Best Anti-e Post-cycle?
- Thread starter yourdaddy
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Bone
Member
[font="verdana, arial, helvetica"]By William Llewellyn
Introduction
I have received a lot of heat lately about my preference for Nolvadex over Clomid, which I hold for all purposes of use (in the bodybuilding world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting drug, and as a testosterone-stimulating compound. Most people use Nolvadex to combat gynecomastia over Clomid anyway, so that is an easy sell. And for cholesterol, well, most bodybuilders unfortunately pay little attention to this important issue, so by way of disinterest, another easy opinion to discuss. But when it comes to using Nolvadex for increasing endogenous testosterone release, bodybuilders just do not want to hear it. They only seem to want Clomid. I can only guess that this is based on a long rooted misunderstanding of the actions of the two drugs. In this article I would therefore like to discuss the specifics for these two agents, and explain clearly the usefulness of Nolvadex for the specific purpose of increasing testosterone production.
Clomid and Nolvadex
I am not sure how Clomid and Nolvadex became so separated in the minds of bodybuilders. They certainly should not be. Clomid and Nolvadex are both anti-estrogens belonging to the same group of triphenylethylene compounds. They are structurally related and specifically classified as selective estrogen receptor modulators (SERMs) with mixed agonistic and antagonistic properties. This means that in certain tissues they can block the effects of estrogen, by altering the binding capacity of the receptor, while in others they can act as actual estrogens, activating the receptor. In men, both of these drugs act as anti-estrogens in their capacity to oppose the negative feedback of estrogens on the hypothalamus and stimulate the heightened release of GnRH (Gonadotropin Releasing Hormone). LH output by the pituitary will be increased as a result, which in turn can increase the level of testosterone by the testes. Both drugs do this, but for some reason bodybuilders persist in thinking that Clomid is the only drug good at stimulating testosterone. What you will find with a little investigation however is that not only is Nolvadex useful for the same purpose, it should actually be the preferred agent of the two.
Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using Nolvadex instead of Clomid for increasing testosterone levels (1). Here, researchers looked the effects of Nolvadex and Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant. What was found, just in the early parts of the study, was quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum testosterone levels to 142% of baseline, which was on par with the effect of 150mg of Clomid daily for the same duration (the testosterone increase was slightly, but not significantly, better for Clomid). We must remember though that this is the effect of three 50mg tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the Nolvadex side.
Pituitary Sensitivity to GnRH
But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The tests showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.
The Estrogen Clomid
The above discrepancies are likely explained by differences in the estrogenic nature of the two compounds. The researchers' clearly support this theory when commenting in their paper, "The difference in response might be attributable to the weak intrinsic estrogenic effect of Clomid, which in this study manifested itself by an increase in transcortin and testosterone/estradiol-binding globulin [SHBG] levels; this increase was not observed after tamoxifen treatment". In reviewing other theories later in the paper, such as interference by increased androgen or estrogen levels, they persist in noting that increases in these hormones were similar with both drug treatments, and state that," …a role of the intrinsic estrogenic activity of Clomid which is practically absent in Tamoxifen seems the most probable explanation".
Although these two are related anti-estrogens, they appear to act very differently at different sites of action. Nolvadex seems to be strongly anti-estrogenic at both the hypothalamus and pituitary, which is in contrast to Clomid, which although a strong anti-estrogen at the hypothalamus, seems to exhibit weak estrogenic activity at the pituitary. To find further support for this we can look at an in-vitro animal study published in the American Journal of Physiology in February 1981 (2). This paper looks at the effects of Clomid and Nolvadex on the GnRH stimulated release of LH from cultured rat pituitary cells. In this paper, it was noted that incubating cells with Clomid had a direct estrogenic effect on cultured pituitary cell sensitivity, exerting a weaker but still significant effect compared to estradiol. Nolvadex on the other hand did not have any significant effect on LH response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.
Conclusion
To summarize the above research succinctly, Nolvadex is the more purely anti-estrogenic of the two drugs, at least where the HPTA (Hypothalamic-Pituitary-Testicular Axis) is concerned. This fact enables Nolvadex to offer the male bodybuilder certain advantages over Clomid. This is especially true at times when we are looking to restore a balanced HPTA, and would not want to desensitize the pituitary to GnRH. This could perhaps slow recovery to some extent, as the pituitary would require higher amounts of hypothalamic GnRH in the presence of Clomid in order to get the same level of LH stimulation.
