From
www.t-nation.com/free_online_article/spo...rugs/research_update
Research Update #3 — Anastrozole (Arimidex) and Letrozole: Not So Equipotent After All?
Back when anastrozole and letrozole first seemed to gain popularity among bodybuilders, the data—which many were forced to rely on—indicated that both compounds at the dosages employed for labeled use would suppress estradiol by 80-90%, often leading to suppression below the range of detection, in postmenopausal women. Furthermore, in vitro data indicated that the two compounds were equipotent in terms of their ability to inhibit aromatase. With that available data, it was often applied to healthy men as well.
Although this wasn't the intended purpose of it, a new study has revealed that the initial conclusions were wrong. This most recent study had shown that when 10 mg/day of anastrozole was given to two groups (young and older) of normal men, it only resulted in a decrease in levels of estradiol by about 25-50%, allowing estradiol to remain in the normal physiological range.
Actually, the 50% reduction in the younger men (18-33) remained in the physiological range while the older men (60-76) were just below the normal range after the 50% reduction. This is to be expected though, as the older men are starting with lower estradiol to begin with.
Another study in which men ages 60-90 were supplemented with 100 mg of Testosterone enanthate per week concurrently with 1 mg of anstrozole per day, again found a 50% reduction in estradiol. Previous studies in normal men, one using 10 mg/day, another using 1 mg/day, again have found an approximate 50% reduction in estradiol, leaving it within the normal physiological range. An older study using 15 elderly, eugonadal men, found a 29% reduction of estradiol when given 2 mg/daily for 9 weeks.
Letrozole, on the other hand, was able to decrease estradiol by 50% in men after they were given only 100 micrograms! Furthermore, it only takes around .5 to 2.5 mg to suppress estradiol below the normal physiological range in normal men (age range of 20-48).
As I’ve pointed out in a previous column, letrozole is an extremely potent aromatase inhibitor and should either be used sparingly or not at all. However, Anastrozole seems to have a lot more room for error in terms of not suppressing estradiol to subphysiological levels.
So, why the discrepancy between the efficacy in postmenopausal women versus normal healthy men? Simple. Postmenopausal women are obviously deficient in estradiol to begin with and are obviously lacking a great deal of the necessary substrate (i.e., Testosterone and via more indirect pathways, 4-androstenedione and DHEA) for estradiol formation.
Healthy, younger men have plenty of substrate with fully functioning testicles and thus you then see a postmenopausal woman’s top end of the normal range equating to less than half of what a normal man’s would be. That is, a normal postmenopausal woman has a serum estradiol concentration of around 72 pmol/L or less, while a normal adult male's is around 37-184 pmol/L.
Other things worthy of note include a study in which the decrease in estradiol from anastrozole over a 12-week period, using 1 mg/day versus 1 mg, twice weekly (Mondays and Thursdays) wasn't statistically significant.
The Bottom Line
Letrozole appears to be a much more potent aromatase inhibitor than anastrozole in men. However, due to letrozole’s pharmacokinetic properties and extreme potency, anastrozole would be preferable over letrozole as it allows room for error.
Anastrozole at a dose of .5 to 1 mg/day could be used effectively to moderately reduce estradiol, allowing you to still remain within the physiological range. There’s also some preliminary data that suggests using anastrozole at 1 mg twice per week (for men) may be as effective as daily administration of the same dose.
Research Update #4 — More Anastrozole (Arimidex) News
The update is actually derived from one of the same studies mentioned above. In it (double-blind, placebo-controlled and randomized), they took both 31 young (ages 18-33) and 20 older (60-76) healthy males and gave them 10 mg/day of anastrozole for five days.
They then measured serum concentrations of LH, Testosterone, SHBG and the molecular ratio of Testosterone to SHBG. What they found was that the older men had a diminished response to the aromatase inhibitor in terms of LH pulse amplitude and frequency, as well as total Testosterone and the Testosterone/SHBG ratio.
The authors, based upon this study and a good deal of previous data, concluded that the two most likely causes for such results are:
1) An impairment of GnRH release/secretion from the hypothalamus or some sort of impairment in the ability of GnRH to reach the gonadotropic cells of the anterior pituitary.
2) Impairment of steroidogenesis in the leydig cells as evidenced by a reduced responsiveness to recombinant LH, hCG, as well as estrogen antagonists and GnRH in terms of endogenous Testosterone production.
Now, whether this impairment at the leydig cells is G protein-coupled receptor-mediated or whether the defect is post receptor-mediated with the defect occurring downstream somewhere, is an important question. I tend to believe it’s the former.
In any event, this provides the perfect opportunity for use of a compound which works directly at the testicular level, and obviously not via a receptor-mediated mechanism. Compounds which would potentially fit this category would be eurycoma as well as those that directly and potently activate adenylate cyclase, bypassing the LH/hCG receptor on the leydig cells. Sclaremax would be an example.
The Bottom Line
As men age, we tend to experience a disruption in normal homeostatic function. Specifically, it’s likely that both an impairment of GnRH secretion (or access to the anterior pituitary) and decreased testicular steroidogenesis contribute to the decrease in endogenous Testosterone.
Compounds which increase testicular steroidogenesis via non-receptor-mediated mechanisms are most preferable in terms of a potential means of combating this age-related decline. (1-9)
