This application is being submitted as a supplement to grant RO1AG19100 entitled "Cognition and Estrogen in Middle-Aged Female Monkeys". Ovarian hormone deficiency of menopause brings on changes that can have far reaching consequences on the future health and well being of women. In addition to the physical symptoms associated with menopause, postmenopausal women experience alterations in cognitive function, particularly memory and attention. However, determining the relationship between ovarian hormones and cognitive function in menopause can be difficult to study in women because of a variety of confounding factors. We have developed a monkey model of menopause that allows us to more rigorously control many of these factors and, additionally, that will permit us to identify the potential mechanisms of ovarian hormone action in the primate brain. The focus of the studies in the parent project is to determine the effects of ovariectomy and unopposed continuous estrogen replacement therapy (ERT) on cognitive abilities in a unique colony of middle-aged female rhesus monkeys at the Oregon Regional Primate Research Center (ORPRC). The purpose of this supplemental application is to expand the breadth of valuable information that could be obtained from the parent project by adding another group of ovariectomized monkeys that will be treated with a combined therapy of continuous estrogen and progesterone (HRT) and by performing MRI studies in all monkeys (supplemental and original groups). The addition of the new group of monkeys will permit the direct comparison between ERT and HRT treatments on cognitive function. Combined HRT is not only the most commonly prescribed ovarian hormone replacement therapy of postmenopausal women; it also represents a hormone replacement therapy that more closely mimics the natural physiological exposure to estrogen and progesterone in premenopausal women than continuous unopposed ERT alone. The MRI studies will determine the extent to which ovariectomy or ovarian hormone therapy influence measures of brain volume that decline with age, and whether there is a correlation between these volumetric changes and cognitive function. The experiments in this supplemental application will address key issues of women's health by taking advantage of the existence of the treatment and control groups already supported by the parent grant. The findings from these novel experiments in middle-aged monkeys will significantly advance our understanding of the effects of different ovarian hormone therapies on cognitive and neurobiological profiles of primates.