SERM use good or bad??? GREAT READ! NOLVA USERS MUST SEE!
- 04-18-2009, 02:13 AM
SERM use good or bad??? GREAT READ! NOLVA USERS MUST SEE!
Found this on primordial performance site today. Not sure my stance on the article but definitely makes you think! Like it or not, yes, Serms are great for PCT and do get the job done but they do have serious side effects too and the references made in this article are all very reputable. Good to read some non-broscience every now and then Hope this wasnt posted previously!
Clomid & Nolvadex - The Dark Side
By Eric M. Potratz (Email)
Eric M. Potratz has developed his education in the field of endocrinology and performance enhancement through years of research, counseling, and real world experience. Over the past five years he has been a private consultant for hundreds of athletes and bodybuilders alike, and is the founder & president of Primordial Performance.
Preface - Over the past 15 years, the use of Clomid and Nolvadex, as Selective Estrogen Receptor Modulators (SERMs) has become a staple in the HRT and bodybuilding communities.
The popularity of these drugs stems from the popular advice to use these drugs for everything from testosterone recovery, bloat reduction, to gyno prevention. In many communities SERMs have become akin to vitamins -- vitamins that can do no wrong and provide seemingly endless benefits.
This article is not intended to examine the proper use or possible applications of Clomid or Nolvadex. Instead, we will be exploring the historical development of these drugs, the short-term side-effects and long-term consequences.
As I will illustrate, these drugs are true danger to men’s health.
Synthetic estrogens, the beginning -
It was the 1930’s and there was a new age of hormone-dependant pathologies on the rise. Scientists were eager to determine the structural requirements of estrogen for new drug design.
In 1937 Sir Charles Dodd of the Middlesex Hospital of London found estrogenic activity in a molecule with two benzene rings linked together via a short carbon chain (eg, diphenylethane). (1) Soon thereafter, a synthetic, non-steroidal estrogen known as diethylstilboestrol (DES) was created from this basic molecular backbone. (1) By 1941, DES was an FDA approved drug, and by the 1950’s, DES gained widespread popularity as the drug of choice for menopausal symptoms, cancer treatment, and prevention of miscarriages. (2)
DES sparked the interest of ambitious drug manufactures that saw this synthetic molecule as a potential “molecular backbone” which could be tailored for estrogenic activity, and patented for maximum profit.
Within months, a research group from the University of Edinburgh found that the addition of a benzene ring to the original diphenylethane structure created an somewhat of an anti-estrogen known as triphenylethylene. (1) Although it had very weak estrogenic activity, it was called an anti-estrogen because it competed with the body’s more powerful estradiol for the ER receptors.
Although the complex estrogenic action of triphenylethylene was not fully understood, it was considered the perfect molecular platform for future drug development because of its high oral bioavailability and extended half-life due to its lipophilicity (fat solubility). As it was later discovered, the estrogenic action could be manipulated with structural modifications for more specific agonist/antagonist actions. (3) Despite the lack of understanding for its full physiological effects, triphenylethylene would become the molecular backbone for generations of SERM’s to come.
By the early 1940’s, the world’s largest chemical manufacturers, including Imperial Chemical Industries (ICI), got word of the triphenylethylene development, and seized the opportunity to expand this new class of compounds. By the 1950’s, the synthesis of new triphenylethylene based molecules had began picking up momentum, as the first FDA approved SERM’s started appearing on the market.
One of the first was Triparanol, which was sold as a cholesterol lowering SERM, until it was eventually pulled from the market in the 1950’s for causing cataracts in patients. (7) Later, Ethamoxytriphetol (MER-25) was discovered and found to be a reliable contraceptive and anti-cancer agent in rats, but failed in humans due to the drug’s severe toxicity and stimulation of “acute psychotic episodes”. (6)
Despite these early warning signs, development continued.
Among one of the newer SERM’s to appear in the late 1950’s, was a mixture of two stereoisomers -- zuclomiphene and enclomiphene -- both having unique estrogenic and anti-estrogen actions. This mixture was collectively called clomiphene, and later marketed as Clomid.
