Is torem MORE liver toxic than nolva?

[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]

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]

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]

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]

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]

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 :think:

 

[Travis]

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 :think:

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/11078796?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_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/11495041?ordinalpos=164&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_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/11896754?ordinalpos=144&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_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/14510798?ordinalpos=100&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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

http://www.ncbi.nlm.nih.gov/pubmed/15538040?ordinalpos=76&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_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/16734724?ordinalpos=32&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_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/18001802?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_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/17436422?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Toremifene might improve side effects of ADT.

 

[bioman]

Nice finds.

 

[neoborn]

Nice Find x 2

Is this a good thing?

CONCLUSIONS: Toremifene significantly increased hip and spine bone mineral density in men receiving androgen deprivation therapy for prostate cancer.

 

[pudzian2]

interesting. lets keep this going and hopefully draw some conclusions....

what about the liver toxicities/ general toxicities of SERMS like clomid and ralox>?

 

[pudzian2]

like mentioned earlier, it is also important to consider how long cancer patients remain on these drugs... whereas PCT lengths are MUCH shorter

 

[Interlocutor]

Nice Find x 2

Is this a good thing?

yes. low estrogen, such as from AIs, or androgen deprivation therapy, such as for prostate cancer, may aparenly reduce bone density over time. this is a major concern for long term therapy (e.g. self-treatment of gyno etc.).

increasing bone density indicates that it works as estrogen receptor agonist (i.e. like estrogen) in bone tissue, which is a positive aspect.

T.I.

 

[Ziquor]

There's some inaccurate info in here too. Nolva is actually the only serm that decreases cholesterol just as much as actual lipid lowering meds such as Zocor & Lipitor. Though Torem is better for a quicker recovery back to natural test. I'd prefer to use Nolva most of the time except when using super strong gear/ph. I always keep both on hand because both have their place.

 

[pudzian2]

There's some inaccurate info in here too. Nolva is actually the only serm that decreases cholesterol just as much as actual lipid lowering meds such as Zocor & Lipitor. Though Torem is better for a quicker recovery back to natural test. I'd prefer to use Nolva most of the time except when using super strong gear/ph. I always keep both on hand because both have their place.

decreasing cholesterol isnt as favorable is IMPROVING THE RATIO, (increasing HDL whilst decreasing LDL).... Torem does this. To each his own i suppose. But new generation compounds are developed for a reasons. Torem has been tried and true for me so i will stick to that. no reason to go back in time IMO.

 

[poopypants]

this is an awsome read, thanks for all the studies Interlocutor, just goes to show even more why I prefer Torem to Tamox, besides the fact I rocover in about half the time ending up with larger peices then I started typically and feel great the entire PCT and not moody.

 

[Steveoph]

"For men with advanced prostate cancer undergoing androgen-deprivation therapy (ADT), toremifene might counter side effects associated with this treatment, according to two multicentre studies presented at the 3rd Prostate Cancer Symposium (Orlando, FL, USA; Feb 22–24, 2007). Increased fracture risk, and more recently, increased risk of cardiovascular disease associated with ADT have been previously reported.

Matthew R Smith (Massachusetts General Hospital Cancer Center, Boston, MA, USA) and colleagues report that preliminary data from both studies showed a significant increase in bone-mineral density (BMD) and significant improvement in lipid profiles in men given ADT who were treated with toremifene.

Both studies included 1392 men undergoing ADT for advanced prostate cancer. The first study assessed the efficacy of toremifene on BMD. Interim analysis of 200 men at 1 year showed that, compared with placebo, men treated with toremifene had a significant increase in BMD in the lumbar spine (−0·7% vs 1·6%, p<0·001), hip (−1·3 vs 0·7%, p=0·001), and femoral neck (−1·3% vs 0·2%, p=0·009).

