AI's
By: Mr. Humdiddly
What is an AI?
AI is the abbreviation for aromatase inhibitors. AI's differ from SERM's (Selective Estrogen Receptor Modules). SERM's are chemical compounds that effect estrogen receptors. A SERM binds to an estrogen receptor and prevents the estrogen from binding to the receptor. Unlike SERM's AI's do not bind to estrogen receptor modules. AI's are utilized to prevent androgens from converting into estrogen. This mechanism of conversion would normally take place in the chest, fat, muscle, and brain tissue. AI's are used on cycle and cannot take the place of SERM's forPCT.
Popular AI's include Anastrazole (Arimidex, Liquidex), Exemestane(Aromasin) and letrozole (femara).
Why is estrogen an issue during cycle?
Estrogen is the primary female hormone. Any hormone that exhibits the effects of estradiol are considered estrogens. The most bio-active forms of estrogen in the body are estradiol and estrone. The primary male hormones are referred to as androgens. An androgen is any hormone that exhibits the properties pertaining to testosterone. Thus anabolic steroids are considered androgens.
These two hormone groups are related in a manner similar to andro prohormones. Just as androdiol has a hydroxy (or –ol) group at both the 3- and 17- positions, estradiol likewise has a hydroxy group at those positions. Estrone, like androstenedione, has keto (or –one, pronounced “oan”) groups at those positions.
The most potent estrogen per milligram is estradiol. Estradiol can be synthesized from both testosterone and estrone. When converted form testosterone an enzyme called aromatase is utilized. When converted from estrone, enzme 17b-HSD is utilized.
Comparatively on a per milligram basis estrone is less potent then Estradiol. However, by increasing the levels of estrone concentration the hormone can be quite potent. Similar to estradiol, estrone can be synthesized in the body from androstendione via the aromatase enzyme or from estradiol via the same 17b-HSD enzyme used in estrone to estradiol conversion.
Okay so now we are through all that science garbage so why is estrogen an issue on cycle. During the course of an androgen cycle, androgen levels are artificially raised. This is where a concept called homeostasis occurs. Homeostasis is a term used to signify a variety of actions that your body uses to keep an internal balance. One of these balances is the balance of androgens to estrogens. As testosterone levels are artificially raised the body reacts by shutting down HPTA function in order to lower testosterone levels. However, since the androgens are being introduced via an external source HPTA shutdown does not solve the issue. The body then resorts to the use of the aromatase enzyme to bind to androgens and convert them to estrogens. The effect is two-fold, the precious androgens you bought are being reduced in number due to the actions of the aromatase enzyme and being converted to estrogen. A good analogy is you hire a mercenary army to fight a war for you and then the mercenaries start going over to the other side. Not exactly the best way to win a war.
Why is it important to keep Estrogen levels down?
When estrogens bind to receptors the body starts utilizing the estrogen converted from androgens. This increase in estrogenic activity has different effects in different tissue. In the pectoral area increased estrogenic activity results in the formation of female breast tissue commonly referred to as gynecomastia. In other parts of the body estrogen has other side effects including bloating, a decrease in the body's ability to burn fat, and can cause fat to be distributed in a pattern similar to the female body (I.E. Hips and thighs). The use of AI's can also prevent estrogenic sides related to changes in mood.
As if that was not bad enough estradiol actually has metabolites that are carcinogenic (cancer causing). These carcinogenic metabolites are diffused in the liver but can result in hepatic cholestasis.
So now that we understand why keeping estrogen levels in check is important let's take a look at some of the drugs that stop this conversion of androgens to estrogens.
General Information
letrozole is orally bio-available. The brand femara contains 2.5mg of letrozole per caplet. letrozole is a non-steroidal aromatase inhibitor. It prevents androgen conversion into estrogens. letrozole is considered the most potent AI available on the market today. It is considered up to 30 times more effective then anastrozole at the crossing of lipid cell membrane. letrozole has been found to be 95% effective at preventing androgen conversion in lipid cells.
Dosing
A standard preventive dosage of .25mg ED or .5mg EOD is considered effective at preventing estrogenic sides. Doses as high as 2.5mg are utilized by users attempting to reduce gyno lumps. letrozole has a half life of 4 days and requires 60 days of continuous use to stabilize blood levels. As a result letrozole can take a long time to clear the system.
Dosing for Gynecomastia Lump Reduction
letrozole is unique among AI's for its ability to reduce gyno lumps. A typical gyno reduction protocol would involve tapering letro usage up to 2.5mg per day. This dose would be continued until the lump is reduced or eliminated then the dosage should be tapered back down. Some users have used nolvadex post gyno reduction. This is due to nolva's strong affinity to bind to ER receptors in the pectoral region. It should be noted using this dosage for a time period greater than 2 months can result in side effects associated with estrogen deprivation.