Nolvadex also seems preferred from long-term use, for those who find anti-estrogens effective enough at raising testosterone levels to warrant using as anabolics. Here Nolvadex would seem to provide a better and more stable increase in testosterone levels, and likely will offer a similar or greater effect than Clomid for considerably less money. The potential rise in SHBG levels with Clomid, supported by other research (3), is also cause for concern, as this might work to allow for comparably less free active testosterone compared to Nolvadex as well. Ultimately both drugs are effective anti-estrogens for the prevention of gyno and elevation of endogenous testosterone, however the above research provides enough evidence for me to choose Nolvadex every time.[/font]
Introduction
I have received a lot of heat lately about my preference for Nolvadex over Clomid, which I hold for all purposes of use (in the bodybuilding world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting drug, and as a testosterone-stimulating compound. Most people use Nolvadex to combat gynecomastia over Clomid anyway, so that is an easy sell. And for cholesterol, well, most bodybuilders unfortunately pay little attention to this important issue, so by way of disinterest, another easy opinion to discuss. But when it comes to using Nolvadex for increasing endogenous testosterone release, bodybuilders just do not want to hear it. They only seem to want Clomid. I can only guess that this is based on a long rooted misunderstanding of the actions of the two drugs. In this article I would therefore like to discuss the specifics for these two agents, and explain clearly the usefulness of Nolvadex for the specific purpose of increasing testosterone production.
Clomid and Nolvadex
I am not sure how Clomid and Nolvadex became so separated in the minds of bodybuilders. They certainly should not be. Clomid and Nolvadex are both anti-estrogens belonging to the same group of triphenylethylene compounds. They are structurally related and specifically classified as selective estrogen receptor modulators (SERMs) with mixed agonistic and antagonistic properties. This means that in certain tissues they can block the effects of estrogen, by altering the binding capacity of the receptor, while in others they can act as actual estrogens, activating the receptor. In men, both of these drugs act as anti-estrogens in their capacity to oppose the negative feedback of estrogens on the hypothalamus and stimulate the heightened release of GnRH (Gonadotropin Releasing Hormone). LH output by the pituitary will be increased as a result, which in turn can increase the level of testosterone by the testes. Both drugs do this, but for some reason bodybuilders persist in thinking that Clomid is the only drug good at stimulating testosterone. What you will find with a little investigation however is that not only is Nolvadex useful for the same purpose, it should actually be the preferred agent of the two.
Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using Nolvadex instead of Clomid for increasing testosterone levels (1). Here, researchers looked the effects of Nolvadex and Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant. What was found, just in the early parts of the study, was quite enlightening. Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum testosterone levels to 142% of baseline, which was on par with the effect of 150mg of Clomid daily for the same duration (the testosterone increase was slightly, but not significantly, better for Clomid). We must remember though that this is the effect of three 50mg tablets of Clomid. With the price of both a 50mg Clomid and 20mg Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the Nolvadex side.
Pituitary Sensitivity to GnRH
But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with Nolvadex and Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary LH in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more LH will be released. The tests showed that after ten days of treatment with Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more LH was released before treatment). As the study with Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising testosterone and LH levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say Clomid won't increase testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in Nolvadex.
The Estrogen Clomid
The above discrepancies are likely explained by differences in the estrogenic nature of the two compounds. The researchers' clearly support this theory when commenting in their paper, "The difference in response might be attributable to the weak intrinsic estrogenic effect of Clomid, which in this study manifested itself by an increase in transcortin and testosterone/estradiol-binding globulin [SHBG] levels; this increase was not observed after tamoxifen treatment". In reviewing other theories later in the paper, such as interference by increased androgen or estrogen levels, they persist in noting that increases in these hormones were similar with both drug treatments, and state that," …a role of the intrinsic estrogenic activity of Clomid which is practically absent in Tamoxifen seems the most probable explanation".
