Anti-aromatases and aromatase activity

06-03-2002, 08:34 AM

Clin Breast Cancer 2000 Sep;1 Suppl 1:S68-73

Comparison of in vitro exemestane activity versus other antiaromatase agents.

Soudon J.

Anastrozole, letrozole, and exemestane are the most selective and potent oral antiaromatase agents currently available. However, in vitro and in vivo studies comparing these agents are lacking. Anastrozole and letrozole are reversible, competitive nonsteroidal type II inhibitors, whereas exemestane is an irreversible steroidal type I inactivator. The study was conducted to determine the impact of this characteristic on in vitro residual aromatase activity and protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was measured after various incubation times with each antiaromatase agent at a concentration 10 times higher than IC50 (concentration giving 50% inhibition). Only exemestane induced a residual inhibition of aromatase activity after its removal, without any change in the aromatase protein level. Aromatase activity increased after preincubation of JEG-3 cells with either aminoglutethimide or anastrozole without any change in the aromatase protein level. The aromatase protein level increased rapidly when cells were incubated with letrozole and aromatase activity inhibition disappeared immediately after removal of the drug. The breakthrough effects in aromatase activity or protein levels observed after treatment with reversible inhibitors may be a factor in therapeutic failure with these agents. These results suggest a possible advantage for exemestane because it is the only clinically available oral irreversible aromatase inactivator.

06-03-2002, 08:42 AM

Exemestane use resulted in no rise in aromatase protein, and after cessation of exemestane use, aromatase activity remained decreased for awhile [note the difference between aromatase protein levels and aromatase activity levels].

Arimidex increased activity but not aromatase protein levels.

Letrozole rapidly increased the aromatase protein level, and as soon as Letrozole was stopped its inhibition on activity was lost immediately.

So it seems with exemestane no sudden estrogen rebound could be expected when you stopped. With arimidex it would be minimal since there was no increase of aromatase protein. Letrozole however could be expected to have an estrogen rebound. I used letrozole recently and next time will ask my MD to prescribe exemestane.

So it seems exemestane or arimidex would be better agents to end a cycle with, since it is recommended to continue the anti-aromatases for a period of time after stopping the use of AS in order to get ones HPTA to jump start again. However going into the post cycle recovery period using letrozole might be a mistake since it could result in estrogen rebound after cessation.

If someone used letrozole post cycle for recovery it seems that it would be wise to taper the use(from 1 mg day, to 1/2 mg day, to 1/2 mg EOD) in order to allow the body to compensate and lower the aromatase protein level. Then follow with perhaps a week or two of an anti-estrogen like tamoxifen in order to block the estrogen receptors while the body regains equilibrium and reduces its production of aromatase protein.

Comments

06-05-2002, 10:48 PM

44 people looked at this and no one commented. You bunch o' wankers.

archive_Mr. Nobody · 06-06-2002, 05:56 AM

The last 2 paragraphes were all I could read. Is this how the 44 wankers felt, lol?
Good post and very good conclusions, I have posted in the past about arimidex being more proven for us men, since there is actual studies of it raising test in eugonadal men (fancy word for normal if I spelled it right) by 51% and keeping it there.

Disclaimer:
Mr. Nobody is presenting fictitious opinions and does in no way, shape or form encourage, use nor condone the use of any illegal substances or the use of legal substances in an illegal manner.
The information discussed is strictly for entertainment purposes only and shall not take the place of qualified medical advise.

Ivan Drago · 06-06-2002, 08:01 PM

It's good.

Not like I'm trying to escape the o'wanker's status.

Tall Dude · 06-06-2002, 09:27 PM

Here's the key statement:

"These results suggest a possible advantage"

Which means it doesn't prove anything.
Head to head trials in humans are needed to see if there is a significant difference between the therapies.