The second study, assessing the efficacy of toremifene on lipid concentrations, found significant improvment in lipid concentrations with toremifene compared with placebo; interim analysis of 197 men at 1 year showed that toremifene decreased total cholesterol by 7·1%, low-density lipoprotein cholesterol by 9·0%, triglycerides by 20·1%, total cholesterol-to-high-density lipoprotein ratio by 11·7%, and increased high-density lipoprotein by 5·4% compared with placebo.

Anthony D'Amico (Harvard Medical School, Boston, MA, USA) considers the findings of these studies “a work in progress”. He continues, “a lot of data show that by correcting lipid profiles you can prevent coronary artery events down the road, but the data to date only show an association and more follow-up is needed to see if this really decreases coronary artery events”.

D'Amico also thinks that several drugs decrease loss of BMD, but none, including toremifene, have yet shown a significant effect on bone fracture. “BMD is a necessary, but not sufficient, step to get to the endpoint of pathologic bone fracture”, he says.

According to Smith, the final results of these studies should be available in late 2007 or early 2008. “Based on these robust findings of the interim analysis, the observed effects of toremifene on BMD and lipids will almost certainly be confirmed in the final analyses”, he comments. "

That's the last link from TI.

 

[pudzian2]

oh how lovely

 

[Ziquor]

decreasing cholesterol isnt as favorable is IMPROVING THE RATIO, (increasing HDL whilst decreasing LDL).... Torem does this. To each his own i suppose. But new generation compounds are developed for a reasons. Torem has been tried and true for me so i will stick to that. no reason to go back in time IMO.

Good info I wasn't aware of that in regards to Torem. As for Tamox it actually does increase HDL (good) cholesterol & decrease LDL (bad) cholesterol both --> Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial -- Banerjee et al., 10.1093/annonc/mdi322 -- Annals of Oncology <-- Like I said I plan to run Nolva on all the lighter/medium gear & Torem only on extreme stuff. I understand Torem works quicker as it's stronger but IMO more isn't always better. Like all the info lately about the severe negative consequences of serms being run at much too high doses during pct, possible delayed gyno, hepatoxicity, etc. I came across a thread q&a posted by PA where he was talking about how in many cases just as little as 40mg of Tamox starting in pct can even be too much for most people, especially younger guys. I just wish Torem was cheaper, I got 100 x 20mg name brand Tamoxifen for $50 and the 60 x 60mg Toremifenes I got were a little over $200.

 

[poopypants]

Good info I wasn't aware of that in regards to Torem. As for Tamox it actually does increase HDL (good) cholesterol & decrease LDL (bad) cholesterol both --> Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial -- Banerjee et al., 10.1093/annonc/mdi322 -- Annals of Oncology <-- Like I said I plan to run Nolva on all the lighter/medium gear & Torem only on extreme stuff. I understand Torem works quicker as it's stronger but IMO more isn't always better. Like all the info lately about the severe negative consequences of serms being run at much too high doses during pct, possible delayed gyno, hepatoxicity, etc. I came across a thread q&a posted by PA where he was talking about how in many cases just as little as 40mg of Tamox starting in pct can even be too much for most people, especially younger guys. I just wish Torem was cheaper, I got 100 x 20mg name brand Tamoxifen for $50 and the 60 x 60mg Toremifenes I got were a little over $200.

whooowheee thats spensive! why not go the RC route? I understand your super careful but thats a pretty penny for something that can reliably be found elswhere for nearly 1/4 the cost.... although you CANT ingest it yourself its completely legal to obtian.

 

[Ziquor]

Yeah I sorta kicked myself after I ordered it but I never tried RC's so I guess I'm a little cautious about trying them. Plus when I ordered the Torem it was out of stock on the RC side. I should've waited but I'm too damn impatient, even though I really didn't need it for a while yet.

 

[pudzian2]

Yeah I sorta kicked myself after I ordered it but I never tried RC's so I guess I'm a little cautious about trying them. Plus when I ordered the Torem it was out of stock on the RC side. I should've waited but I'm too damn impatient, even though I really didn't need it for a while yet.

yea dosage whise with these serms people tend to take more just in case it wont be enough. They are more concerned with restarting their HPTA than what the extra SERM will do in the short term. HOWEVER, I think there should be a sponsored controlled series of experiments where human males are suppressed via exogenous hormone replacement (TRT patient maybe, but one that has been on TRT for only 2-20 months=typical cycle lengths). That way we can get a quantitative representation of the range of doses needed be optimal at doing their job for us.

to draw a parallel to an economic concept, the law of diminishing returns applies very well to this situation. after a certain dose...the cons of the SERM may outweigh the benefits.

 

[poopypants]

I still think its hard to say its that bad when taken for only 3-4 weeks, even at higher doses these studies are sometimes performed across months to years and would probably exhibit much more sides given the cumulative(doses haveing long halflife) nature of these drugs then we'd ever see in our short periodic runs of these same compounds.

 

[pudzian2]

I still think its hard to say its that bad when taken for only 3-4 weeks, even at higher doses these studies are sometimes performed across months to years and would probably exhibit much more sides given the cumulative(doses haveing long halflife) nature of these drugs then we'd ever see in our short periodic runs of these same compounds.

yea i believe that the relevance of these studies to our research applications is limited. those lipid improvements may not even take place to a great degree during 3-4 weeks. I mean hell 3-4 weeks does NOT compare to the years and months that these cancer patients etc use this stuff.

however I still think there should be some more research to figure out the optimal SERM doses for HPTA stim.

 

[poopypants]

yea i believe that the relevance of these studies to our research applications is limited. those lipid improvements may not even take place to a great degree during 3-4 weeks. I mean hell 3-4 weeks does NOT compare to the years and months that these cancer patients etc use this stuff.

however I still think there should be some more research to figure out the optimal SERM doses for HPTA stim.

agreed, it would be nice to have solid numbers to rely on not hearsay and brotelligence.

 

[pudzian2]

agreed, it would be nice to have solid numbers to rely on not hearsay and brotelligence.

EXACTLY....now whos gonna do it? haha

 

[poopypants]

that would be one expensive study, youd have to basically create the correct environment in a controlled group (dont think TRT guys would be the way to go since its not applicable to our goals, we want healthy guys regaining HTPA equilibrium after steroidal induced shutdown) and then use a placebo and torem group..... would hate to be that shutdown and get the placebo, LMAO

 

[pudzian2]

yea I dont think one or even 10 of us could collaborate an organized enough environment to get anything but unreliable circumstantial data

 

[LakeMountD]

Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats.

* Hard GC,
* Iatropoulos MJ,
* Jordan K,
* Radi L,
* Kaltenberg OP,
* Imondi AR,
* Williams GM.

American Health Foundation, Valhalla, New York 10595.

The hepatoproliferative effects of 2 antiestrogens, tamoxifen and toremifene, were compared in a sequential 15-month study in which 2 doses of each compound were administered by daily gavage to female Sprague-Dawley rats for up to 12 months. The doses were 11.3 and 22.6 mg/kg for tamoxifen and 12 and 24 mg/kg for toremifene. There were scheduled sacrifices at 3, 6, 12, and 15 months, the latter including a 3-month recovery period from the 12th through the 14th month. In the chronic toxicity study, tamoxifen at 22.6 mg/kg produced 100% incidence of hepatocellular carcinoma at the 12- and 15-month sacrifice intervals and 67% and 71% incidences at the 11.3-mg/kg dose. Sequential observations showed an increased incidence of glutathione S-transferase-positive foci of hepatocellular alteration by 3 months with tamoxifen in the absence of hepatotoxicity, with the first liver carcinoma appearing by 6 months of treatment. Unscheduled deaths occurring beyond 7.5 months in the tamoxifen treated groups were due in almost all cases to liver cancer. In striking contrast, toremifene did not produce any hepatoproliferative effects at 12- and 24-mg/kg dose levels, nor in a pilot study at 48 mg/kg. The 24-mg/kg dose of toremifene exerted an inhibiting effect on foci of hepatocellular alteration in rat liver detectable by glutathione S-transferase immunohistochemistry at 3 months and by conventional histology at 12 months. An antiproliferative effect was also evident in mammary gland and anterior pituitary where both toremifene and tamoxifen suppressed tumor incidence in comparison to the control group. The ability of these drugs to modify rat liver DNA after p.o. administration was investigated using the 32P-postlabeling assay. Administration of tamoxifen at 45 mg/kg for 7 days produced liver DNA nucleoside modifications represented by 7 spots on the autoradiogram. Unlike tamoxifen, toremifene did not produce any modified bases in rat liver DNA detectable by the 32P-postlabeling technique. The dose levels of tamoxifen that are strongly hepatocarcinogenic in the rat are compared with doses used in humans in various applications. Taking internal drug exposure into account, we conclude that the margin of safety for use of tamoxifen as an endocrine prophylactic agent for healthy, but breast cancer prone, women is questionable.




Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer
T Saarto, C Blomqvist, C Ehnholm, MR Taskinen and I Elomaa
Department of Oncology, Helsinki University Central Hospital, Finland.
------>To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to- A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.



Effects of toremifene (TOR) and tamoxifen (TAM) on serum lipids
M. Kusama1, K. Miyauchi2, H. Aoyama3, M. Sano4, M. Kimura5, S. Mitsuyama6, K. Komaki7 and H. Doihara8
(1) Third Department of Surgery, Tokyo Medical University, 2-25-9 Nishi-shinjuku, Japan
(2) Miyauchi Clinic, Japan
(3) Nagoya National Hospital, Japan
(4) Niigata Cancer Center, Japan
(5) Gunma Cancer Center, Japan
(6) Kitakyusyu Municipal Medical Center, Japan
(7) School of Medicine, University of Tokushima, Japan
(8) Okayama University Medical School, Japan
------>This study clarified the difference in the effects on serum lipids between toremifene (TOR) and tamoxifen (TAM). To remove influencing factors, we investigated adjuvant therapy for hormone receptor-positive patients with breast cancer without lymph node metastasis. The subjects were 65 patients who were enrolled in a multicenter randomized comparative study between April 1997 and March 2001. As adjuvant therapy, 20 mg of TAM or 40 mg of TOR was administered for 1 year. 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.





T Saarto, C Blomqvist, C Ehnholm, MR Taskinen and I Elomaa
Department of Oncology, Helsinki University Central Hospital, Finland.
------>To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to- A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.

 

[poopypants]

ummm cliff notes? good to see ya here bro.

 

[pudzian2]

all good stuff

 

[Interlocutor]

yea i believe that the relevance of these studies to our research applications is limited. those lipid improvements may not even take place to a great degree during 3-4 weeks. I mean hell 3-4 weeks does NOT compare to the years and months that these cancer patients etc use this stuff.
however I still think there should be some more research to figure out the optimal SERM doses for HPTA stim.

yes, it seems somehow implausibe when the same dosing schedules are recommended for 12 a week test/deca/dbol/tren cycle and for a 4 week havoc 10/20/20/30 cycle. does this cause the same amount of testicular atrophy? of shutdown? of changes in lipids etc.? surely not. why then use the same post cycle therapy?

however, if we consider that a certain amount of people here try to self-treat gyno with SERMs and AIs, and we then see from clinical studies that sucessful treatment of such usually takes several (average 6?) months, then for those people the mid-term risks (bone density, lipids, etc.) may very well be of at least some moderate concern.

the one point about high initial dosing of SERMs, regardless of the amount of shutdown, which i follow is that, due to the very long half-life of SERMs, a higher dosed loading phase appropriate to the compound to reach effective serum level baselines may be beneficial.

however, there seems to at least some anecdotal feedback (e.g. from dinoii, aka Dana Hauser) that this theoretical benefit is not really seen in practical application, and that the negatives of high-dosed SERMs, such as IGF-1 suppression and other sides, may outweigh the benefits, especially for "mild"/short oral cycles.