Side Effects
letrozole is extremely potent and a dose of .20mg has been shown to decrease estrogen levels by 30 percent. It is only recommended for those individuals who are gyno prone or pre-contest. Overuse can result in damage to joints, and changes in cholesterol levels. It also may cause a significant drop in libido. Bone mineral loss has also been reported with high level dosing of letrozole. IGF levels have also been suppressed during letrozole use.
General Information
Exemestane is orally bio-available. The brand Aromasin contains 25mg of exemestane. Exemestane is a steroidal aromatase inhibitor. It is refferred chemically as 6-methylenandrosta-1, 4-diene-3, 17 -dione. Aromasin is usually the most expensive of the three AI's listed on this thread. However it is milder then letrozole and can be used for longer periods of time without sides commonly associated with lack of estrogen. Some studies have shown exemestane to increase LH and IGF levels. Exemestane is a type 1 inhibitor that deactivates the aromatase enzyme and is no longer needed. This is in contrast to letrozole and Anastrozole which require continuous binding to the aromatase enzyme to prevent it's effects.
Dosing
Standard dosing on cycle is 12.5 mg ED as a preventive measure against estrogenic sides. Doses as high as 25mg's are used then tapered down when used as a treatment for halting gyno sides. Unlike letrozole, exemestane cannot be used to treat existing gyno and is better utilized as a preventative measure on cycle.
Side Effects
Opposite to letozole, exemestane has been shown to increase bone mineral and have a positive effect on choleserol making it a preferred choice for on cycle androgen conversion prevention. However exemestane in higher doses can also cause high blood pressure, hair loss, fatigue, and nausea. It should be noted these side effects where a reaction to a higher dosage then what is utilized by bodybuilders for AI.
Anastrozole (Arimidex)
General Information
Anastrozole is the most commonly used AI. Comparetively to letrozole it is 80% effective at preventing androgen conversion. It is manufactured by a variety of companies and predominantly by Zenica Pharmaceuticals. Similar to exemestane it has been shown to increase LH and IGF levels.
Dosing
Doses of .5mg ED are usually utilized by users as a preventive measure against gyno. Doses from 1mg and up are used when attempting to stimulate LH and IGF levels.
Side Effects
Doses over .5mg used for extended periods of time have resulted in a decrease in immune system health and joint pain. Dosed at .5mg side effects seem minimal and can be used safely for extended periods of time.
1. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen, Comhaire. Fertil and Steril 29 (1978) 320-7
2. Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro. Adashi EY, Hsueh AJ, Bambino TH, Yen SS. Am J Physiol 1981 Feb;240(2):E125-30
3. The effect of clomiphene citrate on sex hormone binding globulin in normospermic and oligozoospermic men. Adamopoulos, Kapolla et al. Int J Androl 4 (1981) 639-45
4. A feasibility study of an aromatase inhibitor (AI), letrozole (L) and the antibody to vascular endothelial growth factor (VEGF), bevacizumab (B), in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC). T. A. Traina, M. N. Dickler, et al. Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings. Vol 23, No 16S (June 1 Supplement), 2005: 796
5. Clin Cancer Res. 2005 Apr 15;11(8):2809-21.
6. Epilepsy Behav. 2004 Apr;5(2):260-3
7. J Clin Endocrinol Metab. 2005 Oct;90(10):5717-22. Epub 2005 Jul Comparative assessment in young and elderly men of the gonadotropin response to aromatase inhibition. T'Sjoen GG, Giagulli VA, Delva H, Crabbe P, De Bacquer D, Kaufman JM.
8. Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267[letrozole], in healthy male subjects PF Trunet, P Mueller, AS Bhatnagar, I Dickes, G Monnet and G White Research and Development Department, CIBA-GEIGY Limited, Basel, Switzerland>.
9. Clin Cancer Res. 2003 Jan;9(1 Pt 2):468S-72S. Department of Endocrinology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
10. J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):27-34. Aromatase overexpression transgenic mice model: cell type specific expression and use of letrozole to abrogate mammary hyperplasia without affecting normal physiology.
11. J Clin Endocrinol Metab 2000 Jul;85(7):2370-7, "Estrogen Suppression in Males"
12. Clin Endocrinol (Oxf). 2005 Feb;62(2):228-35.
13. Arimidex Package insert
14. J Steroid Biochem Mol Biol. 2002 Apr;80(4-5):411-8.
15. Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse. Freeman, Topper. Endocrinology. 1978 Jul;103(1):186-92
By: Mr. Humdiddly
What is an AI?