Then, in 1962, ICI synthesized ICI-46474, another mixture of a trans and cis isomers with mixed estrogenic and anti-estrogenic activity. (7) Ultimately, the trans isomer was found to be the predominate anti-estrogen, which was isolated and eventually named tamoxifen, and later marketed as Nolvadex.
Originally, ICI pushed these new SERM’s to market as a “morning after” contraceptives, which were eventually approved by the FDA. (4) Yet again, the profit hungry and presumptuous drug manufacturer based its findings on rat studies, which would prove to be a mistake upon subsequent human research that showed the SERM’s induced, rather than inhibited ovulation. (4) Needless to say, tamoxifien was withdrawn as a contraceptive.
And remember DES, the original synthetic estrogen developed back in the 1930’s? As it turned out, DES was found to increase the risk of breast cancer by 50%. Further research linked DES to millions of vaginal and testicular cancers among the children of mothers who took DES during pregnancy. (2,5)
The light on synthetic anti-estrogens was dim, and by the late 1960’s, there was little enthusiasm to continue R&D with triphenylethylene based SERM’s, especially considering their inherently toxic effects (7, 10)
It wasn’t until 1971, that tamoxifen would be dug up from the dead and considered as a candidate for cancer treatment.
Treating cancer with a carcinogen –
When research is done on anti-cancer drugs (such as SERMs), the aim is to find a drug that prolongs life, with the least amount of acute side-effects. In other words, the goal isn’t so much about finding a cure, as it is finding something that can alleviate the symptoms and/or prolong life.
For an estrogen dependant cancer, the idea was simple – Block the proliferative action of estrogen with an anti-estrogen and slow the cancer growth. What could be more appropriate than an already available, orally active, patentable synthetic estrogen such as tamoxifen? It was a practical shoo-in.
Therefore, in 1971, when drug researchers decided to examine all of the historical anti-cancer SERM data, they found that all of the SERM’s showed anti-proliferative activity on estrogen dependant cancer, and all of them demonstrated some extent of toxicity. (10, 37-39) However, the SERM that happened to show the least amount of toxicity was tamoxifen. (clomiphene missed the mark by showing a high rate of cataract formation)
At the time, Pierre Blais, a well known drug researcher, commented on the finding (5) -
“Tamoxifen is a garbage drug that made it to the top of the scrap heap. It is a DES in the making."
In spite of the criticism from a number of researchers, the FDA approved tamoxifen as a cancer treatment in 1977, and in 1985 ICI was awarded a US patent for tamoxifen in the treatment of breast cancer. (5) Soon, tamoxifen would become the most popularity prescribed cancer drug.
“Its FDA approved for cancer treatment. It must be safe!”
It’s wrong to assume that an “FDA approved” drug has a proven safety profile. The FDA has continually issued stronger health warnings for tamoxifen over the years. For instance, in 1994 the FDA demanded that the tamoxifen manufacturer Zeneca (an ICI sub-division), issue warning letters to health care practitioners about the increased risk of endometrial and gastro-intestinal cancers with tamoxifen use. Zeneca also reported adverse effects similar to those seen with DES, such as reproductive abnormalities in the animals whose mothers received tamoxifen. (remember, DES was the original synthetic estrogen, and also an analog to tamoxifen)
A number of cancer researchers have pointed out the health risks too, such as Elwood et al (6) -
“[Tamoxifen], therefore, is not appropriate for use in the general population because of the known increased risk of endometrial cancer”
“So why is tamoxifen the most popularly prescribed cancer drug, if it’s so toxic?”
The answer is simple. Tamoxifen is the lesser of two evils.
Tamoxifen remains the most popularly prescribed drug because it is one of the few drugs that has shown a “statistically significant” improvement of the survival rate of breast cancer patients.* (Not to mention, tremendous financial motives and intraworking’s from its patent holder Zeneca)
Remember, the goal in cancer treatment is to prolong life -- even if it means committing to therapy that is potentially cancerous or injurious to future health (as confirmed in long-term follow up’s and close examinations of tamoxifen patients).
So, perhaps the risks are worthy for the cancer patient, but are they worthy for the health conscious male?
