This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Menstrual disorders are significant medical problems affecting 30% of women during their reproductive lifetime. Our goal is to identify new treatments for heavy menstrual bleeding in women. Rhesus macaques are menstruating nonhuman primates with reproductive tract anatomy and menstrual cycles that are very similar to those of women. Thus, macaques and are excellent models for studies of menstruation. In preliminary studies we analyzed endometrial RNA and report that cyclooxygenase 2 (COX2;PTGS2) mRNA levels is significantly elevated during menstruation. COX2 enzyme is a limiting step in prostaglandin synthesis and we propose that increased synthesis of prostaglandin E2 (PGE2) is correlated with increased matrix-metalloproteinase (MMP) expression during menses. Our hypothesis is that drugs that disrupt the PGE2 paracrine system will reduce menstrual bleeding. To test this hypothesis we are investigating the effect of PGE receptor inhibitors on menstrual blood loss in rhesus macaques.