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The Differences Between Antiestrogens, Anti-aromatases and Estrogen Antagonists
By Bill Roberts
What does “anti-estrogen” mean? How are anti-estrogens like Cytadren, Clomid, and Nolvadex different from each other? Is Proviron an anabolic steroid, or not?
Anti-estrogens are drugs which act to reduce estrogenic activity in the body. This can be done either by reducing the amount of estrogen, or by reducing the activity of whatever estrogen is present.
Competitive aromatase inhibitors, such as Cytadren, Arimidex, and probably Proviron, bind to the same binding site on the aromatase enzyme that testosterone does. By doing this, they allow less testosterone to bind to aromatase. So, less testosterone is converted to estradiol (estrogen).
Here’s an important thing: the effectiveness of competitive inhibitors decreases as the amount of the normal substrate increases. Suppose that you had equal amounts of inhibitor and normal substrate in the blood, and they bound to the enzyme equally well. Then the inhibitor would at any moment be taking up half the sites that the normal substrate otherwise would, so it would reduce conversion rate by 50%. But if the amount of substrate is increased 10 times while the amount of inhibitor remains the same, then the inhibitor would be outcompeted by the more numerous substrate molecules. It would therefore be rather ineffective.
For example, with more testosterone molecules available, and similar binding strengths, the enzyme will mostly bind testosterone. It will then mostly be working to produce estrogen. To obtain the 50% reduction we had before, then the amount of inhibitor would also have to be increased 10 times.
To be really effective, the inhibitor must either be present in higher concentration than the normal substrate, or must bind more tightly.
With Cytadren or Proviron, it takes quite a lot of inhibitor to outcompete high testosterone levels. With Arimidex, rather little, even 1 mg/day, can be sufficient because it binds so strongly.
The other general approach is estrogen receptor antagonism. If a molecule binds strongly to a hormone receptor, but does not activate that receptor and makes it unresponsive to the normal hormone, then it is a receptor antagonist. Clomid (clomiphene) and Nolvadex (tamoxifen) follow this approach. These drugs are very similar structurally. They are both what are called triphenylethylenes, and are not steroids. The differences are relatively minor, but seem to affect an important characteristic of these compounds: drug metabolism.
Both tamoxifen and clomiphene are metabolized to other related compounds which can be estrogenic or anti-estrogenic. Both act as estrogens in bone tissue, perhaps after metabolism, which is a very useful property for female patients, for whom these drugs are usually intended. (Otherwise, an anti-estrogen could lead to osteoporosis.) Tamoxifen seems particularly prone to acting as an estrogen in the liver, which may account for reduced IGF-1 levels seen when this drug is taken.
Users generally seem to agree that when tamoxifen is used, gains are a little less than what otherwise would be expected. (Let’s not take this too far though: many people have made great gains while using tamoxifen as an anti-estrogen. And it’s always hard to say what “would” have been the case if a drug had not been included.) I’ve heard nothing but good about clomiphene, though.
Proviron, an anabolic steroid, is particularly interesting. I suspect that it not only acts as an antiaromatase but in an unknown DHT-like anti-estrogenic manner. This might involve estrogen receptor downregulation for example. In any case, aromatase inhibition and/or Clomid don’t seem to give the same effect on appearance and muscle hardness as when Proviron is included.
How much of these agents is needed for effective estrogen suppression?
Again, it depends on the dose of anabolic/androgenic steroids (AAS) and it depends what type of AAS is being used.
With Primobolan or trenbolone there is no need for these drugs.
With nandrolone, an aromatase inhibitor will be of no use, because aromatase is not used in the aromatization of nandrolone. A rather small amount of estrogen receptor antagonist can be useful. 12.5 to 25 mg Clomid would be plenty for 400 mg/week Deca.
With testosterone, stacking of an aromatase inhibitor and an estrogen receptor antagonist will give the best results. Cytadren use should not exceed 250 mg/day in my opinion. This alone would not be sufficient for say 1 g/week or more of testosterone. With such a dose, ideally one would add in 50 mg/day Clomid. Proviron at 100 mg/day could substitute for the Cytadren. Or Cytadren and Proviron can be used in combination, 125/50 or higher, together with 50 mg/day Clomid.
For lower doses of testosterone, proportionally less antiestrogens can be used.
Arimidex is very effective but extremely expensive. 1 mg/day of this is at least as effective as 250 mg/day Cytadren. If a milligram per day cannot be afforded, use of half a milligram would allow Cytadren use to be cut in half, which may be desirable.
How does Clomid “stimulate” testosterone production at the end of the cycle?
It really doesn’t. Rather, by acting as an estrogen receptor antagonist, it reduces the inhibition that results from elevated estradiol levels. This helps return LH to normal levels, which helps testosterone to return to normal levels (if the testicles have not atrophied).
How does hCG help?
Acts as an LH receptor agonist, thus substituing for LH. It does nothing to help the hypothalamus and pituitary. Thus, it can be effective during the cycle to help avoid testicular atrophy, but is not best used in the taper when one is attempting to restore LH production. Increases in natural testosterone, stimulated by the hCG, will act to inhibit LH production. Thus, you can see where hCG use is counterproductive in the taper itself.
