Because I was bored...
First of all, after spending a few hours reading studies and reviews for Tamoxifen, Clomiphene, and Toremifene; Toremifene is now the only SERM I will ever recommend. For it definitely seems to be the most effective and safest overall... A few reasons being: it lowers ldl, increases hdl, imporves bone mineral density, can lower prolactin, great at ER binding in breast tissue (seems to be just as good as Nolva, not as good as Ralox though), no progesterone issues, it increases pituitary sensitivity to GnRH just like tamox ie more LH, its the easiest on the liver, you get no emotional sides like clomid, and it seems to be amazing at rebooting HPTA ect ect... Personally, I feel like you get the benefits of Clomid and Nolva with far less of the negative, but as always, to each there own.
Edit: there was a study done by some Greek researchers showing that tamox was slightly better then torem at increasing testosterone and LH. Though, the Torem dosage was lower then most use. Since, the study used 20 mg of tamoxifen and 60 mg of toremifene. Were most would use something like: 120/90/60/30 for toremifene. Regardless the results for 4 weeks of use were still pretty comparable. Also, I feel like overall torem is much safer, and most users seem to feel like Torem seems to kick in a lot sooner. Overall making it a better candidate for PCT
Now in terms of enzyme activity and the following SERMs:
Tamoxifen- requires both CYP2D6 and CYP3A4 to convert to its metabolites, such as 4-hydroxytamoxifen and N-desmethyl-4-hydroxytamoxifen. Without these metabolite there would be significantly less ER binding, leading to a substantial decrease in function. The enzyme CYP2D6 is used by most SSRI. Therefore, they compete for binding, and anti depressants seem to be able to bind more readily then tamoxifen. So, in general anti depressants should be avoided when using tamoxifen. In addition, the enzyme CYP3A4 is inhibited by things such as piperine, milk thistle, and quercetin (this initially inhibits, but later induces expression. Either way it should be avoided). These are found in a vast variety of supplements currently available on the market, all of which you should stay away from when consuming Tamox.
Toremifene- only seems to require CYP3A4, not CYP2D6, to convert to its primarily metabolite: N-demethyltoremifene. Again without this metabolite the SERM would be left more or less essentially ineffective. You are looking at around a 30-100x decrease in effectiveness. Thus, again you should avoid bioperine, milk thistle, and quercetin or anything else that effects CYP3A4. Though, since torem doesnt use CYP2D6 most anti depressants seem to be okay. For example: Cymbalta, Prozac, Paxil, Wellbutrin, Zoloft ect
Clomiphene- The conversion of its metabolites depends on both CYP2D6 and CYP3A4 to produce 4-hydroxy-N-desethylclomiphene, 4-OH-DE-Clom, 4-hydroxyclomiphene ect. So, again you should avoid anti depressants, bioperine, milk thistle, and quercetin
So, in conclusion stay away from bioperine, milk thistle, quercetin and even grapefruit juice with any of the above SERMs. (Grapefruit juice inhibits P450 enzyme activity, which may allow for greater initial build up/concentrations of the above SERMs, but in the long run using grapefruit juice will make them less effective and should thus be avoided.) Also, I want to note there are most likely other P450 enzymes involved ect. I am just trying add the point that Toremifene seems to be the only SERM that can be safely taken with most anti depressants and is also the one with the least drug interactions. Though, always verify drug interactions and consult a doctor before taking anything.
In addition here is a list of a few regularly used products that should be avoided when taking the above SERMs: MyoTEST, Zeus, TestoPRO, original BioForge, PCT Assist, N1-T, Triazole, Stoked ect you get the idea
Edit: I have come across some contradicting studies with milk thistle and CYP3A4. Some claim a 50-100% decrease in activity. Others say most products don't provide a significant amount of extract to have a effect on CYP3A4. Stating, [1] "Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4." Though, I do believe that any effective Milk of Thistle product on the market will have a impact on CYP3A4 activity, and thus your SERM.
[1] van Erp NP, Baker SD, Zhao M, et al.: Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 11 (21): 7800-6, 2005.
