Increases in luteinizing hormone are associated with declines in cognitive performance.

Questions surrounding estrogen therapy for post-menopausal cognitive decline and dementia led us to examine the role of luteinizing hormone that becomes elevated after menopause. We examined hippocampal-associated cognitive performance, as measured with the Y-maze task, in two strains of transgenic mice, one (Tg-LHbeta) which over-expresses luteinizing hormone and another (LHRKO), which has increased circulating luteinizing hormone levels, but its receptors are silenced. Our results demonstrate that Tg-LHbeta, but not LHRKO mice, show decreased Y-maze performance when compared to aged-matched wild-type animals. These findings indicate that increased luteinizing hormone levels, in the presence of functional receptors may, at least in part, be responsible for cognitive decline after menopause. As such, modulation of luteinizing hormone or its receptor levels may prove to be useful therapeutic strategies for cognitive decline associated with aging and age-related neurodegenerative diseases such as Alzheimer disease.