Negative feedback loop. You have low test. Your body realizes that and produces LH which stimulates the testes to produce more test. It's what's supposed to be happening. You just need more time to recover.
This ^^^^^. Heres some info for next time.
SERM's (Selective Estrogen Receptor Modulator) : These block certain estrogen receptors, ***ending on the drug, and dont actually lower estrogen in the blood. Estrogen is left to circulate with nowhere to go. Because of this, SERMS have a positive effect on cholesterol levels. They have a negative effect on IGF-1, so if bulking, only take them if totally necessary. They are good at blocking gyno. Commonly used during PCT, and less often used while cycling. A SERM like nolvadex is widely used in PCT to help kickstart the HPTA back to normal function, in conjunction with other beneficial drugs. To learn how this works, please refer to Anthony Roberts PCT in the PCT section.
AI's (Aromatase Inhibitors) : There are 2 types of AI's. Type I (suicide inhibitor) attaches to the aromatase enzyme and permanently disables it. Type II compete for the enzyme, but dont destroy it. Both are effective at lowering estrogen substantially. Both are commonly used during both cycling and PCT. Used mainly when low estrogen levels are desired, like contest preparation/cutting. Beware that lowering estrogen with strong AI's can have a negative effect on cholesterol levels and low estrogen levels can lead to sore joints, cause your losing estrogens anti-inflammitory effect. Can also have a negative impact on your libido. Estrogen has an important role in mass building and joint health, as noted below where "estrogen" is explained.
RI's (Reductase Inhibitors) : These drugs stop the conversion of testosterone into DHT wherever 5-alpha reductase enzymes are present. RI's work by blocking the action of the 5-alpha. There are 2 5a's. Type I 5a and Type II 5a. Different RI's block one or both of these 5a's. The main reason someone uses RI's is to stop hairloss. They are common anti hairloss drugs. The problem is, when you block the dht conversion, there are less androgens available and may reduce your gains. Sometimes people report less strength, aggression and drive to train.
Estrogen : The first hormone we need to keep an eye on. Many AAS convert to estrogen via the aromatization process. Some AAS are worse than others. Also, estrogen spikes after a cycle. High levels of estrogen leads to gyno, water retention, fat storage etc. Estrogen plays a key role in progesterone related gyno. We either block its receptors with SERMS or reduce its production with AIs. We watch estrogen levels during a cycle and in PCT. Lowering estrogen too much will mess up your blood lipids. Letting it get out of control will cause sides like gyno, water retention etc. Estrogen plays a role in IGF-1 levels, may lower IGF-1 when blocked with a SERM. Estrogen is also beneficial hormone when bulking, promoting higher androgen receptor concentrations (!). It also is beneficial in another way - its supposed to act as an anti-inflammatory - this means blocking or reducing it too much during a heavy bulking cycle can result in injury to joints. Obviously different estrogen levels are desired for different goals, and it is not always good to block its action or its production. Usually, while bulking, estrogen is allowed to rise unless gyno or water retention (leading to high blood pressure) becomes a problem. When cutting and shedding water and lifting a little lighter (contest prep for example) estrogen is usually dropped with an AI. Proper diet and training can help the bad side effects high estrogen can have.
Progesterone : Its not so much progesterone that we watch, which is actually a healthy hormone, but progestins which may act upon its receptors. Progestins, like Tren or Deca (nor-9's), may act on its receptor or lower progesterone in the blood. Gyno and lactating are more common side effects. Some people use progesterone receptor blockers to combat this, or a prolactin production inhibitor.
Cortisol : The third hormone, the stress hormone. When elevated to long, it will store fat. Eat muscle. Cause lethargy. Moodiness. You may crave carbs by the boat load. Cortisol spikes after a cycle because AAS blocks it while on cycle, upping cortisol production and receptor sites. IMO not enough attention is payed to this. It has special functions in the body that are absolutely necessary, like its anti-inflamitory ability. However, when elevated for long periods, it turns into a muscle eating beast. The most important time to watch cortisol is after a cycle, when it spikes. There are a couple ways to help control this, explained below.
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SERMS (Selective Estrogen Receptor Modulation)
Nolvadex (Tamoxifen Citrate) : Nolvadex is a SERM. It selectively binds to certain estrogen receptors, effectively blocking the estrogen and stopping unwanted sides such as gyno. It DOES NOT lower estro levels in the blood, it only blocks it from binding to certain receptors. It also helps your blood fat levels. It does not suppress LH, blocks desired estro receptors and helps stop HCG from desensitizing your testicles to natural LH. Nolva should be used during HCG therapy, at 20 mg a day, for the reason i just mentioned. Can be used during cycle if you see signs of gyno. Its mainly used to block the estrogen spike when you come off cycle, and should be used right through to the end until natural test levels are back. One drawback to consider about Nolva is that it may cause progesterone receptors to become more sensitive. This means that while using progestins such as Deca or Tren, you may become more sensetive to progestin related gyno.
