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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, improves 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 receptor sensitivity issues like with Nolva ie you can use it with Deca and Tren (19-nors ect), it increases pituitary sensitivity to GnRH just like Tamox ie more LH over time (side note: Clomid seems to decrease sensitivity), it’s the easiest on the liver, you get none of the emotional sides or possible optical disturbances like Clomid, and it seems to be amazing at rebooting HPTA ect ect... Personally, I feel like you get all the benefits of Clomid and Nolva with far less of the negative, but as always, to each their own.
Edit: there was a study done by some Greek researchers showing that Tamox was slightly better than Torem at increasing testosterone and LH, which would indicate that it was better at restoring HPTA. Though, the Torem dosage was lower than most use. (The study used 20 mg of Tamoxifen and 60 mg of Toremifene. Where most would use something like: 120/90/60/30 for Toremifene.) Regardless, the results for 4 weeks of use were still pretty comparable ([1] Tamox - FSH: 8.23+/-2.71 LH: 7.65+/-3.37 T: 740.27+/-227.98 || Torem - FSH: 8.15+/-4.59 LH: 6.62+/-2.99 T: 696.13+/-202.21.) Also, I wanted to note that I am unsure if Torem leads to a direct increase in the amplitude of LH release like with Clomid. Though over a extend period of time this mechanism does lead to LHRH insensitivity and a decrease LH.
Regardless, overall Torem seems to be very effective at rebooting HPTA, and is much safer. Plus, most users seem to feel like Torem kicks in a lot sooner, thus helping you recover faster. Though, one downside is it does increase SHBG, which could lower circulating testosterone after extended use. Even so, I still feel like Toremifien is the best overall 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 inhibited by most SSRI. Also, many 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 it’s 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 affects CYP3A4. Though, since Torem doesn’t 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 to add the point that in addition to having the least side effects, Toremifene also seems to be the only SERM that can be safely taken with most anti depressants and seems to have the least overall 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 you may want to avoided when taking the above SERMs: MyoTEST, Zeus, TestoPRO, original BioForge, PCT Assist, N1-T, Triazole, Stoked, Recycle ect you get the idea just check the ingredient list
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 an effect on CYP3A4. Stating, [2] "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 an impact on CYP3A4 activity, and thus you’re SERM.
Additional edit: I want to note that in the second half of this post I am claiming that the intake of various products on the market could lead to a possible interaction with how efficient many SERMs work. I believe this interaction is dependent on many variables, and to what degree it occurs will vary significantly based on a lot of factors. Though, I am in no way claiming that addition PCT products like: AI's, Test boosters, Liver/Organ support, and antioxidant products ect, should not be used with SERMs or during PCT. I just generally feel that if alternative products that don't inhibit enzyme activity are present on the market, they should be utilized as a first choice. I also want to note that everything I have written has been based on what I have personally concluded from reading various publications, posts and speaking with a few company representatives; whether or not you chose to agree is your choice.
[1] Fertil Steril. 2009 Apr;91(4 Suppl):1427-30
[2] 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.
*If you would like to see additional references or studies, please let me know.
Edit: there was a study done by some Greek researchers showing that Tamox was slightly better than Torem at increasing testosterone and LH, which would indicate that it was better at restoring HPTA. Though, the Torem dosage was lower than most use. (The study used 20 mg of Tamoxifen and 60 mg of Toremifene. Where most would use something like: 120/90/60/30 for Toremifene.) Regardless, the results for 4 weeks of use were still pretty comparable ([1] Tamox - FSH: 8.23+/-2.71 LH: 7.65+/-3.37 T: 740.27+/-227.98 || Torem - FSH: 8.15+/-4.59 LH: 6.62+/-2.99 T: 696.13+/-202.21.) Also, I wanted to note that I am unsure if Torem leads to a direct increase in the amplitude of LH release like with Clomid. Though over a extend period of time this mechanism does lead to LHRH insensitivity and a decrease LH.
Regardless, overall Torem seems to be very effective at rebooting HPTA, and is much safer. Plus, most users seem to feel like Torem kicks in a lot sooner, thus helping you recover faster. Though, one downside is it does increase SHBG, which could lower circulating testosterone after extended use. Even so, I still feel like Toremifien is the best overall 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 inhibited by most SSRI. Also, many 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 it’s 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 affects CYP3A4. Though, since Torem doesn’t 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 to add the point that in addition to having the least side effects, Toremifene also seems to be the only SERM that can be safely taken with most anti depressants and seems to have the least overall 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 you may want to avoided when taking the above SERMs: MyoTEST, Zeus, TestoPRO, original BioForge, PCT Assist, N1-T, Triazole, Stoked, Recycle ect you get the idea just check the ingredient list
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 an effect on CYP3A4. Stating, [2] "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 an impact on CYP3A4 activity, and thus you’re SERM.
Additional edit: I want to note that in the second half of this post I am claiming that the intake of various products on the market could lead to a possible interaction with how efficient many SERMs work. I believe this interaction is dependent on many variables, and to what degree it occurs will vary significantly based on a lot of factors. Though, I am in no way claiming that addition PCT products like: AI's, Test boosters, Liver/Organ support, and antioxidant products ect, should not be used with SERMs or during PCT. I just generally feel that if alternative products that don't inhibit enzyme activity are present on the market, they should be utilized as a first choice. I also want to note that everything I have written has been based on what I have personally concluded from reading various publications, posts and speaking with a few company representatives; whether or not you chose to agree is your choice.
[1] Fertil Steril. 2009 Apr;91(4 Suppl):1427-30
[2] 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.
*If you would like to see additional references or studies, please let me know.
