Friday, January 11, 2013

The best estrogen maintenance drug

Formestane is the first in a new line of selective, steroidal-based aromatase inhibitors. It is currently available in a few European countries, and is expected to reach U.S. shelves before long. Formestane is structurally a derivative of androstenedione, most specifically 4-OH androstenedione. Androstenedione is a readily aromatized steroid, so clearly this similarity welcomes interaction with the aromatase enzyme. Its activity in the body is in fact that of a suicide inhibitor, meaning that the compound will become inextricably bound to the aromatase enzyme upon contacting it. Its effect is therefore comparatively much more lasting than that seen with reversible, competitive inhibitors. This is no doubt the reason formestane was shown in studies to be as much as 60 times more potent than aminoglutethimide. As with Arimidex, this compound can help achieve near total suppression of aromatase.
Due to poor oral bioavailability, formestane is commercially prepared as an injectable product. The typical recommendation is an injection of 250mg (typically 1 ampule or injection) every two weeks. Though estrogen suppression can be marked with this dosing pattern, some studies do suggest that by the second week (near the time the dosage is to be repeated) estrogen levels may begin to recover.
The BEST estrogen maintenance drug?
Clearly there is more to consider in choosing an estrogen maintenance drug than just which is the most effective. The discussed differences in cholesterol alterations between anti-estrogens and aromatase inhibitors for example are worth taking into account. In this regard an antiestrogen such as tamoxifen or clomiphene would be most preferred. This is in great contrast to aminoglutethimide, Nolvadex or Clomid, which can cost $100 or less monthly. By measure of which is the most efficient remedy for estrogenic side effects, it would seem that Arimidex and formestane would technically be the most effective. Though more expensive, formestane was actually shown to be slightly less reliable than Arimidex in head to head studies, so its higher price should not automatically lead us into thinking it is the superior of the two. Ultimately however, it is doubtful that either of the new selective aromatase inhibitors (or other related agents slated to be released) will prove to be leagues ahead of the already tried and accepted estrogen maintenance drugs Nolvadex, Clomid and aminoglutethimide in the eyes of athletes. This is simply because the mentioned agents all deal with the action/buildup of estrogen quite effectively (in terms of clinical effectiveness of three agents compare closely to the new selective inhibitors), and outside of a medical setting the high cost of these newer agents will likely prohibit wide spread use.