JimiThing
Moderator
Estrogen on Cycle: The Good, The Bad, and The Proper Management of Both.
The purpose of this article is too look at the effects of estrogen both good and bad, and how we can properly manage them while on cycle using the various compounds available to us. The relevance of Estrogen management is more important than ever now in my opinion. This is due to several factors. First of all the knowledge of Estrogen and its effects in males has grown substantially in the last few years. Also a more basic but very real reason is the trend we have seen in cycles over the last several years. It used to be cycles were 6 - 8 weeks in length. In the past it was common that short ester cycles were run 6 weeks and long estered ones 8 weeks. Now cycle lengths of 12-16 weeks+ have become the norm. This added time and exposure to the deleterious effects of unmanaged or improperly managed estrogen makes the topic more important than ever.
So lets take a look at the effects of Estrogen in Males both positive and negative. While we will see Estrogen plays a key role in several vital functions in males, as well as several functions specifically important to our goals, more is definitely not better when it comes to this Hormone.
On the positive side:
* Estrogen plays a key role in immune system function and inflammatory response.
* It has a positive impact on cholesterol.
* Estrogen is essential for GH and IGF synthesis.
*It plays a role in maintaining proper '"fluid balance" within the body.
*Essential for bone density
*Assists in glucose uptake
The Negatives:
*Increased Risk of Heart Disease
*Increased risk of Prostate cancer
*Increased blood clotting
*Increased risk of Hypertension (high blood pressure)
* Increased risk of cardiovascular event or stroke.
*Gynecomastia
* Improper Fluid Balance (or water retention)
*Estrogens relationship with other hormones. For example, Estrogen has a proportional
relationship with the hormone Prolactin. An increase in Estrogen results in an increase
in Prolactin.
As you can see there are numerous serious positives and negatives when it comes to the effect''s of Estrogen in males. Some of these effects are dependent upon the levels of Estrogen present. For example proper estrogen levels result in improved lipid profiles and cardiovascular health. However elevated estrogen levels result in adverse effects on cardiovascular health and increased risk of heart attack or stroke. Based on this it becomes very clear the optimal situation when it comes to Estrogen while on cycle is to MANAGE it properly. Not eliminate it, not ignore it, but manage it.
To further clarify and specify what I would consider proper Estrogen Management, especially in light of the fact that many positive effects of Estrogen become negative when it is elevated too much, I would define estrogen management as maintaining Estrogen levels in the clinically normal range even while on cycle. In other words keep our E2 levels the same on or off cycle. To take it a step further if Estrogen levels can be kept between 25-30 while on cycle, we can reap the positive effects of Estrogen while virtually eliminating the negative ones.
Lets take a look at Estrogen management while on AAS cycle and how it has evolved over the years, what compounds are available to assist us, and the effects and interactions of these compounds.
Years ago the first attempts at managing Estrogen really didn''t manage it at all;they just eliminated some undesirable side effects while having no impact on Estrogen levels at all. These early attempts were made using serms such as clomid or tamoxifen while on cycle. The specific side effect of elevated estrogen that the use of serms would address is the one of gynecomastia. Serms bind to the Estrogen receptor in breast tissue, blocking estrogen from exerting its effect there and preventing undesired breast tissue growth. As you can see this was an improvement over using nothing at all, however serm use does nothing to address the other negative effects of elevated Estrogen. Some of these negative effects are very serious, much more serious than Gyno from a medical (as well as common sense) not aesthetic perspective. While serms do not address the majority of negative issues of elevated Estrogen it does not mean they do not have a place in this discussion or in treating of addressing this issue. I will get into that more later.
The next progression in Estrogen management is the use of Aromatase Inhibitors to control overall Estrogen levels. This has been a huge advancement in the management of estrogen. Aromatase Inhibitors act upon the Aromatase enzyme. This is the enzyme responsible for the conversion of testosterone to estrogen within the body. Aromatase Inhibitors prevent the binding of Aromatase to testosterone so the process of Aromatozation of Test to Estrogen cannot take place. This sounds like the ultimate solution to the problem of Estrogen Management on cycle and too a large degree it is. However there are different Aromatase Inhibitors that may make one a more prudent choice than the other for certain situations or individuals. Also the value of Serms and their role in estrogen management cannot be dismissed just yet.
