Can estrogen work to augment muscle growth? Is this hormone always unwanted when we are taking anabolic steroids? Anecdotal reports from athletes suggest that the use of estrogen maintenance drugs such as tamoxifen (anti-estrogen) or aminoglutethimide (anti-aromatase) may slightly hinder muscle mass gains during steroid therapy. An explanation or even clarification for this observation has not been easy to come by. Here I would like to take a look at the comparative effectiveness of certain aromatizable and non-aromatizable drugs, as well as the possible mechanism in which estrogen can play a beneficial role to the athlete.

The Androgen Receptor
All anabolic/androgenic steroids promote muscle growth primarily via the cellular androgen receptor (abbreviated as AR in this article). The steroid attaches to and activates the androgen receptor, which ultimately gives the cell an order to increase protein synthesis. This process is well understood. But it has been suggested that other mechanisms may foster muscle growth during steroid therapy as well, which lie outside of the androgen receptor. One way this is evidenced is by the fact that steroids displaying a high affinity for the AR in muscle tissue do not always promote an equally high level of muscle growth. In other words, anabolic potency does not always correspond perfectly to receptor affinity. Clearly there are some disparities that lead into question whether or not the androgen receptor is the only thing at work concerning growth.

Testosterone, Nandrolone and Methenolone
Testosterone is without question one of the most effective steroids for building muscle mass available to athletes. However it does not have the highest affinity for the androgen receptor compared to some other steroids. For example, it has been shown that by eliminating the 19-methyl group (nandrolone) the affinity of the steroid for the androgen receptor is greatly enhanced[i]. Nandrolone thus displays approximately 2-3 times greater affinity for the androgen receptor compared to testosterone, yet its ability to promote muscle growth seems to be considerably lower than testosterone at an equal dosage. One discussed possibility for this occurrence is the reduced androgenic potency of nandrolone. While testosterone converts to the more active steroid dihydrotestosterone (3-4 times greater AR affinity) upon interaction with the 5-alpha reductase enzyme in various androgenic target tissues such as the skin, scalp, prostate, CNS and liver, nandrolone drops to a third of its original potency by converting to the weak steroid dihydronandrolone[ii]. However this action is very site specific, and in muscle tissue nandrolone dominates as the active form of the steroid. Therefore this explanation may not suffice.

Nandrolone also differs from testosterone in its ability to be converted by the aromatase enzyme to estradiol (an active estrogen). In comparison, nandrolone aromatizes at approximately 20% of the rate testosterone does, and as such is not known as a very estrogenic steroid. It is likewise favored when reduced estrogenic side effects such as water retention, fat deposition and gynecomastia are desired. However athletes know that there is a trade off with the reduced tendency for nandrolone to promote side effects, in that it is a less anabolic steroid. With its known high affinity for the AR in muscle tissue, could this suggest that estrogen may also be a key mediator of muscle growth?

When we look at Primobolan� (methenolone) we see a similar trend. Methenolone is at least as good a binder of the androgen receptor as testosterone. By some accounts it is on par with nandrolone[iii]. However it is known to be much weaker than both steroids at promoting muscle growth. We know that methenolone does not interact with 5-alpha reductase, and as such its affinity for the AR does not increase or decrease in androgen target tissues. This would logically seem like a more favorable trait for anabolism over the weakening we see with nandrolone. However methenolone is a markedly weaker anabolic, and requires relatively high doses to promote growth. This also brings into question the role of 5-alpha reductase in promoting an anabolic state. Perhaps the fact that Primobolan� is a non-aromatizable steroid is more relevant.

Estrogen and GH/IGF-1
To date the most common explanation for why anti-estrogens may be slightly counterproductive to growth in the sports literature has been the suggestion that estrogen plays a role in the production of growth hormone and IGF-1. IGF-1 (insulin like growth factor 1, formerly known as somatomedin C) is of course an anabolic product released primarily in the liver via GH stimulus. IGF-1 is responsible for the growth promoting effects (increased nitrogen retention, cell proliferation) we associate with growth hormone therapy. We do know that women have higher levels of growth hormone than men, and also that GH secretion varies over the course of the menstrual cycle in direct correlation with estrogen levels[iv]. Estrogen is likewise often looked at as a key trigger in the release of GH in women under normal physiological situations.

