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Tamoxifen(Nolvadex)(Tamoxifen citrate) 30tabs/10mg(Sopharma Bulgaria)

Item 12707



Systematic (IUPAC) name

(Z)-2-[4-(1,2-diphenylbut-1-enyl)phenoxy]-N,N-dimethylethanamine

Clinical data

Trade names Nolvadex, Istubal, Valodex

AHFS/Drugs.com monograph MedlinePlus a682414

Pregnancy cat. B3 (Au) D (US)

Legal status POM (UK) -only (US)

Routes Oral Pharmacokinetic data

Metabolism Hepatic (CYP3A4, 2C9 and 2D6)

Half-life 5–7 days

Excretion Fecal Identifiers

CAS number 10540-29-1 

 ATC code L02BA01

PubChem CID 2733526

DrugBank APRD00123

ChemSpider 2015313 

 UNII 094ZI81Y45 

 KEGG D08559 

 ChEBI CHEBI:41774 

 ChEMBL CHEMBL83 

 Chemical data

 Formula C26H29NO 

Mol. mass 371.515 g/mol563.638 g/mol (citrate salt)

SMILES eMolecules & PubChem

InChI

InChI=1S/C26H29NO/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3/h5-18H,4,19-20H2,1-3H3/b26-25- 
Key:NKANXQFJJICGDU-QPLCGJKRSA-N

Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist. Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre-menopausal women, and is also a standard in post-menopausal women although aromatase inhibitors are also frequently used in that setting.[1]

Some breast cancer cells require estrogen to grow. Estrogen binds to and activates the estrogen receptor in these cells. Tamoxifen is metabolized into compounds that also bind to the estrogen receptor but do not activate it. Because of this competitive antagonism, tamoxifen acts like a key broken off in the lock that prevents any other key from being inserted, preventing estrogen from binding to its receptor. Hence breast cancer cell growth is blocked.

Tamoxifen was discovered by ICI Pharmaceuticals[2] (now AstraZeneca) and is sold under the trade names Nolvadex, Istubal, and Valodex. However, the drug, even before its patent expiration, was and still is widely referred to by its generic name "tamoxifen."

Breast cancer treatment

Tamoxifen is currently used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- and post-menopausal women.[3] Additionally, it is the most common hormone treatment for male breast cancer.[4] It is also approved by the FDA for the prevention of breast cancer in women at high risk of developing the disease.[5] It has been further approved for the reduction of contralateral (in the opposite breast) cancer.

Comparative studies

In 2006, the large STAR clinical study concluded that raloxifene is equally effective in reducing the incidence of breast cancer, but after an average 4-year follow-up there were 36% fewer uterine cancers and 29% fewer blood clots in women taking raloxifene than in women taking tamoxifen, although the difference is not statistically significant.[6][7][8]

In 2005, the ATAC trial showed that after average 68 months following a 5 year adjuvant treatment, the group that received anastrozole (Arimidex) had significantly better results than the tamoxifen group in measures like disease free survival, but no overall mortality benefit.[9] Data from the trial suggest that anastrozole should be the preferred medication for postmenopausal women with localized breast cancer that is estrogen receptor (ER) positive.[10] Another study found that the risk of recurrence was reduced 40% (with some risk of bone fracture) and that ER negative patients also benefited from switching to anastrozole.[11][12]

Other uses

Infertility

Tamoxifen is used to treat infertility in women with anovulatory disorders. A dose of 10–40 mg per day is administered in days 3–7 of a woman's cycle.[13] In addition, a rare condition occasionally treated with tamoxifen is retroperitoneal fibrosis.[14]

Gynecomastia

Tamoxifen is used to prevent estrogen related gynecomastia, resulting from elevated estrogenic levels. It is taken as a preventative measure in small doses, or used at the onset of any symptoms e.g. nipple soreness/sensitivity. Other drugs are taken for the similar purposeses such as clomiphene citrate and the anti-aromatase drugs which are used in order to try to avoid the hormone related adverse effects. Tamoxifen is also sometimes used to treat or prevent gynecomastia in sex offenders undergoing temporary chemical castration.[15]

Bipolar disorder

Tamoxifen has been shown to be effective in the treatment of mania in patients with bipolar disorder by blocking protein kinase C (PKC), an enzyme that regulates neuron activity in the brain. Researchers believe PKC is over-active during the mania in bipolar patients.[16][17]

