Aromatase Inhibitors, Nolvadex and Cholesterol
Choosing the Right Anti-estrogenic Drug
By William Llewellyn
Aromatase inhibitors are a class of medications that block the enzyme responsible for estrogen formation in the body, and are without question powerful tools in the bodybuilder’s drug arsenal. The common use of these agents in our sport is actually a new phenomenon, despite the fact that drugs of this type were first developed many years ago. (Teslac dates back to the 1960s, for example). It seemed to take the release of Arimidex some years ago, a selective third-generation aromatase inhibitor noted for superior clinical effectiveness and tolerability,1 to finally spark our interest. Prior to this, the anti-estrogen Nolvadex was the drug of choice (both black market and medically), which works by blocking estrogen at its receptor instead of actually lowering its levels.
Aromatase inhibitors and anti-estrogens produce a similar end result, namely countering the effects of estrogen, but have two very different modes of action in doing so. It’s important to understand that as such, there are separate advantages and disadvantages to these drugs, and you may not want to choose one for your next cycle based solely on which is more potent. As you will see, there are important risks, specifically regarding cholesterol, involved with aromatase inhibitors that need to be discussed before jumping headfirst on the Arimidex bandwagon.
Estrogen Suppression and Cholesterol
It is poorly understood that there is a link between estrogen and cholesterol levels in men. We tend to think of this hormone as exclusively relevant to females, which is grossly inaccurate, to say the least. Estrogen plays a vital role in the production of HDL (high-density lipoprotein; the good cholesterol) in both men and women, and is believed similarly to play a protective role from heart disease for both sexes. Cardiac risk relating to cholesterol is really assessed more by looking at the ratio of HDL to LDL (the bad cholesterol) than by the total cholesterol count. Similarly, maintaining a high ratio is looked at as a primary concern for sustaining good cardiovascular health.
It is here that aromatase inhibitors can present a startling risk to the user, as the suppression of estrogen in men can have profound consequences on our cholesterol ratio and cardiac risk profile. In some instances, in fact, a drug such as Arimidex could be more dangerous than the anabolic steroids we would want to use it with.
This suggestion may sound surprising to you, but the consequences of estrogen suppression are actually well documented in the medical literature. One study, for example, demonstrated without question that estrogen is needed to support high-density lipoprotein cholesterol synthesis in men.2 In this study, a group of normal young men were given Nal-Glu, a potent antagonist of GnRH, to suppress endogenous testosterone levels. Testosterone enanthate was given in a dose of 100 milligrams weekly to restore levels to the normal range, allowing the investigators to better control the amount of testosterone and estrogen in the body.
A second group was given the same, plus the aromatase inhibitor Teslac, so as to produce an estrogen deficient state. A third group was given all placebo medications. What the investigators found was quite striking. The group of men with suppressed estrogen levels noticed a profound drop in HDL levels, most specifically in the HDL-2 fraction. This was compared to a slight, but not statistically significant, drop in HDL cholesterol in the TE only group, and no change in hormonal and lipid profiles in the placebo group. The investigators were left to conclude, obviously, that estrogen was important in maintaining HDL cholesterol levels, and may offer protection against cardiovascular disease in men.
A second study, published a few years earlier, might perhaps come across to you as more relevant to the steroid-using athlete.3 This investigation looked at the cholesterol altering effects of 280 milligrams per week of testosterone enanthate, when it was taken with or without (again) Teslac. The 12-week length of intake was typical for a steroid cycle, and the dosage applied at least on the low end of what would be considered acceptable for building muscle. The difference noticed between the two regimens was, again, startling.
HDL cholesterol levels were not significantly altered at all with the use of testosterone only, while they dropped 24 percent by the fourth week for those taking testosterone with the aromatase inhibitor. For this group, levels remained suppressed for the rest of therapy, and for a few weeks after. Based on HDL levels alone, the men in the testosterone + Teslac group were categorized by the researchers as having a remarkably higher risk for coronary artery disease compared to those taking testosterone only. They also noted that this study shows that high-dose testosterone administration does not necessarily have a dramatic effect on one’s risk for heart disease, and that aromatization to estrogen offers some protection by helping to maintain favorable cholesterol levels. The implications for the current en-vogue practice of routinely suppressing estrogen with aromatase inhibitors, as a way to mitigate estrogen-related side effects, are clear.
Nolvadex and Cholesterol
But what about Nolvadex? Since it’s an anti-estrogen, wouldn’t it have the same effect on cholesterol? The answer, surprisingly, is no. This was demonstrated well in a study that took place in 1988 at the Netherlands Cancer Institute, which charted the cholesterol altering effects of Nolvadex on a group of 54 women.4 Noting the important role of estrogen in cardiovascular health, the investigators wanted to see if the recently adopted practice of using tamoxifen long-term to prevent breast cancer could present a danger to cholesterol profiles because of its anti-estrogenic action. The result, surprisingly, was exactly the opposite of what they feared. A 10-milligram daily dose actually increased HDL cholesterol, while simultaneously lowering LDL levels. Cardiovascular risk, as assessed by serum cholesterol levels, was lowered instead of increased. All factors pointed to an estrogenic effect on cholesterol levels rather than an anti-estrogenic one.
It turns out that Nolvadex is a very unique type of drug. It’s a tissue-selective estrogen receptor agonist/antagonist, meaning it exhibits anti-estrogenic properties in some areas of the body while actually acting as an estrogen in others. One place in particular that Nolvadex actually exhibits estrogenic activity is the liver, which is the location responsible for HDL cholesterol synthesis. As a result, instead of lowering HDL levels, Nolvadex actually tends to raise them. It seems our old standard anti-estrogen is still the safest option, at least where cholesterol is concerned. In many regards it is an ideal solution really, being anti-estrogenic in tissues where it counts, such as the breast, while acting estrogenic in one of the most important places to have such activity. It could serve both cardiovascular protective and side-effect mediating purposes; far different from that of aromatase inhibitors.
Choosing the Right Drug
The facts presented in this article should make clear that although aromatase inhibitors can effectively mitigate the unwanted effects of estrogen, they also present significant risks by suppressing estrogen levels. There is no question as to which is the stronger agent. Arimidex would not be as popular as it is today if it were not effective. But, as we see, there is more to choosing the right anti-estrogenic drug than picking the most potent. Steroid use indeed entails some health risks, and the smart athlete is always looking to minimize them. With the relationship between cholesterol and heart disease, the risks related to aromatase inhibitors certainly should not be ignored. I am not calling for an abandonment of these agents at all, as clearly there are times when they can be highly valuable. But, given the general unawareness of their risks in the bodybuilding public, and their far too liberal use at this point, I felt the discussion was sorely needed.
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. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Bonneterre J Cancer 2001 Nov 1;92(9):2247-58
2. Physiological levels of estradiol stimulate plasma high-density lipoprotein2 cholesterol levels in normal men. Bagatell, et al. J Clin Endocrinol Metab v.78(4) 1994 855-61
3. High-Density Lipoprotein It Not Decreased if an Aromatizable Androgen Is Administered. Friedl, Hannan et al. Metabolism v.39(1) 1990 69-74
4. Tamoxifen, serum lipoproteins and cardiovascular risk. Bruning, Bonfrer et al. Br. J Cancer 58(4) 1988 497-9
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