Although these two are related anti-estrogens, they appear to act very differently at different sites of action. Nolvadex seems to be strongly anti-estrogenic at both the hypothalamus and pituitary, which is in contrast to Clomid, which although a strong anti-estrogen at the hypothalamus, seems to exhibit weak estrogenic activity at the pituitary. To find further support for this we can look at an in-vitro animal study published in the American Journal of Physiology in February 1981 (2). This paper looks at the effects of Clomid and Nolvadex on the GnRH stimulated release of LH from cultured rat pituitary cells. In this paper, it was noted that incubating cells with Clomid had a direct estrogenic effect on cultured pituitary cell sensitivity, exerting a weaker but still significant effect compared to estradiol. Nolvadex on the other hand did not have any significant effect on LH response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.
Conclusion
To summarize the above research succinctly, Nolvadex is the more purely anti-estrogenic of the two drugs, at least where the HPTA (Hypothalamic-Pituitary-Testicular Axis) is concerned. This fact enables Nolvadex to offer the male bodybuilder certain advantages over Clomid. This is especially true at times when we are looking to restore a balanced HPTA, and would not want to desensitize the pituitary to GnRH. This could perhaps slow recovery to some extent, as the pituitary would require higher amounts of hypothalamic GnRH in the presence of Clomid in order to get the same level of LH stimulation.
Nolvadex also seems preferred from long-term use, for those who find anti-estrogens effective enough at raising testosterone levels to warrant using as anabolics. Here Nolvadex would seem to provide a better and more stable increase in testosterone levels, and likely will offer a similar or greater effect than Clomid for considerably less money. The potential rise in SHBG levels with Clomid, supported by other research (3), is also cause for concern, as this might work to allow for comparably less free active testosterone compared to Nolvadex as well. Ultimately both drugs are effective anti-estrogens for the prevention of gyno and elevation of endogenous testosterone, however the above research provides enough evidence for me to choose Nolvadex every time.[/font]
ready2explode
New member
I'd recommend using both clomid and nolva...no one really knows which is better...
jminis
Well-known member
Nice info Bone. Before I chose my anti e I read through plenty of articles on the subject, especially those by Big Cat. Anyway all the articles came to the same conclusion as you, Nolvadex is better. I think it's interesting that when you read info on Nolvadex people never say how great it is at bringing test back up. An article said they market Clomid and Nolv differently in order for clomid to maintain it's appeal. They do this with a lot of products, not just supps.
Later
Later
quasar
New member
in my 2nd sem biochem class, we had to read a research article (I'll try to find it to quote later if anyone's interested) about anti-e's and breast cancer that said tamoxifen (nolva) was more effective than anything currently on the market at targeting estrogen-producing cancer cells in the breast and urethral tissues; obviously we don't have to worry about the second as males but the main side of gyno is breast tissue enlargement, making tamoxifen stand alone in this area of tissue targeting
Dwight Schrute
I am faster than 80% of all snakes
quasar said:
Aromasin and letrozole are much better at this than anything.
ready2explode
New member
It is true that nolvadex's anti-estrogenic properties make it by far and away the best anti-e choice. The problem here is yourdaddy asked what is best POST CYCLE. There is a debate on whether nolva and clomid stimulate nat. test. by blocking estrogen or if there are other ways. Some claim that clomid stimulates nat. test. in ways nolva doesnt. It is better to be safe than sorry and use both, IMO. If you had to chose 1, I would go with nolva, but you dont...so use both lol
SlateDrake
New member
I have, and will continue to use both post-cycle. I think using HCG the last 3 weeks while on cycle (to be concurrent with supression from androgens) and than a post-cycle regimine of:
POST CYCLE:
Week 1-4 : Tamoxifen Citrate 20 mg/day
Week 1-2 : Clomiphene Citrate 100 mg/day
Week 3-4 : Clomiphene Citrate 50 mg/day
Is the bomb....maybe some femera is you have it...I used it last time but I may not in future cycles.
Interesting enough, BC has a "safe/sane cycel" article out now that mentions this combo briefly. I think he also has Propecia(??) or something like that thrown in for post-cycle as well...but don't quote me on that...I'll need to review that thread again before I kick off the next fun and games session.
POST CYCLE:
Week 1-4 : Tamoxifen Citrate 20 mg/day
Week 1-2 : Clomiphene Citrate 100 mg/day
Week 3-4 : Clomiphene Citrate 50 mg/day
Is the bomb....maybe some femera is you have it...I used it last time but I may not in future cycles.