Angiogenesis and cancer

Tamoxifen is one of three drugs in an anti-angiogenetic protocol developed by Dr. Judah Folkman, a researcher at Children's Hospital at Harvard Medical School in Boston. Folkman discovered in the 1970s that angiogenesis – the growth of new blood vessels – plays a significant role in the development of cancer. Since his discovery, an entirely new field of cancer research has developed. Clinical trials on angiogenesis inhibitors have been underway since 1992 using myriad different drugs. The Harvard researchers developed a specific protocol for a golden retriever named Navy who was cancer-free after receiving the prescribed cocktail of celecoxib, doxycycline, and tamoxifen – the treatment subsequently became known as the Navy Protocol.[18] Furthermore tamoxifen treatment alone has been shown to have anti-angiogenetic effects in animal models of cancer which appear to be, at least in part, independent of tamoxifen's estrogen receptor antagonist properties.[19]

Control of gene expression

Tamoxifen is used as a research tool to trigger tissue specific gene expression in many conditional expression constructs in genetically modified animals including a version of the Cre-Lox recombination technique.[20]

Riedel Thyroiditis

Tamoxifen has been proposed as part of a treatment plan.[21]

Mechanism of action

Crystallography of 4-hydroxytamoxifen (carbon = white, oxygen = red, nitrogen = blue) complexed with ligand binding domain of estrogen receptor alpha (cyan ribbon).[22]

Tamoxifen competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. It is a nonsteroidal agent with potent antiestrogenic properties which compete with estrogen for binding sites in breast and other tissues. Tamoxifen causes cells to remain in the G0 and G1 phases of the cell cycle. Because it prevents (pre)cancerous cells from dividing but does not cause cell death, tamoxifen is cytostatic rather than cytocidal.

Tamoxifen itself is a prodrug, having relatively little affinity for its target protein, the estrogen receptor. It is metabolized in the liver by the cytochrome P450 isoform CYP2D6 and CYP3A4 into active metabolites such as 4-hydroxytamoxifen (see Afimoxifene) and N-desmethyl-4-hydroxytamoxifen (endoxifen)[23] which have 30-100 times more affinity with the estrogen receptor than tamoxifen itself. These active metabolites compete with estrogen in the body for binding to the estrogen receptor. In breast tissue, 4-hydroxytamoxifen acts as an estrogen receptor antagonist so that transcription of estrogen-responsive genes is inhibited.[24]

Tamoxifen binds to estrogen receptor (ER) which in turn interacts with DNA. The ER/tamoxifen complex recruits other proteins known as co-repressors to stop genes being switched on by estrogen. Some of these proteins include NCoR and SMRT.[25] Tamoxifen function can be regulated by a number of different variables including growth factors.[26] Tamoxifen needs to block growth factor proteins such as ErbB2/HER2[27] because high levels of ErbB2 have been shown to occur in tamoxifen resistant cancers.[28] Tamoxifen seems to require a protein PAX2 for its full anticancer effect.[27][29] In the presence of high PAX2 expression, the tamoxifen/estrogen receptor complex is able to suppress the expression of the pro-proliferative ERBB2 protein. In contrast, when AIB-1 expression is higher than PAX2, tamoxifen/estrogen receptor complex upregulates the expression of ERBB2 resulting in stimulation of breast cancer growth.[27][30]

Side effects

A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.[31]

Bone

A beneficial side effect of tamoxifen is that it prevents bone loss by acting as an estrogen receptor agonist (i.e., mimicking the effects of estrogen) in this cell type. Therefore, by inhibiting osteoclasts, it prevents osteoporosis.[32][33] When tamoxifen was launched as a drug, it was thought that tamoxifen would act as an estrogen receptor antagonist in all tissue, including bone, and therefore it was feared that it would contribute to osteoporosis. It was therefore very surprising that the opposite effect was observed clinically. Hence tamoxifen's tissue selective action directly led to the formulation of the concept of selective estrogen receptor modulators (SERMs).[34] In contrast tamoxifen appears to be associated with bone loss in premenopausal women who continue to menstruate after adjuvant chemotherapy.[35]

Endometrial cancer

Tamoxifen is a selective estrogen receptor modulator.[36] Even though it is an antagonist in breast tissue it acts as partial agonist on the endometrium and has been linked to endometrial cancer in some women. Therefore endometrial changes, including cancer, are among tamoxifen's side effects.[37] With time, risk of endometrial cancer may be doubled to quadrupled, which is a reason tamoxifen is typically only used for 5 years.[38]

The American Cancer Society lists tamoxifen as a known carcinogen, stating that it increases the risk of some types of uterine cancer while lowering the risk of breast cancer recurrence.[39] The ACS states that its use should not be avoided in cases where the risk of breast cancer recurrence without the drug is higher than the risk of developing uterine cancer with the drug.

