The effects of post-ovulatory administration of onapristone on the developmnent of a secretory endometrium.
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 immunolocalization 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 postovulatory fertility control.
Cameron
S T
ST
Department of Obstetrics and Gynaecology, Centre for Reproductive Biology, University of Edinburgh, 37 Chalmers Street, Edinburgh EH3 9EW.
Critchley
H O
HO
Buckley
C H
CH
Chard
T
T
Kelly
R W
RW
Baird
D T
DT
D000328:Adult; D001706:Biopsy; D003276:Contraceptives, Oral / Q000008:administration & dosage* / Q000494:pharmacology; D004717:Endometrium / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects*; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000097:blood; D006067:Gonanes / Q000008:administration & dosage* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis; D008183:Luteal Phase / Q000187:drug effects; D007986:Luteinizing Hormone / Q000652:urine; D010060:Ovulation; D011257:Pregnancy Proteins / Q000097:blood; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D003276:Contraceptives, Oral; D000071816:Glycodelin; D006023:Glycoproteins; D006067:Gonanes; D006727:Hormone Antagonists; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007986:Luteinizing Hormone; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; C053238:onapristone