AI is the abbreviation for aromatase inhibitors. AI's differ from SERM's (Selective Estrogen Receptor Modules). SERM's are chemical compounds that effect estrogen receptors. A SERM binds to an estrogen receptor and prevents the estrogen from binding to the receptor. Unlike SERM's AI's do not bind to estrogen receptor modules. AI's are utilized to prevent androgens from converting into estrogen. This mechanism of conversion would normally take place in the chest, fat, muscle, and brain tissue. AI's are used on cycle and cannot take the place of SERM's forPCT.
Popular AI's include Anastrazole (Arimidex, Liquidex), Exemestane(Aromasin) and letrozole (femara).
Why is estrogen an issue during cycle?
Estrogen is the primary female hormone. Any hormone that exhibits the effects of estradiol are considered estrogens. The most bio-active forms of estrogen in the body are estradiol and estrone. The primary male hormones are referred to as androgens. An androgen is any hormone that exhibits the properties pertaining to testosterone. Thus anabolic steroids are considered androgens.
These two hormone groups are related in a manner similar to andro prohormones. Just as androdiol has a hydroxy (or –ol) group at both the 3- and 17- positions, estradiol likewise has a hydroxy group at those positions. Estrone, like androstenedione, has keto (or –one, pronounced “oan”) groups at those positions.
The most potent estrogen per milligram is estradiol. Estradiol can be synthesized from both testosterone and estrone. When converted form testosterone an enzyme called aromatase is utilized. When converted from estrone, enzme 17b-HSD is utilized.
Comparatively on a per milligram basis estrone is less potent then Estradiol. However, by increasing the levels of estrone concentration the hormone can be quite potent. Similar to estradiol, estrone can be synthesized in the body from androstendione via the aromatase enzyme or from estradiol via the same 17b-HSD enzyme used in estrone to estradiol conversion.
Okay so now we are through all that science garbage so why is estrogen an issue on cycle. During the course of an androgen cycle, androgen levels are artificially raised. This is where a concept called homeostasis occurs. Homeostasis is a term used to signify a variety of actions that your body uses to keep an internal balance. One of these balances is the balance of androgens to estrogens. As testosterone levels are artificially raised the body reacts by shutting down HPTA function in order to lower testosterone levels. However, since the androgens are being introduced via an external source HPTA shutdown does not solve the issue. The body then resorts to the use of the aromatase enzyme to bind to androgens and convert them to estrogens. The effect is two-fold, the precious androgens you bought are being reduced in number due to the actions of the aromatase enzyme and being converted to estrogen. A good analogy is you hire a mercenary army to fight a war for you and then the mercenaries start going over to the other side. Not exactly the best way to win a war.
Why is it important to keep Estrogen levels down?
When estrogens bind to receptors the body starts utilizing the estrogen converted from androgens. This increase in estrogenic activity has different effects in different tissue. In the pectoral area increased estrogenic activity results in the formation of female breast tissue commonly referred to as gynecomastia. In other parts of the body estrogen has other side effects including bloating, a decrease in the body's ability to burn fat, and can cause fat to be distributed in a pattern similar to the female body (I.E. Hips and thighs). The use of AI's can also prevent estrogenic sides related to changes in mood.
As if that was not bad enough estradiol actually has metabolites that are carcinogenic (cancer causing). These carcinogenic metabolites are diffused in the liver but can result in hepatic cholestasis.
So now that we understand why keeping estrogen levels in check is important let's take a look at some of the drugs that stop this conversion of androgens to estrogens.
letrozole (femara)
General Information
letrozole is orally bio-available. The brand femara contains 2.5mg of letrozole per caplet. letrozole is a non-steroidal aromatase inhibitor. It prevents androgen conversion into estrogens. letrozole is considered the most potent AI available on the market today. It is considered up to 30 times more effective then anastrozole at the crossing of lipid cell membrane. letrozole has been found to be 95% effective at preventing androgen conversion in lipid cells.
Dosing
A standard preventive dosage of .25mg ED or .5mg EOD is considered effective at preventing estrogenic sides. Doses as high as 2.5mg are utilized by users attempting to reduce gyno lumps. letrozole has a half life of 4 days and requires 60 days of continuous use to stabilize blood levels. As a result letrozole can take a long time to clear the system.
Dosing for Gynecomastia Lump Reduction
letrozole is unique among AI's for its ability to reduce gyno lumps. A typical gyno reduction protocol would involve tapering letro usage up to 2.5mg per day. This dose would be continued until the lump is reduced or eliminated then the dosage should be tapered back down. Some users have used nolvadex post gyno reduction. This is due to nolva's strong affinity to bind to ER receptors in the pectoral region. It should be noted using this dosage for a time period greater than 2 months can result in side effects associated with estrogen deprivation.
