The Truth About Aromatase Inhibitors
By William Llewellyn
Q: Is it true that taking aromatase inhibitors with testosterone will make it less effective? If so, why?
A: Bodybuilders have long understood that aromatizable steroids like testosterone and Dianabol, as well as the inherently estrogenic agent Anadrol, are among the most integral to a good bulking cycle. Although each is a potent anabolic agent in its own right, conversion to estrogen (or mimicking its activity) is believed to contribute, at some level, to the effectiveness of each drug. We know this by simple trial and error; blocking estrogen with aromatase inhibitors or anti-estrogenic drugs often causes a steroid cycle to lose a little “oomph.” Can you gain good bulk without an estrogenic agent? Of course, you can. But it’s hard to deny that having a little extra around when trying to do this does help out.
Science hasn’t explained fully why this is the case, mainly because understanding why bodybuilders respond to anabolic steroids the way they do has not been a big medical priority. Studies that would relate exactly to such use (higher doses for the sake of muscle growth) are rare, and the few published tend to look more at health effects than underlying mechanisms of action. But there is a good amount for us to look at in the medical texts in general, which can tell us some important things about the way estrogen works in the body. As it turns out, we do find some very interesting actions inherent in the female sex hormone estrogen that would appear very important to male performance, as well.
One such study was published in the Journal of Clinical Endocrinology and Metabolism.1 It looked at the effects of supplemented estrogen and endurance exercise in men. In this investigation, 12 recreationally active males were given oral estrogen supplements and were subjected to moderate-intensity endurance exercise (stationary cycle). Participants took 2 milligrams of estradiol (Estrace) per day, which produced a more than seven-fold increase in serum estrogen levels. This dose also moderately suppressed testosterone levels, which declined from 21 nanomoles per liter (nmol/L) to 17 nmol/L +/- 1 on average.
What was most remarkable, though, were the effects estrogen supplementation had on substrate oxidation during exercise. The hormone caused a substantial shift in the sources of fuel utilized, with carbohydrate and protein (leucine) oxidation being reduced by 5 to 16 percent and 16 percent, respectively. This was largely replaced by fat oxidation, which increased by 22 to 44 percent. This trend results in the sparing of both protein and glycogen during intense exercise, which would be a clear performance benefit.
Earlier papers also show some important actions going on with estrogen. For example, a study was published in the journal Endocrinology that demonstrated testosterone propionate to increase levels of the glucose 6-phosphate dehydrogenase enzyme.2 This enzyme plays a central role in the “Pentose Phosphate Pathway,” which helps dictate how carbohydrates are utilized for repair in skeletal muscle tissue.3 This increase in G6PD, however, was eliminated when an aromatase inhibitor was concurrently given, or when testosterone propionate was substituted with other non-aromatizable steroids (dihydrotestosterone and fluoxymesterone).
Although not normally thought of as vital for muscle growth, carbohydrates (glucose) are indeed important to structural repair and are utilized for such basic purposes as nucleic acid and lipid synthesis within regenerating cells. Glucose 6-phosphate dehydrogenase was long known to be elevated in the regeneration window following exercise-induced damage, and we now understand that estrogen itself is vital to the expression of this enzyme.
Another study was conducted that looked at the effects estrogen has on the activity of male sex hormones, namely testosterone.4 The understanding that one hormone (estrogen) may effect the actions of a very different hormone (testosterone) is not new, but in this case it was isolated mainly to its effects on endogenous testosterone production and levels. This study looked at something different, namely what effect estrogen would have on the level of androgen receptors in various tissues.
The investigators were able to demonstrate that estrogen administration causes an increase in the level of available androgen receptors, which increases sensitivity to this hormone and therefore, its activity. They were not able to show the same increase in skeletal muscle as they were in levator ani (a sex organ muscle with more androgen), however. But given the diverse actions of androgens in the body and how they may relate to performance, one still might expect some performance-enhancing benefit to result, even if this activity does not turn out to be a major one in muscle itself.
There is also a known link between estrogen and GH/IGF-1 secretion. More specifically, this female sex steroid is understood to stimulate the GH/IGF-1 axis, increasing levels of these hormones in both men and women. Scientists looking at the effects of sex steroids in men, and how they relate to GH/IGF-1 secretion, have demonstrated that while testosterone administration itself will increase GH/IGF-1, this benefit is blocked when anti-estrogens are taken at the same time.5 Although GH (or really IGF-1, which is the anabolically active end product of growth hormone) isn’t necessarily a tremendously effective muscle-building hormone, it’s still known to play a role here. Suppressing the normal increase that would be caused by the use of a drug like testosterone would logically not be a benefit.
Together, these studies emphasize that there are activities inherent in estrogen that might make one think twice before always automatically suppressing it during a steroid cycle. A good rule of thumb, at least one that always worked well for me, is to keep an eye on estrogen, but not necessarily take strong suppressive or receptor-blocking drugs unless there were a clear need for it. When I’d notice nipple sensitivity or visible bloat in the mirror, it was time to think about using them. This was most commonly the case during bulking phases of training anyway, when a little fat gain (higher levels of estrogen can sometimes foster the preservation of body fat) wasn’t as important as maximum muscle mass increases. Cutting can be another story, and often involves lowering estrogen to maximize definition. In any event, the take-home message is that estrogen isn’t necessarily your enemy.
William Llewellyn is widely regarded as one of the world’s foremost authorities on the use of performance-enhancing substances. He is the author of the bestselling anabolic steroid reference guide ANABOLICS and CEO of Molecular Nutrition. William is an accomplished researcher/developer in the field of anabolic substances, and is also a longtime advocate for harm reduction and legislative change. He built the website anabolic.org, an extensive online database of information on anabolic steroids and other performance-enhancing drugs.
References:
1. Estrogen supplementation reduces whole body leucine and carbohydrate oxidation and increases lipid oxidation in men during endurance exercise. J Clin Endocrinol and Metab, March 8, 2005.
2. Aromatization of androgens to estrogens mediates increased activity of Glucose 6-Phosphate Dehydrogenase in rat levator ani muscle. Endocrinology, 196 (1980) pg. 440.
3. The pentose phosphate pathway in regenerating skeletal muscle. Biochem J (1978) 170, 17-22.
4. Modulation of the cytosolic androgen receptor in striated muscle by sex steroids. Endocrinology, 115 (1984) pg. 862-66
5. Activation of the somatotropic axis by testosterone in adult males: Evidence for the role of aromatization. J Clin Endocrinol and Metab, (1993) 76: 1407-12.
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