by Mike Arnold
Everything tends to move in phases. This is true of training, diet, drug use, and even the smaller, less recognized aspects of the bodybuilding experience. Although some of the younger guys won’t remember this, it was only about 15 years ago that the use of aromatase inhibitors was heavily frowned upon when attempting to build muscle mass. We were taught that estrogen was an integral component of the muscle building process and therefore, if a little was good, more must be better. Despite a complete lack of scientific evidence in support of this claim, many bodybuilders chose to forego estrogen management almost entirely, even when employing large dosages of highly aromatizable compounds. Although Nolvadex was the usual go-to treatment for dealing with gynecomastia, as a S.E.R.M it was entirely ineffective at lowering estrogen levels. This allowed systematic estrogen to continue wreaking havoc on one’s health and appearance; both internal and external.
In time, as science failed to establish a connection between estrogen elevation and muscle growth, bodybuilders began to shift their attention away from its benefits and start focusing on its negatives characteristics, such as water retention, fat gain, etc. In an effort to curb these unwanted effects, the off-season use of A.I.’s (aromatase inhibitors) became standard practice. Unfortunately, in the same way that bodybuilders had once sought to keep estrogen levels elevated, we now started to see the exact opposite, with many individuals oversuppressing estrogen production to the point of deficiency. However, neither of these extremes are ideal as both tend to produce many of the same side effects. An example of estrogen’s paradoxical nature can be observed when evaluating its affect on the cardiovascular system. In this instance, both elevation and deficiency tend to increase the risk of developing heart disease/atherosclerosis; a serious consequence that should give any bodybuilder cause for concern.
While most of us are fairly well informed regarding estrogen’s ability to cause feminizing side effects, much fewer seem to be aware of just how critical it is to the recovery and growth process. This misconception developed as a result of its close association with the female sex; a belief which has kept it from receiving it’s just dues for decades and even now causes many to view it as some sort of antithesis to testosterone. While these two hormones do display some antagonistic activity, neither gender can claim ownership, as estrogen plays an important role in the development and maintenance of physiological function in both men and women. In fact, many of the anabolic/anti-catabolic effects typically associated with PEDs are also directly/indirectly influenced by estrogen to one degree or another.
Fortunately, obtaining the best of both worlds is rather easy, requiring us only to maintain estrogen levels within an optimal range. Although opinions on this subject vary, most experts in the field agree that a reading of about 30 pg/ml is ideal for maximizing the hormone’s risk to benefit ratio. With the over-use of AI’s causing many of today’s bodybuilders to sink in the 15-20 pg/ml range, I felt it appropriate to spend some time discussing the many ways in which estrogen can positively impact a bodybuilder’s goals, but before I do so, I have a confession to make. While I would like to see every one of you maximize your bodybuilding progress, my primary motive for writing this article isn’t to help you gain another 20 pounds of muscle, but to help you avoid the potentially serious consequences associated with estrogen mismanagement. With steroids, growth hormone, and insulin all adversely affecting cardiovascular function through multiple mechanisms, it only makes sense to eliminate risk whenever possible, especially when that risk carries no additional benefit.
To be blunt, if someone is willing to spend thousands of dollars a year on gear, as well as additional funds on steroid and growth hormone testing, spending a few bucks on lab work shouldn’t be too much of a financial setback. For those of you who have insurance, getting one’s estrogen level checked can often be done for a one-time fee of $20-$40, and when included as part of a more comprehensive panel, it is frequently included at no extra charge. Still, the promise of more muscular and leaner body is all the incentive most of you will need to demonstrate responsibility in this area. With that said, let’s get right into it.
As one of bodybuilding’s most highly regarded PEDs, growth hormone is something that nearly every bodybuilder wants more of, but which few can afford to use with consistency. While having an unlimited GH budget might be nice, it simply isn’t reality for most of us, so we may as well do what we can to extract maximum benefit from the GH our bodies already produce. Oddly enough, few of us take the time to consider our natural GH levels, viewing them as static in nature and unworthy of potential manipulation. This is unfortunate, as GH production can fluctuate significantly and is affected by several different variables within our control, one of which is estrogen.
