Estrogen Aromatization

Testosterone is the primary substrate used in the male body for the synthesis of estrogen (estradiol), the principal female sex hormone. Although the presence of estrogen may seem quite unusual in men, it is structurally very similar to testosterone. With a slight alteration by the enzyme aromatase, estrogen is produced in the male body. Aromatase activity occurs in various regions of the male body, including adipose, liver, gonadal, central nervous system, and skeletal muscle tissues. In the context of the average healthy male, the amount of estrogen produced is generally not very significant to one's body disposition, and may even be beneficial in terms of cholesterol values (See Side Effects: Cardiovascular System). However, in larger amounts it does have potential to cause many unwanted effects including water retention, female breast tissue development (gynecomastia), and body fat accumulation. For these reasons, many focus on minimizing the build-up or activity of estrogen in the body with aromatase inhibitors such as Arimidex and Cytadren, or anti-estrogens such asClomid orNolvadex, particularly at times when gynecomastia is a worry or the athlete is attempting to increase muscle definition. We must, however, not be led into thinking that estrogen serves no benefit. It is actually a desirable hormone in many regards. Athletes have known for years that estrogenic steroids are the best mass builders, but it is only recently that we are finally coming to understand the underlying mechanisms why. It appears that reasons go beyond the simple size, weight, and strength increases that one would attribute to estrogen-related water retention, with this hormone actually having a direct effect on the process of anabolism. This is manifest through increases in glucose utilization, growth hormone secretion,and androgen receptor proliferation.

Glucose Utilization and Estrogen

Estrogen may play a very important role in the promotion of an anabolic state by affecting glucose utilization in muscle tissue. This occurs via an altering of the level of available glucose 6-phosphate dehydrogenase, an enzyme directly tied to the use of glucose for muscle tissue growth and recuperation. More specifically, G6PD is a vital part of the pentose phosphate pathway, which is integral in determining the rate nucleic acids and lipids are to be synthesized in cells for tissue repair. During the period of regeneration after skeletal muscle damage, levels of G6PD are shown to rise dramatically, which is believed to represent a mechanism for the body to enhance recovery when needed. Surprisingly, we find that estrogen is directly tied to the level of G6PD that is to be made available to cells in this recovery window.

The link between estrogen and G6PD was established in a study demonstrating levels of this dehydrogenase enzyme to rise after administration of testosterone propionate to estradiol was directly responsible for this increase, and not the androgenic action of this steroid. The nonaromatizable steroids dihydrotestosterone and fluoxymesterone. Furthermore, the positive effect of testosterone propionate was blocked when the aromatase inhibitor 4-hydroxyandrostenedione (formestane) was added, while 17-beta estradiol administration alone caused a similar increase in G6PD to tesosterone propionate. The inactive estrogen isomer alpha estradiol, which is unable to bind the estrogen receptor, failed to do anything. Further tests using testosterone propionate and the antiandrogen flutamide showed that this drug also did nothing to block the positive action of testosterone, establishing it as an effect independent of the androgen receptor.

Estrogen and GH/IGF-1

Estrogen may also play an important role in the production of growth hormone and IGF-1. IGF-1 (insulin-like growth factor) is an anabolic hormone released in the liver and various peripheral tissues via the stimulus of growth hormone (See Drug Profiles: Growth Hormone). IGF-1 is responsible for the anabolic activity of growth hormone such as increased nitrogen retention/protein synthesis and cell hyperplasia (proliferation). One of the first studies to bring this issue to our attention looked at the effects of the anti-estrogen tamoxifen on IGF-1 levels, demonstrating it to have a suppressive effect. A second, perhaps more noteworthy, study took place in 1993, which looked at the effects of testosterone replacement therapy on GH and IGF-1 levels alone, and compared them to the effects of testosterone combined again with tamoxifen. When 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 300 mg of testosterone enanthate weekly to cause a slight IGF-1 increase in normal men. Here the 300 mg of testosterone ester caused an elevation of estradiol levels, which would be expected at such a dose. This was compared to the effect of the same dosage of nandrolone decanoate; however, this steroid failed to produce the same increase. This result is quite interesting, especially when we note that estrogen levels were actually lowered when this steroid was given. Yet another demonstrated 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.

Estrogen and the Androgen Receptor

It has also been demonstrated that estrogen can increase the concentration of androgen receptors in certain tissues. This was shown in studies with rats, which looked at the effects of estrogen on cellular androgen receptors in animals that underwent orchiectomy (removal of testes, often done to diminish endogenous androgen production). According to the study, administration of estrogen resulted in a striking 480% increase in methyltrienolone (a potent oral androgen often used to reference receptor binding in studies) binding in the levator ani muscle. The suggested explanation is that estrogen must either be directly stimulating androgen receptor production, or perhaps diminishing the rate of receptor breakdown. Although the growth of the levator ani muscle is commonly used as a reference for the anabolic activity of steroid compounds, it is admittedly a sex organ muscle, and different from skeletal muscle tissue in that it possesses a much higher concentration of androgen receptors. This study, however, did look at the effect of estrogen in fast-twitch skeletal muscle tissues (tibialis anterior and extensor digitorum longus) as well, but did not note the same increase as the levator ani. Although discouraging at first glance, the fact that estrogen can increase androgen receptor binding in any tissue remains an extremely significant finding, especially in light of the fact that we now know androgens to have some positive effects on muscle growth that are mediated outside of muscle tissue.

Estrogen and Fatigue

“Steroid Fatigue” is a common catchphrase these days, and refers to another important function of estrogen in both the male and female body, namely its ability to promote wakefulness and a mentally alert state. Given the common availability of potent third-generation aromatase inhibitors, bodybuilders today are (at times) noticing more extreme estrogen suppression than they had in the past. Often associated with this suppression is fatigue. Under such conditions, the athlete, though on a productive cycle of drugs, may not be able to maximize his or her gains due to an inability to train at full vigor. This effect is sometimes also dubbed “steroid lethargy.” The reason is that estrogen plays an important supporting role in the activity of serotonin. Serotonin is one of the body's principle neurotransmitters, vital to mental alertness and the sleep/wake cycle. Interference with this neurotransmitter is also associated with chronic fatigue syndrome, so we can see how vital it is to fatigue specifically. Estrogen suppression in menopause has also been associated with fatigue, as has the clinical use of newer (more potent) aromatase inhibitors like anastrozole, letrozole, exemestane, and fadrozole in some patients. These things may be important to consider when planning your next cycle. Although not everyone notices this problem when estrogen is low, for those that do, a little testosterone or estrogen can go a long way in correcting this. It is also of note that the use of strictly non-aromatizable steroids sometimes causes this effect as well, likely due to the suppression of natural testosterone production (cutting off the main substrate used by the male body to make estrogen).

Anti-Estrogens and the Athlete

So what does this all mean to the bodybuilder looking to gain optimal size? Basically I think it calls for a cautious approach to the use of estrogen maintenance drugs if mass is the key objective (things change, of course, if we are talking about cutting). Obviously, anti-estrogens should be used if there is a clear need for them due to the onset of estrogenic side effects, or at the very least, the drugs being administered should be substituted for nonestrogenic compounds. Gynecomastia is certainly an unwanted problem for the steroid user, as are noticeable fat mass gains. But if these problems have not presented themselves, the added estrogen due to a cycle of testosterone or Dianabol, for example, might indeed be aiding in the buildup of muscle mass, or keeping you energetic. An individual confident they will notice, or are not prone to getting, estrogenic side effects, may therefore want to hold off using estrogen maintenance drugs so as to achieve the maximum possible gains in tissue mass.


Wlliam Llewellyn (2011) - Anabolics

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