It is also suggested that the aromatization of androgens to estrogens in men plays an important role in the release and production of GH and IGF-1. This was evidenced by a 1993 study of hypogonadal men, comparing the effects of testosterone replacement therapy on GH and IGF-1 levels with and without the addition of tamoxifen[v]. When the anti-estrogen tamoxifen was given, GH and IGF-1 levels were notably suppressed, while both values were elevated with the administration of testosterone enanthate alone. Another study has shown 300mg of testosterone enanthate weekly (which elevated estradiol levels) to cause a slight IGF-1 increase in normal men, whereas 300mg weekly of nandrolone decanoate (a poor substrate for aromatase that caused a lowering of estradiol levels in this study) would not elevate IGF-1 levels[vi]. Yet another study shows that GH and IGF-1 secretion is increased with testosterone administration on males with delayed puberty, while dihydrotestosterone (non-aromatizable) seems to suppress GH and IGF-1 secretion, presumably due to its strong anti-estrogenic/gonadotropin suppressing action[vii]. All of these studies seem to support a direct, estrogen-dependant mechanism for GH and/or IGF-1 release in men. It is difficult to say at this point just how important estrogen is to IGF-1 production as it relates to the promotion of anabolism in the steroid using athlete, however it remains an interesting subject to investigate.

Glucose Utilization and Estrogen
Estrogen may play an even more vital role in promoting an anabolic state by affecting glucose utilization in muscle tissue. This occurs via an altering the level of available glucose 6-phosphate dehydrogenase. G6PD is an important enzyme in the support anabolism, as it is directly tied to the use of glucose for muscle growth and recuperation[viii] [ix]. During the period of regeneration after skeletal muscle damage, levels of G6PD are shown to rise dramatically. G6PD enzyme plays a vital role in what is known as the pentose phosphate pathway, and as such this rise is believed to enhance the PPP related process in which nucleic acids and lipids are synthesized in cells; fostering the repair of muscle tissue.

A 1980 study at the University of Maryland has shown that levels of glucose 6-phosphate dehydrogenase rise after administration of testosterone propionate, and further that the aromatization of testosterone to estradiol is directly responsible for this increase.[x] In this study neither dihydrotestosterone nor fluoxymesterone could mimic the affect of testosterone propionate on levels of G6PD, an affect that was also blocked by the addition of the potent anti-aromatase 4-hydroxyandrostenedione to testosterone. 17-beta estradiol administration caused a similar increase in G6PD, which was not noticed when its inactive estrogen isomer 17-alpha estradiol (unable to bind the estrogen receptor) was given. An anti-androgen could also not block the positive action of testosterone. This study provides one of the first palatable explanations for a direct and positive effect of estrogen on muscle tissue.

What does this all mean?
It is a long held belief among athletes that estrogen maintenance drugs can slightly hinder muscle gains during steroid therapy with a strong aromatizable steroid such as testosterone. Whether or not we have plausibly explained this remains to be seen, however the above evidence certainly does provide strong support for a direct and positive affect of estrogen on growth. Does this mean we should abandon estrogen maintenance drugs? I don�t think that should be the case. It is important to remember that estrogen can deliver many unwanted effects such as increased water retention, fat deposition and the development of female breast tissue when it becomes too active in the male body. Clearly if we plan a high-dose cycle with an aromatizable steroid, anti-estrogens will be an important inclusion. However we cannot ignore the suggestion of using estrogen maintenance drugs only when they are necessary to combat visible side effects during mild to moderately dosed cycles, especially if bulk is the ultimate goal of the athlete.

Bibliography

[i] Comparison of the receptor binding properties of Nandrolone and Testosterone under in vitro and in vivo conditions. J Steroid Biochem 22(6) 831-36 1985

[ii] Relative binding affinities of testosterone, 19-nortestosterone and their 5-alpha reduced derivatives to the androgen receptor and to other androgen-binding proteins� J Steroid Biochem 17 653-60 1982

[iii] Relative Binding affinity of anabolic-androgenic steroids� Endocrinology 114(6) 2100-06 1984

[iv] Pulsatile growth hormone release in normal women during the menstrual cycle. Clin Endocrinol 36: 591-96 1992