Faslodex (Fulvestrant) : Approved for use in 2002 for breast cancer research, this drug is unlike most we have seen. It is classified as an estrogen receptor downregulator. It prevents estrogen from exerting its influence on the estrogen receptor. Similar to Nolvadex, but is not selective. It hits all estrogen receptors. It also does this to progesterone receptors to a lesser degree. It is injectable, at 250mg a month. No information on how it affects blood lipids. It is also very expensive.
Clomid (Clomiphene Citrate) : This drug is also a SERM, almost identicle to Nolva. It is said to be a weaker blocker mg for mg than Nolva. Its common use is in PCT, usually for about a month, used after HCG and all AAS esters have run out of your body. Even though it is weaker than Nolva at blocking, it is believed to be quicker at bringing HPTA back to balance. Both are commonly used during PCT. It binds to different receptors than Nolva. There is a lot of debate on this, but until there is solid proof, it may be prudent to include this in your PCT. Commonly taken at about 100mg a day.
Fareston (Toremifene Citrate) : This is a second generation SERM. Approved for use in 1997. Chemically very similar to Nolva and Clomid, it is less powerful mg for mg. Fareston may have a stronger posotive effect on your cholesterol levels. For those who find this an important issue, this is a drug of choice. Used every day at around 60mg.
Evista (raloxifene) : A newer SERM, Evista is shown to be a blocker in breast tissue, but acts as a receptor agonist in bone tissue (unlike Nolvadex). This action promotes bone density. Taken at about 60mg a day. Evista may prove to be very beneficial, as it also helps cholesterol levels (like Nolvadex). Evista is supposed to have a more powerful gyno blocking effect than Nolvadex.
Cyclofenil : Much like Nolvadex, this is also a SERM. Used at about 600mg a day, it is weaker mg for mg. A good alternative if Nolva is not available, which is usually not the case.
AI (Aromatase Inhibitors)
Teslac (Testolactone) : This is a first generation steroidal aromatase inhibitor. Like a suicide, it permanently attaches to the aromatase enzyme. Taked at a maximum of 250mg a day. It is not as strong as the newer AI's, but some people still like to use it. It can lower estrogen about 50%. Streroidal in structure, it has no anabolic effect.
Aromasin (Exemestane) : This drug is classified as a Type I Suicide AI. It binds to the aromatase enzyme and kills it. It is effective at lowering estrogen up to 85%. Once again, you have to watch out for your cholesterol levels. Used mainly for cutting when low estrogen levels are desired. Aromasin is shown to help bone density. Clinical doses are about 25mg a day, but it has been shown that as little as 2.5mg a day can be as effective.
Lentaron (Formestane) : A Type I Suicide AI. Lentaron is not classified as a drug, and can be sold over the counter as a suppliment. Not as strong as the third generation AIs (arimidex, femera). Can lower estrogen by about 60%. Used as an injectable, it is dosed at about 250mg every 2 weeks. Due to poor bioavailability, daily doses of oral Lentaron are about 250mg.
Arimidex (Anastrozole) : This is a widely used type II AI. It competes with estrogen for the aromatase enzyme. This effectively lowers estrogen up to 80% in the blood. Approved for use in 1995 to fight breast cancer. At doses up to 1mg a day, it has been shown to be very effective at controlling estrogen while on cycle or in PCT. It is usefull for curbing the effects that come with aromatizing AAS's while in cycle, and can be used in PCT. Nolvadex is shown to decrease the effectiveness of Arimidex when used together. In this case a suicide inhibitor may be more well suited, like in PCT. It is also called L-dex, in its liquid form.
Femera (Letrozole) : Letro is a competative Type II AI also. Also farely new compared to other compounds, it is shown to be effective at lowering estrogen by blocking the aromatase enzyme. Doses up to 2.5mg a day are used, but usually as low as .5mg a day can be just as effective. Clinical studies show Femera to lower estrogen by 75-78%, sometimes up to 95%. Once again, watch out for your blood lipids (cholesterol) to get out of whack. There may a noted rebound effect of estrogen levels that goes along with Letro use.
Cortisol Control
Cytadren (aminoglutethimide) : This drug has the ability to reduce cortisol at higher doses (1000mg a day), and act as an AI at lower doses (250mg a day). The cortisol effect is shortlived if taken for a number of consecutive days. Can lower estrogen a lot, anbout 90%. The higher dose has a long list of sides. More effective as an AI.
