Ask Bill Roberts #1

Q: 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?

A: 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 out-competed 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 out-compete 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.

Can Clomid, taken throughout a cycle, completely eliminate inhibition?

I do not believe so. There is also androgenic inhibition mediated by the androgen receptor, which has nothing to do with the estrogen receptor. Androgenic inhibition is unavoidable and cannot be helped by estrogen receptor antagonists. However, use of Clomid throughout a cycle can definitely reduce the degree of the inhibition and allow a speedier recovery at the end of the cycle.

Is it safe to take Clomid for so many weeks? I heard it should only be taken for 2 weeks.

The two week idea comes from the fact that medically its main use is to help women with fertility problems. Because of the menstrual cycle, there are only certain times of the month when there is any chance of ovulation. It is pointless, then, for these women to take the drug for more than two weeks at a time. Some have misconstrued this to apply to males.

Men have taken the drug in clinical studies for a year continuously. It is a rather safe drug.

Why do you say not to use more than 250 mg/day of Cytadren?

Cytadren has two main therapeutic activities. At high doses, such as a gram per day, it is a very effective inhibitor of the enzyme desmolase, which is required for all steroid production, and is rate limiting for the production of cortisol. So the drug is very useful for treating patients with Cushing’s Syndrome, who produce abnormally high levels of cortisol.

It is also an inhibitor of aromatase, and it is a better aromatase inhibitor than a desmolase inhibitor. About 250 mg/day is sufficient for fairly good inhibition of aromatase, resulting in only fairly low levels of desmolase inhibition.

As dosage increases, aromatase inhibition does not improve much, but desmolase inhibition increases greatly.

Even at 250 mg day, there is still significant desmolase inhibition. Other side effects, such as lethargy, may bother some individuals even at this dose.

Why is desmolase inhibition bad? I have read that cortisol is the enemy of our muscles, and we want to reduce it.

Those articles are written by people trying to sell you alleged cortisol-reducing supplements.

While abnormally high levels of cortisol are indeed muscle wasting, abnormally low levels of cortisol do not result in extra muscle growth, and cause joint problems.

Dear Bill,

You’ve talked about tapering off Cytadren. Why?

There is a feedback mechanism for production of cortisol. Low levels of cortisol enhance release of corticotropin releasing hormone from the hypothalamus, and ACTH from the pituitary. Both will result in higher production of cortisol.

So moderate inhibition of desmolase will temporarily reduce cortisol, but soon it will be back to normal as this feedback mechanism compensates.

If you then suddenly discontinue the drug, then these elevated ACTH levels will result in abnormally high cortisol for a time, until the body adjusts again. This can be avoided simply by tapering down over about a week.

Should Cytadren be taken all at once, or in divided doses?

Because the half life is only 6 or 8 hours, if the drug is taken only once, then through part of the day there will be little drug in the system, and little anti-aromatase activity.

I think the best approach is to use half the dose on arising (or an hour or two afterwards) to get blood levels from a somewhat low level up to the desired maintenance level. This would then be followed by quarters of the dose at 7 or 8 hour intervals twice after that.

You talked about a gram per week of testosterone. Isn’t that ridiculous? What about say 200 mg?

It is my view that the farther one is from one’s natural, untrained state, the harder it is to gain more muscle. There comes a point where the body essentially finds a new balance and may remain at the same muscular weight (give or take a pound or two) for a year or more, even with excellent training, if hormonal conditions remain the same.

Under different hormonal conditions – for example, more testosterone – growth can resume and a new balance point, if reached, will be at a considerably higher muscular weight. At that point, even if one were to stay on that dose of drug continually, little gains would be seen. But with higher yet levels of testosterone, rapid growth could again resume.

So a person who has already made a lot of gains is probably not going to see much, if anything, from 200 mg/week testosterone. And if he used steroids to get there, and is already more muscular than he’d be as a natural trainer, he may see nothing at all, just maintenance.

A true beginner, on the other hand, can make plenty of gains with natural levels of testosterone.

From the medical standpoint, 600 mg/week has been shown to be quite safe. Furthermore, in double blind studies and so forth, doses of less than 300 mg/week generally have resulted in nothing. These studies have usually been with athletes training the same during the cycle as they were beforehand. They’re generally useless for our purposes but they do make a point here. If the dose is 300 mg/week and an athlete trains and eats the same as before, no miracle results.

Yes, I know I’ll come under criticism: you or your buddy did great on 250 mg/week. But in every case I have ever seen, such trainers were guys who were not that dedicated to lifting until they went on their cycle. They weren’t in their peak condition at the start of the cycle, and so they had some muscle memory to help them. Or they were fairly novice lifters. They trained and ate better than they ever did before. They probably would have regained 10 lb. of muscle and gained a new 10 lb. just on Placebobolan, thanks to the training, nutrition, intensity, and muscle memory. Those who ate enough to get fat will also attribute some of the fat weight as being muscle weight.

Now there is one regard where a low dose can be quite effective. This is in fat loss. Many people, especially natural endomorphs, can enjoy easy fat loss for the first time in their lives on quite moderate doses such as 250 mg/week.

I would say that 500 mg/week is a reasonable minimum for muscle gains, except for an advanced trainer, who may need a gram a week to make much further gains. To advance to today’s pro BB status, even if one has the genetics, requires more yet, not just in quantity but in supplementary drugs such as GH and insulin, which I will not be discussing.

Dear Bill,

Isn’t it true that such-and-such, because it converts to DHT, will . . . ?

No.

The only commercially available AAS for human use which converts to DHT is testosterone.

All others have modifications to the structure which make it absolutely impossible for them to be converted to DHT per se (dihydrotestosterone).

Any time a steroid book goes on and on about various steroids “converting to DHT” and presenting theories about this, the author does not know anything about steroid chemistry. It is as simple as that.

By the way, there is a veterinary steroid which can convert to DHT, though not significantly, and no one should change their opinion of it because of this. I thank Pat Arnold for pointing out to me that boldenone can do so, although rather negligibly.

What about all those “DHT-based steroids”?

That is more nonsense. The AAS which have been so described in popular books are no more similar to DHT than to testosterone. This statement makes about as much sense as calling all anabolic steroids diosgenin (wild yam) based, or androstenedione “DHEA based” (oh no, I hope I have not started a new rumor. . .)

One simply has to look at the activity of each AAS in its own right without trying to use theories which aren’t based on correct information anyway.

Dear Bill,

Is it true though that a drug such as nandrolone is less likely to cause hair loss than testosterone?

Yes. This may be because nandrolone is converted to DHN rather than DHT. Dihydronandrolone is almost the same molecule as DHT, but without the 19-methyl group. While DHT binds to the androgen receptor (AR) more strongly than testosterone does, DHN binds fairly weakly to the AR, less so than nandrolone itself does.

Nandrolone itself is a 5a -reductase inhibitor (although it yields DHN in the process). So less DHT is produced if nandrolone is present. Nandrolone will also inhibit natural production of testosterone, so there is less testosterone available to be converted to DHT.

The testosterone user has high levels of DHT in the scalp, and therefore a lot of androgen in the scalp. The nandrolone user has low levels of DHT, instead having DHN, which is less potent.

Furthermore, DHT probably has hair loss activities not mediated by the androgen receptor, but by other proteins in the scalp and via the immune system. DHN may not have these activities.

More importantly, what is observed is that nandrolone is quite good for keeping one’s hair, whereas testosterone is not, for those genetically predestined to lose their hair.

The price one pays for this, though, is that nandrolone is not as effective an anabolic as testosterone.