Several types of anabolic steroid drugs, including testosterone, can convert into estrogen. That occurs whenever a steroid encounters the enzyme aromatase, which converts androgens into estrogens. Aromatase exists all over the body—in muscles, brain and bodyfat. When free, or unbound, testosterone meets aromatase, the test is rapidly converted into estradiol, the most potent form of estrogen. Aromatase converts weaker androgens, usually secreted from the adrenal gland, such as androstenedione, into weaker forms of estrogen, such as estrone. That, in fact, was a major problem with the initial generations of pro-hormone supplements. They were supposed to convert directly into testosterone, making them superior to the old standby, DHEA. In reality, most of them converted more reliably into estrogen. Later versions proved more stable, but even then, any free testosterone derived from such supplements had to deal with aromatase.
Estrogen in men is considered a problem for bodybuilding purposes because when the hormone rises to above normal levels, it produces a number of undesirable effects, including water retention and an increase in subcutaneous fat, a combination that effectively obscures muscular definition. Even worse, excess estrogen in men interacts with estrogen receptors in the chest area to produce gynecomastia, or male breast-tissue formation. Nodules just under the nipple are particularly evident when the arms are raised. Gyno, or the more sexist term “bitch tits,” is considered a certain sign of anabolic steroid usage. The cure is to either get off the steroids that caused it or use drugs that block or inhibit estrogen function.
In years past a popular drug for that purpose was tamoxifen citrate, better known by its trade name Nolvadex. Nolvadex is structurally similar to estrogen and can block estrogen receptors, thereby preventing estrogenic activity. It wasn’t designed for bodybuilding use but for treating estrogen-sensitive breast cancer, particularly in older women.
What many bodybuilders didn’t realize—and still don’t—is that Nolvadex is both an antagonist and agonist of estrogen. That means it can have a paradoxical effect, acting more like an active estrogen than an estrogen blocker, especially when it’s taken in either too large a dose or for too long a time. In addition, Nolvadex blocks at least two enzymes that testes require for testosterone synthesis. Clearly, it wasn’t ideal for dealing with excess estrogen in men.
Enter the aromatase-inhibiting drugs. They deal with estrogen in a different way. They don’t just block estrogen receptors; they knock out the aromatase enzyme that produces estrogen from androgens. The effect results in a dramatically reduced level of estrogen in the body. Since 0.8 percent of testosterone is converted daily into estrogen in any man, just using an aromatase-inhibiting drug alone will lead to elevated T levels.
In fact, various aromatase inhibitors, such as anastrozole, letrozole and examestane, are being evaluated for use in treating hypogonadism, or low testosterone levels, in men. Initial studies show that these drugs can elevate testosterone to a normal range without the possible side effects linked to using actual testosterone. The body may, however, require some estrogen for sperm production and cardiovascular protection, since estrogen boosts nitric acid production in blood vessels and helps maintain vital high-density-lipoprotein levels.
With the advent of potent aromatase-inhibiting drugs, it seemed that the estrogen problem had finally been effectively solved in men who chose to use certain types of anabolic steroids.
Or had it?
According to a recent study, even if you effectively inhibit estrogen synthesis through aromatase-inhibiting drugs, you can still get estrogenic effects from other sources.1 Anything that can positively interact with estrogen cell receptors can produce estrogenic side effects, even if the substance in question isn’t a direct estrogen.
The study examined two types of isolated cells, one from breast cancer cells, the other from noncancerous cells. According to the authors, the estrogen cell receptor can be activated by certain androgens. One is androstane-3-beta, 17-beta diol (3BD), a nonaromatizable steroid derived from dihydrotestosterone. DHT itself is converted from testosterone by way of the 5-alpha reductase enzyme, which, like aromatase, is present throughout the body in such tissues as skin, liver, brain and prostate.
DHT is often considered to be testosterone’s evil twin. It earned its notorious reputation because it’s linked to the onset of such steroid side effects as male-pattern baldness, acne and prostate gland enlargement. The interesting aspect of this is that anabolic steroids that are based on the DHT structure are immune to the effects of aromatase and thus cannot be converted into estrogen.
Yet the new study shows that at least one DHT-derived androgen can interact with estrogen receptors to produce effects similar to those linked with an excessive level of estrogen itself. The information, however, is still theoretical because it’s unknown whether the concentration of 3BD used in the isolated-cell study can be produced in an intact human body. On the other hand, the authors note that the level of the estrogen-mimicking steroids depends on the level of testosterone in the body, the activity of 5-alpha reductase and the metabolic level of the steroids. All of those factors are high in athletes who use anabolic steroids.
