The Law of Unintended Consequences Strikes Again
Androstenedione -
Mother Nature's Little Joke

Androgen: the word conjures images of macho males with bulging biceps and an attitude to match. What boy or man has not wished for bigger, stronger muscles, the better to belt a baseball or carry a swooning female into the bedroom?

It's tempting, for those whom Mother Nature has not endowed as generously as they might have wished, to help things along by taking male sex hormones or anabolic steroids in order to bulk up. The Schwarzenegger Standard may be an impossible dream, but we do what we can. The trouble is, though, that the Law of Unintended Consequences often prevails, especially when things are more complicated than we thought.

Consider the difficulty of understanding living organisms. Every living cell contains billions of molecules of thousands of different kinds, caught up in a maelstrom of frenzied motions and interactions - stupendous complexity is an understatement here. So it's hardly surprising that our ability to predict exactly what will happen when we mess around, molecularly speaking, with such a system leaves much to be desired, and that Mother Nature still has more tricks up her sleeve than Houdini ever dreamed of.

Oh, the Irony!
A beauty that has fallen out of Mom's bounteous sleeve has to do with androstenedione ("andro" for short), the over-the-counter male sex hormone. Many hopeful boys and men (including the awesome Mark McGwire, who doesn't need it) have been taking it to bulk up. Because andro is a close chemical precursor of testosterone, the principal virilizing hormone, taking it as a supplement should boost testosterone levels and thus help build muscle mass, right?

Wrong! Not only does it not do that, what it does instead - are you ready for this - andro boosts estrogen levels and can thus build breast mass. (You weren't ready.) This perverse little joke of Ma Nature's, at our expense, is revealed in a rigorous new study of andro - the first really good one - by a team of researchers from the Exercise Biochemistry Laboratory at Iowa State University.1

The Experiment
In an 8-week-long, randomized, double-blind experiment, 30 healthy young men aged 19-29 were selected on the basis of normal testosterone levels; no recent use of androstenedione or any other nutritional supplements or anabolic steroids; no use of illicit drugs or abuse of alcohol; no recent history of resistance training (pumping iron or similar muscle-building exercises); and no health problems that would preclude such training.

Throughout the 8-week period, ten of the men were given andro, ten were given placebo, and all 20 were put through a very carefully controlled and monitored regimen of whole-body resistance training designed to increase the strength of all major muscle groups.

The dosage of andro was 300 mg/day, the high end of the 100-300-mg/day dosage recommended by the manufacturers. The men were instructed to follow their normal diets, which the researchers monitored and analyzed for nutritional composition. The men's serum testosterone levels were measured, as well as, their body mass and strength were measured at the outset and after 2, 5, and 8 weeks of training.

The remaining ten men in the study participated in a different way. They were given a single 100-mg dose of andro, or a placebo, on two separate days, one week apart. Their serum testosterone levels were measured before taking the pill and then afterward at 30-minute intervals for the next 6 hours. They did not undergo the training.

The Sad Truth About Andro
Among the principal findings of this study were that:

  • Short-term and long-term androstenedione supplementation did not increase serum testosterone levels in these healthy young men; overall, the effect was nil.
  • Although the resistance training did increase body mass and muscle strength significantly, these were independent of the androstenedione, which had no effect on the outcomes.
  • A significant proportion of the ingested androstenedione was converted to estrogens.
Yes, estrogens! To a physiologist or biochemist, this is not all that surprising, though, because it is well known that androstenedione is a chemical precursor not only of testosterone but of estrone and estradiol (among others) as well. Which way andro will convert in any given circumstance depends on a great many factors, some of them well understood and some not.

One thing that is well understood is that prolonged, elevated levels of estrogen in men can lead to increased risks of heart disease, pancreatic cancer, and prostate cancer. They also induce gynecomastia, the abnormal enlargement of breasts in men (this is probably not what Mark McGwire had in mind, and it could interfere with his mighty swing).

A Cautionary Tale  
What can we learn from this tragicomic story? Simply this: There is no substitute for rigorous scientific research to find what the truth really is, as opposed to what we think it ought to be or what we wish it were. And that is why Life Enhancement places strong emphasis on well-documented, controlled scientific studies as the sole basis for their views and recommendations on the nutritional supplements they offer.

It is precisely because there was no such study on androstenedione until now - and because there has long been good reason to be suspicious of the claims made for it - that we have previously warned our readers, in very strong terms, against the use of this substance.

In Don't Be An Andro Guinea Pig - November 1998, we emphatically warned of the potential dangers of using andro and of the strong likelihood that it would do what solid research has now confirmed: lead to increased production of the female sex hormones rather than testosterone!

Vindication is sweet, but we will not rest on our laurels. We will continue to bring you, every month, the best, most scientifically reliable information we possibly can on life-enhancing nutritional supplements. Meanwhile, if you know anyone who's using andro, or thinking about it, please show him this article (with references).

Finally, two special notes. First, a comment regarding this study in the same issue of JAMA sounds a predictable and familiar alarm: the federal government should step in and  remove androstenedione from the market.2 We take a different view: that the market itself will be the fairest and most efficient mechanism for deciding andro's fate, once the truth gets out. And unlike government intervention, which engraves its own mistakes in stone so that they will outlast us all, a free market can and does turn swiftly to rectify its mistakes.

Second, the research described above was financed by a manufacturer of oral androstenedione, who must surely have hoped for (prayed for?) a different outcome. It is greatly to the researchers' credit that they apparently did not allow the source of their funding to compromise their scientific objectivity in letting the chips of truth fall where they may. Bravo!


  1. King DS, Sharp RL, Vukovich MD, Brown GA, Reifenrath TA, Uhl NL, Parsons KA. Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. JAMA 1999;281(21):2020-8.
  2. Yesalis CE III. Medical, legal, and societal implications of androstenedione use JAMA 1999;281(21):2043-4.

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