Letrozole (20 μg/d, p.o.) impairs spatial working memory, possibly by E2 in the hippocampus. A, Procedure for a delayed matching-to-sample (DMP) test trial includes the sample phase, when a monkey is presented with a red token placed over 1 of the 4 wells, and is allowed to displace the token to obtain a reward (dehydrated mini marshmallow). The test tray is then concealed from view for 1 s, during which time the reward is replaced and the token is repositioned over the sample location along with an identical token placed over a different well. During the test phase, the monkey must displace the token located in the same position to obtain the reward. Performance was averaged across trials given during a baseline phase, and after 4 weeks of drug treatment. Performance, which was measured as percentage of trials correct, was compared across phases within each experimental group (vehicle: n = 4; letrozole: n = 5). B, Mean accuracy of each group during the baseline and treatment week. Reduced performance was observed in the letrozole group (n = 5), whereas performance in the vehicle group (n = 4) did not change. *p < 0.05. Error bars indicate SEM. C, A larger reduction in performance is associated with higher E2 levels in the hippocampus within the letrozole group (r = −0.87, p = 0.058).