* Most research has shown tamoxifen to improve the survival rate by 4-14%. For instance, over a 5 year period, 74% of the women survived who used tamoxifen, compared to 70% of the women on placebo. Depending on the type of cancer, this may translate into an extra 2-3 years of life for a cancer patient. (9) Continuing tamoxifen therapy for more than 5 years, results in increased tumor recurrences and serious side effects. (8)
Translating the science, for men’s health -
Fast forward 30 years, through hundreds of human and animal trials and we find that the research is quite extensive, and contradicting. (21)
The damaging evidence from many early rat studies showed severely toxic effects, including the development of cancer in the liver, uterus, or testes upon tamoxifen administration. (30-34,41) However, this evidence was largely disregarded by further test tube studies on human cell-lines which appeared to show a lack of toxic effects. (21)
This misleading test tube data gave the green flag to perform large scale human studies with tamoxifen in the 80’s and 90’s. Even more misleading, was the majority of the human research described tamoxifen as having a “low incidence of troublesome side effects” and that the “side effects where usually trivial”. (22)
As science would uncover, the lack of human toxicity reported in original tamoxifen research was a result of insufficient study duration, inability to detect low level DNA damage with insensitive methodologies, and/or misdiagnosis of collateral cancers as metastasis infections from the breast cancer itself. (15, 21, 28-34)
A word on clomiphene (Clomid) –
Clomiphene (Clomid) consists of two stereoisomers which possess radically different pharmacodynamics. Zuclomiphene has predominantly estrogenic effects and slow clearance while the enclomiphene isomer has predominately anti-estrogenic effects and quick clearance. (9) This creates a dichotomy between estrogen blockage and estrogen stimulation and an acute imbalance once Clomid administration is discontinued. Bodybuilders will often complain of “estrogenic rebound” after stopping Clomid, which could be attributed to the lingering estrogenic isomer zuclomiphene as the anti-estrogenic enclomiphene has long cleared the system. (Recently, enclomiphene has been isolated by the pharmaceutical company Repros, for use in Androxal™.)
For all intents and purposes, tamoxifen is a superior SERM, simply for the fact that tamoxifen provides a purely anti-estrogenic isomer, whereas Clomid provides a mix of anti and pro estrogenic effects.
In regards to the health consequences about to be listed, it can be safely assumed that Clomid will share similar detrimental effects as tamoxifen, since it shares the same triphenylethylene backbone and carcinogenic tendencies. (44,45,57,58)
Liver cancer -
Originally, tamoxifen was accepted as being non-toxic to human liver upon finding that tamoxifen did not cause noticeable liver damage (DNA adducts) during short-term test tube studies with human liver cells. (35,36)
However, it became apparent that test tuberesearch was largely flawed due to the low rate of metabolism in such a superficial environment. (21) It was soon discovered that the hepatotoxic effects from tamoxifen are from the metabolism and buildup of the a-hydroxytamoxifen and N-desmethyltamoxifen metabolites, which would only appear in an in vivo environment. (15) Surely enough, the results from the original rat studies showing dramatic carcinogenic effects on the liver, 30-34,41 soon correlated with human data when researchers found the same type of liver DNA adducts in tamoxifen patients. (15, 28-34)
More recent human research has reported tamoxifen treated women to have 3x the risk of developing fatty liver disease, which occurs as soon as 3 months into therapy at only 20mg/day. (24-26) In some cases, the disease lasts up to 3 years, despite cessation from tamoxifen therapy. Five and ten year follow-ups with patients on long term tamoxifen therapy shows cases of deadly hepatocellular carcinoma. (27-29)
In 2002, a bizarre study examined the use of tamoxifen for hepatocellular carcinoma treatment in humans. It was assumed that since tamoxifen could inhibit proliferation of breast cancer, it could offer the same benefit for liver cancer. The devastating results could not have been further indicative of tamoxifen’s hepatotoxic nature, as the tamoxifen treatment significantly increased the rate of death, compared to the group not receiving tamoxifen. (14)
Finally, in a case study reviewing tamoxifen induced liver disease; D.F Moffat et al made a profound statement –
“hepatocellular carcinoma in tamoxifen treated patients may be under-reported since there may be reluctance to biopsy liver tumours which are assumed to be secondary carcinoma of the breast.”