Interesting enough, BC has a "safe/sane cycel" article out now that mentions this combo briefly. I think he also has Propecia(??) or something like that thrown in for post-cycle as well...but don't quote me on that...I'll need to review that thread again before I kick off the next fun and games session.
ready2explode
New member
Actually, this is not true. In men, these 2 inhibitors will block approx. 60% of estrogen (by ways of stopping it from converting). Nolva will block a much higher percentage (because of a higher affiliation to the receptor itself).Bobo said:
ready2explode
New member
Also note: Letro (femara) and nolva interact with each causing the letro to be 30-40% less effective. I would not use an anti-aromatase and an anti-estrogen post cycle. It is not clear if adex will have the same interaction with either clomid or nolva. It is also not clear if letro will interact this way with clomid. Again, to be on the safe side, I would not use an anti-aromatase post cycle...
ready2explode
New member
I like this post cycle therapy (with hcg ofcourse) a lot. Sometimes, I bump the nolva up to 40 mgs for the first 2 weeks with the high clomid...SlateDrake said:
Dwight Schrute
I am faster than 80% of all snakes
ready2explode said:
But using letro will also help equalize IGF-1 which Letro raises and Nolva lowers. Using Letro even though its 30-40% less effective is still good because you still getting more estrogen suppression with Nolva. I know several people, including Wardog that have raved about this post cycle. Said they had the best recovery ever. I'm trying it myself in a couple of months.
Dwight Schrute
I am faster than 80% of all snakes
ready2explode said:
But your forgetting about circulating estrogen still present and the effects progesterone, prolactin, etc...Aromasin has been shown to have no effect on those while completely eliminating estrogen formation.
Either way if you any of these your going to be fine.
ready2explode
New member
I dont understand what you mean by this comment. Progesterone is only a problem when estrogen is present. If one was to block estrogen, progesterone wouldnt be of any worry. Please clarify this for me...Bobo said:
I'm not too sure about Aromasin post cycle. It wouldnt do anything to help estrogen that is already circulating, so you would def need nolva and/or clomid with it. I dont know if nolva will interact with aromasin, like it does with letro, either. I can say that some claim clomid stimulates nat. test. in other ways besides just blocking estrogen. Aromasin couldn't help in this aspect. Aromasin does have an affinity to the androgen receptor which could cause negative feeback...im just babblin'...when I get home I'll look into this more and get back to you guys...
Dwight Schrute
I am faster than 80% of all snakes
ready2explode said:
Technically yes but then one would never get gyno from Fina only cycle and I've seen people experience this. Now whether its through prolactin or progesterone is still up in the air but I know that gyno can be produced through many pathways and not just estrogen. Letrozole seems to take care of it nicely along with many potent metabolites that we don't account for.
I agree not too use Aromasin post cycle. It completely eliminates estrogen and would be couterproductive in the long run, not to mention the possibibily for a massive rebound once its discontinued. I'm more concerned with letrozole as it seems to have the most positive effects on IGF-1 and eliminates estrogen very well. The elevation in IGF-1 is reaslly what I'm looking at because this would do nicely post cycle when test levels are low. As you can see, wardog seemed to like it.
On a side note I know PA likes the use of aromatase blockers post cycle as this is what 6-oxo is based upon.
BTW- I was doing a search for something last night and saw your little debate with Billy Bathgate. Its funny how that guy never gives up even though he is completely wrong on so many things
ready2explode
New member
I think you will like this post by nandi (admin of cuttingedgemuscle.com)Bobo said:
"I was visiting another board the other day and noticed a thread where a member was being flamed for saying he got gyno from anavar. Macro, a knowledgeable Mod there pointed out that anavar elevates GH and IGF-1, and this could very well tip the scales toward gyno in sensitive people.
I added my comments on the possibility that non-aromatizing steroids could induce gyno by lowering natural DHT levels:
In addition to elevated IGF-1, lowered DHT levels resulting from endogenous testosterone suppression may contribute to gyno from non aromatizing steroids. Gyno is a reported side effect from finasteride use. Some have attributed this to elevated estrogen levels due to the fact that there is more testosterone to be aromatized, since less test is being converted to DHT. Other researches think that DHT has a direct antiestrogenic effect on breast tissue.