06-03-2002, 08:34 AM	#1 (permalink)
Guest Posts: n/a	Anti-aromatases and aromatase activity Clin Breast Cancer 2000 Sep;1 Suppl 1:S68-73 Comparison of in vitro exemestane activity versus other antiaromatase agents. Soudon J. Anastrozole, letrozole, and exemestane are the most selective and potent oral antiaromatase agents currently available. However, in vitro and in vivo studies comparing these agents are lacking. Anastrozole and letrozole are reversible, competitive nonsteroidal type II inhibitors, whereas exemestane is an irreversible steroidal type I inactivator. The study was conducted to determine the impact of this characteristic on in vitro residual aromatase activity and protein levels after incubation of JEG-3 cells with aminoglutethimide (a type II inhibitor), anastrozole, exemestane, or letrozole. Aromatase activity was measured after various incubation times with each antiaromatase agent at a concentration 10 times higher than IC50 (concentration giving 50% inhibition). Only exemestane induced a residual inhibition of aromatase activity after its removal, without any change in the aromatase protein level. Aromatase activity increased after preincubation of JEG-3 cells with either aminoglutethimide or anastrozole without any change in the aromatase protein level. The aromatase protein level increased rapidly when cells were incubated with letrozole and aromatase activity inhibition disappeared immediately after removal of the drug. The breakthrough effects in aromatase activity or protein levels observed after treatment with reversible inhibitors may be a factor in therapeutic failure with these agents. These results suggest a possible advantage for exemestane because it is the only clinically available oral irreversible aromatase inactivator.

06-03-2002, 08:42 AM	#2 (permalink)
Guest Posts: n/a	Does this seem logical? Exemestane use resulted in no rise in aromatase protein, and after cessation of exemestane use, aromatase activity remained decreased for awhile [note the difference between aromatase protein levels and aromatase activity levels]. Arimidex increased activity but not aromatase protein levels. Letrozole rapidly increased the aromatase protein level, and as soon as Letrozole was stopped its inhibition on activity was lost immediately. So it seems with exemestane no sudden estrogen rebound could be expected when you stopped. With arimidex it would be minimal since there was no increase of aromatase protein. Letrozole however could be expected to have an estrogen rebound. I used letrozole recently and next time will ask my MD to prescribe exemestane. So it seems exemestane or arimidex would be better agents to end a cycle with, since it is recommended to continue the anti-aromatases for a period of time after stopping the use of AS in order to get ones HPTA to jump start again. However going into the post cycle recovery period using letrozole might be a mistake since it could result in estrogen rebound after cessation. If someone used letrozole post cycle for recovery it seems that it would be wise to taper the use(from 1 mg day, to 1/2 mg day, to 1/2 mg EOD) in order to allow the body to compensate and lower the aromatase protein level. Then follow with perhaps a week or two of an anti-estrogen like tamoxifen in order to block the estrogen receptors while the body regains equilibrium and reduces its production of aromatase protein. Comments

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06-05-2002, 10:48 PM	#3 (permalink)
Guest Posts: n/a	44 people looked at this and no one commented. You bunch o' wankers.

06-06-2002, 05:56 AM	#4 (permalink)
archive_Mr. Nobody Senior Member Join Date: Nov 2000 Posts: 5,080 Rep Power: 11937	The last 2 paragraphes were all I could read. Is this how the 44 wankers felt, lol? Good post and very good conclusions, I have posted in the past about arimidex being more proven for us men, since there is actual studies of it raising test in eugonadal men (fancy word for normal if I spelled it right) by 51% and keeping it there. Disclaimer: Mr. Nobody is presenting fictitious opinions and does in no way, shape or form encourage, use nor condone the use of any illegal substances or the use of legal substances in an illegal manner. The information discussed is strictly for entertainment purposes only and shall not take the place of qualified medical advise.

06-06-2002, 08:01 PM	#5 (permalink)
Ivan Drago Senior Member Join Date: Dec 2000 Posts: 811 Rep Power: 6726	It's good. Not like I'm trying to escape the o'wanker's status.

06-06-2002, 09:27 PM	#6 (permalink)
Tall Dude Senior Member Join Date: Feb 2001 Posts: 244 Rep Power: 5987	Here's the key statement: "These results suggest a possible advantage" Which means it doesn't prove anything. Head to head trials in humans are needed to see if there is a significant difference between the therapies.