In other words, it appears that the liver carcinoma from a large number of breast cancer patients on tamoxifen therapy has been misdiagnosed as an infection from the breast cancer itself. (28)
Although the tamoxifen induced liver cancer make take years to manifest in a healthy male, its damaging effects could easily be exaggerated by other popular hepatotoxc , including 17aa oral steroids. (15)
Prostate cancer -
In 1996, the International Agency for Research on Cancer (IARC) concluded that tamoxifen clearly promotes uterine cancer in humans – at a standard 20mg/day dose. (16,23,42) This is due to tamoxifen acting as an estrogen agonist in the uterus, presumably from the 4-hydroxytamoxifen metabolite, which triggers abnormal growth of the uterus and the formation of cancer causing DNA adducts. (33, 40)
Contrary to popular thought, these implications are quite scary for a male when we realize the male equivalent to the uterus is the prostate – which differentiates from the same embryonic cell line, shares the same oncogene, Bcl-2, and high concentration of estrogen receptors. In fact, there is no reason to assume that tamoxifen would not initiate the same the same cancerous growth in the prostate. (60-62) It is no wonder that tamoxifen failed as a treatment for prostate carcinoma. (43)
Note: This same risk would be applicable to Clomid, which has also been linked to uterine cancer and ovarian hyper-stimulation. (18, 19, 57, 59)
Libido reduction & erectile dysfunction -
Erectile dysfunction, low libido, and general impotence are typical complaints from men recently discontinuing steroids or HRT therapy, which is often combated by Clomid or Nolvadex, paradoxically so.
Regardless of any positive effects on fertility or testosterone levels, Clomid and Nolvadex use is highly correlated with erectile dysfunction, libido suppression, and even emotional disorders. (10,47)
Research with male breast cancer patients has also reported decreased libido, and thrombosis associated with tamoxifen use. (47) The thrombotic effect (blood vessel clogging) could explain the mechanism by which SERM’s may inhibit erectile function, by reducing circulation to erectile tissue. (47, 52)
Increased susceptibility to gyno -
Tamoxifen is often used to combat gyno during cycle when “flare ups” occur. While tamoxifen may provide immediate inhibition of proliferation, and serve as valuable tool, it can actually increase future susceptibility to gyno.
This is caused by tamoxifen’s ability to up-regulate the progesterone receptor. (54-56) This can dramatically increase the chances of developming gyno in future cycles when utilizing progestin based anabolics such as Nandrolone (Deca) or Trenbolone (or any pro-hormone acting upon the progesterone receptor).
It is interesting to speculate. Is tamoxifen use directly related to the increased gyno occurrences seen with modern day steroid users?
Ocular toxicity –
Another possible side effect associated with SERMs is visual cloudiness, loss of vision and even cataract formation. Although this tends to be a more common side effect from high dosed SERM therapy, standard 20mg/day tamoxifen regimes have been reported to cause these symptoms of ocular toxicity. (17, 46)
Newer SERM’s -
As the medical community became more aware of the side-effects associated with tamoxifen treatment, newer and safer SERMs, such as toremifene and raloxifene hit the developmental fast track. Toremifene appears to be less liver toxic, but it is a closely related analog of tamoxifen, so it also carries many of the related genotoxic effects. (48,49)
Raloxifene is a newer SERM based off a benzothiophene structure, which appears to make it less toxic in the liver, uterus or prostate. (50-52) Unfortunately, Raloxifene has been associated with a higher incidence of thromboembolism (52), and also has very low oral absorption, making it an expensive alternative at a typical dose (120mg/day). (53) Still, Raloxifene could presumably be equally effective as Clomid or Nolvadex at restoring HPTA function, while imparting less side effects. (53)
Newer SERMs are already being evaluated such as bazedoxifene, arzoxifene, and lasofoxifene, in hopes of reducing risk even further. (further enumerating the evidence of toxicity with the tamoxifen generation of SERM’s)
What to do now?
Firstly, it should become a priority to create awareness about the possible side effects of SERMs. Once educated, users will be able to start reducing their requirements of these drugs, and begin adopting healthier, more responsible alternatives.
Carefully planned cycles, and the proper use of aromatase inhibitors (AIs) must pursue over haphazard combinations of excessively dosed aromatizing AAS’s -- which require high doses of SERM’s to reduce possible side-effects. Whereas avoiding SERM’s in HRT will involve the natural clearance and management of endogenous estrogens.
It will be important to maintain testicular function during cycle for a quick and efficient recovery of natural testosterone production for PCT – negating the need for high dose 2-3 month SERM based PCT’s. (For more information on the proper use of hCG during cycle, visit here)
Thus, abolishing the bad habit of SERMing will involve community wide enlightenment with careful, comprehensive planning of worthy alternatives.
- 04-18-2009, 02:13 AM
1. Drug Discovery
By Walter Sneader
2. D.E.S., the bitter pill.
Meyers, Robert (1983).
New York: Seaview/Putnam. ISBN 0-399-31008-8
3. Geometric isomers of substituted triphenylethylenes and antiestrogen action
VC Jordan, B Haldemann, and KE Allen
Endocrinology, Apr 1981; 108: 1353.
4. Antioestrogens: a review.
LUNAN, C.B. et al.
Clin. Endocrinol., 4, 551–572. (1975).
5. Patient No More: The Politics of Breast Cancer,
Batt, Sharon et al
Spinifex Press, Melbourne, Australia, 1994, page 118
6. The Estrogen Receptor: A model for molecular medicine
Elwood V et al.
Department of Cell Biology. Vol 9, 1980-1989
7. Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer
V Craig Jordan
British Journal of Pharmacology (2006) 147, S269-S276
8. Selective estrogen receptor modulation: concept and consequences in cancer.
Cancer Cell, March 1, 2004; 5(3): 207-13.
9. A pharmacological review of selective oestrogen receptor modulators
Steven R. Goldstein, Suresh Siddhanti, Angelina V. Ciaccia, and Leo Plouffe, Jr
Hum. Reprod. Update, May 2000; 6: 212 - 224.
10. Clomiphene citrate (Clomid).
The Wm. S. Merrell Company
Clin. Pharmacol. Therap., 8: 891–897, 1967.
11. Cole, M. P., Jones, C. T., and Todd, I. D. A new anti-oestrogenic
agent in late breast cancer. An early clinical appraisal of ICI46474. Br. J.
Cancer, 25: 270–275, 1971.
12. Ward, H. W. Anti-oestrogen therapy for breast cancer: a trial of
tamoxifen at two dose levels. Br. Med. J., 1: 13–14, 1973.
13. Breast Cancer? Breast Health!
Weed, Susan S.,
Ash Tree Publishing, Woodstock, New York, 1996, page 203
14. High-dose tamoxfen in the treatment of inoperable hepatocellular carcinoma: A multiicenter randomized controlled trial.
Chow et al.
Hepatology, 36: 1221-1226, 2002
15. Liver Cancer: New Research
By Felix Lee
Publisher: Nova (2006)
16. IARC Tamoxifen: Monographs on the evaluation of carcinogenic risks to humans.
66: 253-365, 1996
17. Eye problems in breast cancer patients treated with tamoxifen
Paganini Hill et al.
Breast Cancer Res Treat, 60: 167-172 2000
18. Ovarian hyperstimulation and oophorectomy following accidental daily clomiphene citrate use over three consecutive months.
ES Sills, EA Poynor, and M Moomjy
Reprod Toxicol, Nov 2000; 14(6): 541-3.
19. Uterine Cancer after Use of Clomiphene Citrate to Induce Ovulation
Michelle D. et al
Am. J. Epidemiol., Apr 2005; 161: 607 - 615
20. Detoxifying Cancer Causing Agents to Prevent Cancer
Margaret Hanausek, Zbigniew Walaszek, and Thomas J. Slaga Integr
Cancer Ther, Jun 2003; 2: 139 - 144.
21. Understanding the genotoxicity of tamoxifen?
David H. Phillips
Carcinogenesis, Jun 2001; 22: 839 - 849.
22. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors
B Fisher, et al.
N. Engl. J. Med., Feb 1989; 320: 479 - 484
23. Tamoxifen treatment and its consequences
Adrian Shulman, Ilan Cohen, Ron Maymon, and Marco M. Altaras
Hum. Reprod., Aug 1995; 10: 2174 - 2175
24. Tamoxifen induced hepatotoxicity in breast cancer patients with pre-existing liver steatosis: the role of glucose intolerance.
Elefsiniotis et al.
European Journal of Gastroenterology and Hepatology 2004;16:593-598.
25. Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial
Savino Bruno el al.
BMJ 2005;330;932-; originally published online 3 Mar 2005;
26. Fatty liver and transaminase changes with adjuvant tamoxifen therapy.
Liu, Chien-Liang a c; Huang, Jon-Kway b; Cheng, Shih-Ping a
Anti-Cancer Drugs. 17(6):709-713, July 2006
27. The association between tamoxifen and the development of hepatocellular carcinoma: case report and literature review.
Law CH, Tandan VR.
Can J Surg 1999;42:211-4.
28. Hepatocellular carcinoma after long-term tamoxifen therapy
D. F. Moffat, K. A. Oien, J. Dickson, T. Habeshaw and D. R. McLellan
Volume 11, Number 9 / September, 2000
29. Tamoxifen-associated hepatocellular damage and agranulocytosis.
Ching,C.K., Smith,P.G. and Long,R.G. (1992)
Lancet, 339, 940.
30. Tamoxifen induces hepatocellular carcinoma in rat liver: a 1-year study with two antiestrogens.
Hirsimaki P, Hirsimaki Y, Nieminen L, et al.
Arch Toxicol. 1993; 67: 49–4
31. Epigenetic reprogramming of liver cells in tamoxifen-induced rat hepatocarcinogenesis.
VP Tryndyak, O Kovalchuk, L Muskhelishvili, B Montgomery, R Rodriguez-Juarez, S Melnyk, SA Ross, FA Beland, and IP Pogribny
Mol Carcinog, Mar 2007; 46(3): 187-97
32. Antiestrogens and the formation of DNA damage in rats: a comparison.
Kim SY, Suzuki N, Laxmi YR, Umemoto A, Matsuda T, Shibutani S.
Chem Res Toxicol. 2006 Jun;19(6):852-8.
33. Activation of 4-hydroxytamoxifen and the tamoxifen derivative metabolite E by uterine peroxidase to form DNA adducts: Comparison with DNA adducts formed in the uterus of Sprague-Dawley rats treated with tamoxifen
Deena N. Pathak, Krisztina Pongracz, and William J. Bodell
Carcinogenesis, Sep 1996; 17: 1785 - 1790
34. Activation of the Tamoxifen Derivative Metabolite E to Form DNA Adducts: Comparison with the Adducts Formed by Microsomal Activation of Tamoxifen
Krisztina Pongracz, Deena N. Pathak, Takemichi Nakamura, Alma L. Burlingame, and William J. Bodell
Cancer Res., Jul 1995; 55: 3012 - 3015.
35. Activation of tamoxifen and its metabolite -hydroxytamoxifen to DNA-binding products: comparisons between human, rat and mouse hepatocytes.
Phillips,D.H., Carmichael,P.L., Hewer,A., Cole,K.J., Hardcastle,I.R., Poon,G.K., Keogh,A. and Strain,A.J.
Carcinogenesis, 17, 88–94. (1996)
36. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers.
Fornander,T., Rutquist,L.E., Cedermark,B., Glas,U., Mattsson,A., Silfversward,C., Skoog,L., Somell,A., Theve,T., Wilking,N., Askergren,J. and Hjalmar,M.-L.
Lancet, i, 117–120.(1989)
37. Reduced genotoxicity of [D5-ethyl]-tamoxifen implicates -hydroxylation of the ethyl group as a major pathway of tamoxifen activation to a liver carcinogen.
Phillips,D.H., Potter,G.A., Horton,M.N., Hewer,A., Crofton-Sleigh,C., Jarman,M. and Venitt,S. (1994)
Carcinogenesis, 15, 1487–1492
38. Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s.
Styles,J.A., et al (1994)
Carcinogenesis, 15, 5–9.
39. Clastogenic and aneugenic effects of tamoxifen and some of its analogues in hepatocytes from dosed rats and in human lymphoblastoid cells transfected with human P450 cDNAs (MCL-5 cells).