Having been known in the scientific community for several decades, estrogen’s ability to increase growth hormone production is well documented. This effect is readily observable in women, whose test results consistently report higher levels of growth hormone than men across all populations. However, this advantage is lost during menopause as a result of the dramatic decrease in estrogen levels that accompany this transitionary state. A similar effect has been witnessed in pre-pubertal children, in whom a single dose of estradiol administered pre-bed produces a statistically significant rise in growth hormone levels relative to control subjects. Although a boost in growth hormone production is a good enough reason for most bodybuilders to keep estrogen levels optimized, estrogen has also been shown to have other desirable effects on this hormone, one of which is the ability to enhance growth hormone receptor expression and receptor binding. In short, this means that estrogen potentiates the effect of GH at the receptor level, making any growth hormone you already have in your body work even better.
With estrogen involved in the regulation of 51 genes in skeletal muscle alone, it shouldn’t come as a surprise to learn that its effect on our musculature is much more complex than what most of us originally thought. Although its ability to increase growth hormone production is fairly well known, its ability to stimulate angiogenesis (the development of new blood vessels) is not. Estrogen plays a direct role in this process by up-regulating a protein coding gene called Angpt1, which is critical to endothelial cell survival, pericyte recruitment, and vascular branching. Estrogen has also been shown to down-regulate the Thbs1 gene; a potent inhibitor of angiogenesis. By enhancing those aspects of our physiology which promote blood vessel development and impeding those which oppose it, overall vascularization is increased, leading to improved microcirculation in muscle tissue. As a result, oxygen and nutrient delivery capacity is increased, as is recovery rate via the accelerated removal of metabolic waste products accumulated during training. Increased angiogenesis also provides cosmetic benefits by contributing to overall surface vascularity.
Next up is nitric oxide. Most bodybuilders are at least moderately familiar with this stuff, as it is the primary molecule responsible for initiating vasodialation (the expansion of blood vessels) and has been responsible for inspiring the formulation and sale of hundreds of bodybuilding supplements over the last 15 years. Even today, it remains (usually as part of a more comprehensive pre-workout formula) a popular category of supplementation. Estrogen has the capacity to increase nitric oxide levels via the activation of nitric oxide synthase; a family of enzymes responsible for catalyzing the production of nitric oxide (NO) from L-arginine. This provides multiple benefits for the bodybuilder, such as enhanced muscle pumps, increased nutrient delivery, and all the other perks associated with increased blood flow. However, unlike dietary supplements that only increase N.O. levels for a few hours, estrogen has a positive impact on nitric oxide all day long.
Another lesser known benefit of estrogen is the ability to alter fuel metabolism, which it accomplishes by regulating intermediary genes involved in glucose and lipid utilization. It does this in several ways, one of which is the up-regulation of pyruvate carboxylase. By up-regulating this enzyme, the rate at which oxaloacetate is formed from pyruvate is increased. This in turn stimulates glyconeogenesis—the formation of glycogen from protein and/or fats. Estrogen has also been shown to up-regulate the Fbp2 gene; a critical player in the glyconeogenesis pathway. Lastly, estrogen has been demonstrated to enhance glucose uptake via increased Glut-4 translocation (Glut-4 is a carrier protein responsible for transporting glucose inside the cell wall), as well as by activating key steps in the PI3K/Akt signaling pathway cascade. Why is this significant? Because it leads to greater glycogen storage within muscle tissue, which is vital for optimizing muscle fullness/size, recovery, growth, and performance. It also has a positive impact insulin sensitivity (the benefits of which are too numerous to mention here) by reducing the amount of insulin required to properly regulate blood sugar levels.
Most bodybuilders tend to view estrogen as a fat storage hormone, but its actions on adipose tissue are not so simple. In excessive amounts it can indeed lead to body fat acquisition, but in quantities compatible with male physiology it has a positive effect on bodyfat, making it both more difficult to store fat and easier to lose fat. It does this by up-regulating the Ce3 gene, which is responsible for mediating lipase independent lipolysis (the release of fatty acids from fat cells). This is the same mechanism through which growth hormone stimulates fat loss and the first step in the fat loss process. Now that we are aware of estrogen’s effect on both glycogen synthesis and fat loss, are there any practical applications we can take away from this?
First and foremost, I want to discourage bodybuilders from going crazy with the A.I’s, although what is considered optimal (in terms of estrogen levels) will vary depending on the circumstances. I already touched on the issue of off-season estrogen levels earlier in this article (see Part #1), but I have not yet addressed estrogen levels in contest prep. Conventional wisdom dictates that we should attempt to lower estrogen levels as much as possible during the last few weeks of prep in order to become as dry as possible. Some have even gone so far as to over-suppress estrogen levels during the earlier stages of prep, as they believe this will eliminate estrogen’s pro-fat storage effects and allow them to get leaner easier.
While this all sounds plausible in theory it doesn’t work out that way in the real world. For one, as we have already seen, lowering estrogen levels too far will actually have a negative effect on fat loss by reducing lipase independent lipolysis via the down-regulation of Ce3. For this reason, regardless of whether it is off-season or pre-contest, I recommend keeping estrogen levels around 30 pg/ml. This doesn’t change until the bodybuilder enters the later stages of prep—the final 2-3 weeks. At that point it would be beneficial to lower estrogen to around 15 pg/ml. This will allow the individual to eliminate any estrogen-induced subcutaneous water retention, while still leaving enough estrogen floating around to facilitate adequate glycogen synthesis. At this point I have experimented with several different estrogen control strategies during prep and this approach seems to produce the best results.
When it comes to muscle growth, few endogenous molecules have as profound of an effect as IGF-1. Stimulating hypertrophy directly and indirectly through at least a half-dozen different mechanisms, IGF-1 is considered one of the big dogs of the PED world. In fact, the main reason most people use growth hormone is because of its ability to substantially increase IGF-1 levels. Anyway you look at it, IGF-1 is an important part of the muscle growth process…and one more reason not to over suppress estrogen production.
While most estrogen-mediated effects are pretty cut and dry in terms of what to expect, its impact on IGF-1 mediated muscle growth is less clear. Some studies show elevations in IGF-1 levels with estrogen supplementation, while others show no increase. Still, some others show a decrease in IGF-1 levels. This discrepancy is due to the route of administration, rather than some unknown variable causing test results to fluctuate. In reality, only oral administration has been shown to adversely affect IGF-1 production (and increase IGFBP-1 levels), while estrogen which is present as a result of aromatization has a positive effect on IGF-1 levels and no affect on binding proteins.
There is some bad news, though. Even when estrogen is produced via aromatization, estrogen tends to reduce local IGF-1 expression in muscle tissue. In other words, although IGF-1 levels may go up, the muscles’ ability to respond to IGF-1 is diminished. Think of it as a form of desensitization—same principle, but a different process. Although both of these effects (IGF-1 elevation and reduced gene expression) are relatively mild in terms of intensity, we can’t really weigh them in the balance simply because we have no way of obtaining an accurate measurement for either of them. Although this might sound like a big deal it’s real not. As mentioned earlier, not only is this effect very mild, but it will be counteracted through AAS use—a class of drugs that nearly every estrogen-concerned bodybuilder is using. I am sure you’re waiting for an explanation, so here goes. Many steroids, including DHT, decrease the expression of a gene referred to as Grb10. This gene is a negative regulator of IGF1, so by suppressing it, the body’s ability to respond to IGF-1 is enhanced. This directly counteracts estrogen’s mild negative effect on IGF-1 expression, making it null and void. So basically, anyone who uses steroids is unknowingly eliminating the issue.
