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,22 liver,23 gonadal,24 central nervous system,25 and skeletal muscle26 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 Disease). 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 antiestrogens such as Clomid or Nolvadex, 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 playa 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.27 28 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 bo.dy 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. The investigation further showed that the aromatization of testosterone to estradiol was directly responsible for this increase, and not the androgenic action of this steroid.29 The non-aromatizable steroids dihydrotestosterone and fluoxymesterone were tested alongside testosterone propionate, but failed to duplicate the effect of testosterone. 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 testosterone propionate.The inactive estrogen isomer 17alpha estradiol, which is unable to bind the estrogen receptor, failed to do anything. Further tests using testosterone propionate and the anti-androgen 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·l
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 I the effects of the anti-estrogen tamoxifen on IGF-1 levels, demonstrating it to have a suppressive effect.30 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.3' When tamoxifen was given, GH and IGF-l 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-l 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 lowered32 when this steroid was given. Yet another demonstrated that GH and IGF-l secretion is increased with testosterone administration on males with delayed puberty, while dihydrotestosterone (non-aromatizable) seems to suppress GH and IGF-l secretion.33
