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RU 486 in Women with Normal or Anovulatory Cyles

  • Gilbert Schaison
  • Martine George
  • Nelly Lestrat
  • Etienne-Emile Baulieu
Part of the Reproductive Biology book series (RBIO)

Abstract

The antiprogesterone steroid RU 486 was given orally to 32 normally cycling women for four days, starting on the fourth day after the basal body temperature shift. Uterine bleeding occurred on the third day of RU 486 administration in all 14 women treated with 100 mg per day, in seven out of the eight women treated with 50 mg, and in eight out of ten women receiving 25 mg per day. Luteal regression was observed in eight women treated with 100 mg per day, in three treated with 50 mg, and in two receiving 25 mg per day. Plasma LH was measured every 15 minutes from 0800 h to 1200 h for five days in 17 patients. Mean levels decreased, and its computerized pulsatile release disappeared in seven of the eight subjects treated with 100 mg, in two out of four receiving 50 mg, and in one out of five treated with 25 mg. RU 486 had no effect when given to five patients with anovulatory cycles for four days, starting on day 18 of their cycle.

In conclusion: 1) RU 486, given to normally cycling women at mid-luteal phase, induces uterine bleeding. 2) This effect occurs whether or not luteal regression is induced by the compound, indicating that RU 486 acts directly upon the endometrial tissue, very likely at the progesterone receptor level. 3) The drug may impair both luteal function and gonadotropin secretion in a dose-dependant manner. 4) At the dosage of 100 mg per day, the lack of antiglucocorticosteroid activity suggests that RU 486 may be promising as a new agent for fertility control.

Keywords

Plasma Renin Activity Corpus Luteum Uterine Bleeding Gonadotropin Secretion Luteal Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Balmaceda, J. P., Coy, Borghi, M. R., Schally, A. V., and Asch, R. H., 1983, Suppression of post ovulatory gonadotropin levels does not affect corpus luteum function in rhesus monkeys, J. Clin. Endocrinol, Metab., 57:866.CrossRefGoogle Scholar
  2. Bertagna, X., Bertagna, C., Luton, J. P., Husson, J. M., and Girard, F., 1984, The new steroid analog RU 486 inhibits glucocorticoid action in man, J. Clin. Endocrinol. Metab., 59:25PubMedCrossRefGoogle Scholar
  3. Filicori, M., Butler, J. P., and Crowley, W. F., 1984, Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion, J. Clin. Invest., 73:1638.PubMedCrossRefGoogle Scholar
  4. Gaillard, R. C., Riondel, A., Herrmann, W., Muller, A. F., and Baulieu, E. E., 1983, The antifertility steroid RU 486 is an antiglucocorticosteroid depressing the pituitary-adrenal system in the human but only at a specific time during the day, 65th Annual Meeting of the Endocrine Society, San Antonio, Texas, Abstract 219.Google Scholar
  5. Gravanis, A., Schaison, G., George, M., DeBrux, J., Satyaswaroop, P. B., Baulileu, E. E., and Robel, P., 1984, Endometrial responses to the antiprogesterone steroid RU 486 in post menopausal women, 7th International Congress of Endocrinology, Quebec, Canada, Abstract 1183.Google Scholar
  6. Halberg, F., Johnson, E. A., Nelson, W., Runge, W., and Sothern, R., 1972, Autorhythmometry procedures for physiologic self measurements and their analysis, Physiologic Teacher 1:1Google Scholar
  7. Healy, D. L., Baulieu, E. E., and Hogden, G. D., 1983a, Induction of menstruation by an antiprogesterone steroid (RU 486) in primates; site of action, dose response relationships, and hormonal effects, Fertil. Steril., 40:253.Google Scholar
  8. Healy, D. L., Chrousos, G. P., Schulte, H. M., Williams, R. F., Gold, P. W., Baulieu, E. E., and Hodgen, G. D., 1983b, Pituitary and adrenal response to the antiprogesterone and antiglucocorticoid steroid RU 486 in primates, J. Clin. Endocrinol. Metab., 57:863.CrossRefGoogle Scholar
  9. Herrmann, W., Wyss, R., Riondel, A., Philibert, D., Teutsch, G., Sakiz, E., and Baulieu, E. E., 1982, Effet d’un stéroide antiprogestérone chez la femme: interruption du cycle menstruel et de la grossesse au debut, CR Acad Sci Paris 294:933.Google Scholar
  10. Kreitmann-Gimbal, B., Kreitman, O. L., Sopelak, V. M., Kurman, R. J., Baulieu, E. E., and Hodgen, G. D., 1983, Menstrual induction in the primate fertile and non fertile cycle: antiprogesterone RU 486 binds to endometrial progesterone receptors without affecting luteal cells, J. Steroid. Biochem., Supp. 19: 12 S, abstract 336.Google Scholar
  11. Nieman, L. K., Chrousos G. P., Spitz, I., Nisula, B. C., Cutler, G. B., Merriam, G. R., Bardin, C. W., and Loriaux, D. L., 1984, Successful treatment of Cushing’s syndrome with the glucocorticoid-antagonist RU 486, 7th International Congress of Endocrinology, Quebec, Canada, Abstract 1718.Google Scholar
  12. Rothchild, I., 1981, The regulation of the mammalian corpus luteum, Rec. Prog. Horm. Res., 37:183.PubMedGoogle Scholar
  13. Schaison, G., George, M., Lestrat, N., Lagoguey, M., and Baulieu, E. E., 1984, Inhibitory effects of the antiprogesterone steroid RU 486 on gonadotropin secretion in women, 7th International Congress of Endocrinology, Quebec, Canada, Abstract 2278.Google Scholar
  14. Soules, M. R., Steiner, R. A., Clifton, D. K., Cohen, M. L., Aksel, S., and Bremner, W. J., 1984, Progesterone modulation of pulsatile luteinizing hormone secretion in normal women, J. Clin. Endocrinol. Metab., 58:378.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Gilbert Schaison
    • 1
  • Martine George
    • 1
  • Nelly Lestrat
    • 1
  • Etienne-Emile Baulieu
    • 1
  1. 1.Department of Endocrinology and Reproductive MedicineHopital de BicetreBicetreFrance

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