So we see we have 2 categories of compounds that can be of use to us in properly managing Estrogen or its side effects, Serms and AIs. Let''s take a look at our options in categories, their differences and potential interactions with one another, and how they might be used together to accomplish our goal.
First we will look at AIs as in my opinion they are the core of our Estrogen Management program. We essentially have 2 types of AI''s to choose from. Type 1 AIs like Exemestane and Type 2 AI''s such as Letrozole or Anastrozole (arimidex). The difference in these types is as follows. A Type 1 Aromatase inhibitor (AI) like Exemestane binds permanently to the site on the Aromatase Enzyme where it binds to testosterone allowing its conversion to Estrogen. This permanent binding renders the Aromatase totally and permanently inactive. In contrast Type 2 AIs temporarily bind to this site on the Aromatase Enzyme rendering it inactive as long as the Aromatase inhibitor (AI) is being used. Onçe use of type 2 Aromatase inhibitor (AI) stops the aromatase will reactivate. So whats the difference in these Aromatase inhibitor (AI) types for our purposes? Well Due to the '"reactivation" if you will of existing Aromatase with a Type 2 Aromatase inhibitor (AI), when you stop using it a spike in Estrogen (often referred to as rebound) will occur due to the sudden increase availability of Aromatase Enzyme. Another important distinction when it comes to Type 1 and Type 2 AI''s. A Type 1 Aromatase inhibitor (AI) like Exemestane remains unaffected by the introduction of a serm into your Estrogen management program. Type 2 AIs like Letrozole and Arimidex suffer a reduced in blood levels and effectiveness with the introduction of some serms. I will touch more on why we may need to introduce a serm a little farther on in this article.
When it comes to the strength of these AI''s Letrozole would be the strongest followed by Arimidex and then by Exemestane. Now people might be up in arms saying Exemestane is stronger than Arimidex however when one looks and compare data from studies done on MALES the order of strength is exactly as I stated it, quite often much confusion comes in to play when people recite data on AI's taken from studies on women. The fact is AI's behave differently in males, they are less effective in males, and for our purposes it is only prudent to compare data gathered from studies on males to portray an accurate picture.
The next aspect to be considered when looking at AIs are the effects they indirectly illicit in other areas. We stated the positive effects of Estrogen, we must realize by lowering Estrogen via Aromatase inhibitor (AI) use some of these positive effects may be compromised. It is important to look at the various Aromatase inhibitor (AI) options available and possibly use the data to help pick which Aromatase inhibitor (AI) we use. Letrozole is an extremely potent Aromatase inhibitor (AI) and its effects demonstrate this as would be expected. Letrozole has an adverse effect on lipid profile and somewhat on IGF levels. On the other hand Arimdex has a small impact in the area of IGF and depending upon which studies you cite a small adverse impact on lipids to no adverse impact on lipids. Exemestane seems to have no clinical impact on either IGF or lipids.
It is important to realize that it may seem like Exemestane shines as a clear cut winner when it comes to choice of Aromatase inhibitor (AI), however I do not necessarily believe this to be the case for everyone. In some cases or maybe better said in some people, an extremely powerful Aromatase inhibitor (AI) like Letrozole must be used to manage Estrogen properly. Some may respond better to Arimidex than Exemestane. I believe there is a place for all 3 of these. That being said, if possible my personal first choice of Aromatase inhibitor (AI) is Exemestane due to its lack of interaction with other compounds we may need to introduce such as certain serms, its positive effects on IGF and Lipids over other options, and also its lack of potential "rebound"(although I think that is an overstated issue quite often).
Regardless of which Aromatase inhibitor (AI) you choose for the vast majority of us our goal can be accomplished of maintaining Estrogen levels in the normal range while on cycle. It might seem like the discussion is over. Why do we even need to look at Serms? Read on:
So we have our Estrogen levels managed, all should be good. Well yes in most cases it will be but what if it isn't? What if you start to get sensitive, itchy or painful nipples? What if you get a lump around your nipple area? What if you are so predisposed to gyno you still get symptoms using an AI? It shouldnt happen but if it does your immediate solution should be a serm.
So we know what serms do. As stated above they bind to the Estrogen receptor in breast tissue, preventing Estrogen from eliciting its effects, which in this case is undesired breast development and tissue growth. However all serms are not created equal for this purpose. I am of the opinion that Raloxifene and Tamoxifen are the 2 best suited serms for this purpose.
