Estrogen suppression in males: Metabolic effects

We have shown that testosterone (T) deficiency per se is associated with ma rked catabolic effects on protein, calcium metabolism, and body composition in men independent of changes in GH or insulin-like growth factor I produc tion. It is not clear, however, whether estrogens have a major role in whol e body anabolism in males. We investigated the metabolic effects of selecti ve estrogen suppression in the male using a potent aromatase inhibitor, Ari midex (Anastrozole). First, a dose-response study of 12 males (mean age, 16 .1 +/- 0.3 yr) was conducted, and blood withdrawn at baseline and after 10 days of oral Arimidex given as two different doses (either 0.5 or 1 mg) in random order with a 14-day washout in between. A sensitive estradiol (E-2) assay showed an approximately 50% decrease in E-2 concentrations with eithe r of the two doses; hence, a l-mg dose was selected for other studies. Subs equently, eight males (aged 15-22 yr; four adults and four late pubertal) h ad isotopic infusions of [C-13]leucine and Ca-42/Ca-44, indirect calorimetr y, dual energy x-ray absorptiometry, isokinetic dynamometry, and growth fac tors measurements performed before and after 10 weeks of daily doses of Ari midex. Contrary to the effects of T withdrawal, there were no significant c hanges in body composition (body mass index, fat mass, and fat-free mass) a fter estrogen suppression or in rates of protein synthesis or degradation; carbohydrate, lipid, or protein oxidation; muscle strength; calcium kinetic s; or bone growth factors concentrations. However, E-2 concentrations decre ased 48% (P = 0.006), with no significant change in mean and peak GH concen trations, but with an 18% decrease in plasma insulin-like growth factor I c oncentrations. There was a 58% increase in serum T (P = 0.0001), sex hormon e-binding globulin did not change, whereas LH and FSH concentrations increa sed (P < 0.02, both). Serum bone markers, osteocalcin and bone alkaline pho sphatase concentrations, and rates of bone calcium deposition and resorptio n did not change. In conclusion, these data suggest that in the male 1) est rogens do not contribute significantly to the changes in body composition a nd protein synthesis observed with changing androgen levels; 2) estrogen is a main regulator of the gonadal-pituitary feedback for the gonadotropin ax is; and 3) this level of aromatase inhibition does not negatively impact ei ther kinetically measured rates of bone calcium turnover or indirect marker s of bone calcium turnover, at least in the short term. Further studies wil l provide valuable information on whether timed aromatase inhibition can be useful in increasing the height potential of pubertal boys with profound g rowth retardation without the confounding negative effects of gonadal andro gen suppression.