Outstanding post.
Thankyou for this.
In retrospect, I still think Nolva + Arimidex is still something interesting to try to contrast with Clomid + Arimidex. Again, this would be for those whose testes are functioning normally and have low test levels due to something funky happening at the hypothalamus or pituitary.
I think if one uses a SERM, they really need to use an AI as well, to combat the T to E conversion that happens when the testes start pumping out more T.
[quote]KSman wrote:
\OP said:
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Nolva: Usually dosed from 10-100 mgs, Nolva is best dosed at 20-40 mgs. It has a certain affinity for binding to breast tissue receptors that Clomid doesn’t. It can significantly raise Testosterone levels.
However, it can reduce IGF-1 levels. It is commonly said that Nolva can accomplish at 20 mgs what Clomid can at 150mgs. Something to keep in mind. Nolva does not decrease the bodies LH response to LHRH like Clomid can. It can reduce the blood levels of Arimidex and Letro rendering them less effective. It does not affect Aromasin.
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For this to happen, Nolvadex would have to increase the clearance of these AIs from serum.
You can find:
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Tamoxifen
Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. However, the coadministration of anastrozole and tamoxifen did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen.
At a median follow-up of 33 months, the combination of ARIMIDEX and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. [see Clinical Studies]. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole.
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and
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Metabolism
Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. Three metabolites of anastrozole (triazole, a glucuronide conjugate of hydroxy-anastrozole, and a glucuronide conjugate of anastrozole itself) have been identified in human plasma and urine. The major circulating metabolite of anastrozole, triazole, lacks pharmacologic activity.
Anastrozole inhibited reactions catalyzed by cytochrome P450 1A2, 2C8/9, and 3A4 in vitro with Ki values which were approximately 30 times higher than the mean steady-state Cmax values observed following a 1 mg daily dose.
Anastrozole had no inhibitory effect on reactions catalyzed by cytochrome P450 2A6 or 2D6 in vitro. Administration of a single 30 mg/kg or multiple 10 mg/kg doses of anastrozole to healthy subjects had no effect on the clearance of antipyrine or urinary recovery of antipyrine metabolites.
Excretion
Eighty-five percent of radiolabeled anastrozole was recovered in feces and urine. Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance. The mean elimination half-life of anastrozole is 50 hours.
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So, in women who are taking 1mg anastozole â?¦per day driving E2 levels down by 80%, co-administration of nolvadex must be increasing losses of anastrozole via excretion. This probably involves changes to liver function.
The effects of nolvadex on serum E2 levels of males using low dose anastrozole may very well not be as strong as the effects with higher dose anastrozole on females that are pushing their higher E2 levels down by around 80%. These effects may be quite different with male E2 modulation. BB guys who are pushing E2 way low will probably have similar effects.
In any case, even if nolvadex did reduce anastrozole levels by 27% in male BB or TRT settings, increasing the dose of anastrozole is always an option. In a TRT context, one should be doing serum E2 labs and making dose changes to get near E2=22pg/ml and the issue would not even be show up on the radar screen. [/quote]