Androstenedione: Fact & Fiction

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Androstenedione has been much in the news lately. Is it a steroid? Is it performance-enhancing? What's fact and what's fiction?

Due to the large amount of dollars now spent on "sports" supplements, many supplement companies have seized on the huge gray area of hormones, steroids, enzymes and other chemicals in food, that might trigger an anabolic explosion of testosterone in athletes.

Some have genuine but moderate effects on muscle, such as melatonin and dehydroepiandrosterone (DHEA), mostly via the multiple other benefits they afford for health and fitness.( 1) Others, such as pregnenolone, have no supporting evidence, and several good mechanisms by which they might reduce muscle.

Hundreds of other chemical candidates crowd the market horizon. Along the testosterone highway, your body can produce 27 known androgens, and a whole swag of estrogens.( 2) Theoretically, the testosterone molecule is capable of more than 600 variations.

Androstenedione is a direct hormone precursor of testosterone. I've written before how hormone formation and use is under exquisite control of multiple enzymes, hormones, eicosanoids and other body chemicals.( 3) So, the ads and articles intimating that androstenedione will automatically boost testosterone are either naive or lying through their teeth. This is fiction.

If all you had to do was take one or other precursor of testosterone, then I have the perfect supplement for you. It is practically odorless and tasteless, not destroyed by digestion, readily absorbed into the bloodstream, the source of your testosterone, and can be bought for pennies at your corner grocery. And what is this magic chemical? Cholesterol, of course -- the raw material for all your steroid hormones.

I see a lot of fat folk who eat enough cholesterol to stuff a mattress. But it has no effect on their testosterone or muscle, because multiple body controls prevent it. To see whether androstenedione might have an effect, let's take a peek at a few of the main controls.

As the figure on page 10 shows, conversion of cholesterol into the intermediate hormone pregnenolone, requires adrenocorticotropic hormone (ACTH) produced by your pituitary gland. If ACTH production declines, the conversion is inhibited and all your steroid hormones decline.

High ACTH doesn't necessarily boost your steroid hormones, however. You do get a bundle of pregnenolone, which then produces a bundle of progesterone. The progesterone then has to be shared between production of androgens and estrogens, and production of glucocorticoids and mineralcorticoids, your stress reaction and housekeeping steroids.( 4)

The main glucocorticoid is cortisol. Dubbed the "stress hormone", cortisol is essential for appropriate bodily fight-or-flight reactions to danger. It's only in our warped society, where social controls conspire to keep you impotent and immobile while on the physiological boil, that cortisol becomes a problem.) Under such circumstances, it is highly catabolic.

That's one reason pregnenolone is no good for athletes. Unless you're a hockey player, and free to use up your cortisol by beating the bejesus out of anyone in your way, supplements of pregnenolone could easily raise cortisol levels to catabolize a lot of muscle.

This catabolism only happens, however, if you have normal supplies of the gatekeeper enzymes, one of which, 21-hydroxylase, is shown in the figure. These enzymes are essential for all glucocorticoid and mineralcorticoid production. I've shown 21-hydroxylase, because it is the most common inherited disorder of steroid hormone synthesis, and provides a great example of the complexity of the hormone cascade.

Low levels of 21-hydroxylase inhibit progesterone conversion to cortisol and corticosterone. The body frantically signals the brain to make more ACTH to boost steroid production, so it can look after salt and water balance, and multiple other housekeeping functions. Progesterone goes through the roof, but it still can't convert for lack of the enzyme. So it all flows to make androstenedione and other androgens (male hormones). Bingo! The afflicted child shows high androgen levels, sexual precocity, virilization, and, in girls, growth of male genitalia. This is not a happy situation. Folk with an inherited 21-hydroxylase deficiency, suffer all sorts of nastiness.

As the figure shows, when steroid production gets to androstenedione, it can go two ways. Either it makes testosterone or the potent estrogen estrone. (There are other possibilities but we're keeping it simple). Which way your androstenedione goes depends on multiple controls. If your gatekeeper, luteinizing hormone, is low for example, testosterone production is low also. You can take androstenedione until it flows out your ears, but conversion to testosterone occurs only to the tune of the gatekeeper.

Worse, androstenedione itself is highly androgenic.( 5) I've met some guys who don't seem to mind trading their hair for a remote chance of half-an-inch on the biceps. But add baldness, threats of all-over acne, and gorilla butt, and it can give pause to even the vainest.

