Return to the Cognitive Enhancement Research Institute Home Page or Q&A Page.
Excerpted from the August 20th, 1998 issue of Smart Life News. Copyright (c) 1998-1999. All rights reserved.

Question: Androstenedione is being touted as a safe and effective steroid for increasing testosterone levels in men (and women). Is it effective? Are there any down-side risks for its use. ——OTP

Answer: Androstenedione (an-dro-steen-dye-own) is an intermediate in the steroid pathway from DHEA to testosterone (see Figure 1, below). When androstenedione is administered, it causes a rapid increase in testosterone levels, which last only for a few hours. It does not increase testosterone in any lasting way. For men and women who may want a brief testosterone surge for 1) enhancing anabolic gains from strength exercises, or 2) enhancing libido for prosexual purposes, androstenedione can be an effective option.

The traditional method of administering testosterone is by intramuscular injection of a depot of esterified testosterone. Esterified testosterone is testosterone chemically bound to a fatty acid molecule. This reservoir of fat-bound testosterone slowly hydrolyzes (breaks down) to provide a sustained release of free testosterone over the course of many days to possibly more than a week. The problem with this depot injection method is that it delivers testosterone in an unnatural manner. Not only does it not mimic the natural circadian (daily) testosterone rhythm which peaks in the early morning hours before dawn, but immediately following the injection testosterone levels become quite high for a day or two. Elevated testosterone stimulates negative feedback receptors in the hypothalamus, which inhibit natural testosterone production. When the depo-injection wears off after a few days to a week, testosterone levels often fall below desired levels, until the testosterone deficiency provides the feedback to upregulate (restore) natural testosterone production to minimal (and possibly quite deficient) levels.

Transdermal testosterone delivery (via patches, creams and lotions) has recently become a popular alternative to injections. Transdermal testosterone can be applied on and absorbed through the skin to provide a smoother, less volatile testosterone profile which 1) reduces negative feedback to the hypothalamus, and 2) can more closely follow the natural circadian rhythm for testosterone. Testosterone creams are far less painful than injections and often much more convenient for people to use.

Androstenedione offers a fast-acting, over-the-counter alternative to prescription-only testosterone patches, creams and lotions. It is sold in capsules or pills for oral use, and it has recently become available in a liquid spray for sublingual use. The sublingual spray raises testosterone levels in less than 30 minutes.

The problem with androstenedione is that it is quickly metabolized into estrogens. Estrogens have strong anti-testosterone-like metabolic effects that last for a long time (days as opposed to hours). Androstenedione produces estrogens through two separate pathways. First, it can be directly metabolized into estrone (see Figure 1). Second, it can be metabolized to testosterone and then to estradiol. Both estradiol and estrone are “strong” estrogens which suppress the anabolic, metabolism-enhancing, fat-loss and tissue-healing properties of testosterone. I believe that many people will suffer estrogen-related side effects from androstenedione that will have far more negative impact on their health than the positive effects from androstenedione or testosterone.

The estrogen problem can be clinically managed by measuring before-and-after estrogen levels. This can be done with blood tests that are available through a physician, or with saliva tests that are available over the counter (call Vitamin Research Products or Smart Basics). Such tests can give you some idea of the magnitude of the estrogen risks that may be associated with your use of androstenedione (or its immediate precursor DHEA, which can also be metabolized into estrogens).

Estrogen is not something to be trifled with. In men, estrogen levels increase with age as testosterone and DHEA levels decrease with age. It is possible, and maybe even likely, that some aspects of aging are directly due to the increasing influence of estrogen with advancing age. It is also possible that rising estrogen levels play a major role in prostate enlargement, and prostate and testicular cancers. Androstenedione is more closely linked to the estrogen branches of the steroid tree than DHEA, which also has potential estrogen-related risks.

Androstenediol, a close cousin of androstenedione, is able to be directly metabolized into testosterone but only indirectly into estradiol and estrone (see Figure 1). It is reportedly more efficient at producing testosterone than androstenedione. It is possible that it produces less estrogen as well. As far as I know, the estrogen-enhancing effect of all these compounds has not been systematically evaluated or compared. Even if we knew the comparative risks, testing would still be needed. Clinicians report large differences among their patients in how steroids are metabolized into estrogens. Test and be sure.

Androstenedione is available through Smart Basics, Vitamin Research Products and Olympia Nutrition, all on our Resources Listing. Androstenediol is available through Olympia, and Anabol Power Dist. (011-31- 26-381-0668, in The Netherlands). Olympia also has a combination formula. ——SWF

Click here to go on to a follow up question four issues later.