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Bodybuilding Pharmacology: Estrogen-Blocking Supplements

Until two years ago bodybuilders who wanted to increase testosterone levels without using anabolic steroids could purchase pro-hormone supplements. The original forms of those supplements weren’t effective. For example, DHEA, an adrenal steroid produced in the human body, is used in the synthesis of other hormones, including testosterone and estrogen. Based on that, DHEA supplements were touted for increasing testosterone in bodybuilders. DHEA did do that—but only in women. In men under age 40 it was converted into either estrogen or dihydrotestosterone, a testosterone metabolite associated with acne, male-pattern baldness and prostate enlargement.

Noting the problems, several entrepreneurs scoured the scientific literature and came up with compounds that, on paper, provided more direct routes to testosterone conversion. The most popular was androstenedione, which was said to be more effective than DHEA because it was a step closer in the synthesis process: In the body DHEA converted into andro, which then converted directly into testosterone.

Andro peaked in popularity after being linked to pro baseball player Mark McGwire. During his 1998 home-run spree, which broke a Major League record, a reporter noticed a bottle of andro in his locker. McGwire didn’t deny using the supplement, noting that it was perfectly legal in baseball. He’s been evasive in denying his use of anabolic steroids.

While it would be wrong to overlook the natural ability of players such as McGwire or Barry Bonds, consider the findings of American physicist Roger Tobin of Tufts University. Tobin estimated that using anabolic steroids can help batters hit 50 percent more home runs by boosting muscle 10 percent. With 10 percent more muscle, a batter can swing about 5 percent faster, which increases the speed of the ball 4 percent as it leaves the bat. Added speed can lead to home runs 50 percent more often—up to 100 percent according to Tobin. Then again, muscle and steroids are only part of the home-run equation; there’s no shortage of muscular ball players who come nowhere near the home-run record.

But I digress. Andro was wildly popular for a while among bodybuilders. Shortly after it hit the market, I looked at the testosterone pathway and noticed that it could easily be converted into estrogen. When I said so on an Internet forum, I was accused of being “jealous” of andro’s success, but medical studies proved me right. Rather than being converted into testosterone, andro tended to take the estrogen route in men. In women, however, as with DHEA, andro did raise testosterone levels.

So it was back to the drawing board for pro-hormone purveyors. They came up with a few esoteric androgens that flew under the FDA radar for a while. None were ever definitively shown to build muscle, but some produced such side effects as acne and liver enzyme elevations.

It was left for more technically oriented supplement gurus to turn to the musty old steroid textbooks of the late 1960s and search for more effective compounds. Thousands of potential drugs were originally researched from the 1950s to the late 1960s, but most never reached the market. They were described in arcane chemical guides, most notably in Androgens and Anabolic Agents: Chemistry and Pharmacology, a 1968 tome by Julius A. Vida. Several of the compounds—nothing less than full-fledged anabolic steroids, by the way—were resurrected and released as commercial pro-hormones. But not for long. In 2005 the federal anabolic steroid law, as amended, formally prohibited them.

The last generation of pro-hormones before the ban was unquestionably the most effective. How could they not be, as they were the real thing? Nobody bothered to raise the obvious question of why the drug companies that had done all that R&D didn’t put them on the market. Two words: side effects. Most of the drugs were harder on the liver than the oral anabolics that did reach the market, and they attacked the cardiovascular system even more rapidly. To avoid liability, the manufacturers relegated them to pharmaceutical limbo.

With the demise of such effective but problematic compounds, companies turned to the only other legal means of boosting testosterone: substances that inhibit the activity of an enzyme called aromatase, which is found in such tissues as liver, brain, muscle and fat in the legs and arms, and which converts free testosterone circulating in the blood into estrogen. Aromatase may explain the failure of the first generation of pro-hormones. Even if they did raise free testosterone in the blood, it didn’t take long for aromatase to kick in and convert it into estrogen.

Bodybuilders who use anabolic steroids have long been familiar with gynecomastia, or “bitch tits,” a common side effect characterized by an accumulation of excess glandular tissue in male breasts. The culprit is an overbalance of estrogen vs. testosterone, which can also cause water retention or even interfere with brain chemistry and impede testosterone synthesis.

The original way of dealing with excess estrogen was to take tamoxifen citrate, trade name Nolvadex, which was and still is prescribed mainly for older women who have breast cancer. It’s molecularly similar to and binds to the estrogen cell receptor, thus blocking the path of actual estrogen and rendering it inert. Trouble is, Nolvadex is not only an antagonist but also an agonist of estrogen. That is, it can bind to estrogen itself. So when taken too long or in too great a dose, it interferes with testosterone synthesis. ALL Drug research has produced other compounds that work more directly than Nolvadex in reducing estrogen levels. They block the activity of aromatase and considerably diminish the estrogen count. Newer forms of aromatase inhibitors, such as Arimidex or Aromesin, are extremely effective. Many pro bodybuilders rely on them to prevent estrogen-related side effects. Despite that, you often see gyno in competing bodybuilders—not because of estrogen but because of progesterone, another female sex hormone. Heavy use of anabolic steroids, such as Deca-Durabolin and the infamous designer steroid THG, ups the body’s progesterone content.