Another cool effect associated with estrogen is the ability to enhance growth potential by increasing androgen receptor density. In laymen’s terms, this means that estrogen increases the number of androgen receptors in muscle tissue. Being that AR activation is the main pathway through which steroids initiate their beneficial effects on muscle growth, the more ARs we have, the more AAS one can effectively utilize before reaching receptor saturation. While most people aren’t going to use an amount of AAS capable of filling up all available receptors, there are plenty of bodybuilders out there who will and do. In these cases, an increase in AR density can pay dividends by allowing the individual to take advantage of larger doses of anabolics.
Out of all the positive effects estrogen has on our bodybuilding efforts, this next one is my favorite. I am talking about the ability to increase muscle strength. Recent studies reveal that this effect is not mediated by an increase in muscle size, but through a direct effect on muscle function, which researchers refer to as an improvement in muscle “quality”. More specifically, estrogen improves a muscle’s ability to generate force by causing myosin to bind to actin more strongly during the contraction process. Evidence reveals that this effect is almost certainly mediated through estrogen receptor binding, rather than some poorly understood or yet to be identified non-genomic effect. While an increase in muscle strength is not necessarily correlated with muscle growth, it can stimulate growth indirectly by allowing the individual to lifter heavier weights within the hypertrophy rep range. As we all know, heavier weights leads to increased muscular stress, muscular stress then leads to a greater growth stimulus, and a greater growth stimulus then leads to increased hypertrophy.
Despite possessing a much lower levels of testosterone in the bloodstream, research has repeatedly shown that women experience less muscle damage after weight training and tend to recover more quickly than their male counterparts. When attempting to determine the underlying cause for this gender specific anomaly, researchers traced the cause back to…you guessed it…estrogen. Acting as a muscle protectant, estrogen helps prevent exercise induced muscle damage through 3 different mechanisms: a reduction in muscle oxidative damage, reduced production of pro-inflammatory compounds, and the increased production of heat shock proteins.
When it comes to inhibiting oxidation, one of the ways in which estrogen benefits us is by increasing the expression of genes involved the glutathione metabolic pathway that protect cells from oxidative damage. Of these, the most influential of the bunch of is the Gpx3 gene. When estrogen up-regulates this particular gene, it not only prevents muscle cell oxidation, but also improves skeletal muscle insulin sensitivity by mediating the antioxidant effect of PPARg. To sidestep for a second, a recent report revealed that myosin (one of the two main contractile proteins in muscle fiber) is susceptible to oxidation and that this oxidation significantly impairs contractile function. Therefore, up-regulating Gpx3 also preserves muscle strength. As you can see, estrogen enhances strength through multiple mechanisms, making it an important hormone for strength athletes and all others attempting to maximize strength levels.
In addition to inhibiting oxidation, estrogen also blunts the production of interleukin-6 and interleukin-8; two inflammatory compounds produced in response to weight training and which are largely responsible for the development of delayed onset muscle soreness (D.O.M.S) the day after a hard workout. Heat shock proteins, which are activated by various forms of muscle stress (ex. heat, exercise, trauma, etc.), provide a further level of protection by facilitating muscle protein assembly and working to maintain protein structure. Through the manipulation of all these processes (oxidation, inflammation, and HSP activation), estrogen can protect muscles from damage, accelerate recovery rate, increase muscular strength, and improve growth rate.
While I have touched on several of estrogen’s most important bodybuilding related benefits, this article is by no means exhaustive. Rather, my purpose here was to provide the reader with a general idea of just how extensive this hormone’s role is in the overall bodybuilding process. Going forward, we should dispense with silly notions which peg estrogen as a decidedly “female” sex steroid and rather, view it as it really is—a unisex hormone with a wide variety of beneficial and even pro-male effects. So long as levels remain within a male appropriate range, feminization will remain a non-issue, just as much as testosterone does not promote masculinization in women when levels remain in a female appropriate range. Never the less, the over-suppression of estrogen should be strictly avoided, as it provides no benefits and a multitude of unwanted side effects.