personally, i am still somewhat undecided, but now tend to favour lower dosed and shorter SERM regimes for mild/short oral cyces (but still using some preload), especially if combined with an AI, as we frequently see. as for more hardcore/long term cycles, i have no opinion, as i don't use these myself due to legality issues.

ummm cliff notes?

multiple studies shows that toremifene does improve overall cholesterol and "good" to "bad" cholesterol ratios in a more benficial way than does tamoxifen.

yea I dont think one or even 10 of us could collaborate an organized enough environment to get anything but unreliable circumstantial data

lol, you mean like the good Dr. P's abortive attempt to get a study rolling with DHEA+ATD? how many applicants did he get from all of bb.com, after a lot of initial interest? 3?

T.I.

 

[Ziquor]

Test was done on female rats. I'd venture to say in male humans any tests could be a quite a bit different.

 

[Interlocutor]

Test was done on female rats. I'd venture to say in male humans any tests could be a quite a bit different.

only one of the four studies he posted was on rats. the other three were on humans.

THE INTERLOCUTOR

 

[pudzian2]

yes, it seems somehow implausibe when the same dosing schedules are recommended for 12 a week test/deca/dbol/tren cycle and for a 4 week havoc 10/20/20/30 cycle. does this cause the same amount of testicular atrophy? of shutdown? of changes in lipids etc.? surely not. why then use the same post cycle therapy?

however, if we consider that a certain amount of people here try to self-treat gyno with SERMs and AIs, and we then see from clinical studies that sucessful treatment of such usually takes several (average 6?) months, then for those people the mid-term risks (bone density, lipids, etc.) may very well be of at least some moderate concern.

the one point about high initial dosing of SERMs, regardless of the amount of shutdown, which i follow is that, due to the very long half-life of SERMs, a higher dosed loading phase appropriate to the compound to reach effective serum level baselines may be beneficial.

however, there seems to at least some anecdotal feedback (e.g. from dinoii, aka Dana Hauser) that this theoretical benefit is not really seen in practical application, and that the negatives of high-dosed SERMs, such as IGF-1 suppression and other sides, may outweigh the benefits, especially for "mild"/short oral cycles.

personally, i am still somewhat undecided, but now tend to favour lower dosed and shorter SERM regimes for mild/short oral cyces (but still using some preload), especially if combined with an AI, as we frequently see. as for more hardcore/long term cycles, i have no opinion, as i don't use these myself due to legality issues.



multiple studies shows that toremifene does improve overall cholesterol and "good" to "bad" cholesterol ratios in a more benficial way than does tamoxifen.



lol, you mean like the good Dr. P's abortive attempt to get a study rolling with DHEA+ATD? how many applicants did he get from all of bb.com, after a lot of initial interest? 3?

T.I.

what is an example of your SERM taper for a 4 week oral or injectable cycle

 

[Interlocutor]

what is an example of your SERM taper for a 4 week oral or injectable cycle

i do not comment on injectable cycles.

i am currently using tamo 20/10/10 / aPCT (6-bromo) 3/2/1 for a short/mild 3 week 1-test ether oral cycle.

Edit: my ralo arrived today (stupid post office) i am still on day 2 of PCT, so switching to ralo 60/30/30.

as for now, i'd say, based on half-life considerations:

tamo (HL = 9 days) = 40 (9) / 20 (5) / 20 / 20
torm (HL = 5 days) = 120 (5) / 60 (2) / 60 / 60 / 30
ralo (HL = 27-32 hours) = 120 (1) / 60 (6) / 60 / 60 / 30
clomid (HL = 5-7 days) = 100 (6) / 50 (1) / 50 / 50 / 25

for most compounds. this should allow for a quick approach to effective long-term baseline levels, which then are kept stable for an extended duration, followed by a graceful decline period of serum levels.

