Anti-Androgenic Effect of ATD

A few month ago a study by Svensson (Svensson. 2010) caused quite a fuss in the supplement world. The scientist had injected huge amounts of ATD into his laboratory rats and found that "the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD; 60 mg/kg/day s.c.) decreased behavioral disinhibition in testosterone-treated rats (without affecting accessory sex organ weights)". In view of the huge dosage, I simply ignored the results of that study until I recently stumbled across a whole bunch of papers which support the notion that ATD is in fact anti-androgenic, in that it does reduce testosterone receptor binding in the brain (Kaplan. 1989).

The negative effect of ATD administration on mating behavior and success (2x ejaculation) in testosterone treaded rats is alarming (cf. figure 1):

Figure 1: Effect of ATD supplementation on sexual performance of hypogonadal rats treated with testosterone + propylene glycol (T+PG), testosterone + ATD (T+ATD) or ATD alone.
(Kaplan. 1989. Figure 1)

These observation lead the scientists to conclude that:

it is clear that the aromatase inhibitor, ATD, suppresses sexual activity in male rats, although it is more effective following systemic administration than bilateral MPOA implants. While these data may be viewed as consistent with the hypothesis that aromatization of T is an essential step in the activation of sexual behavior in male rats, our biochemical data have provided an alternative explanation. Specifically, we suggest that because ATD inhibits AR binding, it may not allow T to bind to androgen receptors in order to initiate sexual behavior. Previous work from our laboratory (McGinnis and Mirth, 1986) has demonstrated that the androgen receptor blocker Sch16423 prevents restoration of male sexual behavior, thus further strengthening the concept that AR activation is necessary for the induction of male sexual behavior. 

With 15mg (human dose equivalent ca. 225mg for a male human being), the scientists still used a comparatively high dose that is about 3x the 75mg (i.e. 3x25mg) ATD many supplement producers suggest. Notwithstanding, the results of this and other studies should remind you of the simple truth that more is not always better. So stick is what is necessary to get rid of excess estrogen as it may appear in the course of a post cycle therapy, but abandon use of ATD as soon, as aromatization is not an issue anymore.

Non-systemic administration via platelet implant, as it has been used in a more recent study by Roy & Goy (Roy. 2004), however, did not influence copulatory behavior in male rats (it did so to a large extent in female rats, though); the scientists missed however to investigate whether there was a similar, unwelcome effect on repeated ejaculation as it was observed by Kaplan et.al. About 15 years before Steel & Hutchinson (Steel. 1989) had found that even the ability of male rats to distinguish between male and females was greatly affected by high dose ATD implants.

Other than Kaplan, et.al. Steel & Hutchinson explain this effect along the conventional hypothesis of peripheral aromatization in the brain being necessary for normal sexual behaviour. In view of the in-vitro data Kaplan et.al. are referring to (ATD competing with androgens for receptor binding) I would assume that it is a combination of both, low estrogen and competitive binding, which induces the negative effects on libido seen in high dose ATD treatment.

Edit: I am currently (08/25/2010) having an interesting discussion on the M&M board on ATD vs. PES new aromatase Inhibitor "Erase" - join the battle ;o)