Cardiovascular and metabolic

Tamoxifen treatment of postmenopausal women is associated with beneficial effects on serum lipid profiles. However, long-term data from clinical trials have failed to demonstrate a cardioprotective effect.[40] For some women, tamoxifen can cause a rapid increase in triglyceride concentration in the blood.[citation needed] In addition there is an increased risk of thromboembolism especially during and immediately after major surgery or periods of immobility.[41] Tamoxifen is also a cause of fatty liver, otherwise known as steatorrhoeic hepatosis or steatosis hepatis.[42]

Central nervous system

Tamoxifen treated breast cancer patients show evidence of reduced cognition[43] and semantic memory scores.[44] However memory impairment in patients treated with tamoxifen was less severe compared with those treated with anastrozole (an aromatase inhibitor).[45]

A significant number of tamoxifen treated breast cancer patients experience a reduction of libido.[46][47]

Premature growth plate fusion

While tamoxifen has been shown to antagonize the actions of estrogen in tissues such as the breast, its effects in other tissues such as bones has not been documented fully. There have been studies done in mice showing tamoxifen mimic the effects of estrogen on bone metabolism and skeletal growth. Thus increasing the possibility of pre-mature bone fusion. This effect would be less of a concern in adults who have stopped growing.[48]

Pharmacogenetics and drug interactions

Patients with variant forms of the gene CYP2D6 (also called simply 2D6) may not receive full benefit from tamoxifen because of too slow metabolism of the tamoxifen prodrug into its active metabolite 4-hydroxytamoxifen.[49][50] On Oct 18, 2006 the Subcommittee for Clinical Pharmacology recommended relabeling tamoxifen to include information about this gene in the package insert.[51]

Certain CYP2D6 variations in breast cancer patients leads to a worse clinical outcome for tamoxifen treatment.[52] Genotyping therefore has the potential for identification of women who have these CYP2D6 phenotypes and for whom the use of tamoxifen is associated with poor outcomes.

Recent studies suggest that taking the selective serotonin reuptake inhibitors (SSRIs) antidepressants; paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft), can decrease the effectiveness of tamoxifen, as these drugs compete for the CYP2D6 enzyme which is needed to metabolize tamoxifen into the active form; endoxifen.[53] A U.S study presented at the American Society of Clinical Oncology's annual meeting in 2009 found that after two years, 7.5 percent of women who took only tamoxifen had a recurrence, compared with 16 percent who took either paroxetine, fluoxetine or sertraline; drugs considered to be the most potent CYP2D6 inhibitors. That difference translates to a 120 percent increase in the risk of breast cancer recurrence. Patients taking the SSRIs; Celexa (citalopram), Lexapro (escitalopram), and Luvox (fluvoxamine), did not have an increased risk of recurrence, due to their lack of competitive metabolism for the CYP2D6 enzyme.[54] A newer study demonstrated a clearer and stronger effect from paroxetine in causing the worst outcomes. Patients treated with both paroxetine and tamoxifen have a 67% increased risk of death from breast cancer, from 24% to 91%, depending on the duration of coadministration.[55]

Recent research has shown that 7-10% of women with breast cancer may not receive the full medical benefit from taking tamoxifen due to their unique genetic make-up. DNA Drug Safety Testing can examine DNA variations in the CYP2D6 and other important drug processing pathways. More than 20% of all clinically used medications are metabolized by CYP2D6 and knowing the CYP2D6 status of a person can help the doctor with the future selection of medications.[56] Other molecular biomarkers may also be used to select appropriate patients likely to benefit from tamoxifen.[57]

Market

Global sales of tamoxifen in 2001 were $1,024 million.[58] Since the expiration of the patent in 2002, it is now widely available as a generic drug around the world. Barr Labs Inc had challenged the patent (which in 1992 was ruled unenforcable) but later came to an agreement with Zeneca to licence the patent and sell tamoxifen at close to Zeneca's price.[59] As of 2004, tamoxifen was the world's largest selling hormonal drug for the treatment of breast cancer.[60]

In the US, 20 mg tamoxifen tablets cost under $20 per month in quantity.[61] In the UK, the NHS pays £1.90 a month (patients receive them either free or for the standard prescription charge of £7.10 in England, £4 in Scotland,[62] £3 in Northern Ireland[63] and free in Wales). In Estonia tamoxifen costs less than $2 for 30 tablets of 20 mg when used for treatment of a neoplasm or lymphangioma.[64] Other countries report similar prices.[citation needed]

Discovery

In the late 1950s, pharmaceutical companies were actively researching a newly discovered class of anti-estrogen compounds in the hope of developing a morning-after contraceptive pill. Arthur L Walpole was a reproductive endocrinologist who led such a team at the Alderley Park research laboratories of ICI Pharmaceuticals. It was there in 1966 that Dora Richardson first synthesised tamoxifen, known then as ICI-46,474.[65] Walpole and his colleagues filed a UK patent covering this compound in 1962, but patent protection on this compound was repeatedly denied in the US until the 1980s.[66] Tamoxifen did eventually receive marketing approval as a fertility treatment, but the class of compounds never proved useful in human contraception. A link between estrogen and breast cancer had been known for many years, but cancer treatments were not a corporate priority at the time, and Walpole's personal interests were important in keeping support for the compound alive in the face of this and the lack of patent protection.[2]

