THE EFFECTS OF POSTOVULATORY ADMINISTRATION OF ONAPRISTONE ON THE DEVELOPMENT OF A SECRETORY ENDOMETRIUM

The purpose of this study was to assess the ability of the anti-proges tin onapristone administered in the immediate post-ovulatory period to disrupt endometrial differentiation as a potential method of fertilit y control, In all, 10 healthy female volunteers were given 400 mg onap ristone 2 days after the mid-cycle luteinizing hormone (LH) surge in u rine (LH+2), An endometrial biopsy was taken 4 or 6 days after the LH surge (i.e. LH+4 or LH+6) in a control cycle and on the corresponding day of the treatment cycle, Biopsies were assessed for histological da ting and immunolocalization of oestrogen receptors, progesterone recep tors and 15-hydroxyprostaglandin dehydrogenase (PGDH), On day LH+12, b lood was taken for the measurement of insulin-like growth factor bindi ng protein-1 (IGFBP-1) and placental protein 14 (PP14), Hormonal measu rements in blood and urine were used to monitor the effects on the men strual cycle, In addition, the concentration of cortisol in plasma was measured to determine if this dose of onapristone exerted significant anti-glucocorticoid activity. Treatment with onapristone retarded the development of secretory changes within the endometrium without affec ting the length of the luteal phase, Intense nuclear immunostaining of oestrogen and progesterone receptors was evident in glands and stroma after treatment, suggesting that the progesterone-dependent down-regu lation of steroid receptors was inhibited by the anti-progestin. Onapr istone also affected the production of luteal phase endometrial protei ns, as judged by the pronounced reduction in immunostaining of PGDH wi thin the glands and the significant reduction in plasma concentrations of PP14, However, plasma concentrations of IGFBP-1 did not differ bet ween cycles, Onapristone did not appear to exert significant anti-gluc ocorticoid activity because concentrations of cortisol were unaffected , These findings suggest that onapristone could potentially be used as a method of postovulatory fertility control.