FORMS OF GONADOTROPINS AS MARKERS OF MENOPAUSE

With the extension of the human life span, women spend a third of their lives beyond the reproductive years. The transition into menopause is associated with physical risks and psychological adjustments. Major research initiatives are currently under way to improve understanding of these of these changes but these efforts are hampered by the hampered by the lack of diagnostic tools for determining how close a woman is to menopause. If a reliable test existed to differentiate a premenopausal woman from a woman early in menopause, new research initiatives would be posible since menopausal changes could be placed in relation to the stage of the menopusal transition. Such a test would also help diagnose patients whose symptoms are dissociated from current critria as FSH levels, women who have no uterus and thus no menses by which to gauge menopause, and as a possible guide to estrogen replacement dosing. We propose a novel approach of developing urinary assays to determine how close a woman is to menopause based on the excreted metabolities of the beta subunits of hLH and hFSH. Heterodimeric gonadotropins are not stable in urine but these metabolites are highly stable, without any additives, to storage and freeze-thaws. Based on our experiences with the diagnostic utility of urinary metabolites of hCG and new findings (reported in this application) on metabolites of hLH, we propose to develop tools to measure FSH urinary metabolites and use these immunogical tools, along with those hLH, to test the hypothesis that measurement of excreted metabolites of FSH may provide better markers of the entry into menopause than does the current unreliable marker of serum FSH concentration. We propose to: 1. Isolate and characterize the beta subunit fragments of FSH from the urine of postmenopausal women. 2. Develop specific monoclonal antibodies to FSH metabolites and two site immunoassays for measuring the FSH metabolites in urine. 3. Test applicability of measurement of LH and FSH fragments as markers of the onset of menopause and as response markers to estrogen replacement therapy.