Proper Understanding of Anti-estrogen Usage

[Spook]

Proper Understanding of Anti-estrogen Usage



Introduction:

For several years I have witnessed on fitness boards the discussion of various anti-estrogens, make recommendations about usage of anti-estrogens, and most boards will have profiles for each anti-estrogen drug. Rarely do I see articles or threads that discuss all of the anti-estrogens, their modes of action, and contrasts of the anti-estrogens to inform the user which anti-estrogens should be used, which should not be used, and when anti-estrogens are of no benefit—at least not in large summary as information all can glean over. Anti-estrogens were originally developed for the treatment and management of endocrine responsive breast cancers. Anti-estrogens are not just used to compete with the estrogen aromatase enzyme or the competition with androgens to bind with the estrogen receptor (ER), but competitive athletes and bodybuilders have found the use of anti-estrogenic drugs to be valuable for aesthetic purposes to reduce the possibility of steroidal aromatization affecting breast tissue. Anti-estrogens may also have other effects with various tissues that may be disfavorable, but normally these alterations are somewhat minimal depending upon the circumstances, amount of usage, frequency and duration of anti-estrogen usage. Some of the changes may be cell membrane function and structural alterations, oxidative stress response, and a myriad of other changes.

There are several very popular anti-estrogens that are used by bodybuilders that include partial agonist/antagonists and anti-aromatases. To date there are no known anti-progesterone drugs that have been tested with men. The RU-486 (Morning-After-Pill) is a progesterone receptor antagonist in the uterine tissues for women, but nothing is known yet about its effectiveness in men. The goal of this article is to examine which anti-estrogens would be most beneficial to the bodybuilder and competitive athlete.


Examining the Anti-estrogens:

Partial Agonists and Antagonists:

1. Tamoxifen citrate (Nolvadex): This drug is normally referred to as Nolvadex with Tamoxifen being the generic name. Tamoxifen is a partial agonist and antagonist drug meaning that in some tissues the agonist action will modulate the estrogen receptor to become active, while in other tissues it is an antagonist that competes with steroidal hormones in binding to and deactivating the receptor. SERMs (Selective Estrogen Receptor Modulators) such as tamoxifen can be quite beneficial in its agonist/antagonist action to activate some estrogen receptors while deactivating other receptors. The receptors that are deactivated are the ERb (receptors that are commonly found in breast and skin tissue). The ERb are the receptors that are desirable to block as estrogen can cause gynocomastia in breast tissue. However, in the ERa tamoxifen acts as an estrogen agonist. It is the ERa that can be found in the bones and it is here that the SERMs will encourage osteoblast activity and mineral absorption in the bones. Another interesting fact about tamoxifen is that it can affect and stimulate the hypothalamic and pituitary glands’ activity as much as 172% release of LH (luteinizing hormone) which in turn stimulates the leydig cells of the testes to produce endogenous testosterone. When a bodybuilder uses tamoxifen, it is ideal to use 20-40 mg/day with doses split regularly throughout the day if steroidal usage is low (<1,000 mg/wk of total aromatizable compounds), or up to 80 or possibly 100 mg/day as the total aromatizable steroid usage increases.



2. Clomiphene citrate (Clomid): Clomid is another estrogen partial agonist and antagonist much like tamoxifen. Both, Clomid and tamoxifen are very similar structurally and they both act on the ERa and the ERb in similar ways. Clomid is primarily used for post cycle therapy (PCT); however, more information seems to be revealing that Clomid can desensitize the pituitary gland and limit LH secretion. Within a 14-day period, Clomid can stimulate the pituitary to release almost as much LH as the tamoxifen can, but shortly after 2 weeks, it appears to desensitize the pituitary whereas tamoxifen does not desensitize the pituitary. Clomid will not be discussed beyond this as an anti-estrogen due to it having been traditionally used as a PCT drug, and also due to its lack of cost effectiveness during a cycle.

3. Raloxifene (previously known as Keoxifene): I mention Raloxifene because it is an estrogen receptor partial agonist and antagonist, but it should not be mistaken as a similar compound to the SERMs such as tamoxifen or clomiphene. The previously mentioned SERMs are tryphenylethylenes, whereas Raloxifene is a benzothiophene. The mode of action for Raloxifene is similar to tamoxifen, but due to its availability and cost, tamoxifen remains a better choice.


Figure 3: A comparison of estrogen binding with its alpha-receptor and Raloxifene binding to the receptor site, thus, deactivating the receptor.