as you see i'm still afraid to give lower dosed recommendations. but i'm working on it. honestly i believe that for short/mild cycles (such as moderately dosed havoc) recommendations of half the ones given above would suffice, especially if combined with an AI or a product such as PCS or even Dermacrine in post cycle therapy.

i'd wager that going over the abovementioned dosages, though, will simply add more sides (such as IGF-1 suppression, higher risk of blood clots or ocular events, higher stress on the liver, etc.) without providing additional benefits concerning HPTA recovery and gyno prevention. if you look at e.g. torm, there have been studies for up to 300mg daily which have not shown better hormone values than 60mg daily.

i may be wrong, though. there are people much more suited than i am to define the "perfect" post cycle therapy. i can only reflect the reasoning behind what i'm doing or what i'd do.

T.I.

 

[pudzian2]

excellent way to put it man. nice posting

 

[Ziquor]

Nice post. Is that chart actual info from blood results?

 

[Interlocutor]

Nice post. Is that chart actual info from blood results?

lol. no, that's just very very simplified schematic info of the expected situation based on available half-life data. real-life data would look MUCH more erratic and volatile, with saw-tooth patterns reflecting the bi-phasic elimination half-lifes and the uptake times. there are just to many parameters to ever allow a simple pattern like this.

for example are the half-lifes for the initial few doses lower, but increase with the number of doses, which is not reflected in this at all.

it's just a very basic model to clarify my point of view and as base for discussion. life is never as simple as just that.

this is definitely more broscience than science, but i'm 'fraid it's all i've got. however, you've got to start a discussion with something, don't you?

T.I.

 

[celc5]

TI, you really summed up the whole point of discussions like this in your last statement. I simply get frustrated when things are dosed "just like what everyone else does." :rant:

My grinding question is this: with your last serm 1/2 life chart, do they remain active in terms of estrogen control or in terms of hpta rejuvenation?

I think I'm asking the same question over and over regarding the hpta because I'm sold on the serms in terms of estrogen control. I'm basically sold on NOTHING in terms of hpta recovery. Maybe you can help unconfuse this jabroni :fool2:

I think we all appreciate the way you explain your logic. I think you and I are darn close in the way we approach post cycle

Btw, your posts are drawing me back to login to this forum more than I ever have before. If I haven't said it already, welcome to AM bro :cheers:

 

[Smiler51]

Fantastic posts guy with lots of valuable info.

I' kinda worried about the DNA adducts "Hepatic TAM-DNA adducts were formed even after 1 week of treatment with TAM with either dose."

The doeses are kinda high that were used on the rats but should nevertheless make us think twice about the dosing on the SERMs. Especially because of the long half-life, we get pretty high serum levels of them.

 

[LakeMountD]

Fantastic posts guy with lots of valuable info.

I' kinda worried about the DNA adducts "Hepatic TAM-DNA adducts were formed even after 1 week of treatment with TAM with either dose."

The doeses are kinda high that were used on the rats but should nevertheless make us think twice about the dosing on the SERMs. Especially because of the long half-life, we get pretty high serum levels of them.

Typically though to magnify the results they will use ridiculously high dosages so the results appear faster. Take it with a grain of salt!

 

[Interlocutor]

Typically though to magnify the results they will use ridiculously high dosages so the results appear faster. Take it with a grain of salt!

yeah. there is a study which shows that tamo caused liver cancer in about 100% of the rats used... at 20mg/kg

still, why then not simply use one of the 2nd generation types, if available? i'd rather spend 10$ more and have one worry less.

T.I.

 

[LakeMountD]

yeah. there is a study which shows that tamo caused liver cancer in about 100% of the rats used... at 20mg/kg

still, why then not simply use one of the 2nd generation types, if available? i'd rather spend 10$ more and have one worry less.

T.I.

Yeah, although the interesting part was, at those high dosages that Toremifene did not cause it in 100% of rats, which is very interesting indeed. I agree though, might as well get the safest one even if it is only a little better at this or that.