[celc5]

Source: Fareston® toremifene citrate

During FARESTON® clinical trials involving 1157 patients treated with FARESTON® or tamoxifen, there was a low incidence of serious side effects, including cardiac events (2.03% vs 2.42%), stroke (3.21% vs 3.28%), and elevated standard liver tests (26.2% vs 23.7%), respectively.

According to those who are marketing the brand name fareston (torem), it seems to have had MORE cases of elevated liver values than with tamoxifen (nolva) in this particular study.

[MentalTwitch]

Excellent idea...spread it around.
Watching.

[Iron Warrior]

Is the difference really that significant ?

Which is worse for the vision ?

Is Nolva much more toxic in other aspects ?

We gotta answer those questions before reaching a conclusion, just food for thought.

[celc5]

Originally Posted by Iron Warrior

Is the difference really that significant ?

Which is worse for the vision ?

Is Nolva much more toxic in other aspects ?

We gotta answer those questions before reaching a conclusion, just food for thought.

Good questions. Also this studies shows similar INCIDENCE of liver toxicity, but not necessarily the degree of toxicity. So the "board opinion" that torem is less toxic could still be correct despite the results of this study.

[Iron Warrior]

Originally Posted by celc5

Good questions. Also this studies shows similar INCIDENCE of liver toxicity, but not necessarily the degree of toxicity. So the "board opinion" that torem is less toxic could still be correct despite the results of this study.

Another thing to consider is the quality of recovery. We're not gonna be using these compounds long enough to do permanent damage IMO so if Torem outperforms Tamox than it would be the go to guy for PCT. It's good to analyze these things though because they bring out more discussion and analysis ! I wish Dr.D could see this because he's very well schooled in this.

[Travis]

I'd like to see the study or at least the abstract. Doesnt seem like its referenced anywhere on that site?

[celc5]

Originally Posted by Travis

I'd like to see the study or at least the abstract. Doesnt seem like its referenced anywhere on that site?

Here's the direct link:

http://www.fareston.com/b_about/b3.html

[PumpingIron]

Do we know dosages of each used?

[drksun]

torem will improve lipids though, so even though its slight more heptatoxic its a lot better at getting lipids back to baseline.

[Travis]

Originally Posted by PumpingIron

Do we know dosages of each used?

This is what I was wondering. I would assume dosages being used are equal? But that is a somewhat bad assumption. Also another factor could be length of time each SERM was used. A lot of these studies are done over significantly longer periods of time than a typical 4-5 week PCT.

[Iron Warrior]

Originally Posted by Travis

A lot of these studies are done over significantly longer periods of time than a typical 4-5 week post cycle therapy.

This is a great point. We probably won't be subjected to these side effects since we use it on a limited basis. A lot of these studies aren't applicable to BBers since they're studied for other medical purposes. It kind of reminds me about the whole cabergoline warning but if used for short periods of time than we shouldn't suffer permanent damage. It's all about smart use, not abuse.

[celc5]

We can probably assume that there was no liver support either and the study was on women.

I'm not trying to bash serms, just presenting some info that I found.

You guys mentioned dosing and I suspect that we dose overkill on our serms. Hopefully someone with a bigger brain than me will chime in on that one for us

[Travis]

Originally Posted by celc5

We can probably assume that there was no liver support either and the study was on women.

I'm not trying to bash serms, just presenting some info that I found.

You guys mentioned dosing and I suspect that we dose overkill on our serms. Hopefully someone with a bigger brain than me will chime in on that one for us

I'd agree with you on that x2.

[Interlocutor]

i'd just wanted to update this old thread with some comparative studies:

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

We have described fatty liver, diagnosed by computed tomography scanning (CT) in more than 30% of patients with breast cancer who received tamoxifen. Therefore, it is urgent to elucidate the frequency and the degree of fatty liver induced by toremifene, an analogue of tamoxifen, which is also used in breast cancer. We enrolled 52 breast cancer patients who were treated with breast-conservation treatment and administered oral toremifene for 3-5 years as adjuvant endocrine therapy. We evaluated the degree of fatty liver by abdominal CT performed annually. CT demonstrated toremifene-induced fatty liver in four (7.7%) of 52 breast cancer patients. Toremifene-induced fatty liver did not correlate with abnormal levels of AST, ALT, GGT or total cholesterol. One patient who demonstrated moderate fatty liver by CT was histologically diagnosed as non-alcoholic steatohepatitis (NASH) by liver biopsy. The incidence of toremifene-induced fatty liver was significantly lower than that induced by tamoxifen. Accordingly, in terms of fatty liver and NASH, toremifene is considered to be more appropriate agent than tamoxifen. Though toremifene is less likely to induce fatty liver, the possibility remains that toremifene-induced steatohepatitis occurs.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

