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Twoguns said:
no. But tamoxifen at moderate to high doses with extended use can cause DNA adducts in the liver.
what to use in replace of pct
- Thread starter 23CALIBRO
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no. But tamoxifen at moderate to high doses with extended use can cause DNA adducts in the liver.
macrophage69alpha
New member
AIFM can be used alone, however do reccomend clomifen as well.
Oh boy, Im going to be here all night pulling up references for this... ;-)
Yes, nolva, clomid, raloxifene and any other SERM are turned into toxic quinones once metabolized by 2 and 4-hydroxylating enzyme. Since these hydroxylation enzymes are found at the highest concentration in the liver, thats where most of the problem will occur, however these toxic metabolites of SERMs can circulate the body … and well…. Cause problems just about anywhere. The damage to the DNA is a result of the adduct formation from the disruptive properties of the quinones (SERM metabolites).
This is just something to be aware of. A lot of bros use these SERMs like candy figuring they could do wrong. Just be cautious and limit your dosage.
-Pp
Yes, nolva, clomid, raloxifene and any other SERM are turned into toxic quinones once metabolized by 2 and 4-hydroxylating enzyme. Since these hydroxylation enzymes are found at the highest concentration in the liver, thats where most of the problem will occur, however these toxic metabolites of SERMs can circulate the body … and well…. Cause problems just about anywhere. The damage to the DNA is a result of the adduct formation from the disruptive properties of the quinones (SERM metabolites).
This is just something to be aware of. A lot of bros use these SERMs like candy figuring they could do wrong. Just be cautious and limit your dosage.
-Pp
macrophage69alpha
New member
1: Chem Res Toxicol. 2006 Jun;19(6):852-8. Links
Antiestrogens and the formation of DNA damage in rats: a comparison.Kim SY, Suzuki N, Laxmi YR, Umemoto A, Matsuda T, Shibutani S.
Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, 11794-8651, USA.
Tamoxifen (TAM) has been used as an agent for the treatment and prevention of breast cancer. However, long-term treatment of TAM in women increases the risk of developing endometrial cancer. The secondary cancer may be due to the genotoxicity of TAM. To find safer alternatives, four selective estrogen receptor modulators (SERMs), 4-hydroxytamoxifen (4-OHTAM), toremifene (TOR), raloxifene (RAL), and ICI 182,780, were administered to rats with an equimolar dose of TAM [54 micromol/kg (20 mg/kg)/day, p.o. for 7 days]. To evaluate the genotoxicity of each SERM, the presence of bulky DNA adducts was determined by (32)P-postlabeling/polyacrylamide gel electrophoresis and (32)P-postlabeling/high-performance liquid chromatography. The formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was analyzed as a marker of typical oxidative damage, using liquid chromatography electrospray tandem mass spectrometry. Among the SERMs, bulky DNA adducts were detected in the livers of rats treated with TAM; the total amount of TAM-DNA adducts was 26.1 adducts/10(7) nucleotides. However, with a detection limit of approximately 2 adducts/10(9) nucleotides, no bulky DNA adducts were observed with 4-OHTAM, TOR, RAL, or ICI 182,780. In addition, no significant increase of hepatic 8-oxodG lesions was detected in rats treated with any of the antiestrogens. Therefore, TOR, RAL, and ICI 182,780 are likely to be less genotoxic than TAM.
as a note- what that means is that 4-hydroxylated tamoxifen is LESS toxic than tamoxifen
There is no evidence that clomifen present any risk of DNA damage in males at dosages used, though extended high end dosing may lead to follicular changes. there is some evidence that it may present issues in women, though that is very limited.
Antiestrogens and the formation of DNA damage in rats: a comparison.Kim SY, Suzuki N, Laxmi YR, Umemoto A, Matsuda T, Shibutani S.
Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, 11794-8651, USA.
