If you read my earlier posts you would see how I outlined that in terms of effectiveness
(castration = 150mg bicalutamide = gnrh analogues)>low dose bicalutamide=flutamide>>>cyproterone acetate>spironolactone>>>>>dutasteride>>finasteride
I outlined this in terms of clinical drops in PSA which is a biological marker of androgenic activity In androgenic tissues (i.e. hair follicles)
bicalutamide and castration and gnrh analogs all inhibit PSA from 93% to 97% due to 1)castration ridding the source of androgens in the body 2)gnrh analogues disinhibit the HPG-axis and prevent the creation of LH > Testosterone by 95% and 3)Bicalutamide at 1mg can block from 10ng/dl or more of androgens from effecting the Androgen Response Element from interacting with the KLK3 proteins that signal PSA, aka androgenic activity
I added Bicalutamide to my regimen because it doesn't lower androgen levels (it actually increases them peripheral to AR signaling blockage) and therefore doesn't have anti-anabolic effects or sexual side effects which would both be side effects of castration / gnrh analogues. Its also tons more effective than Estrogen or common MtF medications like spironolactone/cpa because it lacks the partial agonist activity of progesterone derivatives.
==================================================================
Anyways I continued my research on Antiandrogens and came a cross a new medication that is more effective than Bicalutamide (the previously thought to be strongest Antiandrogen)
Enzalutamide (WARNING INSANELY DANGEROUS AND POWERFUL DRUG)
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer.[2][6] It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic castration-resistant prostate cancer.
The drug is often given after patients develop a resistance to Bicalutamide in Metastatic Castration-resistant Prostate Cancer, hence why it is considered a Second Generation NSAA
How strong is Enzalutamide?
"An up to 89% decrease in serum prostate specific antigen (PSA) levels have been reported after a month of taking the drug. PSA level decreased more than 50% in 40 of 65 chemo-naive patients and 38 of 75 chemotherapy-treated patients. Median time to radiographic progression was 56 weeks for chemo-naive patients and 25 weeks for the post-chemotherapy population."
As a reference, Bicalutamide takes 3 months to reduce PSA to the same extent and in less patients who take the drug (due to mutant AR).
Side Effects
Notable side effects of enzalutamide seen in clinical trials have included gynecomastia, breast pain/tenderness, fatigue, diarrhea, hot flashes, headache, sexual dysfunction, and, less commonly, seizures. Other "common" side effects reported in clinical trials have included neutropenia, visual hallucinations, anxiety, cognitive disorder, memory impairment, hypertension, dry skin, and pruritus (itching). Enzalutamide monotherapy is regarded as having a moderate negative effect on sexual function and activity, significantly less than that of GnRH analogues but similar to that of other NSAAs such as bicalutamide.
Mechanism of Action (Why its more Effective than Bicalutamide)
Enzalutamide acts as a selective silent antagonist of the androgen receptor (AR). Unlike bicalutamide, enzalutamide does not promote translocation of AR to the cell nucleus and in addition prevents binding of AR to deoxyribonucleic acid (DNA) and AR to coactivator proteins. As such, it has been described as an AR signaling inhibitor in addition to antagonist. The drug is described as a "second-generation" NSAA because it has greatly increased efficacy as an antiandrogen relative to so-called "first-generation" NSAAs like flutamide and bicalutamide. The drug has only 2- to 3-fold lower affinity for the AR relative to DHT, the endogenous ligand of the AR in the prostate gland.
(note Bicalutamide has a 30-100 fold lower affinity than DHT)
Here the drug resists mutant ARs that Bicalutamide would not have
When LNCaP cells (a prostate cancer cell line) engineered to express elevated levels of AR (as found in patients with advanced prostate cancer) were treated with enzalutamide, the expression of androgen-dependent genes PSA and TMPRSS2 was down regulated in contrast to bicalutamide where the expression was upregulated. In VCaP cells which over-express the AR, enzalutamide induced apoptosis whereas bicalutamide did not. Furthermore, enzalutamide behaves as an antagonist of the W741C mutant AR in contrast to bicalutamide which behaves as a pure agonist when bound to the W741C mutant.
