was greater than that determined by the RIA (81 +/- 4%), presumably due to improved ability to measure very low estradiol levels. We conclude that plasma estradiol is suppressed by letrozole to lower levels than previously observed, with equivalent suppression at all doses studied. A slight, although not statistically significant, rebound in estradiol levels occurs during the second 6 weeks of therapy compared to the first 6 weeks. Maximum inhibition of aromatase is achieved at letrozole doses as low as 100 micrograms.



    Now, with regards to the "EOD" reccomendation, letrozole has a very long 1/2 life, and if you want to ever achieve a steady-state plasma level of it, you need to take a daily dose of it, and even then, it takes a month at .5mgs/day to two months at 2.5mgs/day in order to achieve a constant level of it in your blood. It stands to reason every other day dosing, (especially at 1.25mgs/EOD) would make it difficult to get a steady level of it in your blood, reflective of the accumulation that occurs with letrozole over long-term dosing :



    Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients.

    Bajetta E, Zilembo N, Dowsett M, Guillevin L, Di Leo A, Celio L, Martinetti A, Marchiano A, Pozzi P, Stani S, Bichisao E.

    Division of Medical Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

    Letrozole is an orally competitive aromatase inhibitor. This double-blind, randomised, multicentre trial was carried out to evaluate the endocrine effects of two doses of letrozole, 0.5 mg versus 2.5 mg orally daily, in postmenopausal advanced breast cancer patients progressing after tamoxifen . The pharmacokinetics of letrozole was also assessed. 46 patients entered the trial, 22 on letrozole 0.5 mg and 24 on 2.5 mg. A significant suppression of oestrone and oestradiol levels was achieved by both letrozole doses. Neither letrozole dose induced any changes in cortisol and aldosterone production at rest or after Synacthen stimulation. Androstenedione, testosterone , 17 alpha-OH progesterone, triiodothyronine (T3) thyroxine, (T4) and thyroid-stimulating hormone (TSH) plasma levels did not show any significant changes. Sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels increased significantly over time. Plasma letrozole concentrations increased until reaching steady-state values after 1 month at the dose of 0.5 mg and after 2 months at 2.5 mg. In conclusion, both letrozole doses suppressed oestrogen levels without affecting adrenal activity.

  12. #12
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    Quote Originally Posted by hooker
    Incorrect. Both the dosage as well as the EOD reccomendation are incorrect.

    First, regarding the reccomendation of "1.25mg" it's way too much. You can use 100mcgs/day for maximum inhibition of aromatase:

    J Clin Endocrinol Metab. 1995 Sep;80(9):2658-60.



    Use of ultrasensitive recombinant cell bioassay to measure estrogen levels in women with breast cancer receiving the aromatase inhibitor, letrozole.

    Klein KO, Demers LM, Santner SJ, Baron J, Cutler GB Jr, Santen RJ.

    Children's Hospital of Orange County, California 92668, USA.

    The development of well tolerated, potent, specific, and nontoxic aromatase inhibitors for the treatment of postmenopausal women with estrogen-dependent breast cancer has been a major goal of recent studies. The third generation inhibitors now under investigation are nearly 10,000-fold more potent than first generation compounds. Currently available RIAs for plasma estradiol lack sufficient sensitivity to measure levels during aromatase inhibition and, thus, to assess drug potency precisely. The availability of an ultrasensitive bioassay for estradiol provided the opportunity to accurately assess the potency of a new third generation triazole aromatase inhibitor, letrozole (CGS 20267). We used this assay to measure estradiol levels in 14 women with metastatic breast cancer given letrozole at doses of 100 micrograms to 5.0 mg/day over a 12-week period. The lack of differences between doses and sampling times allowed pooling of data. Basal estradiol levels of 7.2 +/- 1.9 pmol/L (mean +/- SEM, 1.95 +/- 0.52 pg/mL) fell to 0.26 +/- 0.11 pmol/L (0.07 +/- 0.03 pg/mL) during the first 6 weeks of therapy and to 0.48 +/- 0.18 pmol/L (0.13 +/- 0.05 pg/mL) during the second 6 weeks of therapy. Although plasma estradiol levels measured by RIA were significantly correlated with levels measured by bioassay (r = 0.79; P < 0.01), the degree of suppression assessed by the bioassay (95 +/- 2% after 6 weeks) was greater than that determined by the RIA (81 +/- 4%), presumably due to improved ability to measure very low estradiol levels. We conclude that plasma estradiol is suppressed by letrozole to lower levels than previously observed, with equivalent suppression at all doses studied. A slight, although not statistically significant, rebound in estradiol levels occurs during the second 6 weeks of therapy compared to the first 6 weeks. Maximum inhibition of aromatase is achieved at letrozole doses as low as 100 micrograms.