The female rats consuming intoxicating amounts of ethanol diet for 6 weeks developed massive microvesicular/macrovesicular steatosis, frequent inflammatory foci and spotty necrosis. Serum alanine aminotransferase increased 7-fold. Toremifene treatment did not affect steatosis, but significantly reduced inflammation and necrosis. Ethanol increased the expression of CD14 and tumor necrosis factor- (TNF) alpha mRNA and also the production of TNF-alpha by isolated Kupffer cells, but toremifene had no significant counteracting effect. However, toremifene significantly alleviated both ethanol induction of the pro-oxidant enzyme CYP2E1 and ethanol reduction of the oxidant-protective enzyme Se-glutathione peroxidase. CONCLUSIONS: The partial protection by toremifene against ethanol-induced liver lesions suggests a pathogenic contribution of estrogens, possibly associated with an oxygen radical mediated mechanism.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Tamoxifen, toremifene, droloxifene, and idoxifene are polyphenylethylene antiestrogens, whereas the pure antiestrogen, ICI 182,780 or faslodex, as well as raloxifene, is of a different structure. Tamoxifen has been shown to be genotoxic in several studies. It induces unscheduled DNA synthesis in rat hepatocytes and micronuclei in MCL-5 a cells in vitro. Tamoxifen also induces aneuploidy in rat liver in vivo and chromosome aberrations and micronuclei in mouse bone marrow. Toremifene has also shown to be genotoxic, but to a far lower extent, by inducing micronuclei in MCL-5 a cells in vitro and by inducing aneuploidy in rat liver in vivo. Tamoxifen has been shown to be hepatocarcinogenic in the rat in at least four independent long-term studies. The initiation of tumors in the rat is the result of metabolic activation by cytochrome P450 isoenzymes to an electrophile(s) that binds irreversibly to DNA. The other antiestrogens have not been shown to be carcinogenic in rodents.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

annual cataract rates of 6.8% and 6.2% in the tamoxifen and toremifene groups, respectively

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A-1), apolipoprotein A(Apo B), and lipoprotein a (Lp(a)) were measured prior to administration and 3, 6, and 12 months after the start of administration. TC, LDL-C, Lp(a) and Apo B significantly decreased from the third month of administration compared with values before the start of administration in both the TOR and TAM groups. HDL-C significantly increased from the third month only in the TOR group. TG significantly increased in the TAM group but significantly decreased in the TOR group in the 12th month of administration. When these two groups were compared, HDL-C was significantly higher (p < 0.01) and TG was significantly lower (p < 0.01) in the TOR group in the 12th month. Improvement of abnormal values of TG, HDL-C and LDL-C was better in the TOR group than in the TAM group after administration for 12 months. The effect on lipid metabolism showed different profiles between the two selective estrogen receptor modulators (SERMs), and TOR gave better results than TAM.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Hepatic TAM-DNA adducts were formed even after 1 week of treatment with TAM at either dose, and the adduct levels increased in a dose- and treatment period-dependent manner, whereas no DNA adducts were detected in any of the TOR-treated rats. Conversely, TAM and TOR showed almost the same capacity for increasing the gene expression of drug-metabolizing enzymes responsible for metabolic activation and detoxification, at least up to the 2-week treatment mark. Accordingly, differences in DNA adduct formation between TAM- and TOR-treated rats would not be primarily dependent on the capacity for inducing hepatic drug-metabolizing enzymes. In addition, a drastic increase in the gene expression of cytochrome P4503A2 (CYP3A2), an activation enzyme of TAM, by the 8-week treatment with TAM might have contributed to the increased formation of DNA adducts. Gene expressions of DNA repair enzymes/proteins responsible for a nucleotide excision repair system were not significantly changed in any of the rats treated with either drug. The present findings suggest that the difference between TAM and TOR in hepatocarcinogenic potency is dependent on the capacity to form DNA adducts rather than modulating the expression of drug-metabolizing enzymes and DNA repair enzymes/proteins.

http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Compared with the placebo group men in the toremifene group had significant increases in bone mineral density at each evaluated skeletal site. Lumbar spine bone mineral density decreased 0.7% in the placebo group and increased 1.6% in the toremifene group (between group comparison p <0.001). Total hip bone mineral density decreased 1.3% in the placebo group and increased 0.7% in the toremifene group (p = 0.001). Femoral neck bone mineral density decreased 1.3% in the placebo group and increased 0.2% in the toremifene group (p = 0.009). Between group differences in the change in bone mineral density from baseline to month 12 were 2.3%, 2.0% and 1.5% for the lumbar spine, total hip and femoral neck, respectively. CONCLUSIONS: Toremifene significantly increased hip and spine bone mineral density in men receiving androgen deprivation therapy for prostate cancer.

T.I.

P.S.: does anyone have the full text (or abstract) of: http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum

Toremifene might improve side effects of ADT.

[bioman]

Nice finds.