The first clinical study took place at the Christie Hospital in 1971, and showed a convincing effect in advanced breast cancer,[67] but nevertheless ICI's development programme came close to termination when it was reviewed in 1972. Tamoxifen's further development may have been bolstered by a second clinical study by Harold W.C. Ward [68] at the Queen Elizabeth Hospital, Birmingham. Ward's study showed a more definitive response to the drug at a higher dosage. It appears to have been Walpole again who convinced the company to market tamoxifen for late stage breast cancer in 1973.[66] He was also instrumental in funding V. Craig Jordan to work on tamoxifen. Approval in the US followed in 1977, but the drug was competing against other hormonal agents in a relatively small marketplace and was not at this stage either clinically or financially remarkable.

1980 saw the publication of the first trial to show that tamoxifen given in addition to chemotherapy improved survival for patients with early breast cancer.[69] In advanced disease, tamoxifen is now only recognised as effective in estrogen receptor positive (ER+) patients, but the early trials did not select ER+ patients, and by the mid 1980s the clinical trial picture was not showing a major advantage for tamoxifen.[70] Nevertheless, tamoxifen had a relatively mild side-effect profile, and a number of large trials continued. It was not until 1998 that the meta-analysis of the Oxford based Early Breast Cancer Trialists' Collaborative Group showed definitively that tamoxifen saved lives in early breast cancer.[71]

See also

  • Afimoxifene, a skin gel of an active metabolite of tamoxifen

References

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48.   ^ Karimian E, Chagin AS, Gjerde J, Heino T, Lien EA, Ohlsson C, Sävendahl L (August 2008). "Tamoxifen impairs both longitudinal and cortical bone growth in young male rats". J. Bone Miner. Res. 23 (8): 1267–77. doi:10.1359/jbmr.080319. PMID 18348701.

49.   ^ Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Flockhart DA, Desta Z, Perez EA, Ingle JN (2005). "Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes". J Clin Oncol 23 (36): 9312–8. doi:10.1200/JCO.2005.03.3266. PMID 16361630.

50.   ^ Beverage JN, Sissung TM, Sion AM, Danesi R, Figg WD (2007). "CYP2D6 polymorphisms and the impact on tamoxifen therapy". J Pharm Sci 96 (9): Epub ahead of print. doi:10.1002/jps.20892. PMID 17518364.

51.   ^ Information about CYP2D6 and tamoxifen from DNADirect's website

52.   ^ Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Boländer J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H (October 2009). "Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen". JAMA 302 (13): 1429–36. doi:10.1001/jama.2009.1420. PMID 19809024.

53.   ^ Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA (2005). "CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment". J Natl Cancer Inst 97 (1): 30–9. doi:10.1093/jnci/dji005. PMID 15632378.

54.   ^ Staff Reports (Summer, 2009). "ASCO Updates: Antidepressants Reduce the Effectiveness of Tamoxifen.". CURE (Cancer Updates, Research and Education).

55.   ^ BMJ 2010;340:c693

56.   ^ Information about Tamoxitest and how DNA testing can help in the selection of the best treatment methodology from Genelex's website

57.   ^ Criscitiello C, Fumagalli D, Saini KS, Loi S (2011). "Tamoxifen in early-stage estrogen receptor-positive breast cancer: overview of clinical use and molecular biomarkers for patient selection". Onco Targets Ther 4: 1–11. doi:10.2147/OTT.S10155. PMC 3084302. PMID 21552410.

58.   ^ "Cancer the generic impact". BioPortfolio Limited. Archived from the original on 2008-05-16. Retrieved 2008-11-14.

59.   ^ "Tamoxifen". Lawsuits & Settlements. Prescription Access Litigation. Retrieved 2008-11-14.

60.   ^ Vose B. "AstraZenecain Cancer: Slide #15:". AstraZeneca Annual Business Review. www.astrazeneca.com. Retrieved 2009-03-28. "2004 tamoxifen market share: 70% Source: IMS HEALTH, IMS MIDAS Monthly. July 2004. Aromatase Inhibitors + Tamoxifen"

61.   ^ Drugstore.com accessed on 21 August 2009

62.   ^ http://www.scotland.gov.uk/News/Releases/2007/12/05141211

63.   ^ http://www.northernireland.gov.uk/news/news-dhssps/news-dhssps-december-2008/news-dhssps-301208-prescription-charges-reduced.htm

64.   ^ http://www.raviminfo.ee/apthkiri.php?apteek=?&regioon=01&atc=L02BA01

65.   ^ Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 472 pages. ISBN 0-471-89979-8.