Tamoxifen (TAM) has been used as an agent for the treatment and prevention of breast cancer. However, long-term treatment of TAM in women increases the risk of developing endometrial cancer. The secondary cancer may be due to the genotoxicity of TAM. To find safer alternatives, four selective estrogen receptor modulators (SERMs), 4-hydroxytamoxifen (4-OHTAM), toremifene (TOR), raloxifene (RAL), and ICI 182,780, were administered to rats with an equimolar dose of TAM [54 micromol/kg (20 mg/kg)/day, p.o. for 7 days]. To evaluate the genotoxicity of each SERM, the presence of bulky DNA adducts was determined by (32)P-postlabeling/polyacrylamide gel electrophoresis and (32)P-postlabeling/high-performance liquid chromatography. The formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was analyzed as a marker of typical oxidative damage, using liquid chromatography electrospray tandem mass spectrometry. Among the SERMs, bulky DNA adducts were detected in the livers of rats treated with TAM; the total amount of TAM-DNA adducts was 26.1 adducts/10(7) nucleotides. However, with a detection limit of approximately 2 adducts/10(9) nucleotides, no bulky DNA adducts were observed with 4-OHTAM, TOR, RAL, or ICI 182,780. In addition, no significant increase of hepatic 8-oxodG lesions was detected in rats treated with any of the antiestrogens. Therefore, TOR, RAL, and ICI 182,780 are likely to be less genotoxic than TAM.
as a note- what that means is that 4-hydroxylated tamoxifen is LESS toxic than tamoxifen
There is no evidence that clomifen present any risk of DNA damage in males at dosages used, though extended high end dosing may lead to follicular changes. there is some evidence that it may present issues in women, though that is very limited.
A
ALIN
Guest
23CALIBRO said:
PCT are readily found everywhere,,,look around.
DJ_UFO
Banned
macrophage69alpha said:
Macro,
The rats using 4-OHA tamoxifen may have escaped liver cancer, but unfortunately they probably didn’t escape uterine cancer -- Being that 4-hydroxy tamoxifen is the primary cancer cancer causing metabolite of tamoxifen in the uterus.
Activation of 4-hydroxytamoxifen and the tamoxifen derivative metabolite E by uterine peroxidase to form DNA adducts: Comparison with DNA adducts formed in the uterus of Sprague-Dawley rats treated with tamoxifen
Deena N. Pathak, Krisztina Pongracz, and William J. Bodell
Carcinogenesis, Sep 1996; 17: 1785 - 1790
Activation of the Tamoxifen Derivative Metabolite E to Form DNA Adducts: Comparison with the Adducts Formed by Microsomal Activation of Tamoxifen
Krisztina Pongracz, Deena N. Pathak, Takemichi Nakamura, Alma L. Burlingame, and William J. Bodell
Cancer Res., Jul 1995; 55: 3012 - 3015.
Teratogenic effects of clomiphene, tamoxifen, and diethylstilbestrol on the developing human female genital tract.
GR Cunha, O Taguchi, R Namikawa, Y Nishizuka, and SJ Robboy
Hum Pathol, Nov 1987; 18(11): 1132-43.
Either way, we have to be careful when interrupting results from a rat studies. Remember, rats have a notable difference in their P450 gene characterizes and a pleiotropic drug such as tamoxifen is going to complicate things even further. Besides, debating over which tamoxifen metabolite has the most carcinogenic effects in whatever part of the body seems moot to me. I think it is clear that nolvadex is a toxic drug.
As far as clomid goes, I don’t think we need a study with male bodybuilders to realize it can cause problems. I personally wouldn’t want to use a substance with known tetrogenic effects. Besides, the last time I was on clomid, I had a non-existent sex drive and I cried about 4 times while sitting through “The Notebook”. That was the deal breaker for me.
-Pp
macrophage69alpha
New member
1.men dont have a uterus.
2. agree that tamoxifen has toxicity issues, just disagree with your explanation as to why, it also has effectiveness issues. However while recognizing toxicity issues one must also consider that low dose, short term, usage is unlikely to present these issues.
3. clomid is proven effective in restoration of the HPGA- the fact that it is a teratogen is irrellevant- unless you are pregnant. the emotional sides of clomid are generally mild with no frontload.
2. agree that tamoxifen has toxicity issues, just disagree with your explanation as to why, it also has effectiveness issues. However while recognizing toxicity issues one must also consider that low dose, short term, usage is unlikely to present these issues.
3. clomid is proven effective in restoration of the HPGA- the fact that it is a teratogen is irrellevant- unless you are pregnant. the emotional sides of clomid are generally mild with no frontload.