Raloxifene is the serm with the highest binding affinity to the Estrogen receptor in breast tissue. Tamoxifen would be second. This means Raloxifene is the most effective serm available for gyno treatment and or prevention. Another point that bears mentioning, when using a Type 2 Aromatase inhibitor (AI) like Arimidex or Letrozole, Tamoxifen reduces blood levels of both of these AI's. Raloxifene on the other hand has no effect on blood levels of these AI's, allowing them to be run in conjunction with Raloxifene with no decrease in Aromatase inhibitor (AI) effectiveness. As was mentioned above any serm can be run with Exemestane (a Type 1 AI) with no impact on Exemestane's effectiveness.
Tamoxifen is the serm with probably the most clinical data supporting its use for gyno prevention and treatment, in all likelihood due to the age of the drug. It is very effective for this purpose and very versatile as it is equally if not more effective in the area of pct as well, meaning often it is likely on hand so it is readily available for most to use in the case of gyno symptoms.
So let's begin to put this all together. An Aromatase inhibitor (AI) should be the core of your Estrogen management program; the goal should be Estrogen levels in the clinically normal range even while on cycle. Id say between 25-30. I cannot emphasize enough the importance of blood work as a management tool. It really is the only effective means of proper Estrogen management (hormone profile management for that matter).
All AI''s can effectively manage Estrogen. My preference in order for this purpose would be Exemestane , then Arimidex , then Letrozole however as stated earlier they all have their place. If Exemestane works well for you you have the luxury of the least amount of undesirable side effects and the most versatility as far as combining with a serm should the need arise for gyno prevention and treatment.
The logical question is why do even need to worry about a serm if I mange Estrogen with an Ai? Well hopefully you don't however in some cases it may become necessary due to predisposition, preexisting gyno , very high dosages of aromatizing steroids and so on. For this purpose Raloxifene is in my opinion the top choice offering no reduction in effectiveness of any Aromatase inhibitor (AI) you are running and the most powerful protection against gyno due to its binding affinity to the E receptor in brest tissue. Tamoxifen is also a very solid option especially if running Exemestane as your Aromatase inhibitor (AI). If you are running letrozole or arimidex a corresponding increase in the dosage of Aromatase inhibitor (AI) may be required due to tamoxifen reducing blood levels and effectiveness of these 2 AIs.
Bringng it to theReal World:
1- Manage Estrogen levels with an AI: Exemestane offers the most versatility with fewest adverse effects.
2- Have a Serm on hand in case of Gyno flare up. Raloxifene is most effective and has no adverse interactions with any AIs.
Run a low dose Aromatase inhibitor (AI) with your cycle to try to keep estrogen in the clinically normal range so you can reap the benefits and reduce the deleterious effects. Have a serm on hand just in case gyno rears its head. If it does start a serm immediately. At this point you NEED blood work so you can properly assess your situation and possibly adjust Aromatase inhibitor (AI) dosage up which may allow discontinuation of serm. It may not. You may need to run a serm and Aromatase inhibitor (AI) in conjunction on cycle but it is very unlikely. An Aromatase inhibitor (AI) should be able to manage Estrogen properly for the vast majority of us. If you do need to run a serm and Aromatase inhibitor (AI) together I cannot emphasize enough that you need to reevaluate your situation. Elevated estrogen has some serious effects as I mentioned above. You should consider this option as I would encourage many too do anyway. Reduce the amount of aromatizing steroids in your cycle and replace them with non-aromatizing compounds. I cannot emphasize this enough. For example a lower test dose will allow for easier estrogen management. This is probably the single biggest thing any of us can do to help ensure proper estrogen management (besides blood work', which again is essential).
One more topic I want to touch on is Gyno. Gyno is considered the worst side effect of elevated estrogen but the fact is it is far from it. There are many much more serious issues going on inside of you if you start growing breasts. That being said when it does occur or start to occur we want to stop it. So often I see people recommend Letrozole to treat gyno. This is a horrible idea in my opinion. Letrozole works to treat gyno by lowering overall Estrogen levels so much there is no circulating Estrogen to bind to the Estrogen receptor in breast tissue. If you paid attention above you saw the beneficial effects of Estrogen. Some aren''t even beneficial, they are essential. I think to eliminate estrogen to this point throughout your entire body is foolish. Introduce a serm such as raloxifene, block the Estrogen receptor in the breast. The gyno then cannot grow. Then again using blood work adjust your Aromatase inhibitor (AI) dose to MANAGE estrogen levels while taking the serm to prevent the continuation of the gyno.
