Within cohort 2 (red dots), serum CTX levels increased significantly more than in the controls in every testosterone group ( P < for each comparison), with increases exceeding those observed in cohort 1 by 50%–100%. Serum CTX even increased substantially more in cohort 2 than in cohort 1 in men who received placebo testosterone ( Figure 3A ), possibly because serum estradiol levels were higher in men who received placebo testosterone alone (cohort 1, ± pg/ml) than in men who received placebo testosterone plus anastrozole (cohort 2, ± pg/ml). Within cohort 2, there was a significant inverse relationship between the testosterone dose and the increase in serum CTX levels. CTX levels increased more in the groups that received 0, , or grams of testosterone gel daily than in the 2 higher-dose groups, and these differences persisted even when the results were adjusted for the small differences in serum estradiol levels between testosterone-dose groups in cohort 2. Serum P1NP tended to increase more in groups that received anastrozole than in those that did not, though most of the individual comparisons were not statistically significant.