    Now, with regards to the "EOD" reccomendation, letrozole has a very long 1/2 life, and if you want to ever achieve a steady-state plasma level of it, you need to take a daily dose of it, and even then, it takes a month at .5mgs/day to two months at 2.5mgs/day in order to achieve a constant level of it in your blood. It stands to reason every other day dosing, (especially at 1.25mgs/EOD) would make it difficult to get a steady level of it in your blood, reflective of the accumulation that occurs with letrozole over long-term dosing :



    Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients.

    Bajetta E, Zilembo N, Dowsett M, Guillevin L, Di Leo A, Celio L, Martinetti A, Marchiano A, Pozzi P, Stani S, Bichisao E.

    Division of Medical Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.

    Letrozole is an orally competitive aromatase inhibitor. This double-blind, randomised, multicentre trial was carried out to evaluate the endocrine effects of two doses of letrozole, 0.5 mg versus 2.5 mg orally daily, in postmenopausal advanced breast cancer patients progressing after tamoxifen . The pharmacokinetics of letrozole was also assessed. 46 patients entered the trial, 22 on letrozole 0.5 mg and 24 on 2.5 mg. A significant suppression of oestrone and oestradiol levels was achieved by both letrozole doses. Neither letrozole dose induced any changes in cortisol and aldosterone production at rest or after Synacthen stimulation. Androstenedione, testosterone , 17 alpha-OH progesterone, triiodothyronine (T3) thyroxine, (T4) and thyroid-stimulating hormone (TSH) plasma levels did not show any significant changes. Sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels increased significantly over time. Plasma letrozole concentrations increased until reaching steady-state values after 1 month at the dose of 0.5 mg and after 2 months at 2.5 mg. In conclusion, both letrozole doses suppressed oestrogen levels without affecting adrenal activity.
    This is a study perfomed on women not men running hormone aromatizing steroids . But I will try the ED doses to help with steady plasma levels.

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    Quote Originally Posted by TheMudMan
    This is a study perfomed on women not men running hormone aromatizing steroids. But I will try the ED doses to help with steady plasma levels.
    I assume that's a rhetorical answer, because as you know, such a study is biomedically unethical ,and could never be performed in any credible institution under current legislation.

    However, I see nothing in the pharmacology of letrozole that would indicate greatly disparate effects with regards to dose within the two groups mentioned (men on aas vs/ woman with mestatic breast cancer). In fact, letrozole has been used just as successfully to treat men with certain issues (like mestatic breast cancer) resulting from overexpression of the aromatase enzyme, similar to that experienced with use of anabolic steroids (or, naturally, women with mestatic breast cancer, which was why I posted that first study, which I cited showing letrozole to be useful at 100mcgs). This is because the strength of letrozole is probably dependant on it's mechanism of action moreso than simply it's dose, and is such that it produces profound pathological responses in the majority of estrogen receptor rich tumours (as well as a reduction in estrogen, progesterone, aromatase activity, etc...)which have been manifested by reduced cellularity and/or increased fibrosis, resulting in letrozole's strong influence on proliferation of most tumours, at astoundingly low doses. It would also appear that Arimidex has this same (almost non-dose dependant) property, as .5mgs/day vs/ 10mgs/day produces very little more worthwhile inhibition of aromatase, in my estimation.

    There are, of course situations and circumstances where this isn't always applicable, but I don't feel that the one at hand is such a situation or circumstance. I could, however, be overlooking something, and if so, I invite you to enlighten me on what that is...
    Last edited by Property of Steroid.com; 09-02-2005 at 11:33 AM.

  14. #14
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    I am running both Hooker. Should i drop the nolva? What dose of letro would you run ED? considering i already had some gyno issues before the steroid use .