66.   ^ a b Jordan VC (2003). "Tamoxifen: a most unlikely pioneering medicine". Nature reviews. Drug discovery 2 (3): 205–13. doi:10.1038/nrd1031. PMID 12612646.

67.   ^ Cole MP, Jones CT, Todd ID (1971). "A new anti-estrogenic agent in late breast cancer. An early clinical appraisal of ICI46474". Br. J. Cancer 25 (2): 270–5. doi:10.1038/bjc.1971.33. PMC 2008453. PMID 5115829.

68.   ^ Ward HW (January 1973). "Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels". Br Med J 1 (5844): 13–4. doi:10.1136/bmj.1.5844.13. PMC 1588574. PMID 4567104.

69.   ^ Baum M, Brinkley DM, Dossett JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Lea JC, Richards D, Ellis SH (1983). "Improved survival among patients treated with adjuvant tamoxifen after mastectomy for early breast cancer". Lancet 2 (8347): 450. doi:10.1016/S0140-6736(83)90406-3. PMID 6135926.

70.   ^ Furr BJ, Jordan VC (1984). "The pharmacology and clinical uses of tamoxifen". Pharmacol. Ther. 25 (2): 127–205. doi:10.1016/0163-7258(84)90043-3. PMID 6438654.

71.   ^ Early Breast Cancer Trialists' Collaborative Group (1998). "Tamoxifen for early breast cancer: an overview of the randomised trials". Lancet 351 (9114): 1451–67. doi:10.1016/S0140-6736(97)11423-4. PMID 9605801.

 

Tamoxifen Citrate

 

Nolvadex and Gynocomastia

This drug is used as a first line defense against breast cancer. In the late 80s, Dan Duchaine speculated that it could also be used by bodybuilders to halt the development of another type of tumor in the mammary gland, Gynocomastia. He introduced this find to the Steroid-using-community in his "Contest Prep" issue of the UnderGround Steroid Handbook Update Newsletters (the contest prep-issue was actually 3 issues in one, for those who had a subscription to the newsletter).

 

Nolvadex is commonly referred to in quite a few ways: as a SERM (Selective Estrogen Receptor Modulator), as an anti-estrogen (that is actually incorrect, as we will later see), and finally as a triphenylethylene. I happen to stick with calling Nolvadex a SERM, because out of my three options, it happens to be correct (as we know that calling it an anti-estrogen is incorrect), and pronouncable (as we know that I have no idea how to say "triphenylethylene"). Selective estrogen receptor modulators (SERMs) act as either estrogen receptor agonists or antagonists in a tissue-selective manner, lets see what that means to us&

Nolvadex actually has quite a few applications for the steroid using athlete. First and foremost, its most common use is for the prevention of gynocomastia. Nolvadex does this by actually competing for the receptor site in breast tissue, and binding to it. Thus, we can safely say that the effect of tamoxifen is through estrogen receptor blockade of breast tissue (1), especially since total body estradiol increases with use of tamoxifen. Clearly, if you are on a cycle which includes steroids which convert to estrogen, you may want to consider nolvadex as a good choice to run along side them.

Nolvadex Cycle

Nolvadex, however, is not the most potent ancillary compound we can use on a cycle, but it is probably the safest considering it doesnt actually reduce estrogen in your body keeping some estrogen floating around could have many benefits on muscle growth, as well. Estrogen is also important for a properly functioning immune system, and not only that, but your lipid profile (both HDL and LDL) should also show marked improvement with administration of tamoxifen (4). Many bodybuilders actually use this stuff during their cycle for the health benefits provided by it. If, however, you are preparing for a bodybuilding contest, you need to use something which will suck most (if not all) of the estrogen out of your body. I am speculating that you may be able to use Nolvadex for the majority of a contest prep cycle, to keep yourself relatively healthy, and then switch over to Letrozole for the last 8 weeks.

Nolvadex also has some important features for the steroid using athlete. In hypogonadic and infertile men given nolvadex, increases in the serum levels of LH, FSH, and most importantly, testosterone were all observed (2)(3). The best (rough) estimate I can give you from my research is that 20mgs of Nolvadex will raise your testosterone levels about 150% (5)...and this would of course greatly aid post-cycle-recovery. What this means to us is that if you take Nolvadex after a cycle, when you are trying to raise your levels of testosterone, LH, and FSH back to normal, it will greatly aid recovery. In fact, if I were limited to just one compound to aid me in post-cycle-recovery, Nolvadex would be my choice. If you want a comparison, it would require 150mgs of Clomid to accomplish that type of elevation in testosterone, but nolvadex also significantly increased the LH (Leutenizing Hormone) response to LHRL (5), after 6 weeks.

Some of the more harsh ancillary compounds available today will give you a more "dry" look that nolvadex cant, but nolvadex is simply safer to use in long (over 16 week) cycles.

Nolvadex Side Effects

Unfortunately, Nolvadex isnt perfect. Anecdotally, it has been linked to reduced gains in some bodybuilders. This isnt due, as previously thought, to its reducing estrogen levels (which it doesnt), but rather to its ability to possibly reduce IGF (Insulin-like-Growth-Factor) levels, which are important for muscle growth.

To Buy Nolvadex Online

Personally, Ive had many successful cycles with nolvadex as well as without, but I can certainly testify to its effectiveness in preventing gynocomastia. Back in the late 90s I purchased 30 tabs of 10mg Nolvadex for $30, and recently I have found it for much less on various internet sites. Its well worth the money.

References:

 

  1. Klin Padiatr. 1987 Nov-Dec;199(6):389-91.
  2. Stimulation of calcitonin secretory capacity by increased serum levels of testosterone in men treated with tamoxifen. Int J Androl. 1987 Dec;10(6):747-51.
  3. Hormonal changes in tamoxifen treated men with idiopathic oligozoospermia Exp Clin Endocrinol. 1988 Dec;92(2):211-6.
  4. 2 Bruning PF, Bronfer JMG, Hart AAM, Jong-Bakker M, tamoxifen, serum lipoproteins and cardiovascular risk, Br. J. Cancer 1988 Oct, 58 (4) 497-9
  5. Fertil Steril. 1978 Mar;29(3):320-7.

Nolvadex and Clomid

 

Nolvadex and Clomid are two of the most popular Selective Estrogen Receptor Modulators (SERMs) in the world and part of the supplemental plan for many performance enhancing athletes. In many ways Nolvadex and Clomid are identical; in-fact, the same results can be obtained with either form assuming dosing is applied to match depending on the one you use. Without question the most common use of Nolvadex and Clomid is during what is known as Post Cycle Therapy (PCT) the period of time in-which an anabolic steroid cycle comes to an end and the recovery process begins. While the PCT period is a common points of use for these very effective SERMs some will also supplement during the actual anabolic steroid cycle itself in-order to combat possible side-effects such as Gynecomastia. Nolvadex and Clomid are both useful for on cycle Gynecomastia prevention but they will not equal the power of other options and are typically best served in a PCT role.

 

The Power of Nolvadex and Clomid:

For years many have argued that Nolvadex is the better SERM and far more effective than Clomid but this is a bit of an inaccurate statement. It is true, on a milligram for milligram basis Nolva, as it is commonly known is stronger than Clomid; 1mg of Nolvadex carries more potency than 1mg of Clomid. With that in mind if we equal the dosing, meaning, we increase the dosing of Clomid to match the potency of Nolva on a per milligram basis we largely have the same effect, the same results; those who typically do not like Clomid, especially during PCT usually are simply not taking enough.

Nolvadex and Clomid for PCT:

The purpose of PCT is simple and twofold; to stimulate natural testosterone production that has been suppressed due to the use of anabolic steroids and to simply normalize the body in-order to remain healthy. Of course, most are also concerned with hanging onto the gains they made from their performance cycle but effectively achieving the two previously mentioned factors will promote just that and in a positive fashion.

Nolvadex and Clomid are both fine choices for your PCT purpose; truly you only need one or the other. Both SERMs have the ability to greatly stimulate the release of the Luteinizing Hormone (LH) thereby promoting the production of testosterone. As you understand testosterone is produced in the testicles and such production occurs due to the release of LH by the pituitary gland. When the pituitary releases LH this signals the testicles to begin producing testosterone; without LH there is no production and without production there is no testosterone.

On Cycle Use:

As SERMs Nolvadex and Clomid have the ability to combat certain anabolic steroid related side-effects, most notably Gynecomastia. Such side-effects occur due to the buildup of estrogen in the body; many anabolic steroids convert into estrogen due to their aromatizing nature and this can cause unwanted side-effects. Make no mistake, estrogen is a very important hormone but like many things in life we can have too much of it. A common assumption many make is that Nolvadex and Clomid reduce estrogen in the body and this is simply not true as they do not carry this ability. SERMs such as these act in a very specific manner and simply prevent the estrogen from binding to the receptors where they can cause a problem. While this binding effect can be useful in many cases it will not be enough and stronger measures must be taken. For this reason many choose to supplement with aromatase inhibitors (AIs) as AIs have the ability to inhibit the conversion of estrogen while also decreasing the amount of estrogen in the body.

The Bottom Line:

In the end the truth is simple, Nolvadex and Clomid are both fine SERMs and for PCT you cannot go wrong with either one. As for side-effect prevention they can do a fair job at preventing Gynecomastia but they will generally do little else and are in many cases ill-equipped to handle even Gynecomastia; AIs are simply more efficient. If you are considering using Nolvadex and Clomid you will be best served saving it for your PCT plan and regardless of which one you go with if you have the ability to include hCG you will experience a very positive PCT plan.

Nolvadex Dosage

 

The average Nolvadex dosage can vary quite dramatically depending the purpose of use as well as whos using it. In most cases the compound comprised of Tamoxifen Citrate will be used for on cycle side-effect prevention, Post Cycle Therapy (PCT) and by females for a testosterone boosting effect or as part of a physique competition preparation. In any case the average Nolvadex dosage will range from 10mg to 40mg and in most cases never exceed this mark. In order to determine the right Nolvadex dosage for you we only need to examine the three common points of use.

 

Female Nolvadex Dosage:

Tamoxifen Citrate can be an excellent performance enhancing tool for the female athlete as it has the ability to increase testosterone production as well as bind estrogen. Many female athletes will opt for this testosterone boosting effect instead of anabolic steroids due to the possibility of virilization that many of them can bring about. More commonly is however the use by females in the physique sports competitions; not only bodybuilding but figure and bikini as well. Such use can promote a leaner and tighter looking physique and often be the difference in how well the athlete places. For most women the most common Nolvadex dosage will be at 10mg per day with very few ever exceeding 20mg per day and most will never need this much.

On Cycle Nolvadex Dosage:

For decades many performance enhancing athletes have supplemented with Tamoxifen Citrate while on cycle in order to protect against Gynecomastia (male breast enlargement.) The manner in-which it works is simple; Gyno as it is commonly known is brought on by an increase of estrogen in the body; this increase is caused by anabolic steroids that aromatize. As the excess estrogen exists it may then bind to the receptors in the chest causing Gyno. Fortunately a good 10mg Nolvadex dosage can often protect against this onset action. As estrogen buildup occurs Tamoxifen Citrate binds in the estrogens place preventing it from binding and causing Gyno. While 10mg will work many men will need a Nolvadex dosage of 20mg every day and when enough aromatizing steroids are taken there is no amount of Nolvadex on earth that will prevent it. If you are sensitive to Gynecomastia due to high doses or simply being sensitive by nature you will need to seek out aromatase inhibitors as they will be all that protects you.

Post Cycle Nolvadex Dosage:

PCT has been and will always be the most common period of Tamoxifen Citrate use and as such more will be interested in the correct Nolvadex dosage for this period beyond any other. The purpose of use during PCT is simple; to stimulate natural testosterone production that has been suppressed due to anabolic steroid use and more than likely tremendously so. For most men daily therapy will begin at 40mg per day, eventually dropping to 20mg per day until use is discontinued. The average man will need at least 4 weeks of total therapy with many men needing 6 total weeks if their steroid cycle was long and suppressive in nature. However long your PCT plan is a Nolvadex dosage of 40mg per day for the first half of the plan followed by a 20mg every day the final weeks will suffice.

Nolvadex PCT

 

Tamoxifen Citrate, most common known as Nolvadex is one of the most popular SERM’s any performance enhancer will ever use and as such Nolvadex PCT use remains the most common purpose. Post Cycle Therapy (PCT) is a very important part of the anabolic steroid plan as this is the period after use is discontinued that allows the body to normalize; an important factor in maintaining good health as well as protecting gains made while on cycle. A plan based on a Nolvadex PCT can readily and efficiently produce the desired end very thoroughly and make ones experience not only more enjoyable but more effective as well.

 

The Basic Nolvadex PCT Plan:

In most cases a good Nolvadex PCT plan will run for approximately 4 weeks; in some cases 5-6 weeks may be needed but 4 weeks is a good general rule of thumb. Most will find a dosing of 40mg per day to be an efficient starting point with a tapering down as the week’s progress and then discontinuing altogether. The basic Nolvadex PCT plan should be as follows:

Week
 1: 40mg every day Week
2: 40mg every day Week
3: 20mg every day Week
4: 20mg every day

In some cases, generally referring to those who have cycled for a far extended period of time with high doses an additional week of 40mg per day may be warranted as well as an added week of 20mg per day. In either case this will provide the adequate stimulation of testosterone production the individual needs as Tamoxifen Citrate actively by its nature stimulates and promotes the release of the Luteinizing Hormone (LH) thereby stimulating natural testosterone production.

Super-Sized Nolvadex PCT Plan:

While this will not be necessary for many PCT plans for quite a few it can be highly advised. Cycles that extend into the 12 week duration and beyond are often benefited by the following plan, especially those that include very suppressive anabolic steroids. For this super-sized version we are simply adding Human Chorionic Gonadotropin (hCG) into the equation thereby promoting a more efficient recovery. With this plan the same Nolvadex PCT plan listed above will be used, the only change will be the introduction of hCG ten days prior to Nolvadex therapy. A steady daily dose of hCG at 1,000iu per day is often a very effective dosing when applied every day for ten days before the Nolvadex PCT portion of the plan is implemented.