Studies have shown that DHT can actually block estrogen from binding to the estrogen receptor in mammary tissue (1). DHT also is an aromatase inhibitor (2). Even more interesting is the fact that transdermal DHT cream has been used successfully to treat gyno (3).
It may be that the estrogen/DHT ratio is more important to the development of gyno than the estrogen/testosterone ratio.
(1) J Clin Invest 1984 Dec;74(6):2272-8
Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor.
Casey RW, Wilson JD
(2) J Clin Endocrinol Metab 1984 Mar;58(3) 467-72
The intracellular control of aromatase activity by 5 alpha-reduced androgens in human breastcarcinoma cells in culture.
Perel E, Stolee KH, Kharlip L, Blackstein ME, Killinger DW.
(3) Clin Infect Dis 2001 Sep 15;33(6):891-3
Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring during highly active antiretroviral therapy: four cases and a review of the literature.
Benveniste O, Simon A, Herson S."
I def dont believe, although they arent any studies backing me up, that letro increases IGF-1. If you block estrogen, you're going to get a decrease in IGF-1 similar to the one seen when administering adex. Also note my above post mentioning that letro interacts with nolva causing the letro to be 30-40% less effective. Again, its not known to interact with clomid in the same way, but I'd be wary. I do not think we are going to find a place for anti-aromatases or inhibitors post cycle, only anti-es. I could be wrong, but i've got this sneaky suspicion. Lots of ppl do like anti-aromatases though...i personally would not use one. If you wanna go on personal experiences, there are many, especially on CEM (including nandi), that do not use them post cycle.Bobo said:
Can you believe I took **** for that thread? That is why I dont visit the board much anymore...a couple of the mods were sticking up for him...I was in aww...still am...Bobo said:BTW- I was doing a search for something last night and saw your little debate with Billy Bathgate. Its funny how that guy never gives up even though he is completely wrong on so many things
Dwight Schrute
I am faster than 80% of all snakes
I'm familiar with what Nandi posted along with Big Cat. I saw the Fonz debate(prolactin debate) and it was a prelude to the one me and Big Cat did with him on the d-bol bridge crap. Check that one out if you haven't. It was fun.
THis was the basis for my recommednation for in cycle use of letrozole.
Update on clinical role of tamoxifen.
Benson JR, Pitsinis V.
PURPOSE OF REVIEW Breast cancer is the most common malignancy amongst women in the United States and decreased mortality over the past decade has been attributed to a combination of screening and adjuvant therapies. There has been a resurgence of interest in hormonal therapies and this article discusses the clinical status of tamoxifen in the context of emerging alternative agents for treatment and prevention of breast cancer.RECENT FINDINGS Tamoxifen has served as a prototype for the development of selective estrogen receptor modulators at the laboratory-clinical interface. Molecular technologies have permitted elucidation of mechanisms for tissue specific action and led to newer selective estrogen receptor modulators with potentially greater antitumour efficacy and attenuated uterotrophic profile. Publications over the past 12 months have emphasized the risks of thromboembolism and endometrial carcinoma associated with tamoxifen use which has accelerated application of other hormonal agents for treatment of advanced disease and as neoadjuvant therapy. This article reviews the current role of tamoxifen in the treatment of early and advanced breast cancer together with its potential for chemoprevention. Models for quantitative risk assessment are being developed to identify women for whom chemoprotection is justified.SUMMARY Recent data showing a survival advantage for the aromatase inhibitor letrozole compared with tamoxifen in the advanced setting and improvement in disease-free survival for the aromatase inhibitor anastrozole versus tamoxifen as adjuvant treatment may herald a major shift in standard first-line endocrine therapies for both advanced and early disease and ultimately chemoprevention of breast cancer. Other agents including newer SERMs and pure antiestrogens are undergoing phase III clinical trials and future endocrine and biological therapies are likely to include more selective and targeted therapies, which may be efficacious in both hormone-sensitive and receptor-negative disease.
Letrozole's superiority over progestins and tamoxifen challenges standards of care in endocrine therapy for metastatic breast cancer.
Piccart MJ, Cardoso F, Atalay G.