Androstenedione was first synthesized in 1935.( 6) In 1936, world expert on steroid hormones, Dr. Charles Kochakian, was the first to show that androstenedione produced both androgenic and anabolic effects. But the anabolic effects were significant only in castrated dogs, and even then were much weaker than effects of testosterone.( 7) Like dozens of other androgens, androstenedione was consigned to research limbo.

It was briefly revived in 1962, when in a crude experiment, Mahesh and Greenblatt gave normal women either 100 mg of DHEA or 100 mg of androstenedione. The doses were arbitrary and hopelessly mismatched for both bioavailability and known biological activity. Nevertheless, both hormones increased testosterone levels. The proportionately higher dose of androstenedione caused about twice the rise found with DHEA, and increased the women's testosterone to six times above normal.

Sounds great, until you see from the data that the testosterone increase was transient, lasting only a couple of hours or so with a peak level of only a few minutes.( 8) Also, the study made no measurements of effects on strength or other performance.

Nevertheless, East German steroid doctors picked up these scant data in the 70's, and began developing androstenedione as an adjunct to testosterone-based anabolic steroids. After the fall of the Berlin Wall, Dr. Werner Franke obtained State Plan 14-25, the East German steroid "bible", that detailed the steroid programs of over 200 elite East German athletes. Androstenedione featured as a nasal spray formulation, used as a final performance booster just before competition. By the time any of the athletes were drug tested, their testosterone levels would likely have fallen to within the range allowed by the testosterone/epitestosterone ratio test.

Some East German athletes, and American athletes who got hold of the sprays, have since commented that their main effects were a thundering sinus headache, and a real bad mood. Remember how a lot of the East German Olympians had such sweet dispositions?

Androstenedione may have affects on athletes when taken by nose, but I wouldn't recommend snorting it, or other hormone. In any case, the only supplement I know on the American market is Androstene-50 which comes as a 50 mg capsule. There are no studies of this supplement.

The only hint of a study I could find with oral androstenedione on athletes, is an anecdotal mention by Bill Phillips in his latest supplement review of data in a German patent application. Doses of 50 mg and 100 mg of androstenedione apparently raised male testosterone levels by 140-180% and 211-237%.

We don't know how long these increases lasted, or whether they had any effects on strength or whether the study was the usual unpublished, uncontrolled mess found in patent applications. So overall, there are no controlled data that would recommend using oral androstenedione for muscle building.

I doubt that any good data will be forthcoming either. If the stuff was significantly anabolic, then in the 50 years it's been available, researchers would have jumped on it. Androstenedione is no big secret. It's just one of scores of intermediate steroids that have shown no general benefit for health, fitness or muscle.

If you are a drug-free athlete, it's even more murky, because of its chemical classification as an androgen. We are facing a myriad of chemicals like androstenedione, of unknown safety or efficacy, just itching to hit the market and take your money. Anyone advocating their use without controlled evidence of general benefits for long-term health, is off down the slippery steroid slide again, into hypocrisy and disease. If you value your health, don't go there.
REFERENCES

(1.) Colgan M. Hormonal Health. Vancouver: Apple Publishing, 1996.

(2.) Kochakian CD. Metabolites of testosterone. Significance in the vital economy. Steroids, 1990;55:92-97.

(3.) Colgan M. Optimum Sports Nutrition. New York: Advanced Research Press, 1993.

(4.) Stryer L. Biochemistry, 2nd Ed. New York: WH Freeman, 1981.

(5.) Yesalis CE (ed). Anabolic Steroids in Sport and Exercise. Champaign IL: Human Kinetics, 1993.

(6.) Ruzicka L, Wettstein A. The crystalline production of the testicle hormone testosterone (Androsten- 3-ol- 17-ol). Helvetica Chimica Acta, 1935; 18:1264-1275.

(7.) Kochakian CD, Murlin JR. The relationship of synthetic male hormone androstenedione to the protein and energy metabolism of castrated dogs and the protein metabolism of a normal dog. Amer J Physiol, 1936; 117:642-657.

(8.) Mahesh VB, Greenblatt RB. The in-vivo conversion of dehydroepiandrosterone and androstenedione to testosterone in the human. Acta Endocrinol, 1962;41:400-406.

Colgan Chronicles.

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