The above is an interesting topic. I hope this info proved useful to some and I would love to discuss it further.
JimiThing
Refs:
*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. lucashbl@unipa.it Estrogen and prostate cancer: an eclipsed tru... [J Cell Biochem. 2007] - PubMed - NCBI
*Estrogen Makes Men More Likely To Die Of Heart Disease
*Role of Estrogens in Inflammatory Response Expression of Estrogen Receptors in Peritoneal Fluid Macrophages from Endometriosis SILVIA CAPELLINO1,PAOLA MONTAGNA1, BARBARA VILLAGGIO1, ALBERTO SULLI1, STEFANO SOLDANO1, SIMONE FERRERO2, VALENTINO REMORGIDA2, MAURIZIO CUTOLO1Article first published online:30JUN2006DOI:10.1196/annals.1351.024 Role of Estrogens in Inflammatory Response - CAPELLINO - 2006 - Annals of the New York Academy of Sciences - Wiley Online Library
*http://www.eje-online.org/content/157/6/709.full.pdf
*Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model Brian J. Long, Danijela Jelovac,Venkatesh Handratta,pinya Thiantanawat,Nicol MacPherson,Joseph Ragaz,Olga G. Goloubeva and Angela M. Brodie+ Author Affiliations Affiliations of authors: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Health Sciences Facility, Baltimore, MD (BJL, DJ, VH, AT, AMB); British Columbia Cancer Agency, Vancouver, British Columbia, Canada (NM, JR); Division of Biostatistics, University of Maryland Greenebaum Cancer Center, Baltimore (OGG) Correspondence to: Angela M. Brodie, PhD, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Health Sciences Facility, Rm. 580G, 685 West Baltimore St., Baltimore, MD 21201 (e-mail abrodie@umaryland.edu)
*Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model
*Exemestane in the Adjuvant Treatment of Breast Cancer in Postmenopausal Women
*Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males
*Czajka-Oraniec I, Simpson ER (2010). "Aromatase research and its clinical significance". Endokrynol Pol 61 (1): 126***8211;34. PMID 20205115
*Vogel, Victor; Joseph Constantino, Lawrence Wickerman et al. (2006-06-21). "Effects of Tamoxifen vs. Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes". The Journal of the American Medical Association 295 (23): 2727***8211;2741. doi:10.1001/jama.295.23.joc60074. PMID 16754727
*http://humupd.oxfordjournals.org/con...3/212.full.pdf ***8211; Pharmacological Review of Selective Estrogen Recptor Modulators
*Aromatase inhibitors for male infertility. [J Urol. 2002] - PubMed - NCBI
*Safety and Efficacy of Anastrozole for the Treatment of Pubertal Gynecomastia: A Randomized,Double-Blind,Placebo-ControlledTrial Safety and Efficacy of Anastrozole for the Treatment of Pubertal Gynecomastia: A Randomized, Double-Blind, Placebo-Controlled Trial
* Approach to the Patient with Gynecomastia1. Harold E. Carlson- Author Affiliations Department of Medicine, Endocrinology Division, Stony Brook University, Stony Brook, New York 11794-8154 Address all correspondence and requests for reprints to: Harold E. Carlson, M.D., Department of Medicine, Endocrinology Division, HSC T15-060, Stony Brook University, Stony Brook, New York 11794-8154. E-mail: harold.carlson@stonybrook.edu.
* Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males Nelly Mauras, John Lima, Deval Patel, Annie Rini, Enrico di Salle, Ambrose Kwok and Barbara Lippe Author Affiliations Nemours Children***8217;s Clinic and Research Programs (N.M., J.L., A.R.), Jacksonville, Florida 32207; and University of Florida Health Sciences Center (D.P.) and Amersham Pharmacia Biotech (E.d.S., A.K., B.L.), Peapack, New Jersey 07977 Address all correspondence and requests for reprints to: Nelly Mauras, M.D., Nemours Children***8217;s Clinic, 807 Children***8217;s Way, Jacksonville, Florida 32207. E-mail: nmauras@nemours.org.
The purpose of this article is too look at the effects of estrogen both good and bad, and how we can properly manage them while on cycle using the various compounds available to us. The relevance of Estrogen management is more important than ever now in my opinion. This is due to several factors. First of all the knowledge of Estrogen and its effects in males has grown substantially in the last few years. Also a more basic but very real reason is the trend we have seen in cycles over the last several years. It used to be cycles were 6 - 8 weeks in length. In the past it was common that short ester cycles were run 6 weeks and long estered ones 8 weeks. Now cycle lengths of 12-16 weeks+ have become the norm. This added time and exposure to the deleterious effects of unmanaged or improperly managed estrogen makes the topic more important than ever.
So lets take a look at the effects of Estrogen in Males both positive and negative. While we will see Estrogen plays a key role in several vital functions in males, as well as several functions specifically important to our goals, more is definitely not better when it comes to this Hormone.
On the positive side:
* Estrogen plays a key role in immune system function and inflammatory response.
* It has a positive impact on cholesterol.
* Estrogen is essential for GH and IGF synthesis.
*It plays a role in maintaining proper '"fluid balance" within the body.
*Essential for bone density
*Assists in glucose uptake
The Negatives:
*Increased Risk of Heart Disease
*Increased risk of Prostate cancer
*Increased blood clotting
*Increased risk of Hypertension (high blood pressure)
* Increased risk of cardiovascular event or stroke.
*Gynecomastia
* Improper Fluid Balance (or water retention)
*Estrogens relationship with other hormones. For example, Estrogen has a proportional
relationship with the hormone Prolactin. An increase in Estrogen results in an increase
in Prolactin.
As you can see there are numerous serious positives and negatives when it comes to the effect''s of Estrogen in males. Some of these effects are dependent upon the levels of Estrogen present. For example proper estrogen levels result in improved lipid profiles and cardiovascular health. However elevated estrogen levels result in adverse effects on cardiovascular health and increased risk of heart attack or stroke. Based on this it becomes very clear the optimal situation when it comes to Estrogen while on cycle is to MANAGE it properly. Not eliminate it, not ignore it, but manage it.
To further clarify and specify what I would consider proper Estrogen Management, especially in light of the fact that many positive effects of Estrogen become negative when it is elevated too much, I would define estrogen management as maintaining Estrogen levels in the clinically normal range even while on cycle. In other words keep our E2 levels the same on or off cycle. To take it a step further if Estrogen levels can be kept between 25-30 while on cycle, we can reap the positive effects of Estrogen while virtually eliminating the negative ones.
Lets take a look at Estrogen management while on AAS cycle and how it has evolved over the years, what compounds are available to assist us, and the effects and interactions of these compounds.
Years ago the first attempts at managing Estrogen really didn''t manage it at all;they just eliminated some undesirable side effects while having no impact on Estrogen levels at all. These early attempts were made using serms such as clomid or tamoxifen while on cycle. The specific side effect of elevated estrogen that the use of serms would address is the one of gynecomastia. Serms bind to the Estrogen receptor in breast tissue, blocking estrogen from exerting its effect there and preventing undesired breast tissue growth. As you can see this was an improvement over using nothing at all, however serm use does nothing to address the other negative effects of elevated Estrogen. Some of these negative effects are very serious, much more serious than Gyno from a medical (as well as common sense) not aesthetic perspective. While serms do not address the majority of negative issues of elevated Estrogen it does not mean they do not have a place in this discussion or in treating of addressing this issue. I will get into that more later.
The next progression in Estrogen management is the use of Aromatase Inhibitors to control overall Estrogen levels. This has been a huge advancement in the management of estrogen. Aromatase Inhibitors act upon the Aromatase enzyme. This is the enzyme responsible for the conversion of testosterone to estrogen within the body. Aromatase Inhibitors prevent the binding of Aromatase to testosterone so the process of Aromatozation of Test to Estrogen cannot take place. This sounds like the ultimate solution to the problem of Estrogen Management on cycle and too a large degree it is. However there are different Aromatase Inhibitors that may make one a more prudent choice than the other for certain situations or individuals. Also the value of Serms and their role in estrogen management cannot be dismissed just yet.
So we see we have 2 categories of compounds that can be of use to us in properly managing Estrogen or its side effects, Serms and AIs. Let''s take a look at our options in categories, their differences and potential interactions with one another, and how they might be used together to accomplish our goal.
