Menopause is a universal phenomenon affecting all women. Each year, billions of dollars are spent on therapies to alleviate menopausal symptoms, particularly hot flashes. The age of onset of menopause has been linked to specific diseases and longevity. Thus, understanding the genetic controls of menopause could expedite the search for the mechanisms of aging and better treatments of menopausal symptoms. As a first step toward that goal, this proposed pilot and feasibility study will estimate the heritability of the age of menopause and hot flashes, and pave the way for subsequent studies that will eventually identify the genes. This pilot project is designed as an observational cohort study of sister pairs. The participants are drawn from an existing cohort of over 2000 sisters who are participating in a genetic study of bone mass. They are normal, healthy women between ages 20 and 50; who already have a genome scan performed on their DMA, providing genetic markers for subsequent linkage analyses. In this pilot study, about 100 pairs of sisters will be recruited; priority will be given to those closer to menopause. They will use diaries for up to one year to record their menstrual cycles so the onset of menopause can be documented accurately. They will also record the occurrence of hot flashes in order to give more precise measurements of the frequency and severity. Heritabilities will be estimated for the age of onset and symptoms of menopause. The study will also work out the logistics of drawing and storing serum samples on the third and 24th day of a woman's cycle for future measurements of sex hormone levels. When this study is accomplished, the heritability estimates will be used in planning a sib-pair linkage study on the full cohort. After promising regions are identified that may harbor genes that control the age of onset and symptoms of menopause, follow-up molecular genetic studies will attempt to identify the specific genes in the future. ? ?