Because a certain amount of the testosterone men produce is converted into estrogen—about 1 to 8 percent daily—taking a drug that blocks the activity of aromatase would lead to an increase in blood testosterone. That’s the mechanism behind the test-boosting effects of over-the-counter estrogen-inhibiting supplements. Beyond all the hoopla, however, do those supplements really work as advertised, and are they as side effect-free as the ads claim?

Two of the most popular are Novadex XT and 6-OXO. Novadex XT is marketed by Gaspari Nutrition. Two companies sell 6-OXO, one owned by actor Sylvester Stallone, and the other is associated with Pat Arnold, who was instrumental in popularizing the original pro-hormone supplements. Arnold was indicted after being identified as the person who synthesized “the clear”—a.k.a. THG—the designer steroid at the center of the BALCO drug scandal.

A study examined the effects of providing 72 milligrams a day of Nolvadex XT to a group of young men engaged in weight training.1 After eight weeks researchers measured the following increases in hormone levels:

• Total testosterone, 283 percent
• Free, or active, testosterone, 625 percent
• DHT, 566 percent

No increase in fat-free mass occurred in the subjects, but their bodyfat decreased by 3.5 percent more than it did for those in the placebo group. Slight increases in estrogen also occurred, indicating that the supplement only partially blocked estrogen activity.

The same researchers then focused on 6-OXO.2 Sixteen young men, average age 26, used either 300 or 600 milligrams of 6-OXO for eight weeks in a double-blind experiment. Free testosterone rose by 90 percent for the 300-milligram group and 84 percent for the 600-milligram group. DHT rose by 192 percent and 265 percent, respectively, and the testosterone-to-estriadol ratio rose by 53 percent and 67 percent. Estrone, a weaker form of estrogen, increased by 22 percent with the 300-milligram dose and 52 percent with the 600-milligram dose. Estradiol, the most potent of the three forms of estrogen, rose by 27 percent with the 300-milligram and 12 percent for the 600-milligram dose. Once again, there was no change in body composition and no side effects or adverse body chemistry alterations.

The rise in free testosterone likely accounted for the increase in DHT, since 5-alpha reductase, the enzyme that converts test into DHT, wasn’t affected by the supplement. Some published studies suggest that when you inhibit aromatase, the activity of 5-alpha reductase tends to increase, again because there is more free testosterone in the blood available for 5-alpha conversion into DHT. The implications of these studies are that neither Nolvadex XT nor 6-OXO totally blocks estrogen and that both increase testosterone and DHT. The elevation of DHT could prove problematic, as it’s linked to male-pattern baldness, acne and prostate problems. Purveyors of these products suggest using them for limited periods, such as four to six weeks, as lowering estrogen levels for an extended period could adversely affect cardiovascular function. Estrogen is good for maintaining protective high-density-lipoprotein levels, and women tend to have better HDL counts because they have more estrogen. In addition, users of injectable testosterone show no adverse effects with regard to HDL because some of the test is converted into estrogen. If you add an aromatase blocker like Arimidex, that doesn’t happen. Most oral anabolic steroid drugs also lower HDL and thus are a long-term risk.

Since Novadex XT and 6-OXO don’t completely block estrogen, the safeguard mentioned by the sellers of such supplements is mainly a precaution, assuming that some people, such as those at risk for cardiovascular disease, may be more susceptible to potential problems. Thus far, there is no indication that using them will adversely affect cardiovascular health.

Elevated DHT is a more immediate problem, in my opinion. If you have the genes for male-pattern baldness or acne, you may experience flareups if you take too large a dose or stay on the supplements too long. The same holds true for the drug versions. You can remedy that by taking drugs that block 5-alpha reductase, such as Proscar or Avodart. Natural inhibitors of 5-AD include soy in small amounts, as well as green tea.

There is another problem with the OTC supplements. I’ve recommended them to men who are interested in boosting testosterone levels but who don’t want to use anabolic steroids. About half have reported a loss of libido. Since the supplements boost free testosterone, which is associated with elevated sex drive in both sexes, I’m at loss. It’s not a placebo effect, for the men expected increased sex drive, and it doesn’t happen to every man who takes the supplements. As to what the precise cause is, your guess is as good as mine.


1 Willoughby, D., et al. (2007). Eight weeks of aromatase inhibition using the nutritional supplement Novadex XT: Effects on steroid hormones, body composition, and clinical safety markers in young, eugonadal men. Int J Sport Nutr Exer Metab. 17:92-108.

2 Rohle, D., et al. (2007). Effects of eight weeks of an alleged aromatase-inhibiting nutritional supplement 6-OXO on serum hormone profiles and clinical safety markers in resistance-trained, eugonadal males. J Int Soc Sports Nutr. 4:13. IM

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