Styles,J.A., et al. (1997)
Carcinogenesis, 18, 303–313.
40. Effect of tamoxifen on endometrial proliferation
A Decensi, et al.
J. Clin. Oncol., Feb 1996; 14: 434 - 440.
41. Safety Testing of New Drugs. Tamoxifen.
Lawrence,D.R., et al.
Academic Press, London, pp. 125–161. (1984)
42. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14.
Fisher,B et al.and other NSABP contributors (1994)
J. Natl Cancer Inst., 86, 527–537.
43. Phase II trial of tamoxifen in metastatic carcinoma of the prostate.
JH Glick, A Wein, K Padavic, W Negendank, D Harris, and H Brodovsky
Cancer, Apr 1982; 49(7): 1367-72.
44. Biotransformation of the Antiestrogen Clomiphene to Chemically Reactive Metabolites in the Immature Female Rat
Peter C. Ruenitz, et. al
Cancer Res., Aug 1987; 47: 4015 - 4019.
45. Teratogenic effects of clomiphene, tamoxifen, and diethylstilbestrol on the developing human female genital tract.
GR Cunha, O Taguchi, R Namikawa, Y Nishizuka, and SJ Robboy
Hum Pathol, Nov 1987; 18(11): 1132-43.
46. Tamoxifen-associated eye disease. A review
SG Nayfield and MB Gorin
J. Clin. Oncol., Mar 1996; 14: 1018 - 1026.
47. Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients.
Anelli TF, et al.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
48. DNA adducts caused by tamoxifen and toremifene in human microsomal system and lymphocytes in vitro.
Hemminki,K., Widlak,P. and Hou,S.-M. (1995)
Carcinogenesis, 16, 1661–1664.
49. Major difference in the hepatocarcinogenicity and DNA adduct forming ability between toremifene and tamoxifen in female Crl:CD(BR) rats.
GC Hard, et al.
Cancer Res., Oct 1993; 53(19): 4534-41.
50. Selective estrogen receptor modulators: mechanism of action and clinical experience. Focus on raloxifene.
D Thiebaud and RJ Secrest
Reprod Fertil Dev, January 1, 2001; 13(4): 331-6.
51. Raloxifene, an oestrogen-receptor-beta-targeted therapy, inhibits androgen-independent prostate cancer growth: results from preclinical studies and a pilot phase II clinical trial.
RL Shazer, et al.
BJU Int, Apr 2006; 97(4): 691-7.
52. Review on raloxifene: profile of a selective estrogen receptor modulator.
Int J Clin Pharmacol Ther, August 1, 2003; 41(8): 331-45.
53. Comparison of effects of the rise in serum testosterone by raloxifene and oral testosterone on serum insulin-like growth factor-1 and insulin-like growth factor binding protein-3.
EJ Duschek, et al
Maturitas, July 16, 2005; 51(3): 286-93.
54. Effects of tamoxifen on steroid hormone receptors and hormone concentration and the results of DNA analysis by flow cytometry in endometrial carcinoma.
M Nola, et al
Gynecol Oncol, Mar 1999; 72(3): 331-6.
55. Tamoxifen increases the plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal
Gorodeski, G.I., et al.
endometrium. Fertil. Steril, 57, 320-327. (1992)
56. Estrogen and progesterone receptor expressors o£ decidual endometrium in a postmenopausal woman treated with tamoxifen and megestrol acetate.
Cohen, I., Shulman, A., Altaras, M., Tepper, R., Cordoba, M. and Beyth, Y.
Gynecol. Obstet. Invest., 38, 127-129. (1994)
57. Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome.
R Homburg, H Pap, M Brandes, J Huirne, P Hompes, and CB Lambalk
Gynecol Endocrinol, September 1, 2006; 22(9): 506-10.
58. In vivo evaluation of the genotoxic effects of clomiphene citrate on rat reticulocytes: a micronucleus genotoxicity.
B Duran, I Ozdemir, Y Demirel, O Ozdemir, A Cetin, and A Guven
Gynecol Obstet Invest, Jan 2006; 61(4): 228-31.
