SERMs, Aromatase Inhibitors (AIs) for Estrogen Maintenance


Cardiovascular Health and Steroid Risks





By William Llewellyn





Back in the ’60s and ’70s, the early days of the steroid era in bodybuilding, estrogen maintenance was a relatively crude science. Bodybuilders typically had to arrange their stacks in such a way that the use of aromatizable steroids was kept to a moderate level, often balanced by formidable doses of non-aromatizable/less-aromatizable substances. Estrogen was managed, basically, by controlling the level of estrogen-producing drugs administered to the body.





By the 1980s, bodybuilders saw the advent of “estrogen maintenance drugs” and they have undoubtedly changed the landscape of steroid use forever. The first such drug of fame was Nolvadex, a SERM (selective estrogen receptor modulator) that can block the activity of estrogen in certain target tissues, while mimicking its actions in others. Nolvadex proved to be an extremely effective remedy against many of the side effects of estrogen (including gynecomastia) and is still widely used by bodybuilders for this purpose.





The last 30 years has seen a progressive evolution of the drugs used in this area of medicine, many now targeting not the binding of estrogen in target tissues, but the actual production of this hormone. Aromatase inhibitors (AIs) have a remarkable power to block the enzyme responsible for forming estrogens. Agents such as Arimidex (anastrozole), Aromasin (exemestane) and Femara (letrozole) have proven themselves superior to older medications in many facets of clinical medicine and by some accounts are also poised to relegate Nolvadexto permanent obsolescence in the bodybuilding arena. But is “estrogen maintenance” really as simple as choosing the strongest drug? I’d like to take a look at the raging debate over what’s the “best” estrogen maintenance drug and in the process, I hope to present some new considerations you may not have considered.





Tamoxifen and Lipids





We understand the key benefit to both types of drugs; namely an ability to reduce the activity of estrogen in the body. Furthermore, we know that contemporary AIs are much stronger than an older, SERM-like tamoxifen. These points aren’t being debated. What we’re trying to look at here are the comparative advantages and disadvantages of each choice in regard to cardiovascular health. If you must choose an anti-estrogenic drug (due to side effect mitigation), which one should it be? One such point of difference is going to lie in the effect each drug has on serum lipids. Tamoxifen, known to act more as an estrogen in the liver than an anti-estrogen, has been shown under certain conditions to impart a beneficial effect on serum lipids.1,2 This is supported not just by medical evidence on less than perfectly comparable (to steroid using males) populations, but a great deal of anecdotal evidence from bodybuilders. I can personally attest to noticing a positive impact when adding Nolvadex to a steroid cycle and I’m sure many of you reading this can attest to the same as well.





Aromatase Inhibitors and Lipids





There’s been a great deal of misunderstanding concerning the cardiovascular effects of aromatase inhibitors, particularly as they relate to the steroid-using bodybuilder. Often, studies where an aromatase inhibitor (such as exemestane or anastrozole) is given to women or elderly male subjects without significant effect on blood lipids, are misapplied to the steroid-using athlete. It’s all about context, and the situations are very different. These studies typically report no significant change in lipids simply because the physiology was normal and the modest reduction in estrogen the drug caused was not enough to have a “significant” impact. Such studies, however, often still show a slight reduction in HDL cholesterol; it’s just not deemed to be clinically significant by the researchers.





To suggest studies on postmenopausal women, elderly males, or even young males under normal physiology, apply directly to steroid users and what aromatase inhibitors will affect their lipids and what aromatase inhibitors won’t, is to make a grave error. It discounts two very important things. First, it suggests that estrogen suppression itself isn’t important when it comes to lipid profiles, but the method of suppression. This is, of course, incorrect. Estrogen is a direct effecter of cholesterol synthesis and is as important here to men as it is women. The method of estrogen suppression is irrelevant to the effect the loss of hormone has on the body. Second, it infers that normal physiology applies perfectly to the steroid-using bodybuilder. Again, this may be very shortsighted, as the male bodybuilder is in a unique situation, endocrinologically speaking. Hormones are in an exaggerated state, with far more room for imbalance.