Jules Bordet Institute, Chemotherapy Unit, Boulevard de Waterloo 125, 1000, Brussels, Belgium. [email protected]
PMID: 12409074 [PubMed - indexed for MEDLINE]
The abstract isn't availbale for that one but if you look this one up on medline it has the full text.
Here's the one on IGF and letrozole.
The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.
Bajetta E, Ferrari L, Celio L, Mariani L, Miceli R, Di Leo A, Zilembo N, Buzzoni R, Spagnoli I, Martinetti A, Bichisao E, Seregni E.
Medical Oncology B Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.
Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial
PMID: 9459192 [PubMed - indexed for MEDLINE]
THis was the basis for my recommednation for in cycle use of letrozole.
Update on clinical role of tamoxifen.
Benson JR, Pitsinis V.
PURPOSE OF REVIEW Breast cancer is the most common malignancy amongst women in the United States and decreased mortality over the past decade has been attributed to a combination of screening and adjuvant therapies. There has been a resurgence of interest in hormonal therapies and this article discusses the clinical status of tamoxifen in the context of emerging alternative agents for treatment and prevention of breast cancer.RECENT FINDINGS Tamoxifen has served as a prototype for the development of selective estrogen receptor modulators at the laboratory-clinical interface. Molecular technologies have permitted elucidation of mechanisms for tissue specific action and led to newer selective estrogen receptor modulators with potentially greater antitumour efficacy and attenuated uterotrophic profile. Publications over the past 12 months have emphasized the risks of thromboembolism and endometrial carcinoma associated with tamoxifen use which has accelerated application of other hormonal agents for treatment of advanced disease and as neoadjuvant therapy. This article reviews the current role of tamoxifen in the treatment of early and advanced breast cancer together with its potential for chemoprevention. Models for quantitative risk assessment are being developed to identify women for whom chemoprotection is justified.SUMMARY Recent data showing a survival advantage for the aromatase inhibitor letrozole compared with tamoxifen in the advanced setting and improvement in disease-free survival for the aromatase inhibitor anastrozole versus tamoxifen as adjuvant treatment may herald a major shift in standard first-line endocrine therapies for both advanced and early disease and ultimately chemoprevention of breast cancer. Other agents including newer SERMs and pure antiestrogens are undergoing phase III clinical trials and future endocrine and biological therapies are likely to include more selective and targeted therapies, which may be efficacious in both hormone-sensitive and receptor-negative disease.
Letrozole's superiority over progestins and tamoxifen challenges standards of care in endocrine therapy for metastatic breast cancer.
Piccart MJ, Cardoso F, Atalay G.
Jules Bordet Institute, Chemotherapy Unit, Boulevard de Waterloo 125, 1000, Brussels, Belgium. [email protected]
PMID: 12409074 [PubMed - indexed for MEDLINE]
The abstract isn't availbale for that one but if you look this one up on medline it has the full text.
Here's the one on IGF and letrozole.
The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.
Bajetta E, Ferrari L, Celio L, Mariani L, Miceli R, Di Leo A, Zilembo N, Buzzoni R, Spagnoli I, Martinetti A, Bichisao E, Seregni E.
Medical Oncology B Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.
Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial
PMID: 9459192 [PubMed - indexed for MEDLINE]
Dwight Schrute
I am faster than 80% of all snakes
This is one I already had. Just thought since its on this topic I would post it.
[Growth rate can be manipulated. Estrogen production in pubertal boys can be blocked by an aromatase inhibitor]
[Article in Swedish]
Hagenas L.
Barnendokrinologiska enheten, Astrid Lindgrens barnklinik, Karolinska sjukhuset, Stockholm. [email protected]
A review of a twelve month clinical trial [1] using a new, effective aromatase inhibitor treatment in boys with delayed puberty shows that the pubertal increase in estrogen levels can be blocked, with concomitant preserved pubertal growth rate. Circulating testosterone levels are greatly enhanced during treatment due to increased gonadotrophin secretion. Despite this, bone age maturation is slow leading to an increased final height prognosis (mean 5.1 cm) for the boys treated with aromatase inhibitor.
PMID: 11838072 [PubMed - indexed for MEDLINE]
[Growth rate can be manipulated. Estrogen production in pubertal boys can be blocked by an aromatase inhibitor]
[Article in Swedish]
Hagenas L.
