Many studies have indicated that estradiol modulates cognitive function and improves spatial memory.  For example ovariectomy decreases and estradiol treatment restores spatial memory in female rats.  Estradiol has direct effects on the brain, however, another important effect of estrogen is that it exerts negative feedback and keeps luteinizing hormone levels relatively low in eugonadal males and females.  Research from the human clinical literature has increasingly found that this negative feedback role is extremely important as high levels of LH, such as those seen after gonadectomy or menopause/andropause, are a risk factor for aging-related cognitive impairment and Alzheimer’s disease.  This talk will emphasize the role of luteinizing hormone on spatial memory in female rats and provide evidence that high levels of LH (such as those seen after ovariectomy) can act at the dorsal hippocampus to damage spatial memory.  We have found that peripheral injection of the LH homologue human chorionic gonadotropin (hCG) decreases spatial memory and increases amyloid-β levels in female rats.  Consistent with this, blocking (with a GnRH receptor antagonist) the high LH levels that occur after ovariectomy enhances spatial memory.  The hippocampus is amongst the brain regions that contains LH receptors and infusion of an LH homolog (hCG) specifically into the hippocampus blocks the beneficial effects of estradiol on spatial memory.  Consistent with this, infusion of an LH receptor antagonist into the hippocampus enhances spatial memory in ovariectomized females. Moreover, decreasing LH also minimizes spatial memory deficits and cellular damage in a hippocampal, neurotoxin-induced model typical of early Alzheimer’s disease.  These results suggest that at least some of the memory impairments seen in females after ovariectomy or menopause may be due to high luteinizing hormone levels acting upon the hippocampus and that a reduction in luteinizing hormone enhances spatial memory.