Mirtazapine :This is used to lower cortisol. Even though it may be effective in cortisol control, Johan has pointed out that it may cause some phycological side effects, like making you feel like a zombie. Here is a pubmed abstract for is effects on cortisol levels, among other things.
http://www.ncbi.nlm.nih.gov/entrez/...1&dopt=Abstract
Cytodyne (Phosphatidylserine) : This is also used to lower cortisol, but is only effective in lowering about 30%. There are other ingredients in Cytodyne than Phosphatidylserine. Phosphatidylserine is the only real proven ingredient to lower cortisol, or so ive gathered so far. Effective at 800mg a day of PS as an ingredient.
Relacore : This over the counter cocktail of herbs and vitamins and minerals is supposed to reduce the amount of cortisol in your blood. I find it chills me out a little, however i read some places that it may raise estrogen. I used it for a bit, however I dont bother any more.
Vitamin C: At doses of about 1.5 grams a day, can have a lowering effect on elevated cortisol, not to mention its other healthy effects.
LH Replacement Therapy - Testosterone Stimulating Drugs
HCG (Human Chorionic Gonadotropin) : HCG is a replacement for your natural LH (luteinizing hormone). LH is what your body produces to tell your testicles to produce natural testosterone. LH levels drop when using AAS (HPTA suppression). Using HCG while on cycle prevents testicular shrinkage, speeding PCT when the time comes. Using Nolva while using HCG helps stop HCG from de-sensitizing your testicles to natural LH. In my opinion, any decent cycle/PCT should include HCG. It has been suggested to me that HCG can be used throughout a cycle at 500iu E4D, but im unsure of this from practical experience. The most favorable way is to use it in the last couple weeks of your cycle at a higher dose, like 500iu ED. The trick is to end the use of HCG just as the last AAS is running out of your system. So, 3 weeks before the the last ester leaves your blood, you would start the HCG/nolva combo. HCG at about 500iu ED and Nolva 20mg ED. This is done before Nolva/aromasin (for example) PCT starts, and runs about a few weeks longer than the end of the HCG. Always include Nolva with your HCG, they work together well. Be careful not to overdose on HCG and permanently desenstize your testicles to LH. HCG has an active life of about 3 days. Vitamin E is a booster, read the next one :
Vitamin E : As Anthony Roberts pointed out to me, vitamin E increases the response to HCG. This may be useful in making the low doses of HCG we use more effective at growing back shrunken testicles. Doses can be generally 1000iu a day while using HCG.
Progesterone Control
Lilopristone, Onapristone: These are progesterone blockers also, said to be safer and possibly more effective than RU-486 when it comes to progesterone blocking. They were developed after RU-486 in an attempt to make more effective, less harsh drugs to block progesterone.
Dostinex (Cabergoline), Bromo (Bromocriptine), B-6 : These are used for Deca/Tren gyno sides. This type of gyno is related to progesterone and its receptors. Tren/Deca may act on the progesterone receptor, as they are progestins, and may increase prolactin in the blood (causing lactating). These drugs stop production of prolactin at the pituitary gland. Controlling estrogen levels with an AI also helps here, as progestins themsleves haven't been proven to cause gyno.
RU-486 (Mifepristone - abortion pill) : This drug has the ability to block estrogen, progesterone AND cortisol. It may or may not be very well tolerated, but I would like to find out more about it, as it is used in the bodybuilding world. In PCT it is used to block cortisol and progesterone. A powerful drug that may turn out to be a good choice, but i need more evidence and feedback from experience useing RU-486.
RI's (5a Reductase Inhibitors)
Proscar (Finasteride) : This is primarily a Type II 5-alpha blocker. This means that when you are taking a high dose of testosterone, the resulting conversion of test to DHT in certain parts of the body become to high for ones own comfort, mainly hairloss and prostate enlargement. This is where the type II 5a enzymes are mainly found. This will not work against AAS that are already highly androgenic by design, without conversion. AAS like Tren will still exhibit high androgenic properties. Used at doses up to 5mg a day.
Avodart (Dutasteride) : Like Proscar but newer and more effective at blocking the effects of DHT in not only the scalp and prostate (which are Proscar's main strengths) but also in the skin, effectively reducing acne. This is because Avodart will block both Type I and Type II 5-alpha enzymes, covering more of the problem areas due to DHT. Available in .5mg softgels, this is an effective dose. Approved for use in 2002.