[v] Activation of the somatotropic axis by testosterone in adult males: Evidence for the role of aromatization. J Clin. Endocrinol Metab 76:1407-12 1993

[vi] Testosterone administration increases insulin-like growth factor-I levels in normal men. J Clin Endocrinol Metab 77(3):776-9 1993

[vii] Androgen-stimulated pubertal growth:the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. J Clin Endocrinol Metab 76(4)996-1001 1993

[viii] Pentose Cycle Activity in Muscle from Fetal, Neonatal and Infant Rhesus Monkeys. Arch Biochem Biophys 117:275-81 1966

[ix] The pentose phosphate pathway in regenerating skeletal muscle. Biochem J 170: 17 1978

solution: allow greater levels of systemic estrogen?

NO.

Take alpha lipoic acid and other supplements that improve insulin sensitivity and glucose clearance

BTW- Deca does not aromatize into estrogen

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Originally posted by good old Macro!!:

BTW- Deca does not aromatize into estrogen

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The main influx of invalidity comes from the fact that their claims of estrogen being anabolic comes from the injection of testosterone. They are arriving at their claims of anabolic effects of estrogen without injecting estrogen.
They do not have an unbiased control group in this experiment. Nandralone is not a sufficient control.

What would have been a sufficient control would be to inject Methenalone in the control group and inject estrogen into the experimental group.
That would eliminate the exponential number of dependent variables that are there. Lets see if estrogen really does increase the effeciency of the IGF-1 pathway, lets see if estrogen really does influence glucose metabolism, lets see what effect estrogen has if any (besides female specific fat distribution and gyno).

The reason I don't like using testosterone as proof of an estrogen effect is that it leaves open too many other variables. I give this study no merrit. We do not fully know the effects of androgens on our physiology; if we did, we wouldn't need to conduct research like this. This article is scientific lingo filled CRAP.

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Originally posted by yiyangzhi:
I'm planning a mild cycle of primo400mg/wk & winny depot 50mgED. Is it a waste of money to take proviron 25mgED since primo does not aromatise? Could I still take proviron just to enhance muscle hardness?

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Proviron = antiaromitase = testosterone does not turn into estrodiol = you have more test = you have better gains + no gyno + no water retention + no female fat distribution + reduction in post cycle depression = wasting less gear = happier with your cycle results.

-Stew

MACRO, this is not entirely correct. Dihydrotestesterone has been shown to decrease insulin sensitivity (and in some studies, no effect), while nandrolone has been shown to increase glucose disposal. Oxymetholone has been shown to decrease insulin sensitivity, which could be evidence for its theorized progestagenic nature (progestens increase lipolysis which decreases insulin sensitivity).

STEW, the article is a decent review of the literature. Estradiol IS anabolic and this is well documented in the literature, HELL, the cattle industry has capitalized on this fact, ever heard of Ralgro or Compudose? Estrogenic agents have been shown to be anabolic through effects on GH, insulin and IGF modulation. This supports the idea that anti-estrogens would reduce IGF levels.

The Pharmacological Basis of Therapeutics states that estradiol is equipotent in regards to anabolism as test propionate. This may sound crazy, but one must realize that estradiol is effective in women at very low doses.

As for insulin sensitivity, estrogen's effects are not yet definitive. Some studies have shown no effects while some have shown increase in insulin function.

Estrogen HAS NEVER BEEN PROVEN TO HAVE ANY ANABOLIC PROPERTIES. This study did not prove that. It only proved that testosterone is anabolic and that it also converted to estrogen. THAT'S IT. There is no correlation between estrogen and anabolism. The only thing estrogen is anabolic to is FAT. FAT is the reason it is implanted ito heifers. Estrogen will aid in marbleing the meat. Fat makes cattle weight more. Estrogen makes fat and fat does not = muscle.
I say again, this study did not prove anything besides the fact that test is anabolic and that it converts to estrogen. We do not know if the added anabolic of test compared to that of primobolan or nandrolon has anything to do with estrogen. There are hundreds of things that could contribute to that. Hormones are known to cause anabolism through more than one pathway. BUT THAT PATHWAY IS NOT THROUGH ESTROGEN. You will never convince me of that without doing a study where you inject estrogen and see if it causes anabolism.
THAT'S WHAT YOU CALL RESEARCH. Not bull shit.