When to Start your Nolvadex PCT Plan:

The starting point of your Nolvadex PCT plan will be determined by the anabolic steroids being used at the conclusion of your anabolic steroid cycle. If the cycle ends with short ester based anabolic steroids the PCT plan can begin a few days after your last injection; conversely if it ends with long ester based steroids you will need to wait a 2-3 weeks before Nolvadex PCT therapy begins. If the cycle ends with a mixture of both short and long ester based steroids, due to the long esters being present we will still necessarily wait until the 2-3 week mark has passed before beginning therapy.

It needs to be noted, while the above remains true if we are using the super-sized Nolvadex PCT plan things change a little bit. In this case if short ester anabolic steroids are what was used at the end of the cycle the plan remains the same; we will start our PCT with hCG a few days after our last injection, complete our ten day hCG run and then begin Nolvadex therapy once it is complete. If however our cycle ended with long ester gear and we are following the super-sized Nolvadex PCT plan we can begin our hCG therapy about ten days after our last injection, complete the ten days of hCG use followed by our Nolvadex therapy.

Nolvadex Post Cycle

 

While it has a place during anabolic steroid use Nolvadex post cycle use is not only the most common point of use but the most effective as well. A good Nolvadex post cycle plan can often be the difference in maintaining the gains made while on cycle and losing them and not to mention it provides a benefit to our overall health often negated in discussion. As you should understand testosterone is not only a powerful hormone but a very important one at that; in-fact, of all the hormones the body produces testosterone is one of the most important as it affects so many aspects of our physical, mental and sexual functions. When we supplement with anabolic androgenic steroids our natural testosterone production is suppressed and for this reason it is generally advised that most anabolic steroid cycles include some form of exogenous testosterone therapy. Once use is discontinued this is the point where we must stimulate our natural testosterone to come back online and a good Nolvadex post cycle therapy plan can provide just that and in a very efficient manner.

 

Nolvadex Post Cycle Doses:

For a good Nolvadex post cycle plan very few will ever need more than 40mg per day and most will find that ending with a lower dose of 20mg per day to be just about perfect. For the healthy adult male a good Nolvadex post cycle plan will run for approximately 4-6 weeks in total duration; 4 weeks should be the standard with 1-2 additional weeks being added if necessary. In most cases the additional weeks will only be needed if the anabolic steroid cycle was strong, was extended and of a high suppressive nature. A solid Nolvadex post cycle plan for most any man to follow would look something like this:

Basic Plan:
Week 1: 40mg every day
Week 2: 40mg every day
Week 3: 20mg every day
Week 4: 20mg every day

Extended Plan:
Week 1: 40mg every day
Week 2: 40mg every day
Week 3: 40mg every day
Week 4: 20mg every day
Week 5: 20mg every day
Week 6: 20mg every day

hCG & Nolvadex Post Cycle Plans:

Many performance enhancers often experience a higher rate of recovery with the addition of Human Chorionic Gonadotropin (hCG) alongside their Nolvadex post cycle plan. Such an addition is not always necessary but it can be quite beneficial and most any anabolic steroid cycle that extends 16 weeks or more, that is comprised of very suppressive steroids or a combination of both will warrant solid hCG therapy. For those who follow an hCG and Nolvadex post cycle plan the hCG will be used first; a good plan will consist of ten days of hCG use prior to Nolvadex therapy and will generally fall in the range of 1,000iu per day every day for ten days; Nolvadex therapy beginning the day after the last hCG administration.

Implementing Nolvadex Post Cycle Therapy:

We do not simply and arbitrarily end our cycle of anabolic steroids and start our post cycle recovery; you must have an understanding of the steroids you were using in order to determine timing and this is very important. If you begin your Nolvadex post cycle plan too soon and you still have a lot of suppressive anabolic steroids in your system the whole recovery process will be a waste.

If your cycle ends with short ester anabolic steroids you may start your recovery process 2-3 days after your last injection; whether you are going to include hCG or not you will still start 2-3 days after the anabolic steroid cycle ends. If however your cycle ends with any long ester based steroids things will change; in this instance if you are going to include hCG into your Nolvadex post cycle plan you will begin hCG use ten days after your last steroidal injection; if your cycle ended with very long ester gear such as Deca-Durabolin it might be wise to wait a full two weeks. If your cycle ends with long ester steroids and you are not including hCG you will need to wait 2 weeks before Nolvadex post cycle therapy begins with 3 weeks being optimal if steroids such as Deca-Durabolin were being used at the end of the cycle.



PROTECTION

 

  
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