First we will look at AIs as in my opinion they are the core of our Estrogen Management program. We essentially have 2 types of AI''s to choose from. Type 1 AIs like Exemestane and Type 2 AI''s such as Letrozole or Anastrozole (arimidex). The difference in these types is as follows. A Type 1 Aromatase inhibitor (AI) like Exemestane binds permanently to the site on the Aromatase Enzyme where it binds to testosterone allowing its conversion to Estrogen. This permanent binding renders the Aromatase totally and permanently inactive. In contrast Type 2 AIs temporarily bind to this site on the Aromatase Enzyme rendering it inactive as long as the Aromatase inhibitor (AI) is being used. Onçe use of type 2 Aromatase inhibitor (AI) stops the aromatase will reactivate. So whats the difference in these Aromatase inhibitor (AI) types for our purposes? Well Due to the '"reactivation" if you will of existing Aromatase with a Type 2 Aromatase inhibitor (AI), when you stop using it a spike in Estrogen (often referred to as rebound) will occur due to the sudden increase availability of Aromatase Enzyme. Another important distinction when it comes to Type 1 and Type 2 AI''s. A Type 1 Aromatase inhibitor (AI) like Exemestane remains unaffected by the introduction of a serm into your Estrogen management program. Type 2 AIs like Letrozole and Arimidex suffer a reduced in blood levels and effectiveness with the introduction of some serms. I will touch more on why we may need to introduce a serm a little farther on in this article.
When it comes to the strength of these AI''s Letrozole would be the strongest followed by Arimidex and then by Exemestane. Now people might be up in arms saying Exemestane is stronger than Arimidex however when one looks and compare data from studies done on MALES the order of strength is exactly as I stated it, quite often much confusion comes in to play when people recite data on AI's taken from studies on women. The fact is AI's behave differently in males, they are less effective in males, and for our purposes it is only prudent to compare data gathered from studies on males to portray an accurate picture.
The next aspect to be considered when looking at AIs are the effects they indirectly illicit in other areas. We stated the positive effects of Estrogen, we must realize by lowering Estrogen via Aromatase inhibitor (AI) use some of these positive effects may be compromised. It is important to look at the various Aromatase inhibitor (AI) options available and possibly use the data to help pick which Aromatase inhibitor (AI) we use. Letrozole is an extremely potent Aromatase inhibitor (AI) and its effects demonstrate this as would be expected. Letrozole has an adverse effect on lipid profile and somewhat on IGF levels. On the other hand Arimdex has a small impact in the area of IGF and depending upon which studies you cite a small adverse impact on lipids to no adverse impact on lipids. Exemestane seems to have no clinical impact on either IGF or lipids.
It is important to realize that it may seem like Exemestane shines as a clear cut winner when it comes to choice of Aromatase inhibitor (AI), however I do not necessarily believe this to be the case for everyone. In some cases or maybe better said in some people, an extremely powerful Aromatase inhibitor (AI) like Letrozole must be used to manage Estrogen properly. Some may respond better to Arimidex than Exemestane. I believe there is a place for all 3 of these. That being said, if possible my personal first choice of Aromatase inhibitor (AI) is Exemestane due to its lack of interaction with other compounds we may need to introduce such as certain serms, its positive effects on IGF and Lipids over other options, and also its lack of potential "rebound"(although I think that is an overstated issue quite often).
Regardless of which Aromatase inhibitor (AI) you choose for the vast majority of us our goal can be accomplished of maintaining Estrogen levels in the normal range while on cycle. It might seem like the discussion is over. Why do we even need to look at Serms? Read on:
So we have our Estrogen levels managed, all should be good. Well yes in most cases it will be but what if it isn't? What if you start to get sensitive, itchy or painful nipples? What if you get a lump around your nipple area? What if you are so predisposed to gyno you still get symptoms using an AI? It shouldnt happen but if it does your immediate solution should be a serm.
So we know what serms do. As stated above they bind to the Estrogen receptor in breast tissue, preventing Estrogen from eliciting its effects, which in this case is undesired breast development and tissue growth. However all serms are not created equal for this purpose. I am of the opinion that Raloxifene and Tamoxifen are the 2 best suited serms for this purpose.