Elevated estrogen levels have been shown to help counter some of the negative cardiovascular effects of high testosterone levels caused by steroid administration. Aromatase inhibition in such a state will have a much more pronounced impact on lipids than during normal physiology by further exaggerating the imbalance between androgens and estrogens. This was demonstrated in a study published in the journal Metabolism.3 It involved giving a group of young male subjects 280 milligrams per week of testosterone enanthate, with or without aromatase inhibition, and measuring the effects on lipids. Here, the addition of an aromatase inhibitor produced a 25 percent reduction in HDL (good) cholesterol, while no significant change was noted in the testosterone-only group. The researchers concluded, “The aromatization of testosterone to estradiol appears to explain the absence of an expected androgen-induced … decrease in HDL cholesterol.” Bottom line, estrogen has a protective effect on cholesterol values and is important. The third-generation aromatase inhibitors may be stronger anti-estrogens, but they certainly aren’t going to help you maintain healthy lipid profiles while on-cycle, regardless of what some “experts” lead you to believe.





Arterial Relaxation





Estrogen has other important roles in the body when it comes to circulation and cardiovascular health. Much of this involves estrogen’s role in endothelial relaxation. Endothelial cells are thin flat cells that line the entire circulatory system and are responsible for helping to regulate such things as blood pressure (vasoconstriction and vasodilation), inflammation and swelling, and thrombic tendencies (clotting inside blood vessels). Endothelial dysfunction, or the loss of proper endothelial functioning, is a common characteristic of vascular disease and atherosclerosis. Although we may not have a great deal of data in which to base exact risk assessments, given the negative cardiovascular effects that can be associated with steroid use, one may want to take the effect estrogen maintenance drugs may have on endothelial relaxation seriously.





One study conducted with 20 healthy male subjects (aged 18 to 32) demonstrated the importance of estrogen here.4 This investigation made use of the aromatase inhibitor Arimidex (anastrozole) and has demonstrated that the drug can have a marked effect on reducing endothelial relaxation. Six weeks of drug therapy produced an approximate 25 percent reduction in serum estrogen (estradiol) levels, coinciding with a reduction in flow-mediated dilation by approximately 43 percent on average.


Tamoxifen, on the other hand, has been shown to have an estrogenic effect, instead of an anti-estrogenic effect, when it comes to endothelial relaxation.





A study published in the Journal of Pharmacological and Experimental Therapeutics, makes this point well.5 It demonstrated that tamoxifen induced a significant endothelium-dependent relaxation on coronary arteries. The researchers closed their abstract by stating, “These data suggest that tamoxifen has beneficial effects on coronary reactivity that could, at least in part, account for the reduction in risk of [heart attack] in women taking tamoxifen. Clearly, we are seeing two very different and opposing effects depending on the drug used.”





Making the Choice





As you can see, there’s a lot more to estrogen maintenance drugs than simply which one works best. If efficacy is your sole concern, than indeed, the best option will likely be found in a third-generation aromatase inhibitor. Certainly there are times, such as when someone is extremely focused on cutting, that advantages can be seen in potent aromatase inhibitors. These drugs, when taken properly, can minimize the effects of estrogen in the body far better than Nolvadex.





Drugs like Arimidex, Aromasin and Femara, however, are most often used not for drastic body recompositioning, but a simple need to mitigate the side effects of increased estrogen. In such cases, one may definitely find more favor in a SERM-like tamoxifen, which can do the same relative job, but without the same negative implications on cardiovascular health. Don’t get me wrong. I know the risks associated with steroid use are largely overstated, but they still exist. If you’re the kind of person who has made steroid use more of a lifestyle choice than an occasional endeavor, you may want to take such concerns to heart (pun intended).





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. Increased plasma HDL-cholesterol and apo A-I in breast cancer patients undergoing adjuvant tamoxifen therapy. Mastroianni A, Bellati C, Facchetti G, Oldani S, Franzini C, Berrino F. Clin Biochem, 2000 Aug;33(6):513-6.



2. Effects of tamoxifen treatment on plasma lipids and lipoprotein lipid composition. Bagdade JD, Wolter J, Subbaiah PV, Ryan W. J Clin Endocrinol Metab, 1990 Apr;70(4):1132-5.



3. High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Friedl KE, Hannan CJ Jr, Jones RE, Plymate SR. Metabolism, 1990 Jan;39(1):69-74.



4. Endogenous estrogens influence endothelial function in young men. Robert Lew, Paul Komesaroff et al. Circ Res, 2003;93:1127-33.



5. Tamoxifen acutely relaxes coronary arteries by an endothelium-, nitric oxide-, and estrogen receptor-dependent mechanism. Figtree GA, Webb CM, Collins P. J Pharmacol Exp Ther, 2000 Nov;295(2):519-23.



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