tl;dr: Enzalutamide is resistant to overexpression of the AR in sight of mutant AR where Bicalutamide was not
THE STRENGTH OF ENZALUTAMIDE
Enzalutamide has approximately 5- to 8-fold higher binding affinity for the androgen receptor (AR) compared to bicalutamide. One study found an IC50 of 21 nM for enzalutamide and 160 nM for bicalutamide at the AR in the LNCaPcell line (7.6-fold difference), while another found respective IC50 values of 36 nM and 159 nM (4.4-fold difference). In accordance, clinical findings suggest that enzalutamide is a significantly more potent and effective antiandrogen in comparison to first-generation NSAAs such as bicalutamide, flutamide, and nilutamide.
I listed earlier that 1mg of Bicalutamide inhibits 10ng/dl of androgens from effectiving PSA completely and much more when DHT was inhibited with use of finasteride/dutasteride
MATH: Enzalutamide has 4.4-7.6x higher Kd than Bicalutamide
10ng/dl of Androgens *4.4-7.6=44-76ng/dl of Androgens
so we can conclude
1mg of Enzalutamide inhibits between 44-76ng/dl of androgens from effecting PSA completely
the regular dose of Enzalutamide is 160mg and it comes in 40mg tablets
so 160mg of Enzalutamide could block between 7,040-1,2160 ng/dl of Androgens
you could literally take steroids and not have ur hair touched by this drug
Effects on Testosterone: Enzalutamide monotherapy at a dosage of 160 mg/day has been found to increase circulating levels of testosterone by 114.3%, dihydrotestosterone by 51.7%, estradiol by 71.7%, sex hormone-binding globulin by 100.6%, dehydroepiandrosterone by 9.6%, androstenedione by 51.1%, luteinizing hormone by 184.7%, follicle-stimulating hormone by 47.0%, and prolactin by 16.8%. These changes in hormone levels are similar to those of high-dose bicalutamide monotherapy.
so 99% of people would not need more than 40mg of Enzalutamide since that would competetively destroy PSA from anywhere between 1760-3040ng/dl of T.
Hope this was interesting to read!
(castration = 150mg bicalutamide = gnrh analogues)>low dose bicalutamide=flutamide>>>cyproterone acetate>spironolactone>>>>>dutasteride>>finasteride
I outlined this in terms of clinical drops in PSA which is a biological marker of androgenic activity In androgenic tissues (i.e. hair follicles)
bicalutamide and castration and gnrh analogs all inhibit PSA from 93% to 97% due to 1)castration ridding the source of androgens in the body 2)gnrh analogues disinhibit the HPG-axis and prevent the creation of LH > Testosterone by 95% and 3)Bicalutamide at 1mg can block from 10ng/dl or more of androgens from effecting the Androgen Response Element from interacting with the KLK3 proteins that signal PSA, aka androgenic activity
I added Bicalutamide to my regimen because it doesn't lower androgen levels (it actually increases them peripheral to AR signaling blockage) and therefore doesn't have anti-anabolic effects or sexual side effects which would both be side effects of castration / gnrh analogues. Its also tons more effective than Estrogen or common MtF medications like spironolactone/cpa because it lacks the partial agonist activity of progesterone derivatives.
==================================================================
Anyways I continued my research on Antiandrogens and came a cross a new medication that is more effective than Bicalutamide (the previously thought to be strongest Antiandrogen)
Enzalutamide (WARNING INSANELY DANGEROUS AND POWERFUL DRUG)
Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer.[2][6] It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic castration-resistant prostate cancer.
The drug is often given after patients develop a resistance to Bicalutamide in Metastatic Castration-resistant Prostate Cancer, hence why it is considered a Second Generation NSAA
How strong is Enzalutamide?
"An up to 89% decrease in serum prostate specific antigen (PSA) levels have been reported after a month of taking the drug. PSA level decreased more than 50% in 40 of 65 chemo-naive patients and 38 of 75 chemotherapy-treated patients. Median time to radiographic progression was 56 weeks for chemo-naive patients and 25 weeks for the post-chemotherapy population."