Raloxifene is the serm with the highest binding affinity to the Estrogen receptor in breast tissue. Tamoxifen would be second. This means Raloxifene is the most effective serm available for gyno treatment and or prevention. Another point that bears mentioning, when using a Type 2 Aromatase inhibitor (AI) like Arimidex or Letrozole, Tamoxifen reduces blood levels of both of these AI's. Raloxifene on the other hand has no effect on blood levels of these AI's, allowing them to be run in conjunction with Raloxifene with no decrease in Aromatase inhibitor (AI) effectiveness. As was mentioned above any serm can be run with Exemestane (a Type 1 AI) with no impact on Exemestane's effectiveness.
Tamoxifen is the serm with probably the most clinical data supporting its use for gyno prevention and treatment, in all likelihood due to the age of the drug. It is very effective for this purpose and very versatile as it is equally if not more effective in the area of pct as well, meaning often it is likely on hand so it is readily available for most to use in the case of gyno symptoms.
So let's begin to put this all together. An Aromatase inhibitor (AI) should be the core of your Estrogen management program; the goal should be Estrogen levels in the clinically normal range even while on cycle. Id say between 25-30. I cannot emphasize enough the importance of blood work as a management tool. It really is the only effective means of proper Estrogen management (hormone profile management for that matter).
All AI''s can effectively manage Estrogen. My preference in order for this purpose would be Exemestane , then Arimidex , then Letrozole however as stated earlier they all have their place. If Exemestane works well for you you have the luxury of the least amount of undesirable side effects and the most versatility as far as combining with a serm should the need arise for gyno prevention and treatment.
The logical question is why do even need to worry about a serm if I mange Estrogen with an Ai? Well hopefully you don't however in some cases it may become necessary due to predisposition, preexisting gyno , very high dosages of aromatizing steroids and so on. For this purpose Raloxifene is in my opinion the top choice offering no reduction in effectiveness of any Aromatase inhibitor (AI) you are running and the most powerful protection against gyno due to its binding affinity to the E receptor in brest tissue. Tamoxifen is also a very solid option especially if running Exemestane as your Aromatase inhibitor (AI). If you are running letrozole or arimidex a corresponding increase in the dosage of Aromatase inhibitor (AI) may be required due to tamoxifen reducing blood levels and effectiveness of these 2 AIs.
Bringng it to theReal World:
1- Manage Estrogen levels with an AI: Exemestane offers the most versatility with fewest adverse effects.
2- Have a Serm on hand in case of Gyno flare up. Raloxifene is most effective and has no adverse interactions with any AIs.
Run a low dose Aromatase inhibitor (AI) with your cycle to try to keep estrogen in the clinically normal range so you can reap the benefits and reduce the deleterious effects. Have a serm on hand just in case gyno rears its head. If it does start a serm immediately. At this point you NEED blood work so you can properly assess your situation and possibly adjust Aromatase inhibitor (AI) dosage up which may allow discontinuation of serm. It may not. You may need to run a serm and Aromatase inhibitor (AI) in conjunction on cycle but it is very unlikely. An Aromatase inhibitor (AI) should be able to manage Estrogen properly for the vast majority of us. If you do need to run a serm and Aromatase inhibitor (AI) together I cannot emphasize enough that you need to reevaluate your situation. Elevated estrogen has some serious effects as I mentioned above. You should consider this option as I would encourage many too do anyway. Reduce the amount of aromatizing steroids in your cycle and replace them with non-aromatizing compounds. I cannot emphasize this enough. For example a lower test dose will allow for easier estrogen management. This is probably the single biggest thing any of us can do to help ensure proper estrogen management (besides blood work', which again is essential).
One more topic I want to touch on is Gyno. Gyno is considered the worst side effect of elevated estrogen but the fact is it is far from it. There are many much more serious issues going on inside of you if you start growing breasts. That being said when it does occur or start to occur we want to stop it. So often I see people recommend Letrozole to treat gyno. This is a horrible idea in my opinion. Letrozole works to treat gyno by lowering overall Estrogen levels so much there is no circulating Estrogen to bind to the Estrogen receptor in breast tissue. If you paid attention above you saw the beneficial effects of Estrogen. Some aren''t even beneficial, they are essential. I think to eliminate estrogen to this point throughout your entire body is foolish. Introduce a serm such as raloxifene, block the Estrogen receptor in the breast. The gyno then cannot grow. Then again using blood work adjust your Aromatase inhibitor (AI) dose to MANAGE estrogen levels while taking the serm to prevent the continuation of the gyno.