Side Effects
letrozole is extremely potent and a dose of .20mg has been shown to decrease estrogen levels by 30 percent. It is only recommended for those individuals who are gyno prone or pre-contest. Overuse can result in damage to joints, and changes in cholesterol levels. It also may cause a significant drop in libido. Bone mineral loss has also been reported with high level dosing of letrozole. IGF levels have also been suppressed during letrozole use.
Exemestane (Aromasin)
General Information
Exemestane is orally bio-available. The brand Aromasin contains 25mg of exemestane. Exemestane is a steroidal aromatase inhibitor. It is refferred chemically as 6-methylenandrosta-1, 4-diene-3, 17 -dione. Aromasin is usually the most expensive of the three AI's listed on this thread. However it is milder then letrozole and can be used for longer periods of time without sides commonly associated with lack of estrogen. Some studies have shown exemestane to increase LH and IGF levels. Exemestane is a type 1 inhibitor that deactivates the aromatase enzyme and is no longer needed. This is in contrast to letrozole and Anastrozole which require continuous binding to the aromatase enzyme to prevent it's effects.
Dosing
Standard dosing on cycle is 12.5 mg ED as a preventive measure against estrogenic sides. Doses as high as 25mg's are used then tapered down when used as a treatment for halting gyno sides. Unlike letrozole, exemestane cannot be used to treat existing gyno and is better utilized as a preventative measure on cycle.
Side Effects
Opposite to letozole, exemestane has been shown to increase bone mineral and have a positive effect on choleserol making it a preferred choice for on cycle androgen conversion prevention. However exemestane in higher doses can also cause high blood pressure, hair loss, fatigue, and nausea. It should be noted these side effects where a reaction to a higher dosage then what is utilized by bodybuilders for AI.
Anastrozole (Arimidex)
General Information
Anastrozole is the most commonly used AI. Comparetively to letrozole it is 80% effective at preventing androgen conversion. It is manufactured by a variety of companies and predominantly by Zenica Pharmaceuticals. Similar to exemestane it has been shown to increase LH and IGF levels.
Dosing
Doses of .5mg ED are usually utilized by users as a preventive measure against gyno. Doses from 1mg and up are used when attempting to stimulate LH and IGF levels.
Side Effects
Doses over .5mg used for extended periods of time have resulted in a decrease in immune system health and joint pain. Dosed at .5mg side effects seem minimal and can be used safely for extended periods of time.
References
1. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Vermeulen, Comhaire. Fertil and Steril 29 (1978) 320-7
2. Disparate effect of clomiphene and tamoxifen on pituitary gonadotropin release in vitro. Adashi EY, Hsueh AJ, Bambino TH, Yen SS. Am J Physiol 1981 Feb;240(2):E125-30
3. The effect of clomiphene citrate on sex hormone binding globulin in normospermic and oligozoospermic men. Adamopoulos, Kapolla et al. Int J Androl 4 (1981) 639-45
4. A feasibility study of an aromatase inhibitor (AI), letrozole (L) and the antibody to vascular endothelial growth factor (VEGF), bevacizumab (B), in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC). T. A. Traina, M. N. Dickler, et al. Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings. Vol 23, No 16S (June 1 Supplement), 2005: 796
5. Clin Cancer Res. 2005 Apr 15;11(8):2809-21.
6. Epilepsy Behav. 2004 Apr;5(2):260-3
7. J Clin Endocrinol Metab. 2005 Oct;90(10):5717-22. Epub 2005 Jul Comparative assessment in young and elderly men of the gonadotropin response to aromatase inhibition. T'Sjoen GG, Giagulli VA, Delva H, Crabbe P, De Bacquer D, Kaufman JM.
8. Open dose-finding study of a new potent and selective nonsteroidal aromatase inhibitor, CGS 20 267[letrozole], in healthy male subjects PF Trunet, P Mueller, AS Bhatnagar, I Dickes, G Monnet and G White Research and Development Department, CIBA-GEIGY Limited, Basel, Switzerland>.
9. Clin Cancer Res. 2003 Jan;9(1 Pt 2):468S-72S. Department of Endocrinology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium
10. J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):27-34. Aromatase overexpression transgenic mice model: cell type specific expression and use of letrozole to abrogate mammary hyperplasia without affecting normal physiology.
11. J Clin Endocrinol Metab 2000 Jul;85(7):2370-7, "Estrogen Suppression in Males"
12. Clin Endocrinol (Oxf). 2005 Feb;62(2):228-35.
13. Arimidex Package insert
14. J Steroid Biochem Mol Biol. 2002 Apr;80(4-5):411-8.
15. Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse. Freeman, Topper. Endocrinology. 1978 Jul;103(1):186-92