Fat Burning, Anti-Catabolic
Clen (Clenbuterol) : Clenbuterol is a bronchodilator. Everyone knows clen is used to burn fat. Why am I listing it here in a PCT thread? Well, for its anti-catabolic properties. Clen may lower the effect of AAS while on cycle, so I personally dont use it while cycling. It does, however, have an effect on cortisol levels. While on cycle, cortisol is not to much of a problem if you eat right. AAS use increases cortisol production, and increases receptor sites. This means that when you finish a cycle, cortisol spikes along with estrogen. This is a part of the "crash" that is often overlooked. People have reported that blocking cortisol in PCT speeds along fat loss. Clen is supposed to have a blocking effect on cortisol. So, along side of its ability to burn fat, it is anti catabolic in it ability to block cortisol until desired hormone levels are achieved in PCT. For me, it makes sense to use clen in PCT until desired hormone levels are achieved, as it also burns away fat in the process.
SUMMARY and RECOMMENDATIONS
All AAS can supress the HPTA, even in small doses, thus lowering natural LH. Factors that affect ones ability to recover quickly are genetics, cycle length or steroid type. Some AAS will shut you down hard and fast, some not so bad. Some lucky people can rebound quickly without medications, but many need it to avoid a crash and losing muscle/gaining fat. It is in our best interest to use the appropriate medications in the CORRECT doses to keep sides down (like bloat), grow quickly and keep quality mass when we are done our cycles. Most of us can get away with using 2 or 3 compounds to keep sides to a minimum, rebound quickly, and keep gains we worked hard for. Higher levels of AAS (and therefore higher estrogen/progestins) may require more intense hormone control and heavier PCT. Remember, we are aiming to level out estrogen, progesterone, cortisol and testosterone. In PCT, we are trying to achieve equilibrium of the HPTA, getting FSH (follicle stimulating hormone) and LH (luteinizing hormone) back to normal. Keeping our hard earned gains is obviously our first priority.
In short, we generally use :
AI's - While on cycle to "dry up" or lower estrogen because of a persons sensetivity to it (if needed). Used in PCT for the same reason and to help get back to homeostasis. Usually used with a SERM in PCT.
SERM's - to block estrogen while on cycle (if needed) or to help kickstart the HPTA during PCT (most common use). Usually used with an AI in PCT.
HCG - To prevent testicular shrinkage during a cycle, or to encourage them to grow back more quickly. Usually used with an AI and SERM in PCT as the last AAS run out of your body, and stopped a few weeks before your SERM and AI.
Preface – Over the past 15 years, the use of Clomid and Nolvadex, as Selective Estrogen Receptor Modulators (SERMs) has become a staple in the Hormone Replacement Therapy (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 truly dangerous to men’s health.
Synthetic estrogens, the beginning -
It was the 1930s 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 (e.g., 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 1950s, 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 who 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 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 of its many physiological effects, triphenylethylene would become the molecular backbone for generations of SERMs to come.
By the early 1940s, 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 1950s, the synthesis of new triphenylethylene based molecules had begun picking up momentum, as the first FDA approved SERMs 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 1950s 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 SERMs to appear in the late 1950s, 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 SERMs 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 SERMs induced, rather than inhibited ovulation. (4) Needless to say, tamoxifen was withdrawn as a contraceptive.
And remember DES, the original synthetic estrogen developed back in the 1930s? 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 1960s, there was little enthusiasm to continue R&D with triphenylethylene based SERMs, 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 SERMs 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 popularly 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 for 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 ups 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 80s and 90s. Even more misleading, 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 metastases 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 divergent effects 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 the 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 tube research 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 stem 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 of tamoxifen therapy. Five and ten year follow-ups with patients on long term tamoxifen therapy show 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 more 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 liver carcinomas from a large number of breast cancer patients on tamoxifen therapy have been misdiagnosed as an infection from the breast cancer itself. (28)
Although tamoxifen induced liver cancer may take years to manifest in a healthy male, its damaging effects could easily be exaggerated by other popular hepatotoxic drugs, such as 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 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 SERMs 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 developing 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 SERMs -
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 on 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 fewer side effects. (53)
Newer SERMs are already being evaluated such as bazedoxifene, arzoxifene, and lasofoxifene, in hopes of reducing risk even further. (This further underscores the evidence of toxicity with the tamoxifen generation of SERMs)
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 use of these drugs, and begin adopting healthier, more responsible alternatives.
Carefully planned cycles, and the proper use of aromatase inhibitors (AIs) should prevail over haphazard combinations of excessive doses of aromatizing AASs — which require high doses of SERMs to reduce possible side-effects. Whereas avoiding SERMs in HRT will involve the natural clearance and management of endogenous estrogens.
It is important to maintain testicular function during a 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 calls for community wide enlightenment with careful, comprehensive sharing and planning of worthy alternatives.
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