The above is an interesting topic. I hope this info proved useful to some and I would love to discuss it further.
JimiThing
Refs:
*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. lucashbl@unipa.it Estrogen and prostate cancer: an eclipsed tru... [J Cell Biochem. 2007] - PubMed - NCBI
*Estrogen Makes Men More Likely To Die Of Heart Disease
*Role of Estrogens in Inflammatory Response Expression of Estrogen Receptors in Peritoneal Fluid Macrophages from Endometriosis SILVIA CAPELLINO1,PAOLA MONTAGNA1, BARBARA VILLAGGIO1, ALBERTO SULLI1, STEFANO SOLDANO1, SIMONE FERRERO2, VALENTINO REMORGIDA2, MAURIZIO CUTOLO1Article first published online:30JUN2006DOI:10.1196/annals.1351.024 Role of Estrogens in Inflammatory Response - CAPELLINO - 2006 - Annals of the New York Academy of Sciences - Wiley Online Library
*http://www.eje-online.org/content/157/6/709.full.pdf
*Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model Brian J. Long, Danijela Jelovac,Venkatesh Handratta,pinya Thiantanawat,Nicol MacPherson,Joseph Ragaz,Olga G. Goloubeva and Angela M. Brodie+ Author Affiliations Affiliations of authors: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Health Sciences Facility, Baltimore, MD (BJL, DJ, VH, AT, AMB); British Columbia Cancer Agency, Vancouver, British Columbia, Canada (NM, JR); Division of Biostatistics, University of Maryland Greenebaum Cancer Center, Baltimore (OGG) Correspondence to: Angela M. Brodie, PhD, Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Health Sciences Facility, Rm. 580G, 685 West Baltimore St., Baltimore, MD 21201 (e-mail abrodie@umaryland.edu)
*Therapeutic Strategies Using the Aromatase Inhibitor Letrozole and Tamoxifen in a Breast Cancer Model
*Exemestane in the Adjuvant Treatment of Breast Cancer in Postmenopausal Women
*Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males
*Czajka-Oraniec I, Simpson ER (2010). "Aromatase research and its clinical significance". Endokrynol Pol 61 (1): 126***8211;34. PMID 20205115
*Vogel, Victor; Joseph Constantino, Lawrence Wickerman et al. (2006-06-21). "Effects of Tamoxifen vs. Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes". The Journal of the American Medical Association 295 (23): 2727***8211;2741. doi:10.1001/jama.295.23.joc60074. PMID 16754727
*http://humupd.oxfordjournals.org/con...3/212.full.pdf ***8211; Pharmacological Review of Selective Estrogen Recptor Modulators
*Aromatase inhibitors for male infertility. [J Urol. 2002] - PubMed - NCBI
*Safety and Efficacy of Anastrozole for the Treatment of Pubertal Gynecomastia: A Randomized,Double-Blind,Placebo-ControlledTrial Safety and Efficacy of Anastrozole for the Treatment of Pubertal Gynecomastia: A Randomized, Double-Blind, Placebo-Controlled Trial
* Approach to the Patient with Gynecomastia1. Harold E. Carlson- Author Affiliations Department of Medicine, Endocrinology Division, Stony Brook University, Stony Brook, New York 11794-8154 Address all correspondence and requests for reprints to: Harold E. Carlson, M.D., Department of Medicine, Endocrinology Division, HSC T15-060, Stony Brook University, Stony Brook, New York 11794-8154. E-mail: harold.carlson@stonybrook.edu.
* Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males Nelly Mauras, John Lima, Deval Patel, Annie Rini, Enrico di Salle, Ambrose Kwok and Barbara Lippe Author Affiliations Nemours Children***8217;s Clinic and Research Programs (N.M., J.L., A.R.), Jacksonville, Florida 32207; and University of Florida Health Sciences Center (D.P.) and Amersham Pharmacia Biotech (E.d.S., A.K., B.L.), Peapack, New Jersey 07977 Address all correspondence and requests for reprints to: Nelly Mauras, M.D., Nemours Children***8217;s Clinic, 807 Children***8217;s Way, Jacksonville, Florida 32207. E-mail: nmauras@nemours.org.
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Double win as long as you don't hammer down the levels of Estrogen!
