Human Reproduction, Vol. 11, No. 1, pp. 40-49, 1996
© 1996 European Society of Human Reproduction and Embryology
research-article |
The effects of post-ovulatory administration of onapristone on the development of a secretory endometrium
1Department of Obstetrics and Gynaecology, University of Edinburgh 37 Chalmers Street, Edinburgh EH3 9EW 2MRC Unit of Reproductive Biology, Centre for Reproductive Biology, University of Edinburgh 37 Chalmers Street, Edinburgh EH3 9EW 3Department of Pathology, St Mary's Hospital Whitworth Park, Manchester M13 OJH 4Department of Reproductive Physiology, St Bartholomew's Hospital London EC1A 7BE UK
Correspondence: 5To whom correspondence should be addressed
The purpose of this study was to assess the ability of the anti-progestin onapristone administered in the immediate post-ovulatory period to disrupt endometrial differentiation as a potential method of fertility control. In all, 10 healthy female volunteers were given 400 mg onapristone 2 days after the mid-cycle luteinizing hormone (LH) surge in urine (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 dating and immuno-localization of oestrogen receptors, progesterone receptors and 15-hydroxyprostaglandin dehydrogenase (PGDH). On day LH+12, blood was taken for the measurement of insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14). Hormonal measurements in blood and urine were used to monitor the effects on the menstrual 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 affecting 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-regulation of steroid receptors was inhibited by the anti-progestin. Onapristone also affected the production of luteal phase endometrial proteins, as judged by the pronounced reduction in immunostaining of PGDH within the glands and the significant reduction in plasma concentrations of PP14. However, plasma concentrations of IGFBP-1 did not differ between cycles. Onapristone did not appear to exert significant anti-glucocorticoid activity because concentrations of cortisol were unaffected. These findings suggest that onapristone could potentially be used as a method of post-ovulatory fertility control.
Key words: endometrium/endometrial differentiation/fertility control/onapristone
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