Forty-three million women will reach the age of 50 in the United States in this decade, and coronary artery disease (CAD) will be the leading cause of death in this group. Therefore, it is imperative to understand the risk factors which contribute to the pathophysiology of CAD. Among these, alterations in lipoproteins play a major role. However, much remains to be learned about the various forms of high and low density lipoproteins (HDL and LDL) and their regulation. Therefore, the goal of this study is to elucidate the effects of endogenous and exogenous estrogens, progestins and androgens on speciation of HDL and LDL composition in reproductive age and postmenopausal women. To achieve this goal, studies will be performed in three groups of women: 1) women with normal menstrual cycles [before and after administration of a gonadotropin releasing hormone (GnRH) analog] ; 2) hyperandrogenic women of reproductive age (before and after administration of a GnRH analog with and without added estrogen] ; and 3) postmenopausal women [one group without exogenous steroids, one group receiving estrogen only, and a third group receiving estrogen plus progestin]. Women in all studies will have gonadotropins, sex steroids (estrogens, androgens, progesterone), and sex hormone binding globulin, measured by radioimmunoassay. These measurements will be correlated with the distribution of newly identified native species of HDL as assessed by selected affinity immunosorption and immunoassays, and with the quantized speciation state of LDL as assessed by gradient ultracentrifugation and electron microscopy. These correlations will provide new insights into the relationships between sex steroid hormone milieu, age and lipoproteins, and should lend to greater understanding of the etiology, treatment and prevention of CAD in women.