Barnendokrinologiska enheten, Astrid Lindgrens barnklinik, Karolinska sjukhuset, Stockholm. [email protected]
A review of a twelve month clinical trial [1] using a new, effective aromatase inhibitor treatment in boys with delayed puberty shows that the pubertal increase in estrogen levels can be blocked, with concomitant preserved pubertal growth rate. Circulating testosterone levels are greatly enhanced during treatment due to increased gonadotrophin secretion. Despite this, bone age maturation is slow leading to an increased final height prognosis (mean 5.1 cm) for the boys treated with aromatase inhibitor.
PMID: 11838072 [PubMed - indexed for MEDLINE]
Dwight Schrute
I am faster than 80% of all snakes
Here's the one on the lowering of letrozole with Nolva.
Drug and hormone interactions of aromatase inhibitors.
Dowsett M.
Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these three agents has significant effects on other endocrine pathways at its clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact, resulting in letrozole concentrations approximately 35-40% lower than when letrozole is used alone.
Publication Types:
Review
Review, Tutorial
PMID: 10731107 [PubMed - indexed for MEDLINE]
THe thing is that you will still get much more blocking of estrogen even if letrozole is still only 60-65% effective when you combine the too. But your right, looks like Clomid would be a better option.
Drug and hormone interactions of aromatase inhibitors.
Dowsett M.
Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these three agents has significant effects on other endocrine pathways at its clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact, resulting in letrozole concentrations approximately 35-40% lower than when letrozole is used alone.
Publication Types:
Review
Review, Tutorial
PMID: 10731107 [PubMed - indexed for MEDLINE]
THe thing is that you will still get much more blocking of estrogen even if letrozole is still only 60-65% effective when you combine the too. But your right, looks like Clomid would be a better option.
bigbadboss101
Member
Now what are the pros and cons of liquid vs pill forms of clomid or Nolva? Cost wise liquid is more costly? Effectiveness and potency?
Dwight Schrute
I am faster than 80% of all snakes
Its the same substance, just cheaper, especially Arimidex and Femara.
BigPoppaThrilla
New member
anti-estogen- nolva
post cycle-clomid
post cycle-clomid
windwords7
Well-known member
Cons of Tabs: Nothing
Pros of Tabs: Easy and Convienent
Chemo
Brewing Anabolic Minds
Just as with anything else we do...a proper post cycle regime will be tailored for the individual. For instance, if one were cycling with a long acting ester it may be of value to add an anti-aromatase for the immediate week or two following the last pin simultaneously with nolva (or for us old guys, clomid instead).
In the case of fast acting compounds such as with topicals it may be better to just use straight nolva or tamoxifen for recovery needs. Of course, if one were to realize considerable water retention he may still consider an anti-aromatase to help push that off and alleviate further bloat.
It is hard to lump the anti-e's into one large group and say "THIS IS APPROVED FOR THE MASSES" as your body structure, response, and needs will vary greatly from mine and everyone else's. Anti-'s are merely a tool for recovery and in order to successfully employ them would require a thorough understanding of how they work and why you are dosing them to begin with.
With that said, my personal favorite cocktail would be nolva with an anti-aromatase (ari as I haven't tried the letro yet) for the first week or so. Once again, this is the combo that is right for me but may not be the right choice for YOU.
Chemo
In the case of fast acting compounds such as with topicals it may be better to just use straight nolva or tamoxifen for recovery needs. Of course, if one were to realize considerable water retention he may still consider an anti-aromatase to help push that off and alleviate further bloat.
It is hard to lump the anti-e's into one large group and say "THIS IS APPROVED FOR THE MASSES" as your body structure, response, and needs will vary greatly from mine and everyone else's. Anti-'s are merely a tool for recovery and in order to successfully employ them would require a thorough understanding of how they work and why you are dosing them to begin with.
With that said, my personal favorite cocktail would be nolva with an anti-aromatase (ari as I haven't tried the letro yet) for the first week or so. Once again, this is the combo that is right for me but may not be the right choice for YOU.
Chemo
guyrelax
New member
how did you use the letro and for what type of cycle? would anyone here suggest using nolva or letro oncycle and why?