4. Other Selective Estrogen Receptor Modulators: Other SERMs include several other triphenylethylene variations including Toremifene (chloro-TAM) and Droloxifene (3-OH-TAM). These will not receive further attention due to the availability and efficacy of these compounds.


Anti-aromatases:


1. Anastrozole (Arimidex): Is an anti-aromatase that inhibits the aromatase enzyme’s activity. Although AAS drugs and testosterone may be able to bind to the ERa and ERb, but the aromatase will be inactive due to anastrozole binding to the enzyme, thus, deactivating the enzyme’s ability to aromatize the testosterone into estradiol. Anastrozole, however, can be too effective at lowering estradiol in the body, which may not be beneficial. At lower dosages of testosterone, 250-500 mg/day (0.25-0.50 mg/day) or even every other day can be sufficient for inhibiting aromatase action, but, with higher dosages of testosterone, more anastrozole will be needed.

2. Aminoglutethimide (Cytradren): Aminoglutethimide is able to serve effectively as an aromatase inhibitor, but it is also able to act as a desmolase inhibitor. As a desmolase inhibitor, aminoglutethimide rate limits the production of cortisol. Some bodybuilders have in the past used aminoglutethimide as a cortisol blocker during precontest leaning out. Once the drug is discontinued, there is a rebound effect with desmolase activity. This drug is quite effective as an anti-aromatase at 4 split doses of a single 250 mg tablet, but at doctor recommended dosages (typically prescribed for Cushing’s Syndrome patients) of 1,000 mg/day can leave a healthy person with a cannabis-like euphoria, impaired judgment, and a large increase in insomnia.

3. Other Anti-aromatases include letrazole and other compounds, however, at this moment, these compounds typically require a higher dosage to achieve the same effectiveness as anastrozole. The reason for this is due to binding abilities of the compounds. Anastrozole has a much higher bonding affinity with aromatase making it the more effective drug.


Conclusion:

Considering the great efficiency of anti-aromatases, specifically anastrozole, it would seem obvious that anastrozole is the winner by default. However, if long cycles are ran or cycles are frequent, anastrozole could be very unhealthy for the user by potentially derailing osteoblast activity and making bone health fragile as just one example of side effects. Other side effects of extremely low estrogen levels (caused by usage of an universal anti-aromatase) include lowered sex drive, potentially causing an increase in hair loss, heart disease due to the anti-aromatase causing a poor lipid profile, and potentially lowered IGF and other signaling protein levels.

However, in contrast to anti-aromatases, partial agonist and antagonist drugs or SERMs such as Nolvadex (Tamoxifen) would be the best choice for a person to use as an anti-estrogen. Nolvadex serves as an ERb antagonist which serves the purpose for those who desire to negate adverse side effects relating to estrogen in breast tissue, while serving as an ERa agonist in other tissues that serve positive, healthful purposes in everyone. Another advantage of Nolvadex is in its ability to stimulate the pituitary gland (part of the HPTA) to become more sensitive to GnRH (Gonadotropin Releasing Hormone) which in turn will cause more LH (Luteinizing Hormone) to be released from the pituitary gland. Compared to baseline values in some studies, Nolvadex can increase LH release by an average of 172% and an increase of testosterone by 183%.

There are other anti-estrogen drugs that could be discussed, but that will be saved for a much more exhaustive article at a later date.




Spook

MMS Fitness
Administrator/Co-owner
www.**********.com
ADDENDUM


A. Potential AAS progesterone receptor agonists:

1. Nandrolone decoanate (Deca Durabolin) 4. Oxymethalone (Anadrol)
2. Nandrolone phenylproprionate (Durabolin) 5. Trenbolone acetate (Finaplix)I
3. Norethandrolone (Nilevar) I Possible progesterone agonist.


B. Aromatizable AAS Requiring Anti-estrogens:

1. Boldenone undecyclenate (Equipoise) II May not require anti-estrogens due to low doses
2. Fluoxymesterone (Halotestin)II of halotestin usage.
3. Methandrostenlone (Dianabol) III This includes any testosterone-based
4. TestosteroneIII Steroidal compound.


C. Non-aromatizable AAS:

1. Dihydroxytestosterone (DHT) 5. Stanazolol (Winstrol)
2. Drostanolone proprionate (Masteron) 6. Mesterolone (Proviron)
3. Methenolone (Primobolan)IV 7. Stenbolone (Anatrofin)
4. Oxandrolone (Anavar) IV Includes both acetate and enanthate forms.