By Bill Roberts
What does “anti-estrogen” mean? How are anti-estrogens like Cytadren, Clomid, and Nolvadex different from each other? Is Proviron an anabolic steroid, or not?
Anti-estrogens are drugs which act to reduce estrogenic activity in the body. This can be done either by reducing the amount of estrogen, or by reducing the activity of whatever estrogen is present.
Competitive aromatase inhibitors, such as Cytadren, Arimidex, and probably Proviron, bind to the same binding site on the aromatase enzyme that testosterone does. By doing this, they allow less testosterone to bind to aromatase. So, less testosterone is converted to estradiol (estrogen).
Here’s an important thing: the effectiveness of competitive inhibitors decreases as the amount of the normal substrate increases. Suppose that you had equal amounts of inhibitor and normal substrate in the blood, and they bound to the enzyme equally well. Then the inhibitor would at any moment be taking up half the sites that the normal substrate otherwise would, so it would reduce conversion rate by 50%. But if the amount of substrate is increased 10 times while the amount of inhibitor remains the same, then the inhibitor would be outcompeted by the more numerous substrate molecules. It would therefore be rather ineffective.
For example, with more testosterone molecules available, and similar binding strengths, the enzyme will mostly bind testosterone. It will then mostly be working to produce estrogen. To obtain the 50% reduction we had before, then the amount of inhibitor would also have to be increased 10 times.
To be really effective, the inhibitor must either be present in higher concentration than the normal substrate, or must bind more tightly.
With Cytadren or Proviron, it takes quite a lot of inhibitor to outcompete high testosterone levels. With Arimidex, rather little, even 1 mg/day, can be sufficient because it binds so strongly.
The other general approach is estrogen receptor antagonism. If a molecule binds strongly to a hormone receptor, but does not activate that receptor and makes it unresponsive to the normal hormone, then it is a receptor antagonist. Clomid (clomiphene) and Nolvadex (tamoxifen) follow this approach. These drugs are very similar structurally. They are both what are called triphenylethylenes, and are not steroids. The differences are relatively minor, but seem to affect an important characteristic of these compounds: drug metabolism.
Both tamoxifen and clomiphene are metabolized to other related compounds which can be estrogenic or anti-estrogenic. Both act as estrogens in bone tissue, perhaps after metabolism, which is a very useful property for female patients, for whom these drugs are usually intended. (Otherwise, an anti-estrogen could lead to osteoporosis.) Tamoxifen seems particularly prone to acting as an estrogen in the liver, which may account for reduced IGF-1 levels seen when this drug is taken.
Users generally seem to agree that when tamoxifen is used, gains are a little less than what otherwise would be expected. (Let’s not take this too far though: many people have made great gains while using tamoxifen as an anti-estrogen. And it’s always hard to say what “would” have been the case if a drug had not been included.) I’ve heard nothing but good about clomiphene, though.
Proviron, an anabolic steroid, is particularly interesting. I suspect that it not only acts as an antiaromatase but in an unknown DHT-like anti-estrogenic manner. This might involve estrogen receptor downregulation for example. In any case, aromatase inhibition and/or Clomid don’t seem to give the same effect on appearance and muscle hardness as when Proviron is included.
How much of these agents is needed for effective estrogen suppression?
Again, it depends on the dose of anabolic/androgenic steroids (AAS) and it depends what type of AAS is being used.
With Primobolan or trenbolone there is no need for these drugs.
With nandrolone, an aromatase inhibitor will be of no use, because aromatase is not used in the aromatization of nandrolone. A rather small amount of estrogen receptor antagonist can be useful. 12.5 to 25 mg Clomid would be plenty for 400 mg/week Deca.
With testosterone, stacking of an aromatase inhibitor and an estrogen receptor antagonist will give the best results. Cytadren use should not exceed 250 mg/day in my opinion. This alone would not be sufficient for say 1 g/week or more of testosterone. With such a dose, ideally one would add in 50 mg/day Clomid. Proviron at 100 mg/day could substitute for the Cytadren. Or Cytadren and Proviron can be used in combination, 125/50 or higher, together with 50 mg/day Clomid.
For lower doses of testosterone, proportionally less antiestrogens can be used.
Arimidex is very effective but extremely expensive. 1 mg/day of this is at least as effective as 250 mg/day Cytadren. If a milligram per day cannot be afforded, use of half a milligram would allow Cytadren use to be cut in half, which may be desirable.
How does Clomid “stimulate” testosterone production at the end of the cycle?
It really doesn’t. Rather, by acting as an estrogen receptor antagonist, it reduces the inhibition that results from elevated estradiol levels. This helps return LH to normal levels, which helps testosterone to return to normal levels (if the testicles have not atrophied).
How does hCG help?
Acts as an LH receptor agonist, thus substituing for LH. It does nothing to help the hypothalamus and pituitary. Thus, it can be effective during the cycle to help avoid testicular atrophy, but is not best used in the taper when one is attempting to restore LH production. Increases in natural testosterone, stimulated by the hCG, will act to inhibit LH production. Thus, you can see where hCG use is counterproductive in the taper itself.
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