As a reference, Bicalutamide takes 3 months to reduce PSA to the same extent and in less patients who take the drug (due to mutant AR).
Side Effects
Notable side effects of enzalutamide seen in clinical trials have included gynecomastia, breast pain/tenderness, fatigue, diarrhea, hot flashes, headache, sexual dysfunction, and, less commonly, seizures. Other "common" side effects reported in clinical trials have included neutropenia, visual hallucinations, anxiety, cognitive disorder, memory impairment, hypertension, dry skin, and pruritus (itching). Enzalutamide monotherapy is regarded as having a moderate negative effect on sexual function and activity, significantly less than that of GnRH analogues but similar to that of other NSAAs such as bicalutamide.
Mechanism of Action (Why its more Effective than Bicalutamide)
Enzalutamide acts as a selective silent antagonist of the androgen receptor (AR). Unlike bicalutamide, enzalutamide does not promote translocation of AR to the cell nucleus and in addition prevents binding of AR to deoxyribonucleic acid (DNA) and AR to coactivator proteins. As such, it has been described as an AR signaling inhibitor in addition to antagonist. The drug is described as a "second-generation" NSAA because it has greatly increased efficacy as an antiandrogen relative to so-called "first-generation" NSAAs like flutamide and bicalutamide. The drug has only 2- to 3-fold lower affinity for the AR relative to DHT, the endogenous ligand of the AR in the prostate gland.
(note Bicalutamide has a 30-100 fold lower affinity than DHT)
Here the drug resists mutant ARs that Bicalutamide would not have
When LNCaP cells (a prostate cancer cell line) engineered to express elevated levels of AR (as found in patients with advanced prostate cancer) were treated with enzalutamide, the expression of androgen-dependent genes PSA and TMPRSS2 was down regulated in contrast to bicalutamide where the expression was upregulated. In VCaP cells which over-express the AR, enzalutamide induced apoptosis whereas bicalutamide did not. Furthermore, enzalutamide behaves as an antagonist of the W741C mutant AR in contrast to bicalutamide which behaves as a pure agonist when bound to the W741C mutant.
tl;dr: Enzalutamide is resistant to overexpression of the AR in sight of mutant AR where Bicalutamide was not
THE STRENGTH OF ENZALUTAMIDE
Enzalutamide has approximately 5- to 8-fold higher binding affinity for the androgen receptor (AR) compared to bicalutamide. One study found an IC50 of 21 nM for enzalutamide and 160 nM for bicalutamide at the AR in the LNCaPcell line (7.6-fold difference), while another found respective IC50 values of 36 nM and 159 nM (4.4-fold difference). In accordance, clinical findings suggest that enzalutamide is a significantly more potent and effective antiandrogen in comparison to first-generation NSAAs such as bicalutamide, flutamide, and nilutamide.
I listed earlier that 1mg of Bicalutamide inhibits 10ng/dl of androgens from effectiving PSA completely and much more when DHT was inhibited with use of finasteride/dutasteride
MATH: Enzalutamide has 4.4-7.6x higher Kd than Bicalutamide
10ng/dl of Androgens *4.4-7.6=44-76ng/dl of Androgens
so we can conclude
1mg of Enzalutamide inhibits between 44-76ng/dl of androgens from effecting PSA completely
the regular dose of Enzalutamide is 160mg and it comes in 40mg tablets
so 160mg of Enzalutamide could block between 7,040-1,2160 ng/dl of Androgens
you could literally take steroids and not have ur hair touched by this drug
Effects on Testosterone: Enzalutamide monotherapy at a dosage of 160 mg/day has been found to increase circulating levels of testosterone by 114.3%, dihydrotestosterone by 51.7%, estradiol by 71.7%, sex hormone-binding globulin by 100.6%, dehydroepiandrosterone by 9.6%, androstenedione by 51.1%, luteinizing hormone by 184.7%, follicle-stimulating hormone by 47.0%, and prolactin by 16.8%. These changes in hormone levels are similar to those of high-dose bicalutamide monotherapy.
so 99% of people would not need more than 40mg of Enzalutamide since that would competetively destroy PSA from anywhere between 1760-3040ng/dl of T.
Hope this was interesting to read!
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