The solution to this problem is clear. Using a drug that inhibits the 5-alpha reductase enzyme would prevent the synthesis of DHT from testosterone and the downstream metabolites of DHT that can interact with the estrogen receptors. Drugs in this class, or 5-alpha reductase inhibitors, include finasteride, sold as Proscar and Propecia, and dutasteride, sold as Avodart. They treat prostate problems, and Propecia is marketed to treat male-pattern baldness. Many bodybuilders and other athletes are already using them to prevent problems associated with high DHT levels, such as baldness, acne and prostate problems. They may also be useful for preventing estrogenic effects.
Did Clenbuterol Cause This Heart Attack?
Since clenbuterol is based on epinephrine, it has side effects similar to those of epinephrine, including rapid heartbeat, nervousness, tremors, headache, muscle pain and gastrointestinal problems. In animals it provides a repartitioning effect, in that lean muscle mass increases while bodyfat is substantially lowered. That occurs in many animal species and explains why the drug proved attractive for athletic purposes. Some cases of clenbuterol-tainted meat have led to side-effect outbreaks in Europe, leading in turn to a European ban on clenbuterol for livestock purposes.
What many athletes didn’t consider, however, was that the doses of clenbuterol used in animal studies were far higher than could be tolerated by any human. The drug does provide potent—though fleeting—thermogenic effects, which is why it’s considered a “cutting” drug in bodybuilding. The adrenergic cell receptors that clenbuterol interacts with, however, are exquisitely sensitive and tend to close down within a short time, often with as little as two weeks of continuous use.
Athletes work around the considerable downregulation by taking it on a two-days-on/two-days-off pattern, which extends the usage time. Another technique involves using ketotifen (Zaditen), an antihistamine that can maintain the potency of adrenergic cell receptors, thereby extending the usefulness of clenbuterol.
Did Clenbuterol Cause This Heart Attack?
According to a recent case study, in some people the effect may be potent enough to lead to a heart attack in an otherwise healthy person.2 Published reports have linked a combination of clenbuterol and anabolic steroids to a bodybuilder’s heart attack. The 26-year-old man in that case had switched to using clenbuterol after getting off a steroid cycle. His heart attack was attributed to a spasm of his coronary arteries.
In the newly reported case, the subject was a 17-year-old bodybuilder who claimed that he used no anabolic steroids or other drugs with the exception of 20 milligrams a day of clenbuterol, which he took on a two-days-on/two-days-off protocol. That’s not considered a high dose or frequency. Despite that, he turned up at a clinic complaining of acute chest pains. Examination showed that he had a fast heart rate and an elevated level of homocysteine, an amino acid by-product linked to cardiovascular disease. Most of his other tests were normal, although certain elevated enzyme levels pointed to heart damage.
His diagnosis was that of a clenbuterol-induced coronary artery spasm, with possible blood clot in the left anterior descending coronary artery, the most common area of blood clots leading to heart attacks. The case was complicated, however, because the subject had two risk factors linked to the onset of coronary artery spasms—elevated homocysteine levels and increased clotting elements in the blood. Homocysteine is easily controlled in most cases by taking three nutrients: folic acid, and vitamins B6 and B12. The clotting can be controlled by small daily doses of aspirin, which he was given.
The question, then, is whether the heart attack was caused by clenbuterol or his other risk factors. Most likely it was a combination. The adrenergic effect of clenbuterol may have pushed him over the edge. One thing is certain, however: Clen-buterol, even in small amounts, exerts toxic effects on heart muscle tissue. It could cause serious heart problems in anyone. Combining clenbuterol with other thermogenic drugs, such as thyroid hormone, compounds the effect because TH in large doses also stresses the heart. The combination of the two could prove deadly.
In fact, clenbuterol and TH use are likely suspects in the death of a professional bodybuilder several years ago. This man was using large doses of TH and an injectable form of clenbuterol. He was also dehydrated and probably suffering an electrolyte, or mineral, imbalance. With that many things against him, it wasn’t surprising that he succumbed to a heart attack.
References
1 Ishikawa, T., et al. (2006). Aromatase-independent testosterone conversion into estrogenic steroids is inhibited by 5-alpha reductase inhibitor. J Steroid Biochem Molecul Biol. 98:133-138.
2 Kierzkowska, B., et al. (2005). Myocardial infarction in a 17-year-old bodybuilder using clenbuterol. Circulation Journal. 69:1144-1146.
©,2015 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited
