Figure 2.

Aromatase inhibition disrupts estrous cycling and decreases systemic estradiol levels. (A) Aromatase inhibitors, formestane and letrozole, block the conversion of androgens to estrogens. (B) During treatment, aromatase inhibitors increase the percentage of time the female mouse spends in the diestrus phase of the cycle (n = 7–24/group). (C) Uterine indices are decreased in estrus compared to proestrus mice. Treatment with aromatase inhibitors likewise decreases uterine indices (n = 7–14/group). (D) Estradiol-immunoreactivity was quantified in serum directly measured by ELISA (unextracted). Letrozole treatment tended to decrease estradiol levels and proestrus levels were elevated compared to estrus. However, male vehicle serum estradiol levels were high, similar to proestrus female levels. Most values are below the lower limit of detection of the assay (n = 3–8/group). (E) There is a positive correlation between estradiol-immunoreactivity in serum measured by ELISA and uterine index in female mice (n = 20). (F) Estradiol-immunoreactivity was additionally quantified in serum that was extracted prior to ELISA. Again, letrozole treatment tended to decrease estradiol levels and proestrus levels were elevated, though with even larger variability, compared to estrus. With extraction, male serum estradiol levels were below female (n = 2–9/group). Post test p-values are provided above the corresponding comparisons. Individual points represent individual mice and matched points represent a mouse at different time points. Data are presented as mean ± SEM.