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    Quote Originally Posted by MatrixGuy
    I am running both Hooker. Should i drop the nolva? What dose of letro would you run ED? considering i already had some gyno issues before the steroid use.
    I think you should run what has worked for others. These studies are great information but I don't feel they are applicable in these situations.

    Now if hooker conducted a study that were comprised of men on steroids and the findings were conclusive then I would have no reason to question them.

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    Quote Originally Posted by MatrixGuy
    I am running both Hooker. Should i drop the nolva? What dose of letro would you run ED? considering i already had some gyno issues before the steroid use.
    Another thing since Nolva reduces plasma levels of letro 37.6% then there should really be no problem here. You would still be running more letro then the study has in it.

  17. #17
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    so...much....information.....cant....process....ah hhhh!

  18. #18
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    so what does it all mean - does it mean there is no need for nolvadex when running letro? and letro can be easily reduced below .5mg? But does it have to be run for 30-60 days before you cycle?

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    Quote Originally Posted by catlovesfood
    so what does it all mean - does it mean there is no need for nolvadex when running letro? and letro can be easily reduced below .5mg? But does it have to be run for 30-60 days before you cycle?
    It depends on the individual........... some are not effected as much by estrogen related sides but there are those that are very susceptable to estrogen and will have problems with gyno, bloating, high bp............

    So maybe for some of the guys running low amounts of letro/femara will stop enough arominazation to keep the sides away. Also, it will be very hard to dose in the micrograms if you have the tablet form of the drug. But I do feel if you are a person that isn't effected by estrogen a great deal and haven't had problems with gyno .5mg ED would work. It's not much less then what has been stated on the boards anyway. Also, about running nolva along with letro. If you are running lower amounts of letro then it would be less effective. This isn't new information either. The reduction in levels for letro by nolvadex has been stated for a long time as weel.

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    ...I've always used Letro @ 1.25mg EOD in conjunction with Nolva @ 10mg ED with no problems....but that's just been my experience...However, if I had "minimal bloat", I'd run L-dex @ .25mg ED in conjunction with 10mg Nolva ED.....again that's just from past experience......


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    Last edited by almostgone; 09-03-2005 at 06:23 AM.
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    so runing tren , what is best l-dex or letro at what amount and how do u know what take based on the stack u use or is it just what works with the person who is using

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    Quote Originally Posted by doghunter
    so runing tren , what is best l-dex or letro at what amount and how do u know what take based on the stack u use or is it just what works with the person who is using
    Bump...my question also

  23. #23
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    Quote Originally Posted by Vegas67
    I have posted this before but I was doing 1.25 mg Letro ed and I think it smoked my sex drive....I was also on 500 mg prop with winnie and gh and my libido went to zero.
    There are guys running 1,25mg EOD and less that had thier sex drives killed by letro. Unless you are having some major problems that is way too much.

  24. #24
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    Quote Originally Posted by doghunter
    so runing tren , what is best l-dex or letro at what amount and how do u know what take based on the stack u use or is it just what works with the person who is using
    You will be running test with this right? So IMO letro would be a better choice because it will help with aromatization the best. Dosages depends alot on the person and how much is being ran. You could try .5mg ED and see how it goes from there.

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    okay so letro is better with tren with this give me sex drive issues or not and running 125mg ed of tren 200mg ed of test prop how much letro would be needed

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    Quote Originally Posted by doghunter
    okay so letro is better with tren with this give me sex drive issues or not and running 125mg ed of tren 200mg ed of test prop how much letro would be needed

    ...Whoa....Too Much..Too Much......
    .....I'd start @ 50 -75 mg of tren ace ED and 75-100mg ED of prop....Unless this is your first cycle...If it is, hold the tren for your next cycle and make this first run a test prop only cycle.....

    ...If you run only test prop, I'd think about 10 mg of Nolva ED and maybe ,25 L-dex ED....but that's just what I'd do.......
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    Quote Originally Posted by almostgone
    ...Whoa....Too Much..Too Much......
    .....I'd start @ 50 -75 mg of tren ace ED and 75-100mg ED of prop....Unless this is your first cycle...If it is, hold the tren for your next cycle and make this first run a test prop only cycle.....

    ...If you run only test prop, I'd think about 10 mg of Nolva ED and maybe ,25 L-dex ED....but that's just what I'd do.......
    definately too much unless you are well rehearsed and experienced with tren. The sides on tren can truely be horrific, and a higher dose does not always mean better gains, but it does mean worse sides.