59. Clomiphene citrate - end of an era? a mini-review
Hum. Reprod., Aug 2005; 20: 2043 - 2051
60. Selective estrogen receptor modulators: pharmacological profile in the rat uterus.
Bryant H. U., Wilson P. K., Adrian M. D., Cole H. W., Phillips D. L., Dodge J. A., Grese T. A., Sluka J. P., Glasebrook A. L.
J. Soc. Gynecol. Invest., 3: 152A 1996.
61. Molecular perspectives on selective estrogen receptor modulators (SERMs): progress in understanding their tissue-specific agonist and antagonist actions.
Lonard D. M., Smith C. L.
Steroid, 67: 15-24, 2002
62. Defining the "S" in SERMS.
Katznellenbogen B. S., Katznellenbogen J. A.
Science (Wash. DC), 295: 2380-2381, 2002
04-18-2009, 12:04 PM
Well damn; I've run a SERM on all my previous cycles.. I just can't see myself using OTC PCT for any of my harsher cycles- maybe if some better supps get released- but nolva is the cheapest PCT i can find
04-19-2009, 02:33 PM
^^yeah but it is good to know the sides of the stuff thats supposed to "set you back to normal".
just because the article is long, people on this site should know the effects of whats going in their bodies could be...good or bad.
04-22-2009, 10:37 AM
Good post! A lot of people are not aware of just how toxic some of the SERM's really are, combinded with the fact that some do not really think long-term health.
I have used Anastrozole in the past for my sd/pp cycles, because I read it was less toxic. The last two (pp/trn/zol & epi/trn) I have used Tamox Cit. with an AI tapered and have been just fine.
Less toxicity is better for the long term, so I may switch back to Anastrozole or Toremifene Cit. for my next pct (x-mass/epi). Low dose with a tapered AI of course.
05-28-2012, 01:14 PM
05-28-2012, 03:31 PM
06-05-2012, 03:08 PM
06-08-2012, 02:11 PM
06-08-2012, 04:26 PM
Great article, and will be an easy citation for me when people go on the usual "Nolva sux use clomid" nonsense. They are all toxic.
10-19-2012, 02:09 AM
These are one of those articles/posts I read...take in....then push FARRRRRRRRRRRRRRRRR back to my head and try not to think about it. lolhahahaha
Every fuc*ing thing has side effects these days.
02-28-2015, 11:55 PM
03-01-2015, 06:11 PM
03-02-2015, 12:57 AM
03-02-2015, 03:45 PM
03-03-2015, 11:43 AM
03-03-2015, 01:40 PM
excellent article... thx for the repost
TGB SUPPLEMENTS.com Rep / Black Lion Research Rep
Use vujade5 to Save 5% off your order up to $149
Use vujade7 to save 7% off your order over $150
03-05-2015, 02:30 AM
03-05-2015, 10:46 AM
I believe this was based on the long term use of nolva, correct? 4 weeks for a pct isn't long term.
However, yes nolva and all serms are toxic. You have to pay to play.
03-06-2015, 09:19 PM
03-10-2015, 11:49 PM
03-11-2015, 08:15 AM
03-25-2015, 09:42 PM
03-25-2015, 09:46 PM
Exemestane increases testosterone by more than tamoxifene. It works through the same channel, but reduces estrogen rather than making your hpta think estrogen is reduced.
What does not make sense to you,?
03-25-2015, 09:55 PM
Google "Pharmacokinetics and dose finding of a potent aromatase inhibitor aromasin..." for a study that shows an aromasin-induced increase in test an LH.
03-25-2015, 09:59 PM
03-25-2015, 10:04 PM
03-25-2015, 10:05 PM
Then if you're controlling the enzyme aromatase via an AI, that testosterone won't be converted into to estrogen. I don't see how it would ever be able to restart your natural production though :/
03-25-2015, 10:15 PM
03-25-2015, 10:29 PM
Similar Forum Threads
- By waynaferd in forum Post Cycle TherapyReplies: 2Last Post: 11-30-2010, 06:23 PM
- By The Matrix in forum Male Anti-Aging MedicineReplies: 1Last Post: 06-29-2009, 12:19 PM
- By Ari Gold in forum General ChatReplies: 43Last Post: 06-24-2008, 02:04 AM