This proposal is a request for supplemental funding to the Stanford University component of the Post-menopausal Estrogen/Progestin Intervention trial (PEPI). This supplement is to support the addition of a bone density component to a research program in women's productive health granted to Kaiser permanent of Northern California Department of Health Services. The Women's Reproductive Health Study (WRHS) examines the impact of demographic, physical, and environmental factors on ovulatory function, fertility, fecundity, and early fetal loss of 400 women, age 18-39 years. Reproductive function is monitored in this study by collecting daily urine specimens for analysis of steroid hormone metabolites. The method permits description of menstrual cycles as normal of anovulatory and also defines subtle abnormalities, menstrual status and bone mass in young women. Although cessation of menses may lead to loss of bone and increased fracture risk, it has been suggested, that even subtle menstrual irregularities promote accelerated rates of bone loss in young women. The consequences of this observation, if true are substantial, since abnormal menstrual cycles are alleged to affect one third of healthy women. We propose to evaluate this problem in three hundred women participants in WRHS who are characterized with respect to menstrual function an other health-related factors. We will assess bone mineral status at baseline and at 9 and 18 months thereafter. Bone mineral density will be measured at the lumbar spine. proximal femur, and whole body by dual energy x-ray absorptiometry. In addition, we will collect nutrient intake and physical activity data by questionnaire, and will supplement the urinary hormone data by two additional cycles of collections at the time of the bone mineral assessment. This proposal specifically addresses the following primary questions: 1) What is the relationship between current menstrual status and bone mass in young ad women? 2) What is the relationship between menstrual status and the rate of bone loss from the spine, hip and whole body in healthy young women? In addition, the protocol will permit us to address the following secondary questions: 3) To what extent, and at which sites can acquisition of bone be demonstrated by healthy women in the third decade of life? 4) What is the relationship between current nutrient intake and bone mass and between nutrient intake and the rate of change in bone mass? What is the relationship between current physical activity and bone mass and between physical activity and the rate of change in bone mass? 6) What is the relationship between menstrual status and bc composition (e.g. fat and lean mass using dual energy x-ray absorptiometry? 7) Finally, in women to describe the effects of pregnancy, become pregnant during the course of his study, we will able and lactation.