  28. #28
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    hold the phone guys been on high tren for a long time its my drug of choice but even my first cycle i ran high with no prob i get a little acne thats it even without pct this will be my first time adding any anti e

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    It's interesting to still see Type-II Aromatase Inhibitors being reccomended for use with Nolvadex . AI's, as you recall, lower your estrogen by inhibition of the P450 cytochrome enzyme aromatase, which is responsible for the catalyzation of conversion of androgens to estrogens. Type-II's do this in a very different way than Type-I's and thus have vastly differing effects when combined with a SERM like Nolvadex. We know that administration of either Arimidex as well as Letrozole along with Nolvadex decreases the plasma level of with either AI (letro by 38%. and anastrozole by 27%)....we also know that nolvadex increases progesterone receptors, and you are going to take it with tren (a progestin)....doesn't sound like a top notch idea, or even reasonable advice, to me...

    Anyway, together, most patients -women who are trying to reduce or sometimes prevent breast tumors, which is the same thing we're trying to do with regards to gyno, a benign breast tumor - using a combination of Nolvadex with an AI (letro or arim) saw no better results than when using the AI alone. So why waste your time taking them together? I think you'll be better off with a Type-I AI (exemestane).

    To further explain, AIs are classified into two types:type I, suicidal or noncompetitive inhibitors; and and type II, known as competitive inhibitors . Basically, to further explain, Type I inhibitors are actually considered steroidal compounds (technically), and type II inhibitors totally nonsteroidal drugs. This explains the possible androgenic side effects found with exemestane and (the lack of them with Letrozole and Arimidex. Both type I & II mimic normal substrates (essentially androgens), competing with the particular substrate for access to the binding site on the actual enzyme. After this initial binding, the next step is where things differ for the two types of AI’s. Once a noncompetitive inhibitor has bound, the enzyme initiates a sequence of hydroxylation, but in this case, hydroxylation produces an unbreakable covalent bond between the inhibitor and the enzyme protein. This is important because now, enzyme activity is permanently blocked; even if all unattached inhibitor is removed, and now, enzyme activity can only be restored by new enzyme synthesis. Nice, huh? Now, on the other hand, competitive inhibitors, called type II AI’s, reversibly bind to the active enzyme site, and either no enzyme activity is triggered, or the enzyme is somehow triggered without effect. The type II inhibitor can actually disassociate from the binding site, eventually allowing renewed competition between the inhibitor and the substrate for binding to the site. Clearly, this indicates that the effectiveness of competitive aromatase inhibitors depends on the relative concentrations and affinities of both the inhibitor and the substrate. We can safely, therefore, conclude that continued aromatase inhibitory activity requires constant presence of the Type II inhibitor, although probably not the presence of the Type-I. In fact, A plot study with exemestane and tamoxifen concluded that coadministration of tamoxifen does not affect exemestane levels in the body nor exemestane pharmacokinetics or pharmacodynamics.



    In addition, since exemestane is also structurally related to the natural estrogen precursor androstenedione, this similarity gives it some very nice effects on your bone-mineral content as well as cholesterol (just like Nolvedex, actually). Hence...with exemestane you get the good effects of an AI, and not the bad ones, and in addition you get some SERM-like-estrogenic effects, and no reduction in blood plasma levels if you should actually decide to run a serm (like nolvadex) with it.

    I also feel that some of the advice given in this thread (use of nolvadex with a Type-II AI) is less than optimal or well researched. In addition, since nolvadex increases progesterone receptors, using it along with a progestin like Tren is also less than optimal..in fact...it's plain horrible advice, in my opinion.

    Ergo, based on the available research, I now feel the best single compound to run on a cycle for Aromatase Inhibition, is exemestane. This is all through alot of very recent research I'm doing on exemestane, for an article I'm in the process of writing, by the way...

    Finally, I'll add that British Dragon just released exemestane, if what I've presented in this thread interests you. I suspect I've made a decent case for it's use as opposed to all other advice in this thread.
    Last edited by Property of Steroid.com; 09-04-2005 at 07:16 AM.

  30. #30
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    Thanks for the info Hooker. Although i feel my brain is about to explode.

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